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13,200 | 31,985,505 | Conclusion : Both technologies have a high proportion of successful PPL localization with similar sensitivity for malignancy and accuracy . | Background : Lung cancer screening with computed tomography chest is identifying peripheral pulmonary lesions ( PPLs ) suspicious for early-stage lung cancer at increasing rates .
Radial-endobronchial ultrasound ( R-EBUS ) and electromagnetic navigation bronchoscopy ( ENB ) are 2 methods to sample PPLs to diagnose and treat early lung cancer .
ENB has a higher operating financial cost , however , the rationale for its use is possible higher diagnostic accuracy versus R-EBUS .
Objective : The objective of this study was to determine the comparative diagnostic accuracy , sensitivity , and negative predictive value for R-EBUS and ENB in sampling PPLs . | STUDY OBJECTIVE To assess the ability of endobronchial ultrasonography ( EBUS ) using a guide sheath ( EBUS-GS ) to diagnose peripheral pulmonary lesions . METHOD We devised a technique for EBUS-GS covering a miniature probe , and 150 lesions were evaluated in a prospect i ve open study . In this procedure , the probe covered by a guide sheath is introduced into the lesion via the working channel of a bronchoscope . The probe is withdrawn , while the guide sheath is left in situ . A brush or biopsy forceps is introduced through the guide sheath into the lesion . RESULTS One hundred sixteen of 150 EBUS-GS procedures ( 77 % ) were diagnostic . Cases in which the probe was located within the lesion had a significantly higher diagnostic yield ( 105 of 121 cases , 87 % ) than when the probe was located adjacent to it ( 8 of 19 cases , 42 % ) [ p < 0.0001 , chi(2 ) ] . The diagnostic yield from EBUS-GS in lesions < /= 10 mm ( 16 of 21 lesions , 76 % ) , > 10 to < /= 15 mm ( 19 of 25 lesions , 76 % ; p = 0.99 , chi(2 ) ) , > 15 to < /= 20 mm ( 23 of 35 lesions , 66 % ; p = 0.41 , chi(2 ) ) , and > 20 to < /= 30 mm ( 33 of 43 lesions , 77 % ; p = 0.96 , chi(2 ) ) were similar , demonstrating the efficacy of EBUS-GS even in lesions < /= 10 mm in diameter . In 54 of 81 lesions < /= 20 mm , fluoroscopy was not able to confirm whether the forceps reached the lesion . However , the yield was the same with ( 67 % , 18 of 27 lesions ) and without ( 74 % , 40 of 54 lesions ) successful fluoroscopy ( p = 0.96 , chi(2 ) ) . Moderate bleeding occurred in two patients ( 1 % ) ; there were no other complications . CONCLUSIONS EBUS-GS is a useful method for collecting sample s from peripheral pulmonary lesions , even those too small to be visualized under fluoroscopy BACKGROUND Peripheral pulmonary lesions are technically challenging with conventional bronchoscopy in obtaining tissue diagnosis . The recently developed small-caliber ultrasonographic probe can be introduced via the working channel of a flexible bronchoscope to localize peripheral pulmonary lesions ( PPLs ) prior to transbronchial lung biopsy ( TBLB ) . The endobronchial ultrasound-guided transbronchial lung biopsy ( EBUS-TBLB ) is a new diagnostic method for the diagnosis of pulmonary lesions in our center . OBJECTIVE To evaluate the diagnostic yield of EBUS-TBLB in pulmonary lesions . STUDY DESIGN A prospect i ve cross-sectional study . MATERIAL AND METHOD We enrolled 152 patients with pulmonary lesions that were beyond the segmental bronchus and had no evidence of endobronchial lesion , who underwent bronchoscopy in our center . With EBUS assisted , transbronchial lung biopsy was performed after localizing and measuring distance from the tip of bronchoscope to the lesion . The diagnostic yield was calculated . RESULTS The pulmonary lesions were visible on EBUS image in 98.7 % of cases . The overall diagnostic yield of EBUS-TBLB was 66.4 % . The diagnostic yield in the infiltrative and mass lesions were 86.4 % and 63.1 % , respectively . The lesions which EBUS probe located within it were diagnosed by EBUS-TBLB about 74.8 % . The benign and malignant lesions were diagnosed by EBUS-TBLB about 81.1 % and 58.6 % , respectively . The average EBUS time was 3.55 + /- 2.29 minutes . No complication of EBUS and transbronchial lung biopsy were observed in this study . CONCLUSION EBUS-TBLB is a safe procedure for diagnosing pulmonary lesions . Our results indicate that the EBUS-TBLB improves the diagnostic yield compared to conventional brochoscopy PURPOSE To report results of a 5-year prospect i ve low-dose helical chest computed tomographic ( CT ) study of a cohort at high risk for lung cancer . MATERIAL S AND METHODS After informed written consent was obtained , 1520 individuals were enrolled . Protocol was approved by institutional review board and National Cancer Institute and was compliant with Health Insurance Portability and Accountability Act , or HIPAA . Participants were aged 50 years and older and had smoked for more than 20 pack-years . Participants underwent five annual ( one initial and four subsequent ) CT examinations . A significant downward shift was evaluated in non-small cell lung cancers detected initially from advanced stage down to stage I by using a one-sided binomial test of proportions . Poisson regression and Fisher exact tests were used for comparisons with Mayo Lung Project . RESULTS In 788 ( 52 % ) men and 732 ( 48 % ) women , 61 % ( 927 of 1520 ) were current smokers , and 39 % were former smokers . After five annual CT examinations , 3356 uncalcified lung nodules were identified in 1118 ( 74 % ) participants . Sixty-eight lung cancers were diagnosed ( 31 initial , 34 subsequent , three interval cancers ) in 66 participants . Twenty-eight subsequent cases of non-small cell cancers were detected , of which 17 ( 61 % ; 95 % confidence interval : 41 % , 79 % ) were stage I tumors . Diameter of cancers detected subsequently was 5 - 50 mm ( mean , 14.4 mm ; median , 10.0 mm ) . Analysis for a more than 50 % shift in proportion of stage I non-small cell cancer detection did not show statistical significance . Forty-eight participants died of various causes since enrollment . Lung cancer mortality rate for incidence portion of trial was 1.6 per 1000 person-years . There was no significant difference in lung cancer mortality rates of cancers detected in subsequent examinations between this trial and Mayo Lung Project after separation of participants into subsets ( 2.8 vs 2.0 per 1000 person-years , P = .43 ) . CONCLUSION CT allows detection of early-stage lung cancers . Benign nodule detection rate is high . Results suggest no stage shift STUDY OBJECTIVES We evaluated the feasibility and efficacy of transbronchial biopsy ( TBB ) and bronchial brushing by endobronchial ultrasonography ( EBUS ) with a guide sheath ( GS ) as a guide for diagnosing peripheral pulmonary lesions ( PPLs ) without radiographic fluoroscopy . PATIENTS One hundred twenty-one patients with 123 PPLs ( mean diameter , 31.0 mm ) whose bronchoscopic findings were normal . METHODS An EBUS-GS was inserted and advanced to the PPL without fluoroscopy . Once we obtained the EBUS image , the probe was withdrawn and the GS was left in place . TBB and /or bronchial brushing were performed via the GS . When an EBUS image could not be obtained , we changed to the bronchoscopic examination under fluoroscopy . RESULTS Seventy-six of 123 PPLs ( 61.8 % ) were diagnosed by EBUS-GS guidance without fluoroscopy . The diagnostic yield for PPLs > 20 mm in diameter ( 75.6 % ) was significantly higher than that for those < or= 20 mm in diameter ( 29.7 % ; p < 0.01 ) . The PPLs located in the middle lobe and the lingular segment had significantly higher diagnostic yields ( p < 0.05 ) . When the bronchus leading to the PPL was identified on the CT scan , the yield was 79.2 % . Moreover , the solid lesions had a higher diagnostic yield ( 67.0 % ) compared with nonsolid lesions ( 35.0 % ; p < 0.05 ) . Multivariate analysis revealed that the diameter and the location of the PPL were independent predictors of diagnostic sensitivity by EBUS-GS-guided bronchoscopy ( p < 0.05 ) . CONCLUSIONS EBUS-GS-guided bronchoscopy without the use of radiographic fluoroscopy is effective for diagnosing PPLs . The diameter , location , and CT scan appearance of the PPLs , and the identification of the bronchus leading to the PPLs were valuable as factors related to a higher diagnostic sensitivity with this procedure Transbronchial biopsy ( TBBX ) for peripheral lung lesions is usually performed with the help of fluoroscopy , but the yield varies widely . This feasibility study aim ed to assess the ability of endobronchial ultrasound ( EBUS ) to provide imaging guidance for TBBX . In a prospect i ve study , 50 consecutive patients referred for TBBX for peripheral lesions underwent fluoroscopy-guided and EBUS-guided TBBX in r and om order . Diagnostic yields were compared for both modalities and feasibility was assessed for EBUS . Diagnostic material was obtained in 80 % of patients with EBUS and 76 % of patients with fluoroscopy . There was a nonsignificant trend for EBUS to be better than fluoroscopy for lesions <3 cm in diameter . Four lesions could not be visualised with EBUS . There were no significant complications associated with the use of EBUS . Endobronchial ultrasound-guided transbronchial biopsy is feasible . It appears to be at least equivalent to fluoroscopy without the accompanying radiation exposure . Further large-scale studies are indicated to assess the possible role of endobronchial ultrasound as a potential imaging method of choice for the biopsy of peripheral lung lesions Background : Electromagnetic navigation has been approved for use as an adjunct to st and ard bronchoscopy . The diagnostic yield varies depending on the size of the lesion and successful navigation to the lesion . Objectives : The performance of two different biopsy tools , i.e. catheter aspiration and forceps biopsy , in the diagnosis of small pulmonary nodules ( SPN ) guided by electromagnetic navigational bronchoscopy ( ENB ) was examined . Methods : 54 patients referred for suspected lung cancer underwent ENB and 55 SPN ( <3 cm ) were sample d using both techniques . Endobronchial ultrasound ( EBUS ) was used to verify the accuracy of target lesion localization by ENB . Primary end points of the study were successful navigation to the lesion and a positive diagnosis . Patients were followed until a definitive diagnosis was obtained . Results : All 55 lesions were accessed . Two lesions were excluded from data analysis as the patients were lost to follow-up and their diagnoses could not be confirmed . Of the remaining 53 lesions , 40 sample s ( 75.5 % ) were diagnostic . Compared to forceps biopsy , catheter aspiration was positively correlated with the success rate ( 36/40 vs. 22/40 ; p = 0.035 ) . The diagnostic yield was 93 % when EBUS verified the lesion location after navigation and only 48 % when lesion location was not confirmed . There were no significant complications . Conclusions : ENB is a useful tool in the evaluation of SPN <3 cm in diameter . For malignant lesions , sampling by catheter aspiration is associated with a higher diagnostic yield than sampling by forceps biopsy alone , in particular when EBUS could not confirm lesion location prior to sampling The present study prospect ively evaluated the diagnostic yield and safety of electromagnetic navigation-guided bronchoscopy biopsy , for small peripheral lung lesions in patients where st and ard techniques were nondiagnostic . The study was conducted in a tertiary medical centre on 40 consecutive patients considered unsuitable for straightforward surgery or computed tomography (CT)-guided transthoracic needle aspiration biopsy , due to comorbidities . The lung lesion diameter was mean±sem 23.5±1.5 mm and the depth from the visceral-costal pleura was 14.9±2 mm . Navigation was facilitated by an electromagnetic tracking system which could detect a position sensor incorporated into a flexible catheter advanced through a bronchoscope . Information obtained during bronchoscopy was superimposed on previously acquired CT data . Divergence between CT data and data obtained during bronchoscopy was calculated by the system 's software as a measure of navigational accuracy . All but one of the target lesions was reached and the overall diagnostic yield was 62.5 % ( 25–40 ) . Diagnostic yield was significantly affected by CT-to-body divergence ; yield was 77.2 % when estimated divergence was ≤4 mm . Three pneumothoraces occurred and chest drainage was required in one case . Electromagnetic navigation-guided bronchoscopy has the potential to improve the diagnostic yield of transbronchial biopsies without additional fluoroscopic guidance , and may be useful in the early diagnosis of lung cancer , particularly in nonoperable patients Background : The aim of this study was to evaluate the diagnostic utility of endobronchial ultrasound (EBUS)-guided transbronchial biopsy ( TBB ) using a novel 3.4-mm thin bronchoscope and a 1.4-mm ultrasonic probe for peripheral pulmonary lesions . Methods : A total of 86 patients with suspected peripheral lesions were included in this prospect i ve study . EBUS-TBBs were performed using a prototype 3.4-mm thin bronchoscope and a 1.4-mm radial ultrasonic probe under fluoroscopic guidance . Results : Twelve patients with endobronchial lesions within the segmental bronchi and three patients who did not return to follow-up were excluded from this analysis . Thus , a total of 71 patients with peripheral pulmonary lesions ( mean size , 31.2 ± 12.7 mm ) were included in the final analysis . The mean bronchus level reached with the thin bronchoscope was 4.6 generations . Diagnostic histologic specimens were obtained in 49 of 71 patients ( 69%:80 % for malignant lesions and 52 % for benign lesions ) . A definitive diagnosis of malignancy for lesions ≥20 mm and lesions < 20 mm was made in 82 % ( 31 of 38 ) and 67 % ( four of six ) , respectively . There were no significant complications . Conclusion : The EBUS-TBB using a 3.4-mm thin bronchoscope and a 1.4-mm radial probe is feasible , accurate , and safe for the diagnosis of peripheral pulmonary lesions BACKGROUND Computed tomography guided transthoracic needle aspiration ( CT-TTNA ) and endobronchial ultrasonography with guide sheath ( EBUS-GS ) transbronchial lung biopsy are important methods for the diagnosis of peripheral pulmonary lesions ( PPLs ) . Without enough evidence , it is controversial which is a better choice for diagnosing PPLs . In this study , we hypothesized that the complication rate of EBUS-GS would be lower than CT-TTNA and the diagnostic accuracy of EBUS-GS were not inferior to CT-TTNA . METHODS This study was a retrospective analysis of a prospect i ve registry with propensity matching . Patients with PPLs were divided into EBUS-GS group and CT-TTNA group according to patients ' intent to treatment . Pathological results and procedure related complications of EBUS-GS and CT-TTNA were recorded . Propensity score matching(PSM ) was used to eliminate the intergroup bias . Diagnostic yields and complications of two groups were compared . Subgroup analysis was performed to conclude the indications of different procedures . RESULTS A total of 187 patients ( CT-TTNA : 130 ; EBUS-GS : 57 ) were enrolled . After propensity score matching , 54 paired patients were included . Diagnostic yield was 81 % ( 44/54 ) for EBUS-GS and 87 % ( 47/54 ) for CT-TTNA ( P=0.43 ) , respectively . Diagnostic sensitivity in malignancy was 93 % ( 42/45 ) for CT-TTNA and 79 % ( 37/47 ) for EUBS-GS ( P=0.04 ) . Subgroup analysis revealed that the sensitivity of CT-TTNA was significantly higher in diagnosing of lesions close to the chest wall ( 100 % vs. 80 % , P=0.04 ) , and bronchus sign on CT was a predictive factor for accurate diagnosis by EBUS-GS . The overall complication rate was 13 % ( 7/54 ) for CT-TTNA group , which was not significantly higher than that of EBUS-GS group ( 2 % , P=0.06 ) . Subgroup analysis showed that patients combined with pulmonary comorbidities and lesions apart from chest wall were risk factors for complications of CT-TTNA . CONCLUSIONS Both of the two procedures are effective for the diagnosis of PPLs , but CT-TTNA has a higher diagnostic sensitivity for malignancy . EBUS-GS has fewer complications , and it is more suitable for patients combined with pulmonary comorbidities and lesions with bronchus signs BACKGROUND Electromagnetic navigation bronchoscopy ( ENB ) has been developed as a novel ancillary tool for the bronchoscopic diagnosis of pulmonary nodules . Despite successful navigation in 90 % of patients , ENB diagnostic yield does not generally exceed 70 % . We sought to determine whether the presence of a bronchus sign on CT imaging conditions diagnostic yield of ENB and might account for the discrepancy between successful navigation and diagnostic yield . METHODS We conducted a prospect i ve , single-center study of ENB in 51 consecutive patients with pulmonary nodules . ENB was chosen as the least invasive diagnostic technique in patients with a high surgical risk , suspected metastatic disease , or advanced-stage disease , or in those who dem and ed a preoperative diagnosis prior to undergoing curative resection . We studied patient and technical variables that might condition diagnostic yield , including size , cause , location , distance to the pleural surface , and fluorodeoxyglucose uptake of a given nodule ; the presence of a bronchus sign on CT imaging ; registration point divergence ; and the minimum distance from the tip of the locatable guide to the nodule measured during the procedure . RESULTS The diagnostic yield of ENB was 67 % ( 34/51 ) . The sensitivity and specificity of ENB for malignancy in this study were 71 % and 100 % , respectively . ENB was diagnostic in 79 % ( 30/38 ) patients with a bronchus sign on CT imaging but only in 4/13 ( 31 % ) with no discernible bronchus sign . Univariate analysis identified the bronchus sign ( P = .005 ) and nodule size ( P = .04 ) as statistically significant variables conditioning yield , but on multivariate analysis , only the bronchus sign remained significant ( OR , 7.6 ; 95 % CI , 1.8 - 31.7 ) . No procedure-related complications were observed . CONCLUSIONS ENB diagnostic yield is highly dependent on the presence of a bronchus sign on CT imaging STUDY OBJECTIVES To characterize the feasibility , accuracy , and safety of the superDimension/Bronchus system ( SDBS ) [ superDimension , Ltd ; Hertzliya , Israel ] in navigating to previously unreachable peripheral lung lesions and obtaining biopsy specimens . DESIGN Open-label , prospect i ve , controlled clinical study . SETTING Pulmonary institute of a university-affiliated municipal hospital . PATIENTS Thirteen adult c and i date s for nonemergency bronchoscopy who gave informed consent to participate . INTERVENTIONS The patients underwent flexible bronchoscopy using the SDBS , which is based on real-time CT-guided electromagnetic navigation and is capable of reaching peripheral lung masses beyond the reach of the bronchoscope . A position sensor was used to navigate to and sample the various target lesions for biopsy . MEASUREMENTS AND RESULTS Three-dimensional chest CT was followed by SDBS methodology for marking anatomic l and marks and the target lesion on a virtual bronchoscopy screen and for sampling the lesion . The SDBS assisted in obtaining positive biopsy diagnoses in 9 of 13 cases ( 69 % ) , with an average navigation accuracy of 5.7 mm . There were no SDBS-related adverse events . CONCLUSIONS The SDBS is safe and effective in navigating to peripheral lung lesions located beyond the optic limits of a st and ard flexible bronchoscope BACKGROUND Electromagnetic navigation in bronchoscopy is a novel method for assisting in the localization of peripheral lung lesions . STUDY OBJECTIVE To assess the usability , accuracy , and safety of electromagnetic navigation during flexible bronchoscopy in a clinical setting . DESIGN Prospect i ve evaluation . PATIENTS Consecutive patients referred to the bronchoscopy unit for the diagnosis of peripheral infiltrates or solitary pulmonary nodules ( SPNs ) . METHODS Navigation was performed using an electromagnetic tracking system with a position sensor encapsulated in the tip of a flexible catheter that was pushed through the working channel of the bronchoscope . Real-time , multiplanar reconstruction of a previously acquired CT data set provided three-dimensional views for localization of the catheter . To match the position of the sensor with the CT scan , four anatomic l and marks were used for registration . The sensor position generated in the navigation system was controlled by fluoroscopy , and the corresponding error distances were measured . This was performed with all SPNs and at two different peripheral locations of the right upper lobe ( RUL ) . RESULTS Sixteen patients ( 10 men and 6 women ; mean age , 63.7 years ) were studied . Navigation prolonged bronchoscopy by 3.9 + /- 1.3 min ( mean + /- SD ) . The navigation system identified all lesions . The position sensor achieved a direct hit in three of five SPNs . Fluoroscopy failed to recognize three SPNs ( 60 % ) and three infiltrates ( 38 % ) . The mean error distances between sensor tip position and fluoroscopically verified RUL reference position were 10.4 mm ( lateral position ) and 12.5 mm ( apical position ) respectively . The mean error distances between the sensor tip and two endobronchial registration points at the end of the procedure were 4.2 mm and 5.1 mm , respectively . CONCLUSION Electromagnetic navigation is useful , accurate , and safe in the localization of peripheral lung lesions and may help to improve the yield of diagnostic bronchoscopic procedures RATIONALE Endobronchial ultrasound ( EBUS ) and electromagnetic navigation bronchoscopy ( ENB ) have increased the diagnostic yield of bronchoscopic diagnosis of peripheral lung lesions . However , the role of combining these modalities to overcome each individual technique 's limitations and , consequently , to further increase the diagnostic yield remains untested . OBJECTIVES A prospect i ve r and omized controlled trial involving three diagnostic arms : EBUS only , ENB only , and a combined procedure . METHODS All procedures were performed via flexible bronchoscopy and transbronchial forceps biopsies were obtained without fluoroscopic guidance . In the combined group , after electromagnetic navigation , the ultrasound probe was passed through an extended working channel to visualize the lesion . Biopsies were taken if ultrasound visualization showed that the extended working channel was within the target . Primary outcome was diagnostic yield . The reference " gold st and ard " was a surgical biopsy if bronchoscopic biopsy did not reveal a definite histological diagnosis compatible with the clinical presentation . Secondary outcomes were yields by size , lobar distribution , and lesion pathology . Complication rates were also documented . MEASUREMENTS AND MAIN RESULTS Of the 120 patients recruited , 118 had a definitive histological diagnosis and were included in the final analysis . The diagnostic yield of the combined procedure ( 88 % ) was greater than EBUS ( 69 % ) or ENB alone ( 59 % ; p = 0.02 ) . The combined procedure 's yield was independent of lesion size or lobar distribution . The pneumothorax rates ranged from 5 to 8 % , with no significant differences between the groups . CONCLUSIONS Combined EBUS and ENB improves the diagnostic yield of flexible bronchoscopy in peripheral lung lesions without compromising safety BACKGROUND Endobronchial ultrasound ( EBUS ) is an accurate and relatively less invasive procedure for the diagnosis of lung lesions and mediastinal lymph node staging for lung cancer . We aim ed to evaluate the clinical utility and safety of this new EBUS service established in our hospital . METHODS Consecutive patients who underwent EBUS-transbronchial lung biopsy ( EBUS-TBLB ) for biopsy of peripheral pulmonary lesions or for transbronchial needle aspiration ( TBNA ) of mediastinal lymph node enlargement were included in this audit . Demographic and clinical data were obtained prospect ively . Diagnostic yield from the results of EBUS was compared to other clinical information obtained . RESULTS Thirty-eight patients underwent EBUS over a 10-month period . The yield from EBUS-TBLB was 62 % . The average size of the lung lesions biopsied was 3.5 cm and 62 % were located in the upper lobes . Malignancy was diagnosed in 14 cases and a benign aetiology in four . The yield from EBUS-TBNA was 88 % and the average size of the lymph nodes was 2.3 cm . The lymph nodes were all located in the subcarinal station except for two that were in the lower paratracheal station . Malignancy was diagnosed in 10 cases on TBNA and 4 cases had benign pathology . There was one complication seen ( small pneumothorax ) . CONCLUSION EBUS is safe and an effective method for both , diagnosis of peripheral pulmonary lesions and staging for lung cancer BACKGROUND The diagnostic yield of endobronchial ultrasonography (EBUS)-guided transbronchial needle aspiration ( TBNA ) for peripheral pulmonary lesions ( PPLs ) has not been evaluated . The diagnostic impact of TBNA when the EBUS probe is adjacent to lesions remains to be determined . DESIGN A prospect i ve , r and omized trial . METHODS Two hundred two patients with PPLs and positive EBUS findings were enrolled . They were r and omly classified into two groups . In the EBUS conventional diagnostic procedures ( CDPs ) group ( 103 patients ) , both transbronchial biopsy ( TBB ) and bronchial washing ( BW ) were performed . In the EBUS-TBNA plus CDPs group ( 99 patients ) , TBNA , TBB , and BW were performed . The diagnostic yield in each group was compared . RESULTS A total of 182 patients ( 94 in the EBUS CDPs group and 88 in the EBUS-TBNA plus CDPs group ) were analyzed . The yield in the EBUS-TBNA plus CDPs group ( 78.4 % ) was significantly higher than the EBUS CDPs group ( 60.6 % , p = 0.015 ) . Cases in which the EBUS probe was located within the lesions had a significantly higher diagnostic yield ( 78.3 % ) than when the EBUS probe was adjacent to them ( 47.2 % , p < 0.001 ) . Concerning the three different techniques , TBNA showed the highest diagnostic yield ( 62.5 % ) in comparison to TBB ( 48.9 % ) and to BW ( 19.8 % ) . The diagnostic yield of TBNA remained unchanged even when the EBUS probe was adjacent to the lesions ( p = 0.89 ) . No additional adverse effects were observed in the EBUS-TBNA plus CDPs group . CONCLUSIONS Applying TBNA to EBUS-guided CDPs further increased the diagnostic yield of PPLs without additional risk . The diagnostic advantage of TBNA became more obvious if the EBUS probe was adjacent to the lesions . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT00626587 Background : Recent studies have described the promising method of electromagnetic navigated bronchoscopy ( ENB ) for diagnosis of peripheral solitary nodules . However , they require general anaesthesia or intravenous sedation . We wanted to know if ENB could be applied more easily in out patients . Objectives : We prospect ively evaluated the accuracy and the feasibility of ENB under local anaesthesia and nitrous oxide/oxygen inhalation as unique sedation in out patients . Methods : After mapping time , the bronchoscopic procedure was carried out under local anaesthesia and nitrous oxide/oxygen inhalation with the unique help of the ENB to confirm the right position of the extended working channel before sampling . The primary end point was the accuracy of ENB and the secondary end point was the feasibility in out patients . Results : Among 54 screened patients , 53 completed the study protocol . The overall diagnostic success rate to diagnose malignancy was 71.4 % in tumours of 28 mm in median size . ENB classified correctly peripheral lesions according to malignity in 41 cases ( 30 cases of cancer , 11 benign diagnosis ) and failed in 12 cases ( 1 probable lung metastasis , 11 lung cancers ) . All patients but 1 were dismissed 1 h after the procedure and the tolerance of the procedure was excellent in all cases except 2 ( agitation and anxiety ) . In two cases ( 4 % ) a pneumothorax was recorded , 1 requiring drainage with a chest tube during a short hospitalisation . Conclusions : ENB under nitrous oxide/oxygen sedation seems to be an accurate and safe procedure . In our series , it allowed us to obtain the diagnosis in 71.4 % of the tumours , with a good tolerance and an outpatient strategy Introduction : Percutaneous computed tomography (CT)-guided lung biopsy is a st and ard minimally invasive technique for sampling peripheral lung lesions . Radial endobronchial ultrasound ( EBUS ) offers an alternative approach but it has yet to be defined which patients are most suited to this procedure . The primary aim of this study was to investigate whether CT characteristics could predict the success of radial EBUS-guided sampling . Methods : The University Hospital South Manchester provides a radial EBUS service , under conscious sedation without fluoroscopy , double-hinged curettes , or guide sheaths , to a large cancer Network in the United Kingdom . This retrospective analysis of a prospect ively maintained data base included all patients undergoing radial EBUS from January 2011 to June 2013 . Lesion size , structure , location , and presence of a bronchus sign on thoracic CT were analyzed against predefined outcomes using multivariate analysis . Results : One-hundred and seventeen patients underwent radial EBUS in the study period ( mean age 69.5 , mean lesion size 36.6 mm ) . The presence of a bronchus sign on CT was the only independent predictor of all predefined outcomes : ( 1 ) lesion identification with radial EBUS , ( 2 ) positioning of probe within the center of the lesion , and ( 3 ) accurate pathological diagnosis ; odds ratio ( OR ) 31.1 ( 7.8–123.9 , p < 0.0001 ) , OR 44.8 ( 5.6–354.9 , p < 0.0001 ) and OR 46.6 ( 11.1–195.3 , p < 0.0001 ) respectively . The sensitivity and diagnostic accuracy for those patients with a bronchus sign on CT was 87.3 % and 86.7 % compared with 12.5 % and 11.1 % for those lacking the bronchus sign . Discussion : The patients most likely to benefit from radial EBUS , without the use of adjuncts , are those with a bronchus sign on CT AIM To determine diagnostic rate , complications and patient tolerability of endobronchial ultrasound-guide sheath ( EBUS-GS ) and computed tomography (CT)-guided percutaneous core biopsy for peripheral lung lesions . METHODS Lesions > 1 cm diameter on CT were r and omised to either EBUS-GS or CT-guided biopsy . Excluded were patients with severe chronic obstructive airway disease , lesions touching visceral pleura or hilum , and patients with symptoms needing bronchoscopic evaluation . Patients completed preprocedure and postprocedure question naires on tolerability . RESULTS Of 64 participants ( mean lesion size 29 ± 16 mm ) , 57 completed the study . Diagnostic sensitivity was 67 % for EBUS-GS and 78 % for CT-guided biopsy ( P = not significant ) . In those with negative results , in the EBUS group , nine had a CT-guided biopsy as a cross-over , seven of which were positive . In the CT group , four had cross-over EBUS-GS of which three were diagnostic . Sensitivity for malignancy was 17/23 for EBUS-GS ( 74 % ) and 23/26 ( 88 % , P = not significant ) . For lesions < 2 cm , CT-guided biopsy had a significantly better diagnostic yield ( 80 % vs 50 % , P = 0.05 ) . In EBUS-GS cases , for lesions with an air bronchogram , sensitivity was 89 % . Pneumothorax and intercostal catheter insertion occurred in three and two cases , respectively , for EBUS , and 10 and 3 cases for CT-guided biopsy ( P = 0.02 for pneumothorax ) . Nine unexpected admissions occurred after CT-guided biopsy compared with three after EBUS-GS . Overall , tolerability was high for both groups ; however three patients had moderate-to-severe pain after CT-guided biopsy . CONCLUSIONS In lesions < 2 cm , CT-guided biopsy had higher yields ; however , EBUS-GS had better tolerability and fewer complications STUDY OBJECTIVES The aim of our study was to compare the diagnostic yield of two bronchoscopic procedures : endobronchial ultrasound-driven transbronchial biopsy ( EBUS-TBB ) and transbronchial biopsy ( TBB ) in peripheral pulmonary lesions . DESIGN Prospect i ve , r and omized , blinded study . SETTING University Hospital of Rome , Italy . PATIENTS AND METHODS We examined 799 patients with peripheral lung lesions using bronchoscopy . Patients who could undergo a complete clinical diagnostic follow-up ( n = 293 ) were enrolled in the study and r and omly assigned to EBUS-TBB or TBB . We performed these two procedures on 221 patients ( 97 EBUS-TBB and 124 TBB ) . Patients in whom biopsies were not diagnostic underwent more invasive procedures to obtain a final diagnosis , and a complete follow-up was possible in 206 patients ( 87 EBUS-TBB and 119 TBB ) . RESULTS Lung cancer was diagnosed in 61 patients in the EBUS-TBB group and in 83 patients in the TBB group . Pulmonary diseases other than cancer were diagnosed in 26 patients and 36 patients , respectively . For patients with lung cancer , sensitivity was 0.79 in the EBUS group and 0.55 in the TBB group ( p = 0.004 ) , and accuracy was 0.85 and 0.69 , respectively ( p = 0.007 ) . The analysis of a subset of patients with lesions > 3 cm showed no significant difference in diagnostic ability between the two procedures . In lesions < 3 cm , we found a considerable decline in TBB sensitivity and accuracy ( 0.31 and 0.50 ) while EBUS-TBB maintained their diagnostic yield ( 0.75 and 0.83 ) [ p = 0.0002 and p = 0.001 , respectively ] . A similar difference was observed when we compared the sensitivity of the two procedures in lesions < 2 cm ( 0.23 vs 0.71 , p < 0.001 ) . CONCLUSIONS EBUS-TBB can be an important option in the early diagnosis of peripheral lung cancer , especially in small-sized lesions and in patients who are not eligible for surgery STUDY OBJECTIVES Transbronchial biopsy ( TBBX ) for solitary pulmonary nodules ( SPNs ) is usually performed under fluoroscopic guidance , but the diagnostic yield depends on lesion size and varies widely . Nodules < 3 cm frequently can not be visualized fluoroscopically . An alternative guidance technique , endobronchial ultrasound ( EBUS ) , also allows visualization of pulmonary nodules . This study assessed the diagnostic yield of EBUS-guided TBBX in fluoroscopically invisible SPNs . DESIGN The study was a prospect i ve trial using a crossover design . PATIENTS AND METHODS All patients with SPNs and indications for bronchoscopy were included in the study . An EBUS-guided examination was performed in patients with fluoroscopically invisible nodules . The EBUS probe was introduced through a guide catheter into the presumed segment . If a typical ultrasonic picture of solid tissue could be seen , the probe was removed and the catheter left in place . The biopsy forceps were introduced and specimens taken . RESULTS One hundred thirty-eight consecutive patients with SPNs were examined . Of those , 54 patients presented with SPNs that could not be visualized with fluoroscopy . The mean diameter of the nodules was 2.2 cm . In 48 patients ( 89 % ) , the lesion was localized with EBUS , and in 38 patients ( 70 % ) the biopsy established the diagnosis . The 16 patients with undiagnosed SPNs were referred for surgical biopsy ; 10 of those lesions were malignant and 6 were benign . The diagnosis in nine patients ( 17 % ) saved the patients from having to undergo a surgical procedure . The only complication was a pneumothorax in one patient . CONCLUSIONS EBUS-guided TBBX is a safe and very effective method for SPNs that can not be visualized by fluoroscopy . The procedure may increase the yield of endoscopic biopsy in patients with these nodules and avert the need for surgical procedures BACKGROUND Lung cancer is the largest contributor to mortality from cancer . The National Lung Screening Trial ( NLST ) showed that screening with low-dose helical computed tomography ( CT ) rather than with chest radiography reduced mortality from lung cancer . We describe the screening , diagnosis , and limited treatment results from the initial round of screening in the NLST to inform and improve lung-cancer-screening programs . METHODS At 33 U.S. centers , from August 2002 through April 2004 , we enrolled asymptomatic participants , 55 to 74 years of age , with a history of at least 30 pack-years of smoking . The participants were r and omly assigned to undergo annual screening , with the use of either low-dose CT or chest radiography , for 3 years . Nodules or other suspicious findings were classified as positive results . This article reports findings from the initial screening examination . RESULTS A total of 53,439 eligible participants were r and omly assigned to a study group ( 26,715 to low-dose CT and 26,724 to chest radiography ) ; 26,309 participants ( 98.5 % ) and 26,035 ( 97.4 % ) , respectively , underwent screening . A total of 7191 participants ( 27.3 % ) in the low-dose CT group and 2387 ( 9.2 % ) in the radiography group had a positive screening result ; in the respective groups , 6369 participants ( 90.4 % ) and 2176 ( 92.7 % ) had at least one follow-up diagnostic procedure , including imaging in 5717 ( 81.1 % ) and 2010 ( 85.6 % ) and surgery in 297 ( 4.2 % ) and 121 ( 5.2 % ) . Lung cancer was diagnosed in 292 participants ( 1.1 % ) in the low-dose CT group versus 190 ( 0.7 % ) in the radiography group ( stage 1 in 158 vs. 70 participants and stage IIB to IV in 120 vs. 112 ) . Sensitivity and specificity were 93.8 % and 73.4 % for low-dose CT and 73.5 % and 91.3 % for chest radiography , respectively . CONCLUSIONS The NLST initial screening results are consistent with the existing literature on screening by means of low-dose CT and chest radiography , suggesting that a reduction in mortality from lung cancer is achievable at U.S. screening centers that have staff experienced in chest CT . ( Funded by the National Cancer Institute ; NLST Clinical Trials.gov number , NCT00047385 . ) BACKGROUND Major issues in the implementation of screening for lung cancer by means of low-dose computed tomography ( CT ) are the definition of a positive result and the management of lung nodules detected on the scans . We conducted a population -based prospect i ve study to determine factors predicting the probability that lung nodules detected on the first screening low-dose CT scans are malignant or will be found to be malignant on follow-up . METHODS We analyzed data from two cohorts of participants undergoing low-dose CT screening . The development data set included participants in the Pan-Canadian Early Detection of Lung Cancer Study ( PanCan ) . The validation data set included participants involved in chemoprevention trials at the British Columbia Cancer Agency ( BCCA ) , sponsored by the U.S. National Cancer Institute . The final outcomes of all nodules of any size that were detected on baseline low-dose CT scans were tracked . Parsimonious and fuller multivariable logistic-regression models were prepared to estimate the probability of lung cancer . RESULTS In the PanCan data set , 1871 persons had 7008 nodules , of which 102 were malignant , and in the BCCA data set , 1090 persons had 5021 nodules , of which 42 were malignant . Among persons with nodules , the rates of cancer in the two data sets were 5.5 % and 3.7 % , respectively . Predictors of cancer in the model included older age , female sex , family history of lung cancer , emphysema , larger nodule size , location of the nodule in the upper lobe , part-solid nodule type , lower nodule count , and spiculation . Our final parsimonious and full models showed excellent discrimination and calibration , with areas under the receiver-operating-characteristic curve of more than 0.90 , even for nodules that were 10 mm or smaller in the validation set . CONCLUSIONS Predictive tools based on patient and nodule characteristics can be used to accurately estimate the probability that lung nodules detected on baseline screening low-dose CT scans are malignant . ( Funded by the Terry Fox Research Institute and others ; Clinical Trials.gov number , NCT00751660 . ) |
13,201 | 22,790,350 | Conclusion The mortality rate during PEG-IFN/RBV therapy was acceptably low , but the rate of SAEs was not negligible in a treatment for a benign disease , and the rate was affected by treatment regimens | Background Pegylated interferon ( PEG-IFN ) plus ribavirin ( RBV ) therapy is the current st and ard of care for patients with chronic hepatitis C. Determining precisely the risk of serious adverse events ( SAEs ) and mortality from a single study is rather difficult because of the infrequency of such events .
The aim of this systematic review was to assess the rates of SAEs and the mortality of PEG-IFN/RBV therapy in a pooled large sample , and to assess the relationship between SAEs and mortality rates and therapeutic characteristics . | UNLABELLED Successful treatment of chronic HCV with peginterferon ( PEGIFN ) and ribavirin ( RVN ) is often limited by anemia . We performed the present study to determine if utilizing epoetin alpha ( EPO ) with or without a higher dose of RVN could enhance sustained virologic response ( SVR ) . We r and omized 150 treatment-naive patients with chronic HCV genotype 1 into 3 treatment groups : ( 1 ) PEGIFN alpha-2b ( 1.5 microg/kg/week ) + weight-based RVN ( WBR ) 13.3 mg/kg/day ( 800 to 1400 mg/day ) ; ( 2 ) PEGIFN alpha-2b + WBRVN + EPO ( 40,000 U/week ) ; or ( 3 ) PEGIFN alpha-2b + higher dose WBR 15.2 mg/kg/day ( 1000 to 1600 mg/day ) + EPO . We initiated EPO at the onset of therapy to maintain the hemoglobin between 12 and 15 g/dL. When required , we reduced RVN by 200-mg steps . African Americans compose 36 % of the population . A significantly smaller percentage of group 2 patients had a decline in hemoglobin to less than 10 g/dL ( 9 % versus 34 % ; P < 0.05 ) and required that the RVN dose be reduced ( 10 % versus 40 % ; P < 0.05 ) compared to group 1 patients . Despite this , SVR was similar in these groups ( 19 % to 29 % ) . SVR was significantly greater ( P < 0.05 ) in group 3 patients ( 49 % ) . This result ed from a significant decline ( P < 0.05 ) in relapse rate ; only 8 % versus 38 % for groups 1 and 2 . CONCLUSION We conclude that using EPO in all subjects at the initiation of PEGIFN and RVN treatment will not enhance SVR given the same starting dose of RVN . In contrast , a higher starting dose of RVN was associated with a lower relapse rate and higher rate of SVR BACKGROUND Patients with genotype 1 hepatitis C virus ( HCV ) who do not have a sustained response to therapy with peginterferon alfa and ribavirin have a low likelihood of success with retreatment . METHODS We r and omly assigned patients with HCV genotype 1 who had not had a sustained virologic response after peginterferon alfa-ribavirin therapy to one of four treatment groups : 115 patients to the T12PR24 group , receiving telaprevir ( 1125-mg loading dose , then 750 mg every 8 hours ) for 12 weeks and peginterferon alfa-2a ( 180 microg per week ) and ribavirin ( 1000 or 1200 mg per day , according to body weight ) for 24 weeks ; 113 patients to the T24PR48 group , receiving telaprevir for 24 weeks and peginterferon alfa-2a and ribavirin for 48 weeks ( at the same doses as in the T12PR24 group ) ; 111 patients to the T24P24 group , receiving telaprevir and peginterferon alfa-2a for 24 weeks ( at the same doses as in the T12PR24 group ) ; and 114 patients to the PR48 ( or control ) group , receiving peginterferon alfa-2a and ribavirin for 48 weeks ( at the same doses as in the T12PR24 group ) . The primary end point was sustained virologic response ( undetectable HCV RNA levels 24 weeks after the last dose of study drugs ) . RESULTS The rates of sustained virologic response in the three telaprevir groups--51 % in the T12PR24 group , 53 % in the T24PR48 group , and 24 % in the T24P24 group -- were significantly higher than the rate in the control group ( 14 % ; P<0.001 , P<0.001 , and P=0.02 , respectively ) . Response rates were higher among patients who had previously had relapses than among nonresponders . One of the most common adverse events in the telaprevir groups was rash ( overall , occurring in 51 % of patients , with severe rash in 5 % ) . Discontinuation of study drugs because of adverse events was more frequent in the telaprevir groups than in the control group ( 15 % vs. 4 % ) . CONCLUSIONS In HCV-infected patients in whom initial peginterferon alfa and ribavirin treatment failed , retreatment with telaprevir in combination with peginterferon alfa-2a and ribavirin was more effective than retreatment with peginterferon alfa-2a and ribavirin alone . ( Clinical Trials.gov number , NCT00420784 . UNLABELLED Merimepodib ( MMPD ) is an orally administered , inosine monophosphate dehydrogenase inhibitor that has shown antiviral activity in nonresponders with chronic hepatitis C ( CHC ) when combined with pegylated interferon alfa 2a ( Peg-IFN-alfa-2a ) and ribavirin ( RBV ) . We conducted a r and omized , double-blind , multicenter , phase 2b study to evaluate the antiviral activity , safety , and tolerability of MMPD in combination with Peg-IFN-alfa-2a and RBV in patients with genotype 1 CHC who were nonresponders to prior therapy with Peg-IFN and RBV . Patients received 50 mg MMPD , 100 mg MMPD , or placebo every 12 hours , in addition to Peg-IFN-alfa-2a and RBV , for 24 weeks . Patients with a 2-log or more decrease from baseline or undetectable hepatitis C virus ( HCV ) RNA levels at week 24 were then eligible to continue Peg-IFN-alfa-2a and RBV for a further 24 weeks , followed by 24 weeks of follow-up . The primary efficacy endpoint was sustained virological response ( SVR ) rate at week 72 in all r and omized patients who received at least one dose of study drug and had a history of nonresponse to st and ard therapy . A total of 354 patients were r and omized to treatment ( 117 to placebo ; 119 to 50 mg MMPD ; 118 to 100 mg MMPD ) , and 286 completed the core study . The proportion of patients who achieved SVR was similar among the treatment groups : 6 % ( 6/107 ) for 50 mg MMPD , 4 % ( 5/112 ) for 100 mg MMPD , and 5 % ( 5/104 ) for placebo ( P = 0.8431 ) . Adverse-event profiles for the MMPD combination groups were similar to that for Peg-IFN-alfa and RBV alone . Nausea , arthralgia , cough , dyspnea , neutropenia , and anemia were more common in patients taking MMPD . CONCLUSION The addition of MMPD to Peg-IFN-alfa-2a and RBV combination therapy did not increase the proportion of nonresponder patients with genotype 1 CHC achieving an SVR BACKGROUND In patients with chronic infection with hepatitis C virus ( HCV ) genotype 1 , treatment with peginterferon alfa and ribavirin for 48 weeks results in rates of sustained virologic response of 40 to 50 % . Telaprevir is a specific inhibitor of the HCV serine protease and could be of value in HCV treatment . METHODS A total of 334 patients who had chronic infection with HCV genotype 1 and had not been treated previously were r and omly assigned to receive one of four treatments involving various combinations of telaprevir ( 1250 mg on day 1 , then 750 mg every 8 hours ) , peginterferon alfa-2a ( 180 microg weekly ) , and ribavirin ( dose according to body weight ) . The T12PR24 group ( 81 patients ) received telaprevir , peginterferon alfa-2a , and ribavirin for 12 weeks , followed by peginterferon alfa-2a and ribavirin for 12 more weeks . The T12PR12 group ( 82 patients ) received telaprevir , peginterferon alfa-2a , and ribavirin for 12 weeks . The T12P12 group ( 78 patients ) received telaprevir and peginterferon alfa-2a without ribavirin for 12 weeks . The PR48 ( control ) group ( 82 patients ) received peginterferon alfa-2a and ribavirin for 48 weeks . The primary end point , a sustained virologic response ( an undetectable HCV RNA level 24 weeks after the end of therapy ) , was compared between the control group and the combined T12P12 and T12PR12 groups . RESULTS The rate of sustained virologic response for the T12PR12 and T12P12 groups combined was 48 % ( 77 of 160 patients ) , as compared with 46 % ( 38 of 82 ) in the PR48 ( control ) group ( P=0.89 ) . The rate was 60 % ( 49 of 82 patients ) in the T12PR12 group ( P=0.12 for the comparison with the PR48 group ) , as compared with 36 % ( 28 of 78 patients ) in the T12P12 group ( P=0.003 ; P=0.20 for the comparison with the PR48 group ) . The rate was significantly higher in the T12PR24 group ( 69 % [ 56 of 81 patients ] ) than in the PR48 group ( P=0.004 ) . The adverse events with increased frequency in the telaprevir-based groups were pruritus , rash , and anemia . CONCLUSIONS In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously , one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with st and ard therapy . Response rates were lowest with the regimen that did not include ribavirin . ( Clinical Trials.gov number , NCT00372385 . BACKGROUND / AIMS The aim of this study was to increase virologic response rates by individualized treatment according to the early virologic response . METHODS Serum HCV-RNA was frequently quantified in patients with chronic hepatitis C ( n=270 ) treated with peginterferon alfa-2a ( 180 microg/week ) and ribavirin ( 1000 - 1200 mg/day ) . After 6 weeks patients were classified as rapid ( RVR ) , slow ( SPR ) , flat ( FPR ) , or null responders ( NUR ) and r and omized within each viral kinetic class to continue therapy either with an individualized or st and ard regimen . Individualized therapy comprised peginterferon monotherapy ( 48 weeks ) or shorter combination therapy ( 24 weeks ) for RVR , triple therapy with histamine ( 1 mg/day ) ( 48 weeks ) or prolonged combination therapy ( 72 weeks ) for SPR , triple therapy for FPR , and high-dose peginterferon ( 360 microg/week ) plus ribavirin for NUR patients . RESULTS Patients were categorized as RVR ( n=171 ) , SPR ( n=65 ) , FPR ( n=10 ) , or NUR ( n=22 ) . Overall end-of-treatment and sustained virologic response rates were 77 and 60 % in the individualized and 77 and 66 % in the st and ard treatment arm , respectively . Histamine in addition to peginterferon and ribavirin and high-dose peginterferon plus ribavirin did not improve virologic response rates in patients with FPR and NUR , respectively . CONCLUSIONS An improvement in virologic efficacy was not achieved with the available individualized treatment options This study tested the hypothesis that high‐dose peginterferon alfa‐2a ( PEG‐IFNα‐2a ) for the first 12 weeks would increase early and sustained virological response ( SVR ) rates in patients with chronic hepatitis C genotype 1 . Eight hundred ninety‐six patients were r and omized 1:1 to 360 μg ( n = 448 ) or 180 μg ( n = 448 ) PEG‐IFNα‐2a weekly plus ribavirin at 1000‐1200 mg/day for 12 weeks , followed by 36 weeks of 180 μg PEG‐IFNα‐2a weekly plus ribavirin at 1000‐1200 mg/day with 871 patients evaluable for the intention‐to‐treat analysis . Virological responses were assessed by TaqMan ( limit of detection 15 IU/mL ) at week 4 , 8 , 12 , 24 , 48 ( end of therapy ) , and 24 weeks following therapy ( SVR ) . Undetectable hepatitis C virus RNA rates were significantly higher among patients receiving high‐dose induction therapy at week 4 ( 36 % versus 26 % , P < 0.005 ) , week 8 ( 61 % versus 50 % , P < 0.005 ) , and week 12 ( 74 % versus 62 % , P < 0.005 ) . However , SVR was not significantly different between patients receiving high‐dose ( 53 % ) and st and ard ( 50 % ) therapy . Significant baseline prognostic factors for SVR included age , sex , race , histological stage , and viral load . SVR was considerably higher among patients with no or minimal fibrosis ( 64 % and 60 % , respectively ) compared to those with severe fibrosis/cirrhosis ( 28 % and 24 % , respectively ) . The frequency of serious adverse events and drug discontinuations were similar in both groups , whereas PEG‐IFN dose modification , weight and appetite reduction , and grade IV neutropenia were significantly higher in the induction arm . Conclusion : Induction dosing with 360 μg/week PEG‐IFNα‐2a for 12 weeks was well tolerated and enhanced early virological response but not SVR rates . The high SVR rates in patients with minimal fibrosis highlight the benefit of early treatment in patients with hepatitis C virus genotype 1 . ( HEPATOLOGY 2009 . AIMS To evaluate whether higher doses of peginterferon alpha-2a ( 40KD ) [ PEG-IFN alpha-2a ( 40KD ) ] can compensate for lower exposure observed among obese patients with chronic hepatitis C ( CHC ) treated with the st and ard dose of PEG-IFN alpha-2a ( 40KD ) . METHODS Noncirrhotic , obese ( body mass index > or = 30 kg m(-2 ) ) patients with CHC participated in a single-centre , open-label study . Patients were r and omized to 180 or 270 microg week(-1 ) PEG-IFN alpha-2a ( 40KD ) + ribavirin ( 1000/1200 mg day(-1 ) ) for 48 weeks . Blood sample s were collected predose and up to 168 h after the first dose and at week 12 for pharmacokinetic analysis . Trough serum concentrations ( C(trough ) ) were determined up to week 24 . RESULTS In the 180 microg week(-1 ) group mean + /- SD steady-state ( week 12 ) estimates of AUC(0 - 168 ) ( ng h(-1 ) ml(-1 ) ) , C(max ) ( ng ml(-1 ) ) and CL/F ( l h(-1 ) ) were 2154 + /- 919 , 13.8 + /- 6.7 and 0.102 + /- 0.051 , respectively . In the 270 microg week(-1 ) group , estimates were 3374 + /- 1844 , 23.4 + /- 10.7 and 0.090 + /- 0.042 , respectively . The mean ( range ) C(trough ) ( ng ml(-1 ) ) was 11.2 ( 4.4 - 18.5 ) in the 180 microg week(-1 ) group and 16.1 ( 0.4 - 44.2 ) in the 270 microg week(-1 ) group . Overall , 14 of 20 ( 70 % ) and 16 of 20 ( 80 % ) patients in the 180 microg week(-1 ) and 270 microg week(-1 ) groups were infected with hepatitis C virus genotype 1 or 4 . In the 180 microg week(-1 ) and 270 microg week(-1 ) groups 14 of 20 ( 70 % ) and 15 of 19 ( 79 % ) patients , respectively , achieved a sustained viral response . Safety was similar between groups . CONCLUSIONS Mean PEG-IFN alpha-2a ( 40KD ) exposure was dose proportional from 180 to 270 microg week(-1 ) . Increasing PEG-IFN alpha-2a ( 40KD ) from 180 to 270 microg week(-1 ) achieves higher serum drug exposure in obese patients Previous trials investigating the efficacy of treatment duration s shorter than the st and ard of 24 weeks for chronic hepatitis C virus ( HCV ) genotype 2/3 infections have yielded discordant results . The aims of this investigator‐initiated phase III study were to compare the efficacy of 12 or 24 weeks of treatment and to identify patients suitable for short‐term therapy . Three hundred eighty‐two genotype 2/3–infected patients [ intention‐to‐treat ( ITT ) population ] at 31 centers in Denmark , Finl and , Norway , and Sweden were r and omized to 12 or 24 weeks of peginterferon α‐2a ( 180 μg/week ) plus ribavirin ( 800 mg/day ) . Twelve weeks of therapy was inferior to 24 weeks in the ITT population ( sustained viral response [ SVR ] rates : 59 % versus 78 % , P < 0.0001 ) and in the subgroups of patients infected with genotype 2 ( 56 % versus 82 % , P = 0.006 ) or 3 ( 58 % versus 78 % , P = 0.0015 ) . These differences were observed regardless of the fibrosis stage . Age and HCV‐RNA levels on days 7 and 29 were independent predictors of SVR . Short‐term treatment was useful in patients < 40 years old , especially if HCV‐RNA was undetectable on day 29 , and also in patients ≥ 40 years old , provided that HCV‐RNA was below 1000 IU/mL on day 7 in addition to being undetectable on day 29 . If neither of these two criteria were met for patients ≥ 40 years old , 24 weeks of therapy was superior ( P < 0.0001 ) . Conclusion : Peginterferon/ribavirin treatment for 12 weeks in HCV genotype 2/3 infection is overall inferior to 24 weeks of treatment but may be useful in some patients with a rapid initial clearance of virus . ( HEPATOLOGY 2008 . UNLABELLED In patients chronically infected with hepatitis C virus ( HCV ) genotype 4 , the optimum duration of therapy and the predictors of sustained virologic response ( SVR ) have not been adequately determined . In this study , 358 patients with chronic hepatitis C genotype 4 were r and omly assigned to pegylated interferon ( PEG-IFN ) alpha-2b ( 1.5 mug/kg/week ) plus oral ribavirin ( 10.6 mg/kg/day ) for a fixed duration of 48 weeks ( control group , n = 50 ) or for a variable duration ( n = 318 ) . In the variable- duration group , patients with undetectable HCV RNA at week 4 were treated for 24 weeks ( group A , n = 69 ) , patients with undetectable HCV RNA at week 12 were treated for 36 weeks ( group B , n = 79 ) , and the rest of the patients were treated for 48 weeks ( group C , n = 160 ) . The primary endpoint was SVR ( undetectable HCV RNA 24 weeks after treatment cessation ) . Groups A-C and the control group had SVR rates of 86 % , 76 % , 56 % , and 58 % , respectively . After the study was controlled for predictors , a low baseline histologic grade and stage were associated with SVR ( P < 0.029 ) in all groups . In addition , among patients in group C , older age ( P = 0.04 ) , a higher baseline body mass index ( P = 0.013 ) , and low baseline HCV RNA ( P < 0.001 ) were also associated with SVR attainment . The incidence of adverse events and the rate of discontinuation were higher in patients in the variable- duration and fixed- duration groups treated for 48 weeks . CONCLUSION In patients with chronic hepatitis C genotype 4 and undetectable HCV RNA at weeks 4 and 12 , treatment with PEG-IFN alpha-2b and ribavirin for 24 weeks and 36 weeks , respectively , is sufficient BACKGROUND & AIMS Sustained virologic response ( SVR ) rates of 50%-60 % have been achieved in patients with chronic hepatitis C genotype 4 treated with peginterferon plus ribavirin . The safety and efficacy of nitazoxanide plus peginterferon alfa-2a , with or without ribavirin , were evaluated in a r and omized controlled trial at 2 centers in Egypt . METHODS Previously untreated patients with chronic hepatitis C and genotype 4 infection were assigned r and omly to groups that were given st and ard of care ( peginterferon alfa-2a and ribavirin for 48 weeks , n = 40 ) , nitazoxanide monotherapy for 12 weeks followed by nitazoxanide plus peginterferon alfa-2a for 36 weeks ( n = 28 ) , or nitazoxanide monotherapy for 12 weeks followed by nitazoxanide plus peginterferon alfa-2a and ribavirin for 36 weeks ( n = 28 ) . Therapeutics included nitazoxanide ( 500 mg ) twice daily , peginterferon alfa-2a ( 180 microg ) once weekly , and weight-based ribavirin ( 1000 - 1200 mg/day ) . RESULTS The percentages of rapid virologic response ( RVR ) , defined as undetectable HCV RNA at week 4 of combination therapy , and SVR were significantly higher in patients given the triple therapy compared with the st and ard of care ( 64 % vs 38 % , P = .048 ; and 79 % vs 50 % , P = .023 ; respectively ) . Patients given nitazoxanide plus peginterferon alfa-2a had intermediate rates of RVR ( 54 % ) and SVR ( 61 % ) . Adverse events were similar across treatment groups except for higher rates of anemia in the groups receiving ribavirin . CONCLUSIONS The combination of nitazoxanide , peginterferon alfa-2a , and ribavirin increased the percentages of patients with RVR and SVR , compared with patients given peginterferon plus ribavirin , without an increase in adverse events OBJECTIVES : The treatment of patients with hepatitis C virus ( HCV ) genotype 1 with peginterferon plus ribavirin treatment for more than 48 weeks demonstrated high sustained virological response ( SVR ) rates . Although many studies extended the duration of therapy from 48 weeks to 72 weeks , the optimal duration has not yet been determined . METHODS : A total of 113 genotype 1b patients with high viral load were r and omized at baseline to the st and ard ( n=56 ) or extended ( n=57 ) treatment group . The st and ard group patients received 48 weeks of peginterferon plus ribavirin treatment . In the extended group , the treatment was performed for 44 weeks after patients became negative for HCV RNA ( total duration 48–68 weeks ) . RESULTS : The SVR rate of the st and ard and extended group was 36 % ( 20 of 56 ) and 53 % ( 30 of 57 ; P=0.07 ) . However , the extended group patients who became negative for HCV RNA between weeks 16 and 24 had a significantly higher SVR rate ( 78 % ; 7 of 9 ) than that of st and ard group ( 9 % , 1 of 11 ; P=0.005 ) . The predictive factors for the SVR were the treatment regimen ( the st and ard vs. extended treatment ) and the time to HCV RNA negative – status . CONCLUSIONS : The extended treatment significantly increased the SVR rate in patients who were HCV RNA negative at 16–24 weeks BACKGROUND & AIMS Ribavirin ( RBV ) combined with either pegylated interferon ( PegIFN ) alpha2a or PegIFNalpha2b is the st and ard of care for chronic hepatitis C virus ( HCV ) infection . Due to the lack of head-to-head studies , the 2 PegIFNs have not been directly compared . The endpoints of our study were safety and antiviral efficacy of the 2 regimens . METHODS Treatment-naïve patients with chronic hepatitis C were r and omly ( 1:1 ) assigned after stratification for HCV genotype to receive either 1.5 mcg/Kg/week PegIFNalpha2b plus RBV 800 - 1200 mg/day or 180 mcg/week PegIFNalpha2a plus RBV 800 - 1200 mg/day for 24 or 48 weeks according to HCV genotype . The study was powered to detect a difference of at least 10 % in safety and efficacy of the 2 regimens . RESULTS The 212 patients on PegIFNalpha2a and the 219 patients on PegIFNalpha2b had similar baseline characteristics , including cirrhosis ( 20 % vs 18 % , respectively ) . By intention to treat , the 2 groups showed similar rates of treatment-related serious adverse events ( 1 % vs 1 % , respectively ) and drop out rates for adverse effects ( 7 % vs 6 % , respectively ) . Overall , sustained virologic response ( SVR ) rate was higher in PegIFNalpha2a than in PegIFNalpha2b patients ( 66 % vs 54 % , respectively , P = .02 ) , being 48 % vs 32 % in the 222 HCV-1 and -4 patients ( P = .04 ) , and 96 % vs 82 % , respectively , in the 143 HCV-2 patients ( P = .01 ) . PegIFNalpha2a independently predicted SVR in the logistic regression analysis ( odds ratio , 1.88 ; 95 % confidence interval : 1.20 - 2.96 ) . CONCLUSIONS Although the 2 regimens showed a similar safety profile , the PegIFNalpha2a-based treatment yielded significantly more SVR than PegIFNalpha2b OBJECTIVES : The efficacy of combination therapy with pegylated interferon ( PEG IFN ) α plus ribavirin ( RBV ) in the retreatment of chronic hepatitis C ( CHC ) in patients who previously failed combination st and ard IFN plus RBV or IFN monotherapy has not been well established . METHODS : Three hundred and twenty-one CHC patients including virologic nonresponders to combination IFN plus RBV ( n = 219 ) or IFN monotherapy ( n = 47 ) , and relapsers to combination therapy ( n = 55 ) were r and omized to receive PEG IFN α-2b 1.5 μg/kg per wk plus RBV 800 mg per day ( Regimen A , n = 160 ) or PEG IFN α-2b 1.0 μg/kg per wk plus RBV 1,000–1,200 mg per day ( Regimen B , n = 161 ) for 48 wks . RESULTS : Sustained virologic response ( SVR ) occurred in 16 % of the overall study population ( Regimen A vs B , 18 % vs 13 % , p = 0.21 ) , in 8 % of the combination therapy nonresponders ( 10 % vs 6 % , p = 0.35 ) , in 21 % of the IFN monotherapy nonresponders ( 16 % vs 27 % , p = 0.35 ) , and in 42 % of the combination therapy relapsers ( 50 % vs 32 % , p = 0.18 ) . In nonresponders to prior combination therapy , HCV ribonucleic acid levels < 100,000 copies/mL at the end of the prior treatment course were associated with an increased SVR compared with levels ≥100,000 copies/mL ( 21 % vs 5 % , p = 0.002 ) . In the overall study population , genotype 1 patients had lower SVR rates than others ( 14 % vs 33 % , p = 0.01 ) , and African Americans had lower SVR than Caucasians ( 4 % vs 18 % , p = 0.01 ) . CONCLUSION : Combination therapy with PEG IFN α-2b plus RBV is more effective in patients who relapsed after combination st and ard IFN plus RBV than in nonresponders to either combination therapy or IFN monotherapy . There was no significant effect of dosing regimen BACKGROUND & AIMS This r and omized multicenter trial evaluated individualization of treatment duration with peginterferon alfa-2a 180 microg/wk plus ribavirin 1000/1200 mg/day in patients with chronic hepatitis C genotype 1/4 based on the rapidity of virologic response ( VR ) . METHODS Patients with a rapid VR ( RVR ; undetectable hepatitis C virus [HCV]-RNA level ( < 50 IU/mL at week 4 ) were treated for 24 weeks , those with an early VR ( EVR ; no RVR but undetectable HCV-RNA level or > or=2-log(10 ) decrease at week 12 ) were r and omized to 48 ( group A ) or 72 weeks of treatment ( group B ; peginterferon alfa-2a was reduced to 135 microg/wk after week 48 ) . Patients without an EVR continued treatment until week 72 if they had undetectable HCV-RNA levels at week 24 . The primary end point was relapse ; sustained VR ( SVR ; undetectable HCV-RNA level after 24 weeks of follow-up evaluation ) was a secondary end point . RESULTS Of 551 genotype 1/4 patients starting treatment , 289 were r and omized to group A ( N = 139 ) or group B ( N = 150 ) . The relapse rate was 33.6 % in group A ( 95 % confidence interval [ CI ] , 24.8%-43.4 % ) and 18.5 % in group B ( 95 % CI , 11.9%-27.6 % ; P = .0115 vs group A ) and the SVR rate was 51.1 % ( 95 % CI , 42.5%-59.6 % ) and 58.6 % ( 95 % CI , 50.3%-66.6 % ; P > .1 ) , respectively . The overall SVR rate was 50.4 % ( 278 of 551 ; 95 % CI , 46.2%-54.7 % ) , including 115 of 150 patients with an RVR treated for 24 weeks and 4 of 78 patients without an EVR . CONCLUSIONS Extending therapy with peginterferon alfa-2a/ribavirin to 72 weeks decreases the probability of relapse in patients with an EVR . If they can be maintained on extended- duration therapy , SVR rates also may improve BACKGROUND The efficacy and safety of peginterferon alpha-2a ( 40 KD ) ( peg-IFNalpha-2a ) plus ribavirin has not been reported for Japanese patients with chronic hepatitis C. The aim of this study was to evaluate this combination in treatment-naïve patients and in non-responders or relapsers to interferon monotherapy . METHODS Overall , 201 treatment-naïve patients with hepatitis C virus ( HCV ) genotype-1b were r and omly assigned to 180 microg peg-IFNalpha-2a once-weekly plus ribavirin 600 - 1000 mg/day or peg-IFNalpha-2a plus placebo for 48 weeks . Additionally , peg-IFNalpha-2a plus ribavirin was administered for 48 weeks to 100 non-responders or relapsers ( 85 % genotype-1 ) to previous interferon monotherapy . RESULTS A sustained virological response ( SVR ) was attained among significantly more treatment-naïve patients receiving combination therapy than monotherapy ( 61 % vs 26 % , P < 0.001 ) . For patients with high baseline HCV RNA , the SVR rate was 59 % with peg-IFNalpha-2a plus ribavirin versus 24 % with peg-IFNalpha-2a monotherapy . Among non-responders or relapsers to previous interferon monotherapy , 54 % attained an SVR . Adverse events were generally mild , and discontinuations rates due to adverse events or laboratory abnormalities were low . CONCLUSION In Japanese patients , peg-IFNalpha-2a plus ribavirin provided significant improvement in SVR rates compared with peg-IFNalpha-2a alone in treatment-naïve patients , and was effective as re-treatment for non-responders or relapsers to previous treatment with interferon monotherapy UNLABELLED The efficacy and safety of albinterferon alfa-2b ( alb-IFN ) , a novel recombinant protein consisting of interferon alfa-2b genetically fused to human albumin , was evaluated in a phase 2b , open-label study of patients with genotype 1 , chronic hepatitis C. In all , 458 IFN-alfa treatment-naïve patients were r and omized to 48-week treatment with peginterferon alfa (PEG-IFNalpha)-2a 180 microg one time per week ( qwk ) , or alb-IFN 900 or 1,200 microg once every two weeks ( q2wk ) , or 1,200 microg once every four weeks ( q4wk ) , administered subcutaneously , plus weight-based oral ribavirin 1,000 or 1,200 mg/day . Hepatitis C virus RNA was measured by real-time polymerase chain reaction ( limit of detection : 10 IU/mL ) . The primary efficacy endpoint was sustained virologic response ( hepatitis C virus RNA < 10 IU/mL 24 weeks after the end of treatment ) . By intention-to-treat analysis , sustained virologic response rates were 58.5 % ( 69/118 ) with alb-IFN 900 microg q2wk , 55.5 % ( 61/110 ) with 1,200 microg q2wk , and 50.9 % ( 59/116 ) with 1,200 microg q4wk , and 57.9 % ( 66/114 ) with PEG-IFNalpha-2a ( P = 0.64 for overall test ) . Discontinuation rates due to adverse events were 9.3 % with alb-IFN 900 microg q2wk , 18.2 % with 1,200 microg q2wk and 12.1 % with 1,200 microg q4wk , and 6.1 % with PEG-IFNalpha-2a ( P = 0.04 ) . Hematologic reductions were lowest in the q4wk group and comparable across other groups . At week 12 , mean treatment-associated missed workdays were significantly lower with alb-IFN 900 mug q2wk versus PEG-IFNalpha-2a ( 1.1 versus 4.3 days ; P = 0.006 ) . CONCLUSION Alb-IFN administered q2wk or q4wk may offer comparable efficacy , with an improved dosing schedule , compared with PEG-IFNalpha-2a Background : The response rates and duration of peginterferon alpha ( PEG-IFN-α ) and ribavirin combination therapy in chronic hepatitis C genotype 4 , the prevalent genotype in the Middle East and Africa , are poorly documented . Aims : To compare the efficacy and safety of 24 , 36 , or 48 weeks of PEG-IFN-α-2b and ribavirin therapy in chronic hepatitis C genotype 4 . Methods : In this prospect i ve , r and omised , double blind study , 287 patients with chronic hepatitis C genotype 4 were r and omly assigned to PEG-IFN-α-2b ( 1.5 μg/kg ) once weekly plus daily ribavirin ( 1000–1200 mg ) for 24 weeks ( group A , n = 95 ) , 36 weeks ( group B , n = 96 ) , or 48 weeks ( group C , n = 96 ) and followed for 48 weeks after completion of treatment . Early viral kinetics and histopathological evaluation of pre- and post treatment liver biopsies were performed . The primary end point was viral clearance 48 weeks after completion of treatment . Results : Sustained virological response was achieved in 29 % , 66 % , and 69 % of patients treated with PEG-IFN-α-2b and ribavirin for 24 , 36 , and 48 weeks , respectively , by intention to treat analysis . No statistically significant difference in sustained virological response rates was detected between 36 and 48 weeks of therapy ( p = 0.3 ) . Subjects with sustained virological response showed greater antiviral efficacy ( ε ) and rapid viral load decline from baseline to treatment week 4 compared with non-responders and improvement in liver histology . The incidence of adverse events was higher in the group treated for 48 weeks . Conclusion : PEG-IFN-α-2b and ribavirin for 36 or 48 weeks was more effective in the treatment of chronic hepatitis C genotype 4 than treatment for 24 weeks . Thirty six week therapy was well tolerated and produced sustained virological and histological response rates similar to the 48 week regimen Background In patients with chronic hepatitis C virus ( HCV ) genotype 2 or 3 , 24 weeks ' treatment with pegylated interferon alfa ( PEG-IFN-alpha ) and ribavirin induces a sustained virological response ( SVR ) in almost 80 % of cases . Evidence suggests that a similar response rate may be obtained with shorter treatment periods , especially in patients with a rapid virological response ( RVR ) . The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment . Methods Two hundred and ten patients received PEG-IFN-alpha-2a ( 180 ug/week ) and ribavirin ( 800 - 1200 mg/day ) for 4 weeks . Patients with a RVR ( HCV RNA not detectable ) were r and omized ( 1:1 ) to either 12 ( group A1 ) or 24 ( group A2 ) weeks of combination therapy . Patients without a RVR continued with 24-weeks ' combination therapy ( group B ) . HCV RNA was monitored at weeks 4 , 8 , 12 , and 24 , and at week 24 post-treatment . Results At study end , end of treatment response ( ETR ) was observed in 62 ( 86 % ) patients of group A1 and in 55 ( 77 % ) patients of group A2 ( p < 0.05 ) Relapse rate was 3 % each in groups A1 and A2 , and 6 % in group B. Among patients with a HCVRNA test 24 weeks after the end of treatment , SVR was observed in 60 ( 83 % ) of group A1 patients and in 53 ( 75 % ) of group A2 patients . Rapid virological response , low baseline HCV RNA levels , elevated alanine aminotransferase levels and low fibrosis score , were the strongest covariates associated with SVR , independent of HCV genotype . No baseline characteristic was associated with relapse . Conclusion In HCV patients with genotype 2 or 3 , 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR.Trial registration Trial number IS RCT Peginterferon-alpha plus ribavirin is the most effective therapy for chronic hepatitis C. This study was design ed to evaluate the effect of peginterferon alpha-2a ( 40 kDa ) plus ribavirin on sustained virological response ( SVR ) when administered for 24 vs 48 weeks in genotype 1 naïve patients . One hundred and seventeen patients were enrolled in this controlled trial . Genotype 1 patients were r and omized to 24 weeks treatment vs 48 weeks treatment . Genotype non-1 patients received 24 weeks treatment as an observational group . Outcomes were SVR ( defined by hepatitis C virus-RNA-negative at week 24 of follow-up ) and tolerability across the study period . The end-of-treatment response was 59 % for genotype 1 ( 24 weeks treatment ) , 80 % for genotype 1 ( 48 weeks treatment ) and 92 % for genotype non-1 ( 24 weeks treatment ) . The end-of-follow-up response was 19 % ( 95 % confidence interval ( CI ) : 7.2 - 36.4 ) ( genotype 1 , 24 weeks ) and 48 % ( 95 % CI : 30.2 - 66.9 ; P = 0.0175 ) ( genotype 1 , 48 weeks ) . Among genotype non-1 , SVR was 76 % ( 95 % CI : 62.3 - 86.5 ) . There were no unexpected adverse events . Almost half of the genotype 1 patients achieved an SVR after 48 weeks treatment with peginterferon alpha-2a ( 40 kDa ) and low-dose ribavirin and confirmed that they should be treated for 48 weeks . Safety profile was acceptable There are no established therapeutic regimens for hepatitis C virus ( HCV ) patients who relapse following treatment with interferon alpha-2b and ribavirin or those who break through while on interferon alpha-2b and ribavirin . We therefore evaluated various combination therapies in HCV patients who relapsed or experienced a viral breakthrough . Patients ( n = 124 ) were r and omized to 48 weeks of treatment with once-weekly subcutaneous injections of 180 microg pegylated ( peg- ) interferon alpha-2a plus oral ribavirin ( 800 - 1000 mg/day ) , mycophenolate mofetil ( 2 g/day ) , amantadine ( 200 mg/day ) , or ribavirin and amantadine and followed for an additional 24 weeks . The sustained virologic response was higher in patients administered peginterferon alpha-2a plus ribavirin ( 38 % ) or ribavirin and amantadine ( 45 % ) than in those administered peginterferon alpha-2a plus mycophenolate mofetil ( 17 % ) or amantadine ( 10 % ) . As in previous studies , patients with genotype non-1 and those with lower viral loads had better responses than those with genotype 1 and high viral loads , though the differences did not reach significance . The four treatment regimens had similar safety profiles , except that patients receiving ribavirin had greater maximal hemoglobin decreases . These findings suggest that the combination of peginterferon alpha-2a plus ribavirin or with ribavirin and amantadine is effective in some HCV patients who relapse after treatment with interferon alpha-2b plus ribavirin BACKGROUND A sustained virological response ( SVR ) rate of 41 % has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this r and omised trial , peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin . METHODS 1530 patients with chronic hepatitis C were assigned interferon alfa-2b ( 3 MU subcutaneously three times per week ) plus ribavirin 1000 - 1200 mg/day orally , peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin , or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000 - 1200 mg/day for 48 weeks . The primary endpoint was the SVR rate ( undetectable hepatitis C virus [ HCV ] RNA in serum at 24-week follow-up ) . Analyses were based on patients who received at least one dose of study medication . FINDINGS The SVR rate was significantly higher ( p=0.01 for both comparisons ) in the higher-dose peginterferon group ( 274/511 [ 54 % ] ) than in the lower-dose peginterferon ( 244/514 [ 47 % ] ) or interferon ( 235/505 [ 47 % ] ) groups . Among patients with HCV genotype 1 infection , the corresponding SVR rates were 42 % ( 145/348 ) , 34 % ( 118/349 ) , and 33 % ( 114/343 ) . The rate for patients with genotype 2 and 3 infections was about 80 % for all treatment groups . Secondary analyses identified bodyweight as an important predictor of SVR , prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight ( mg/kg ) . Side-effect profiles were similar between the treatment groups . INTERPRETATION In patients with chronic hepatitis C , the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin . The benefit is mostly achieved in patients with HCV genotype 1 infections BACKGROUND / AIMS Chronic hepatitis C ( HCV ) patients who have failed previous treatment have low sustained viral response ( SVR ) rates with repeat treatment . We evaluated whether interferon ( IFN ) induction during retreatment improves response rates . METHODS Two r and omized , controlled trials were conducted in chronic HCV patients who failed IFN . In Study 1 , patients received IFN 3 MU daily plus ribavirin ( RBV ) 1000 mg/day for 4 weeks , followed by IFN 3 MU TIW plus RBV 1000 mg/day for 44 weeks ( induction ; n=232 ) , or IFN 3 MU TIW plus RBV 1000 mg/day for 48 weeks ( non-induction ; n=237 ) . In Study 2 , patients received IFN 5 MU B.I.D. plus RBV 1000 - 1200 mg/day for 2 weeks , followed by pegylated IFN ( PEG-IFN ) 75 - 150 mug weekly plus RBV 1000 - 1200 mg/day for 46 weeks ( induction ; n=201 ) , or PEG-IFN 75 - 150 mug weekly plus RBV 1000 - 1200 mg/day for 48 weeks ( non-induction ; n=206 ) . The primary end point for both trials was SVR . RESULTS Induction did not increase SVR compared with non-induction , but did increase the on-treatment response among genotype non-1 patients in Study 2 . By intention-to-treat ( ITT ) analysis , SVR in Study 1 was 13 % for induction vs. 9 % for non-induction ( P = NS ) . In Study 2 ( ITT ) , SVR was 20 % for induction vs. 24 % for non-induction ( P = NS ) . However , by non-ITT analysis of Study 2 , genotype non-1-previous non-responders showed significantly higher response rates with induction than non-induction . CONCLUSION For chronic HCV patients who have failed IFN , induction with retreatment does not improve SVR , but may be beneficial for patients with genotype non-1 HCV BACKGROUND / AIMS Amantadine may augment virological response rates to interferon-based therapy in chronic hepatitis C patients . Using a novel design , amantadine was studied in naïve genotype 1 patients treated in combination with peginterferon alfa-2a (40KD)/ribavirin . METHODS Patients enrolled in this r and omized , placebo-controlled multicenter trial were stratified by single-dose interferon sensitivity ( stratum I , 24-h HCV-RNA decline > 1.4-log10 ; II , 0.8 - 1.39-log10 ; III , < 0.8-log10 ; a reliable means of identifying nonresponders to interferon/ribavirin ) and fibrosis grade ( F0/1/2 vs. F3/4 ) at baseline . All patients received peginterferon alfa-2a ( 40KD ) 180 microg/week plus ribavirin 1000 - 1200 mg/day and were r and omized to receive amantadine 100 mg twice daily ( N = 114 ) or placebo ( N = 95 ) for 48 weeks . RESULTS Week-24 virological response rates in strata II and III , the primary outcome , were similar in patients treated with amantadine ( 63.7 % ) or placebo ( 65.7 % ) , as were sustained virological response rates at week 72 ( 46.5 and 51.6 % , respectively ) . Adverse event profiles were similar and amantadine did not improve health-related quality of life compared with placebo . Interferon sensitivity was the only significant predictor of treatment outcome . CONCLUSIONS Adding amantadine to peginterferon alfa-2a (40KD)/ribavirin combination therapy does not augment virological response rates in genotype 1 patients . Virological response was almost exclusively determined by interferon sensitivity at baseline BACKGROUND Comparable sustained virologic response ( SVR ) rates have been documented between Asian patients who received 24 weeks of pegylated interferon ( IFN ) plus ribavirin and white patients who received 48 weeks of combination therapy for hepatitis C virus genotype 1 ( HCV-1 ) infection . Whether a 48-week course of combination therapy shows a better SVR rate than a 24-week course of such therapy among Asian patients with HCV-1 infection has not been confirmed in multicenter , r and omized studies . METHODS In this multicenter , r and omized trial , 308 treatment-naive HCV-1-infected Asian patients were r and omly assigned to receive either 24 or 48 weeks of pegylated IFN-alpha-2a ( 180 microg per week ) plus ribavirin ( 1000 - 1200 mg/day ) therapy . The primary end point was SVR , defined as an undetectable serum HCV RNA level 24 weeks after discontinuation of therapy . In addition , rapid virologic response ( RVR ) was defined as an undetectable serum HCV RNA level at week 4 of therapy , and complete early virologic response was defined as an undetectable serum HCV RNA level at 12 weeks of therapy in the absence of RVR . RESULTS By intention-to-treat analysis , patients who received 48 weeks of therapy had a significantly higher SVR rate than did those who received 24 weeks of therapy ( 76 % vs. 56 % ; P < .001 ) . Among patients with a baseline serum HCV RNA level < 800,000 IU/mL and RVR , SVR rates were comparable between 24- and 48-week courses of therapy ( 94 % vs. 100 % ; P = .13 ) . In contrast , 48 weeks of therapy was associated with a significantly higher SVR rate than was 24 weeks of therapy among patients without RVR ( 39 % vs.16 % ; P = .01 ) and among those who achieved a complete early virologic response ( 44 % vs. 20 % ; P = .02 ) . CONCLUSIONS In treatment-naive Asian patients with HCV-1 infection , 48 weeks of pegylated IFN-alpha-2a plus ribavirin therapy is associated with a higher SVR rate , compared with 24 weeks of such therapy . Patients with a baseline serum HCV RNA level < 800,000 IU/mL and who have achieved an RVR can receive a 24-week course of therapy without compromising the SVR rates ; however , those who have not achieved an RVR but who have achieved a complete early virologic response should receive a 48-week course of therapy Pegylated interferon ( peg‐IFN ) and ribavirin ( RBV ) are effective in eradicating the hepatitis C virus in more than half of patients . However , anemia arising from RBV‐induced hemolysis can prompt dose reductions and lower sustained virologic response ( SVR ) rates . In early clinical trials , Viramidine ( VRD , renamed taribavirin ) , an RBV prodrug , was associated with less anemia and VRD given at 600 mg twice daily ( BID ) appeared to provide the best safety with comparable efficacy to RBV . The phase III Viramidine 's Safety and Efficacy versus Ribavirin 1 ( ViSER1 ) study r and omized 972 treatment‐naïve patients with chronic hepatitis C to fixed‐dose VRD ( 600 mg BID ) or weight‐based RBV ( 1000 or 1200 mg/day ) , each given with peg‐IFN alfa‐2b at 1.5 μg/kg/week . The primary efficacy endpoint was SVR rate , and the primary safety endpoint was hemoglobin ( Hb ) event rate ( percent of patients with Hb < 10 g/dL or at least a 2.5‐g/dL decrease from baseline ) . SVR rates were 37.7 % with VRD ( 244/647 ) and 52.3 % with RBV ( 170/325 ) . Thus , the ViSER1 study failed to demonstrate the primary noninferiority efficacy endpoint . Significantly fewer patients had Hb events with VRD ( 353/647 ; 54.6 % ) compared to those with RBV ( 272/325 ; 83.7 % ) ( P < 0.001 ) , and significantly fewer developed anemia ( Hb < 10 g/dL ) with VRD ( 34/647 ; 5.3 % ) compared to those with RBV ( 76/325 ; 23.5 % ) ( P < 0.001 ) . Conclusion : Fixed doses of VRD failed to demonstrate noninferiority to RBV in producing SVR rates . The incidence of anemia was approximately four‐fold significantly lower with VRD than with RBV . These results suggest fixed‐dose VRD given 600 mg BID is insufficient to treat patients with chronic hepatitis C ; a weight‐based dosing trial of viramidine is currently under way . ( HEPATOLOGY 2009 . BACKGROUND Patients infected with hepatitis C virus ( HCV ) genotype 2 or 3 have sustained virologic response rates of approximately 80 % after receiving treatment with peginterferon and ribavirin for 24 weeks . We conducted a large , r and omized , multinational , noninferiority trial to determine whether similar efficacy could be achieved with only 16 weeks of treatment with peginterferon alfa-2a and ribavirin . METHODS We r and omly assigned 1469 patients with HCV genotype 2 or 3 to receive 180 mug of peginterferon alfa-2a weekly , plus 800 mg of ribavirin daily , for either 16 or 24 weeks . A sustained virologic response was defined as an undetectable serum HCV RNA level ( < 50 IU per milliliter ) 24 weeks after the end of treatment . RESULTS The study failed to demonstrate that the 16-week regimen was noninferior to the 24-week regimen . The sustained virologic response rate was significantly lower in patients treated for 16 weeks than in patients treated for 24 weeks ( 62 % vs. 70 % ; odds ratio for 16 weeks vs. 24 weeks , 0.67 ; 95 % confidence interval , 0.54 to 0.84 ; P<0.001 ) . In addition , the rate of relapse ( a detectable HCV RNA level during follow-up in patients who had undetectable HCV RNA at the end of treatment ) was significantly greater in the 16-week group ( 31 % , vs. 18 % in the 24-week group ; P<0.001 ) . The sustained virologic response rates in patients with a pretreatment serum HCV RNA level of 400,000 IU per milliliter or less was 82 % with the 16-week regimen and 81 % with the 24-week regimen . Among patients with a rapid virologic response ( an undetectable HCV RNA level by week 4 ) , sustained virologic response rates were 79 % in the 16-week group and 85 % in the 24-week group ( P=0.02 ) . CONCLUSIONS Treatment with peginterferon and ribavirin for 16 weeks in patients infected with HCV genotype 2 or 3 results in a lower overall sustained virologic response rate than treatment with the st and ard 24-week regimen . ( Clinical Trials.gov number , NCT00077636 [ Clinical Trials.gov ] . ) In patients with chronic hepatitis C , rapid virological response ( RVR ) at week 4 of treatment seems to be strongly associated with a high probability of achieving a sustained virological response ( SVR ) . The aim of this study was to investigate the outcome of different pegylated interferon-alpha2b ( Peg-IFN-alpha2b ) dosages plus ribavirin ( RBV ) in patients with RVR . Forty-five naïve patients chronically infected with hepatitis C virus (HCV)-1b started Peg-IFN-alpha2b ( 1.5 microg/kg/week ) in combination with weight-based RBV doses ( 800 - 1200 mg/day ) . Thirty-one patients ( 68.9 % ) attained RVR at week 4 of therapy , while four further patients showed negative HCV-RNA values for the first time at week 12 and were considered early virological responders ( EVR ) . The 31 RVR patients were r and omized to receive either RBV plus 1.5 microg/kg/week ( 17 pts ) or 1.0 microg/kg/week ( 14 pts ) of Peg-IFN-alpha2b for the remaining 44 weeks . The two groups were matched for age , sex , baseline alanine aminotransferase levels , viral load and fibrosis score . After 6 months of post-treatment follow-up , the prevalence of SVR was 94.1 % ( 16/17 ) among RVR patients treated with 1.5 microg/kg/week and 92.8 % ( 13/14 ) in RVR patients treated with 1.0 microg/kg/week ( P = not significant ) . A high-baseline viral load ( P = 0.01 ) and bridging fibrosis/cirrhosis ( P = 0.02 ) negatively influenced the likelihood of achieving RVR . On the contrary , the ability of RVR patients to achieve SVR did not correlate with these baseline characteristics in either of the treatment group . Finally , the SVR rate among EVR patients who responded after more than 4 weeks of treatment was significantly lower than among RVR patients ( 1/4 = 25%vs 29/31 = 93.5 % ; P = 0.0058 ) , because of a high prevalence of post-treatment relapse among patients with EVR We conducted a r and omized multinational study to determine whether 48 weeks of re-treatment with peginterferon-alpha-2a ( 40 kDa ) plus ribavirin would induce a sustained virological response ( SVR ) in relapsed chronic hepatitis C patients . Patients who had previously relapsed during 24 weeks of untreated follow-up , after having achieved an end-of-treatment virological response with 24 weeks of peginterferon-alpha-2a ( 40 kDa)/ribavirin combination therapy , within a phase III trial , were studied . Although the recommended dosage was the same as that used at the end of the initial trial , adjustments were permitted . Data on serious adverse events , or adverse events that result ed in dose reductions or discontinuations , were collected . Following re-treatment , the overall SVR rate in the 64 patients was 55 % . The SVR rates in patients infected with hepatitis C virus ( HCV ) genotype 1 and non-1 genotypes were 51 % and 63 % , respectively . Early ( week 12 ) virological responses were seen in 39 patients ( 61 % ) and were predictive of an SVR . Re-treatment was well tolerated . The most frequent adverse events recorded were fatigue ( 5 % ) and abdominal pain ( 3 % ) . Dosages of peginterferon-alpha-2a ( 40 kDa ) and /or ribavirin were modified because of adverse events in 3 % and 13 % of patients , and because of laboratory abnormalities in 23 % and 5 % of patients , respectively . Thus , a 48-week course of peginterferon-alpha-2a ( 40 kDa ) plus ribavirin induces an SVR in 55 % of patients who relapsed during follow-up after 24 weeks of combination therapy . Physicians should not hesitate to offer re-treatment to patients who relapse after an initial , 24-week course of combination therapy , or who have prematurely stopped treatment because , for example , of laboratory abnormalities BACKGROUND & AIMS St and ard of care ( SOC ) treatment for chronic hepatitis C ( CHC ) involves weekly pegylated ( PEG ) interferon plus weight-based ribavirin with result ant sustained virologic response ( SVR ) rates at or near 50 % for genotypes 1 and 4 virus . Induction therapy with higher doses of PEG interferon may improve first-phase viral kinetics and thus improve the overall SVR in genotypes 1 and 4 patients . METHODS This multicenter , r and omized , open-label trial enrolled treatment-naive genotypes 1- and 4-infected CHC patients to either initial induction therapy versus SOC . The induction group received PEG interferon alfa-2b 3.0 mcg/kg/wk for 12 weeks followed by PEG interferon alfa-2b 1.5 mcg/kg/wk for 36 weeks and 13 + /- 2 mg/kg ribavirin daily for 48 weeks . SOC patients received PEG interferon alfa-2b 1.5 mcg/kg weekly for 48 weeks and 13 + /- 2 mg/kg ribavirin daily for 48 weeks . The primary end point was SVR . RESULTS There were 610 patients enrolled throughout the United States . Complete early virologic response was 62.6 % versus 57.7 % in induction versus SOC ( NS ) . Overall SVR was 32 % in induction versus 29 % in SOC group ( NS ) . Dose reduction of either PEG interferon ( 24.1 % vs 23.8 % ) or ribavirin ( 26.8 % vs 25.1 % ) was similar between the 2 groups . There was a trend toward a significant difference when comparing the SVR in induction therapy in patients weighing more than 85 kg versus those receiving SOC ( 38 % vs 28 % ; P = .08 ) . CONCLUSIONS Induction therapy does not enhance complete early virologic response or SVR rates in a predominantly genotype 1 CHC population compared with SOC therapy We compared sustained virological response ( SVR ) in chronic hepatitis C patients with severe fibrosis treated with pegylated interferon ( Peg-IFN ) alpha-2b 1.5 microg/kg/week or 0.75 microg/kg/week in combination with ribavirin 800 mg/day for 48 weeks . This was a multicentre r and omized controlled study . SVR was observed in 44.5 % ( 45/101 ) of patients treated with the st and ard dose of Peg-IFN and 37.2 % ( 38/102 ) of patients treated with the low dose ( NS ) . In patients with genotypes 1 , 4 and 5 , SVR was observed in 25.0 % of patients who received the st and ard dose and 16.9 % of patients who received the low dose of Peg-IFN ( P = NS ) . In patients with genotypes 1 , 4 and 5 and low viraemia , SVR was obtained in 27.3 % of patients treated with the st and ard dose and 25.8 % of patients treated with the low dose ( P = NS ) . In the high-viraemia subgroup , SVR was obtained in 24.0 % and 9.1 % of patients , respectively . In patients with genotypes 2 and 3 , SVR was similar in both groups ( 73.2%vs 73.0 % ) . Thus , ( 1 ) patients with genotypes 2 and 3 and severe fibrosis can be treated with low dose of Peg-IFN and ribavirin , ( 2 ) this study suggests that patients with genotypes 1 , 4 and 5 and high viraemia could receive a st and ard dose of Peg-IFN associated with ribavirin for 48 weeks , ( 3 ) side effects limit the efficacy of the treatment with st and ard dose of Peg-IFN in patients with genotypes 1 , 4 and 5 and low viraemia , ( 4 ) more studies are needed for patients with genotype 2 or 3 to define the optimal duration ( 24 or 48 weeks ) in patients with severe fibrosis BACKGROUND Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus ( HCV ) infection . We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin , interferon alfa-2b plus ribavirin , and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. METHODS A total of 1121 patients were r and omly assigned to treatment and received at least one dose of study medication , consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin ( 1000 or 1200 mg , depending on body weight ) , weekly peginterferon alfa-2a plus daily placebo , or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks . RESULTS A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response ( defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy ) than of patients who received interferon alfa-2b plus ribavirin ( 56 percent vs. 44 percent , P<0.001 ) or peginterferon alfa-2a alone ( 56 percent vs. 29 percent , P<0.001 ) . The proportions of patients with HCV genotype 1 who had sustained virologic responses were 46 percent , 36 percent , and 21 percent , respectively , for the three regimens . Among patients with HCV genotype 1 and high base-line levels of HCV RNA , the proportions of those with sustained virologic responses were 41 percent , 33 percent , and 13 percent , respectively . The overall safety profiles of the three treatment regimens were similar ; the incidence of influenza-like symptoms and depression was lower in the groups receiving peginterferon alfa-2a than in the group receiving interferon alfa-2b plus ribavirin . CONCLUSIONS In patients with chronic hepatitis C , once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response , as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone Hepatitis C virus ( HCV ) infection rarely resolves spontaneously once it becomes chronic ( 1 ) . Most patients remain asymptomatic for a long period , with liver cirrhosis developing after approximately 30 years ( 2 , 3 ) . Chronic hepatitis C with cirrhosis is a major risk factor for hepatocellular carcinoma ( 4 - 7 ) . It has been previously shown that the risk increases with the degree of liver fibrosis ( 5 ) . Interferon is the only agent known to be effective against HCV infection ( 8 - 10 ) . It induces a sustained virologic response in 15 % to 30 % of patients ( 11 - 14 ) . Responders usually show biochemical and histologic improvement ( 9 , 11 , 15 ) . Recently , interferon therapy in patients with chronic hepatitis C and cirrhosis was shown to be associated with a reduced incidence of hepatocellular carcinoma ( 16 ) . Because most patients treated with interferon do not have cirrhosis , we included noncirrhotic as well as cirrhotic patients in our analysis of the effect of interferon therapy on the incidence and prevention of hepatocellular carcinoma . A national surveillance program , the Inhibition of Hepatocarcinogenesis by Interferon Therapy ( IHIT ) Study , was begun in 1994 as a multicenter , large-scale , retrospective cohort study supported by the Japan Ministry of Health and Welfare as one of the Comprehensive 10-Year Strategy for Cancer Control Projects ( 17 ) . In this program , patients with chronic hepatitis C who have undergone liver biopsy at one of eight participating institutions are enrolled and followed periodically for development of hepatocellular carcinoma by using several imaging techniques . We analyzed the incidence of hepatocellular carcinoma as of February 1998 by using multivariate proportional hazards regression . Methods Patients The IHIT Study Group approved the design of this study on 21 September 1994 . All patients who were positive by a second-generation HCV antibody assay and who had undergone liver biopsy since 1986 at one of the eight participating institutions were enrolled . Patients who were participants in interferon trials for non-A , non-B chronic hepatitis ( 18 - 21 ) and in whom anti-HCV seropositivity was confirmed by using stored sera were also included ; these patients had undergone liver biopsy in 1986 or later . Patients were excluded if at the time of liver biopsy they presented with hepatocellular carcinoma or other liver diseases , such as chronic hepatitis B , alcoholic liver disease , autoimmune hepatitis , or primary biliary cirrhosis . The minimum follow-up was established as 1 year for two reasons . First , if hepatocellular carcinoma is detected within 1 year after liver biopsy , the possibility that the cancer was present at the time of liver biopsy can not be ruled out . Second , interferon therapy must be started within 1year after liver biopsy according to Japanese health insurance rules . By February 1998 , 3223 patients who fulfilled the inclusion criteria were registered . Of these patients , 333 were excluded from the analysis : 161 patients ( 5.0 % ) transferred to other hospitals without follow-up , and the follow-up period after liver biopsy was less than 1 year for172 patients ( 5.3 % ) . Thus , 2890 patients were included in the present analysis . Figure 1 shows the schema for patient selection . Figure 1 . Schema for patient selection . Interferon therapy was given to 2400 patients ; 490 patients did not receive treatment ( control group ) . Interferon therapy was initiated within 1 year after liver biopsy ( within 6 months in 93 % of patients ) ; 84 % of patients received interferon- , 14 % received interferon- , and 2 % received a combination of interferon- and interferon- . The median total dose was 480 MU ( first quartile , 324 MU ; third quartile , 702 MU ) , and the median duration of administration was 160 days(first quartile , 94 days ; third quartile , 168 days ) . Once interferon therapy was started , a patient was included in the interferon treatment group even if therapy was discontinued because of adverse events or other reasons . The 490 patients who did not receive interferon chose this course of action voluntarily on the basis of concerns about adverse effects ; lack of time for therapy ; or physician recommendation , which took into account depression , severe diabetes mellitus , or other medical conditions . Serum HCV load was quantitatively determined at the timeof liver biopsy by using various commercial and in-house assays . Because it is difficult to correlate the results of different assay methods , only data obtained with two widely used assays , the branched-DNA probe assay ( 22 ) and competitive reverse-transcription polymerase chain reaction ( RT-PCR ) ( 23 ) , were used . HCV RNA genotype was determined by RT-PCR using genotype-specific primers ( 24 ) or by serologic grouping of serum antibody ( 25 ) , assuming that genotypes 1a and 1b correspond to serologic group 1 ( genotype 1 ) and genotypes 2a and 2b correspond to serologic group 2 ( genotype 2 ) ( 11 ) . Histologic Evaluation Liver biopsy specimens were evaluated by a representative pathologist at each institution ( a total of eight pathologists were involved ) and were scored for the stage of liver fibrosis and grade of inflammatory activity according to the classification of Desmet and colleagues ( 26 ) . Stage of fibrosis was assessed from stage F0 ( no fibrosis ) to stage F4 ( cirrhosis ) , and grade of inflammatory activity was scored from grade A1 ( mild ) to grade A3 ( severe ) . To confirm interobserver concordance in scoring , a subsequent blind and independent examination of 350r and omly selected liver biopsy specimens was conducted by two of the eight pathologists . Definition of Interferon Response Virologic and biochemical criteria were used to define response to interferon therapy . Hepatitis C virus RNA was used as a marker of virologic response and was determined by RT-PCR . A virologic sustained response was defined as HCV RNA negativity more than 6 months after termination of interferon therapy ; positivity at the same time point was considered a nonsustained response ( 27 ) . Patients with nonsustained response included those who had temporary disappearance of viremia followed by relapse . In patients treated before the availability of RT-PCR , virologicresponse was determined by using sera stored at 30 C or collected afterward . The serum alanine aminotransferase ( ALT ) level was used as a marker of biochemical response to interferon therapy . Sustained biochemical response was defined as persistently normal serum ALT levels more than 6 months after termination of interferon therapy ; nonsustained response was defined as elevated serum ALT levels at the same time point . Nonsustained response was subdivided into two categories : mildly elevated for a serum ALT level less than two times the upper limit of normal and highly elevated for a serum ALT level two or more times the upper limit of normal . Screening for Hepatocellular Carcinoma Patients were examined for hepatocellular carcinoma by abdominal ultrasonography at least every 6 months . If hepatocellular carcinoma was suspected on the basis of ultrasonographic results , additional procedures , such as computed tomography , magnetic resonance imaging , abdominal angiography , and ultrasonography-guided tumor biopsy , were used to confirm the diagnosis . Statistical Analysis Statistical analysis was performed by using SAS software , version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) . Interobserver concordance of histologic scoring was evaluated by using the Spearman correlation coefficient . Differences between two groups were evaluated by using the unpaired Student t-test or the Mann-Whitney U-test . Categorical data were compared by using the chi-square test or the Fisher exact probability test . Cumulative incidence curves were determined with the Kaplan-Meier method , and the differences between groups were assessed by using the log-rank test . We used the Cox proportional-hazards regression analysis to examine the effect of interferon therapy on the incidence of hepatocellular carcinoma . Because virologic and biochemical responses were mutually dependent , the risk ratio for hepatocellular carcinoma was calculated separately for these factors . The risk ratio attributable to categorical data , such as stage of liver fibrosis and serum ALT level , was calculated by using dummy variables . A P value less than 0.05 was considered statistically significant . Results Patient Characteristics The demographic and clinical features of patients at the time of their enrollment are summarized in Table 1 . The frequency distribution of the stages of liver fibrosis differed between interferon-treated patients and untreated patients . Most laboratory values also differed between the two groups . However , differences in laboratory values between treated patients and untreated patients were not significant at the same stage of fibrosis . This indicated the need to adjust for stage of liver fibrosis , which was done in the following analyses . Table 1 . Demographic and Clinical Characteristics Histologic Evaluation The concordance in scores for stage of fibrosis and grade of inflammatory activity determined at each institution and by the two representative pathologists was strong , with Spearman coefficients ranging from 0.897 to 0.918 for stage of fibrosis and from 0.878 to 0.849 for grade of inflammatory activity . The original score was sustained by at least one of the two pathologists in 319 of 350 cases for fibrosis staging and in 320 of 350cases for grading inflammatory activity . Response to Interferon Therapy Response to interferon therapy was determined in 2357(98.2 % ) of the 2400 interferon-treated patients . Response was not determined in43 patients because of insufficient follow-up ( < 6 months ) after termination of therapy . A sustained virologic response was achieved in 789 patients ( 33.5 % ) . The response rate was similar regardless of the type of interferon used ( 32.3 % , 34.5 % , and 25.6 % for interferon- , interferon- , and the combination of the two , respectively ) . A sustained BACKGROUND & AIMS This study investigated the efficacy and adverse effects of pegylated interferon ( Peg-IFN ) plus ribavirin therapy in aged patients with chronic hepatitis C ( CH-C ) . METHODS A total of 1040 naïve patients with CH-C ( genotype 1 , n=759 ; genotype 2 , n=281 ) , of whom 240 ( 23 % ) over 65 years old ( y.o . ) , were treated with Peg-IFN alfa-2b plus ribavirin and assessed after being classified into five categories , according to age . RESULTS The discontinuance rate was higher for patients over 70 y.o . ( 36 % ) , the most common reason being anemia . In the presence of genotype 1 , the SVR rate was similar ( 42 - 46 % ) among patients under 65 y.o . and declined ( 26 - 29 % ) among patients over 65 y.o . For patients over 65 y.o . , being male ( Odds ratio , OR , 3.5 , p=0.035 ) and EVR ( OR , 83.3 , p<0.001 ) were significant factors for SVR , in multivariate analysis . The Peg-IFN dose was related to EVR , and when EVR was attained , 76 - 86 % of patients over 65 y.o . achieved SVR . SVR was not achieved ( 0/35 , 0/38 , respectively ) if a 1-log decrease and a 2-log decrease were not attained at week 4 and week 8 , respectively . In the presence of genotype 2 , the SVR rate was similar ( 70 - 71 % ) among patients under 70 y.o . and declined among patients over 70 y.o . ( 43 % ) . CONCLUSIONS Aged patients up to 65 y.o . with genotype 1 and 70 y.o . with genotype 2 can be c and i date s for Peg-IFN plus ribavirin therapy . The response-guided therapy can be applied for aged patients with genotype 1 BACKGROUND & AIMS Pegylated interferon alfa-ribavirin combination is the st and ard treatment for chronic hepatitis C , but the mechanisms by which ribavirin enhances the rate of sustained hepatitis C virus ( HCV ) eradication remain unknown . We aim ed to investigate the role of ribavirin in HCV clearance during therapy and to evaluate the consequences of ribavirin discontinuation in patients infected with genotype 1 hepatitis C who cleared HCV RNA at week 24 . METHODS A total of 516 patients were treated with pegylated interferon alfa-2a , 180 microg/wk , plus ribavirin , 800 mg/day . Seventy percent were RNA negative at week 24 . They were r and omized to continue with the combination or receive pegylated interferon alone . RESULTS Responders at week 24 who stopped ribavirin had a significantly higher rate of breakthroughs during , and relapses after , therapy ( sustained virologic response , 52.8 % vs 68.2 % ; P = .004 ) , but their side-effect profile and quality of life tended to improve . Multiple logistic regression analysis in the pegylated interferon alfa monotherapy group allowed identification of responders at week 24 who could stop ribavirin without losing their chance of a sustained virologic response , based on baseline viral load and age . Forty-eight weeks of ribavirin may not be needed when HCV RNA is undetectable at week 2 . CONCLUSIONS We made 3 conclusions from this study . First , ribavirin primarily acts by sustaining the virologic response to pegylated interferon alfa ; second , ribavirin must be administered for the full treatment duration in most genotype 1-infected patients who respond ; third , baseline parameters may help identify patients who could discontinue ribavirin or reduce the dose without losing their chance of success Background With only a third of Latinos achieving sustained virologic response ( SVR ) , there is a need for enhanced HCV treatment . Amantadine has been proposed to improve response rates in addition to st and ard therapy with peginterferon α and ribavirin . Our objective is to evaluate whether triple therapy with amantadine improves SVR rates in this special population . Method Treatment-naïve Latino subjects with HCV genotype 1 infection were r and omized to receive peginterferon α-2a plus weight-based ribavirin for 48 weeks ( double therapy ) or the same regimen plus amantadine 200 mg daily ( triple therapy ) . The primary endpoint was SVR . Predictors of liver fibrosis using APRI and Forns indices were also evaluated . Results We enrolled 124 patients with chronic hepatitis C genotype 1 . Sixty-three received conventional therapy and 61 patients had triple therapy with amantadine . SVR at week 72 was achieved in 25 patients ( 39.7 % ) vs. 26 patients ( 42.6 % ) in the double and triple regimen , respectively ( p = 0.561 ) . After multivariate analysis , advanced fibrosis , obesity , and low pretreatment ALT levels were associated with non-response in both groups ( p = 0.0234 , p = 0.0012 , p = 0.0249 , respectively ) . APRI values delimited an area under the ROC curve ( AUROC ) of 0.724 and Forns index with AUROC of 0.733 . There was no difference between both indices in predicting significant fibrosis ( Knodell index : F3–F4 ) . Conclusion Our study demonstrates that the addition of amantadine to st and ard treatment of chronic HCV does not improve SVR rates in Latino patients with genotype 1 . Further research to improve response rates in this special population is needed BACKGROUND AND AIM To compare the efficacy and safety of pegylated interferon ( PEG-I ) at 1 and 1.5 microg/kg , and in combination with ribavirin ( RBV ) for 24 weeks in naïve Japanese patients infected with hepatitis C virus genotype 2 . METHODS The present study was an open-label , r and omized trial of 55 patients receiving PEG-I ( 1 or 1.5 microg/kg body weight [ BW ] , subcutaneously , once a week ) and RBV for 24 weeks . The patients were followed up for 24 weeks without treatment . RESULTS The intention-to-treat analyses showed that the proportion of patients with a sustained virological response ( SVR ) in the 1-microg/kg PEG-I-RBV group ( 38.5 % , 10/26 ) was lower than that of the 1.5-microg/kg PEG-I-RBV group ( 74.1 % , 20/27 ; P = 0.013 ) . The PEG-I dose was reduced in two of the 26 patients of the 1-microg/kg PEG-I-RBV group ( one because of thrombocytopenia at 2 weeks , and one because of generalized fatigue at 20 weeks ) , and four of the 27 patients of the 1.5-microg/kg PEG-I-RBV group ( one because of neutropenia at 20 weeks , and three because of generalized fatigue at 1 , 5 , and 8 weeks ) . The multivariate analysis identified age ( < 60 years ) and dose of PEG-I ( 1.5 microg/kg ) as significant determinants of SVR . CONCLUSION The dose of PEG-I to be used at the start of therapy should be 1.5-microg/kg BW in naïve Japanese patients infected with hepatitis C virus genotype 2 BACKGROUND We hypothesized that in patients with hepatitis C virus ( HCV ) genotype 2 or 3 in whom HCV RNA is not detectable after 4 weeks of therapy , 12 weeks of treatment is as effective as 24 weeks . METHODS A total of 283 patients were r and omly assigned to a st and ard 24-week regimen of peginterferon alfa-2b at a dose of 1.0 mug per kilogram weekly plus ribavirin at a dose of 1000 mg or 1200 mg daily , on the basis of body weight . Of these , 70 patients were assigned to the 24-week regimen ( st and ard- duration group ) and 213 patients to a variable regimen ( variable- duration group ) of 12 or 24 weeks , depending on whether tests for HCV RNA were negative or positive at week 4 . The primary end point was HCV that was not detectable by polymerase-chain-reaction ( PCR ) assay 24 weeks after the completion of therapy . RESULTS In the st and ard- duration group , 45 ( 64 percent ) patients had HCV that was not detectable by PCR assay at week 4 , as compared with 133 ( 62 percent ) in the variable- duration group ( difference [ the rate in the st and ard- duration group minus that in the variable- duration group ] , 2 percent ; 95 percent confidence interval , -11 to 15 percent ) . Fifty-three patients ( 76 percent ) in the st and ard- duration group and 164 patients ( 77 percent ) in the variable- duration group had a sustained virologic response ( difference , -1 percent ; 95 percent confidence interval , -13 to 10 percent ) . Fewer patients in the variable- duration group receiving the 12-week regimen had adverse events and withdrew than in the group receiving the 24-week regimen ( P=0.045 ) . The rate of relapse ( defined as HCV not detectable at the end of treatment but detectable at the end of follow-up ) was 3.6 percent in the st and ard- duration group and 8.9 percent in the variable- duration group ( P=0.16 ) . Overall , the rate of sustained virologic response was 80 percent among patients with HCV genotype 2 and 66 percent among those with genotype 3 ( P<0.001 ) . CONCLUSIONS A shorter course of therapy over 12 weeks with peginterferon alfa-2b and ribavirin is as effective as a 24-week course for patients with HCV genotype 2 or 3 who have a response to treatment at 4 weeks In patients with hepatitis C virus (HCV)-related advanced fibrosis/cirrhosis , 30 % of sustained HCV clearance has been reported with pegylated interferon alpha-2a ( PEG-IFN ) alone , but the efficacy and tolerability of the PEG-IFN/ribavirin ( RBV ) combination remain poorly defined . A total of 124 treatment-naïve patients with biopsy proved HCV-related advanced fibrosis/cirrhosis ( Ishak score F4-F6 , Child-Pugh score < or = 7 ) were r and omized to 48 weeks of PEG-IFN ( 180 microg sc weekly ) and st and ard dose of RBV ( 1000/1200 mg po daily , STD ) or PEG-IFN ( 180 microg sc weekly ) and low-dose of RBV ( 600/800 mg po daily , LOW ) . Sustained virologic response ( SVR ) rates with PEG-IFN/STD RBV ( 52 % ) were higher -- albeit not significantly -- than that with PEG-IFN/LOW RBV ( 38 % , P = 0.153 ) . In multivariate analysis , genotype 2/3 and a baseline platelet count > or = 150 x 10(9)/L were independently associated with SVR . The likelihood of SVR was < 7 % if viraemia had not declined by > or = 2 log or to undetectable levels after 12 weeks . Nine adverse events in the STD RBV and 15 in the LOW RBV group were classified as severe ( including two deaths ) ; dose reductions for intolerance were required in 78 % and 57 % ( P = 0.013 ) , and treatment was terminated early in 23 % and 27 % of patients ( P = n.s . ) . The benefit/risk ratio of treating compensated HCV-cirrhotics with STD PEG-IFN/RBV is favourable SUMMARY Beside substantial progress in treatment of chronic hepatitis C ( CHC ) particular patients ( genotype 1/4 , high viral load , previous nonresponse , cirrhosis ) remain difficult to treat . The aim of our pilot r and omized study was to compare efficacy and tolerability of st and ard doses of Peginterferon alpha-2b + ribavirin with higher doses of Peginterferon alpha-2b administered twice weekly + ribavirin . Sixty-five out patients with CHC were subsequently enrolled . Group A ( n = 22 ) received recommended doses of Peginterferon alpha-2b and group B ( n = 43 ) , received high doses twice weekly . Groups were comparable for baseline characteristics . All genotype 1/4 patients had high baseline viraemia . Sustained virological response ( SVR ) was significantly higher in group B among naïve patients ( 72%vs 25 % , P = 0.024 ) . A significantly higher rate of SVR was observed in group B both considering only genotype 1/4 patients , ( 46%vs 13 % , P = 0.03 ) and grouping together genotype 1/4 naive and relapsers ( 57%vs 11 % , P = 0.039 ) . Discontinuation rate was 32 % ( 7 of 22 ) in group A and 21 % ( 9 [ corrected ] of 43 ) in group B. Our response rates are the highest reported for genotype 1/4 with high viraemia . Our pilot study supports the need of r and omized studies to evaluate both viral kinetics and efficacy of high dose and twice weekly administration of Peginterferon alpha-2b in genotype 1/4 patients with high viraemia who may need personalized treatment schedules UNLABELLED A recent nonr and omized pilot trial showed that hepatitis C virus ( HCV ) patients with genotype 2/3 and rapid virological response ( RVR ) had a 90 % sustained virological response ( SVR ) rate after 14 weeks of treatment . We aim ed to assess this concept in a r and omized controlled trial . In the trial , 428 treatment-naïve HCV RNA-positive patients with genotype 2 or 3 were enrolled . Patients with RVR were r and omized to 14 ( group A ) or 24 ( group B ) weeks of treatment . Patients were treated with pegylated interferon alpha-2b ( 1.5 microg/kg ) subcutaneously weekly and ribavirin ( 800 - 1400 mg ) orally daily . The noninferiority margin was set to be 10 % between the two groups with a one-sided 2.5 % significance level . RVR was obtained in 302 of 428 ( 71 % ) , and 298 of these were r and omized to group A ( n = 148 ) or group B ( n = 150 ) . In the intention-to-treat analysis , SVR rates were 120 of 148 ( 81.1 % ) in group A and 136 of 150 ( 90.7 % ) in group B ( difference , 9.6 % ; 95 % confidence interval , 1.7 - 17.7 ) . Among patients with an HCV RNA test 24 weeks after the end of treatment , 120 of 139 ( 86.3 % ) patients in group A achieved SVR compared with 136 of 146 ( 93.2 % ) in group B ( difference , 6.9 % ; 95 % confidence interval , -0.1 to + 13.9 ) . CONCLUSION We can not formally cl aim that 14 weeks of treatment is noninferior to 24 weeks of treatment . However , the SVR rate after 14 weeks of treatment is high , and although longer treatment may give slightly better SVR , we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks UNLABELLED The impact of amantadine on virologic response rates of interferon-based treatment of chronic hepatitis C is controversial . The aim of this study was to compare virological response rates in patients with chronic hepatitis C virus (HCV)-1 infection treated with 400 mg amantadine or placebo in combination with peginterferon alfa-2a ( 40 kD ) and ribavirin for 48 weeks . Seven hundred four previously untreated chronically HCV-1-infected patients ( mean age , 46 + /- 12 years ) were r and omized to ( A ) amantadine-sulphate ( 400 mg/day ) ( n = 352 ) or ( B ) placebo ( n = 352 ) , both in combination with 180 microg peginterferon alfa-2a once weekly and ribavirin ( 1000 - 1200 mg/day ) for 48 weeks . End of treatment and sustained virological response after a 24-week follow-up period were assessed by qualitative reverse transcription polymerase chain reaction ( RT-PCR ) ( sensitivity , 50 IU/mL ) . Demographic and baseline virological parameters were similar in both treatment groups . In groups A and B , 231 of 352 patients ( 66 % ) and 256 of 352 patients ( 72 % ) achieved an end of treatment response , and 171 of 352 patients ( 49 % ) and 186 of 352 patients ( 53 % ) a sustained virological response , respectively . On-treatment dropout rate in the amantadine group was significantly higher than in the placebo group ( 32 % versus 23 % ; P = 0.01 ) . However , adverse events and laboratory abnormalities were similar between both groups . Per- protocol analysis revealed similar sustained virological response rates in both treatment groups ( 53 % versus 55 % ) . CONCLUSION In this large placebo-controlled multicenter study , amantadine even at a dose of 400 mg/day did not improve virological response rates of peginterferon alfa-2a and ribavirin in patients with chronic genotype HCV-1 infection BACKGROUND / AIMS Pegylated interferon plus ribavirin can cause dose-limiting anemia . Taribavirin , a ribavirin prodrug , has shown a lower incidence of anemia . We sought to determine the efficacy and safety of taribavirin vs. ribavirin combined with pegylated interferon in patients with chronic hepatitis C ( CHC ) . METHODS This phase 2 open-label study r and omized 180 patients with CHC to receive pegylated interferon alfa-2a 180 microg/week plus taribavirin 800 , 1200 or 1600 mg QD or ribavirin 1000 or 1200 mg QD . Efficacy variables included proportions of patients with undetectable serum HCV RNA levels at end of treatment and after a 24-week follow-up . RESULTS The proportions of patients with undetectable HCV RNA at 12 weeks did not differ significantly between taribavirin ( 38 % , 42 % , and 49 % for the 800 , 1200 , and 1600 mg groups ) and ribavirin ( 49 % ) . The highest proportion of patients with undetectable HCV RNA at end of treatment and at follow-up occurred in both the taribavirin 1200 mg QD ( 63 % and 37 % ) and ribavirin groups ( 62 % and 44 % ) . SVR rates were 23 % , 37 % and 29 % for taribavirin and 44 % for ribavirin . Fewer patients on any dose of taribavirin had severe anemia ( hemoglobin < 10 g/dL ) than on ribavirin ( 6/135 [ 4 % ] vs. 12/45 [ 27 % ] ) . CONCLUSIONS Given with interferon , taribavirin produced SVR rates comparable to those of ribavirin , with a lower occurrence of anemia Background : The recommended treatment for patients infected with hepatitis C virus genotype 2 ( HCV2 ) is pegylated interferon ( peginterferon ) and ribavirin for 24 weeks . Aim : To assess whether a shorter 16-week treatment is as effective as a st and ard 24-week treatment . Methods : Patients with HCV2 infection were r and omised in a 1:2 ratio to either 16 weeks ( n = 50 ) or 24 weeks ( n = 100 ) of treatment with peginterferon α-2a ( 180 μg/week ) and weight-based ribavirin 1000–1200 mg/day , with a 24-week follow-up period . A rapid virological response ( RVR ) was defined as seronegative for HCV RNA at 4 weeks of treatment , and the primary end point , sustained virological response ( SVR ) , as seronegative for HCV RNA at the 24-week follow-up . Results : The rate of RVR and SVR was 86 % ( 43/50 , 95 % confidence interval ( CI ) 76 % to 96 % ) and 94 % ( 47/50 , CI 87 % to 100 % ) , respectively , in the 16-week group , which was comparable to 87 % ( 87/100 , CI 80 % to 94 % ) and 95 % ( 95/100 , CI 91 % to 99 % ) in the 24-week group . Patients with RVR had a significantly higher SVR rate than patients without RVR in both 16-week ( 100 % vs 57 % , p = 0.015 ) and 24-week groups ( 98 % vs 77 % , p = 0.002 ) . Multivariate analysis showed that RVR and age were independent factors associated with SVR . Both treatment arms were equally well tolerated . The incidence of alopecia was significantly higher in the 24-week group ( 49 % ) than in the 16-week group ( 20 % , p = 0.001 ) . Conclusion : 16 weeks and 24 weeks of peginterferon treatment with weight-based ribavirin at a dose of 1000–1200 mg/day provided equal efficacy in patients with HCV2 who achieved RVR at 4 weeks BACKGROUND & AIM Insulin resistance ( IR ) affects sustained virological response ( SVR ) . The use of insulin-sensitizing agents has been proposed to improve therapy outcome . The safety and efficacy of pioglitazone on insulin sensitivity and SVR in treatment-naïve patients with chronic hepatitis C ( CHC ) genotype 4 with IR receiving st and ard antiviral therapy were evaluated in a r and omized-controlled study . METHODS Ninety-seven previously untreated patients with CHC and IR [ homeostasis model assessment ( HOMA>2 ) ] were r and omly assigned into two arms ; ( arm A ; n=48 ) were given pioglitazone 30 mg/day combined with peginterferon (Peg-IFN)-alpha-2b/ribavirin ( RBV ) for 48 weeks , and ( arm B ; n=49 ) were given st and ard of care ( Peg-IFN-alpha-2b/RBV for 48 weeks ) ; HOMA index and hepatitis C virus RNA ( HCV RNA ) levels were measured at baseline , during therapy and follow-up . Treatment was stopped in patients without an early virological response or those who were HCV RNA positive at 24 weeks . RESULTS Baseline data of both groups were comparable , with no significant statistical differences . The percentages of rapid virological response ( RVR ) and SVR were significantly higher in patients given triple therapy compared with st and ard of care ( 27.08 vs. 6.1 % ; P=0.006 and 60.4 vs. 38.7 % ; P=0.04 respectively ) ; patients in arm A showed a greater decrease in the HOMA index than those in arm B ( -1.8 + /- 0.3 , -2.1 + /- 0.3 vs. -1.1 + /- 0.6 , -1.3 + /- 0.7 ) at week 24 and at the end of follow-up ( P=0.001 at both time points ) . The triple therapy was well tolerated . CONCLUSIONS A combination of pioglitazone , Peg-IFN-alpha-2b and ribavirin increased RVR , SVR and decreased IR , compared with patients given Peg-IFN plus ribavirin without an increase in adverse events BACKGROUND A significant proportion of hepatitis C patients treated with unmodified interferon plus ribavirin fail to respond . The optimal therapy for these patients has not been established yet . The objective of this study was to assess the efficacy and safety of peginterferon plus ribavirin with or without amantidine in such patients . METHODS In this open-label , prospect i ve controlled trial , a total of 63 patients were r and omly divided into groups A and B with a ratio of 1:2 . Group A ( 21 patients ) received weekly peginterferon alpha-2b , 1.5 microg/kg concomitantly with ribavirin 1000 - 1200 mg per day . Group B ( 42 patients ) received peginterferon and ribavirin as in group A , plus amantadine [ corrected ] 200 mg per day . RESULTS At the completion of treatment , serum levels of hepatitis C virus RNA were undetectable in 14 % and 12 % of patients in groups A and B , respectively ( P = NS ) . Hepatitis C virus RNA remained undetectable 24 weeks after the end of treatment in one patient ( 5 % ) in group A and three patients ( 7 % ) in group B ( P = NS ) . Sustained viral clearance was associated with sustained normalization of serum alanine aminotransferase level . Both drug regimens had similar side effect profiles . CONCLUSION Peginterferon plus ribavirin therapy with or without amantadine [ corrected ] is associated with a low sustained virological response in patients who failed interferon and ribavirin combination therapy UNLABELLED Recommended treatment for hepatitis C virus genotype 1 ( HCV-1 ) patients is peginterferon plus ribavirin for 48 weeks . We assessed whether treatment duration of 24 weeks is as effective as st and ard treatment in HCV-1 patients with a rapid virological response ( RVR ; seronegative for hepatitis C virus [ HCV ] RNA at 4 weeks ) . Two hundred HCV-1 patients were r and omized ( 1:1 ) to either 24 or 48 weeks of peginterferon-alpha-2a ( 180 microg/week ) and ribavirin ( 1000 - 1200 mg/day ) with a 24-week follow-up . The primary endpoint was a sustained virological response ( SVR ; seronegative for HCV RNA at 24-week follow-up ) . Overall , the 48-week arm had a significantly higher SVR rate ( 79 % ) than the 24-week arm ( 59 % , P = 0.002 ) . For 87 ( 43.5 % ) patients with an RVR , the 24-week arm had a lower SVR rate [ 88.9 % ; 95 % confidence interval ( CI ) : 80%-98 % ] than the 48-week arm ( 100 % , P = 0.056 ) . For 52 patients with low baseline viremia ( < 400,000 IU/mL ) and an RVR , the 24-week arm had rates ( CI ) of relapse and SVR of 3.6 % ( -3%-11 % ) and 96.4 % ( 89%-103 % ) , respectively , which were comparable to those of the 48-week arm ( 0 % and 100 % ) with difference ( CI ) of 3.6 % ( -7.2%-6.6 % ) and -3.6 % ( -14.3 % to -0.6 % ) , respectively . Multivariate analysis in all patients showed that RVR was the strongest independent factor associated with an SVR , followed by treatment duration , mean weight-based exposure of ribavirin , and baseline viral load . CONCLUSION HCV-1 patients derive a significantly better SVR from 48 weeks versus 24 weeks of peginterferon/ribavirin even if they attain an RVR . Both 24 and 48 weeks of therapy can achieve high SVR rates ( > 96 % ) in HCV-1 patients with low viral loads and an RVR BACKGROUND The efficacy and tolerability of Peg-Interferon alpha-2a ( Peg-IFNalpha-2a ) versus Peg-Interferon alpha-2b ( Peg-IFNalpha-2b ) were compared in a patient cohort with hepatitis C virus (HCV)-related active chronic hepatitis , unresponsive to previous antiviral treatment with st and ard IFN ( 6 MU three times/week ) plus ribavirin ( 10.6 mg/kg/day ) for a period of at least 3 months . PATIENTS AND METHODS A total of 143 patients were enrolled and r and omized into two treatment groups ( A-B ) . Group A ( 71 patients ) received one vial of Peg-IFNalpha-2a weekly ( 180 microg ) subcutaneously whereas Group B ( 72 patients ) received 1.5 microg/kg of Peg-IFNalpha-2b weekly subcutaneously . Interferon was combined with ribavirin ( 15 mg/kg/day ) in both groups and all patients who demonstrated nondetectable HCV-RNA or a > or=2(log ) reduction in viral load at week 12 , were treated for 48 weeks , with a 24-week follow up . RESULTS Group A ( 10/71 ) and Group B ( 8/72 ) patients discontinued treatment due to severe side effects . At the end of therapy , HCV-RNA was undetectable in 17/71 ( 23.9 % ) Group A and in 19/72 ( 26.4 % ) of Group B patients . When terminating follow up , a sustained virological response was observed in 14/71 in Group A ( 19.7 % ) and 13/72 in Group B ( 18.0 % ) . CONCLUSIONS Within the limits of the relatively small sample size , Peg-IFNalpha-2a and Peg-IFNalpha-2b demonstrated nonstatistically significant differences in effectiveness in patients nonresponsive to previous antiviral treatment BACKGROUND & AIMS St and ard therapy of patients with chronic hepatitis C virus ( HCV ) infected with HCV genotype-2 or -3 is the combination of pegylated interferon-alpha and ribavirin for 24 weeks . Whether shorter treatment duration s are possible for these patients without compromising sustained virologic response rates is unknown . METHODS Patients chronically infected with HCV-2 ( n = 39 ) , HCV-2/3 ( n = 1 ) , or HCV-3 ( n = 113 ) were treated with peginterferon-alpha-2a ( 180 microg/wk ) plus ribavirin 800 - 1200 mg/day . HCV RNA was quantitatively assessed after 4 weeks . Patients with a rapid virologic response ( HCV RNA below 600 IU/mL ) were r and omized for a total treatment duration of 16 ( group A ) or 24 weeks ( group B ) . All patients with HCV RNA > or = 600 IU/mL at week 4 ( group C ) were treated for 24 weeks . End-of-treatment and sustained virologic response were assessed by qualitative RT-PCR ( sensitivity 50 IU/mL ) . RESULTS Only 11 of 153 patients ( 7 % ) were allocated to group C. End-of-treatment and sustained virologic response rates were 94 % and 82 % , ( group A ) , 85 % and 80 % ( group B ) , and 73 % and 36 % ( group C ) , respectively . In patients infected with genotype HCV-3 and high viral load ( > 800,000 IU/mL ) , a significant lower sustained virologic response rate was found than in patients infected with HCV-3 and a viral load lower or equal to 800,000 IU/mL ( 59 % vs 85 % , respectively ; P = .003 ) . CONCLUSIONS In HCV-2 and -3 ( low viral load)-infected patients who have a rapid virologic response , treatment for 16 weeks with peginterferon-alpha-2a and ribavirin is sufficient . In patients infected by HCV-3 ( high viral load ) , longer treatment may be necessary BACKGROUND Peginterferon-ribavirin therapy is the current st and ard of care for chronic infection with hepatitis C virus ( HCV ) . The rate of sustained virologic response has been below 50 % in cases of HCV genotype 1 infection . Boceprevir , a potent oral HCV-protease inhibitor , has been evaluated as an additional treatment in phase 1 and phase 2 studies . METHODS We conducted a double-blind study in which previously untreated adults with HCV genotype 1 infection were r and omly assigned to one of three groups . In all three groups , peginterferon alfa-2b and ribavirin were administered for 4 weeks ( the lead-in period ) . Subsequently , group 1 ( the control group ) received placebo plus peginterferon-ribavirin for 44 weeks ; group 2 received boceprevir plus peginterferon-ribavirin for 24 weeks , and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon-ribavirin for an additional 20 weeks ; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks . Nonblack patients and black patients were enrolled and analyzed separately . RESULTS A total of 938 nonblack and 159 black patients were treated . In the nonblack cohort , a sustained virologic response was achieved in 125 of the 311 patients ( 40 % ) in group 1 , in 211 of the 316 patients ( 67 % ) in group 2 ( P<0.001 ) , and in 213 of the 311 patients ( 68 % ) in group 3 ( P<0.001 ) . In the black cohort , a sustained virologic response was achieved in 12 of the 52 patients ( 23 % ) in group 1 , in 22 of the 52 patients ( 42 % ) in group 2 ( P=0.04 ) , and in 29 of the 55 patients ( 53 % ) in group 3 ( P=0.004 ) . In group 2 , a total of 44 % of patients received peginterferon-ribavirin for 28 weeks . Anemia led to dose reductions in 13 % of controls and 21 % of boceprevir recipients , with discontinuations in 1 % and 2 % , respectively . CONCLUSIONS The addition of boceprevir to st and ard therapy with peginterferon-ribavirin , as compared with st and ard therapy alone , significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection . The rates were similar with 24 weeks and 44 weeks of boceprevir . ( Funded by Schering-Plough [ now Merck ] ; SPRINT-2 Clinical Trials.gov number , NCT00705432 . ) Context Some patients with chronic hepatitis C virus infection do not respond to initial treatment with pegylated interferon plus ribavirin . Contribution This r and omized trial compared peginterferon-2a plus ribavirin for either 48 or 72 weeks in adults with hepatitis C who had not responded to peginterferon-2b plus ribavirin . Re-treating the nonresponders for 72 weeks increased sustained virologic response rates more than did re-treatment for 48 weeks ( 16 % vs. 8 % ) . Implication Re-treating nonresponders for a longer duration improved response rates , although the rates remained disappointingly low in these patients . The Editors The st and ard of care for patients with chronic hepatitis C is treatment with pegylated interferon plus ribavirin ( 1 , 2 ) . Despite the increasing efficacy of therapy , approximately 50 % of patients with hepatitis C virus ( HCV ) genotype 1 infection and 20 % to 30 % of patients with HCV genotype 2 or 3 infection do not achieve a sustained virologic response ( SVR ) after a first course of therapy ( 3 ) , which adds to the large and growing pool of patients who have not responded to treatment with the st and ard of care and are therefore difficult to treat . These persons are at risk for cirrhosis , liver failure , and hepatocellular carcinoma ( 4 ) . Sustained virologic response to interferon-based treatment is associated with eradication of HCV infection and histologic improvement in liver disease ( 5 ) . Data suggest that re-treatment of patients with pegylated interferon plus ribavirin can eradicate HCV infection in patients who have not responded to a first course of conventional interferon-based therapy ( 6 , 7 ) , but few data exist on the efficacy of re-treatment in patients who have not responded to pegylated interferon plus ribavirin ( 8) . Intensification of therapy by increasing the dose of interferon or ribavirin or extending the duration of treatment has been shown to enhance efficacy , not only in treatment-naive persons ( 9 , 10 ) but also in nonresponders to conventional interferon plus ribavirin ( 11 , 12 ) . Current guidelines ( 13 ) advise against re-treatment with pegylated interferon and ribavirin . We recruited patients who had not responded to previous treatment with peginterferon-2b plus ribavirin to evaluate the efficacy of a 12-week , fixed-dose induction regimen of peginterferon-2a plus st and ard-dose ribavirin and extended treatment with st and ard doses of both drugs . Methods Design Figure 1 shows an overview of the study design . Investigators conducted the study at 106 centers in North America , Europe , and Brazil . Patients were recruited between September 2003 and April 2005 , and the last patient completed follow-up in February 2007 . We r and omly assigned 950 participants to treatment , and 942 received at least 1 dose of a study drug . Figure 1 . Study design . * Only in groups B and D. Only in groups A and C. Eligible patients received treatment with subcutaneous peginterferon-2a ( Pegasys , Roche , Basel , Switzerl and ) plus a st and ard dose of oral ribavirin ( 1000 mg/d for patients weighing < 75 kg and 1200 mg/d for those weighing 75 kg ) ( Copegus , Roche ) . The institutional review boards of each participating center approved the protocol , and all patients provided written informed consent . We conducted this study according to the guidelines of the Declaration of Helsinki and under the provisions of good clinical practice . Setting and Participants We conducted this study in specialist outpatient hepatology clinics . We used no specific methods to recruit patients to the study . Investigators recruited patients from existing patient rolls or through routine referrals from colleagues . Eligible patients were adults age 18 years or older with serologic evidence of chronic hepatitis C ; quantifiable serum HCV RNA levels ( > 600 IU/mL ) , as measured by using the Cobas Amplicor HCV Monitor Test , version 2.0 ( Roche Diagnostics , Basel , Switzerl and ) ; and histologic findings on a liver biopsy specimen consistent with the diagnosis of chronic hepatitis C. Patients with hepatic cirrhosis were eligible if they had compensated liver disease ( 14 ) . We had well-defined criteria for previous nonresponse : eligible patients who had received at least 12 weeks of combination therapy with peginterferon-2b ( 1.0 g/kg per week ) plus ribavirin ( 800 mg/d ) and had detectable serum HCV RNA at every postbaseline assessment , at least 1 of which was performed after week 12 . Treatment must have been discontinued at least 12 weeks before enrollment . Patients were ineligible if they had discontinued treatment with peginterferon-2b plus ribavirin because of hematologic adverse events or had received drugs for HCV infection or immunomodulatory agents within 6 months of enrollment . Patients who were co-infected with hepatitis A or B virus or HIV were also excluded , as were those with a history of chronic liver disease not attributed to chronic hepatitis C , a neutrophil count less than 1.5109 cells/L , platelet count less than 90109 cells/L , or a hemoglobin concentration less than 120 g/L in women or less than 130 g/L in men . Appendix Table 1 lists all inclusion and exclusion criteria used to recruit patients . Appendix Table 1 . Inclusion and Exclusion Criteria R and om Assignment and Interventions We r and omly assigned patients to 1 of 4 open-label treatment groups at baseline in a 2:1:1:2 ratio ( Figure 2 ) . We selected this ratio to optimize the power of the primary comparison and thus maximize the number of patients assigned to groups included in the primary comparison of treatment outcomes . Figure 2 . Study flow diagram . AE = adverse event . The 4 treatment groups were as follows : peginterferon-2a ( 360 g/wk ) plus ribavirin for 12 weeks , then peginterferon-2a ( 180 g/wk ) plus ribavirin to complete 72 weeks of treatment ( group A ) ; peginterferon-2a ( 360 g/wk ) plus ribavirin for 12 weeks , then peginterferon-2a ( 180 g/wk ) plus ribavirin to complete 48 weeks of treatment ( group B ) ; peginterferon-2a ( 180 g/wk ) plus ribavirin for 72 weeks ( group C ) ; or peginterferon-2a ( 180 g/wk , ) plus ribavirin for 48 weeks ( group D ) . Patients were r and omly assigned in permuted blocks of 12 , stratified by geographic region , HCV genotype ( genotype 1 vs. nongenotype 1 ) , and histologic diagnosis ( cirrhosis or transition to cirrhosis vs. no cirrhosis or transition to cirrhosis ) . The computerized r and omization list was generated by the sponsor and incorporated into a central interactive voice-response system managed by S-Clinica ( Brussels , Belgium ) . At the baseline visit , the investigator called the interactive voice-response system to obtain information about a patient 's assignment to a treatment group , which was confirmed by fax to the study site within 1 hour . We used stratified r and om assignment to balance the distribution of regions , genotypes , and histologic diagnoses among the treatment groups . We permitted but did not encourage the use of erythropoietin-stimulating agents and granulocyte colony-stimulating factor . In the event of an adverse reaction or laboratory abnormality , we decreased the dose of peginterferon-2a in steps from 360 g/wk to 180 , 135 , and 90 g/wk for patients in groups A and B and from 180 g/wk to 135 , 90 , and 45 g/wk for patients in groups C and D. We decreased the dose of ribavirin to 600 mg/d in patients whose hemoglobin level decreased to less than 100 g/L but remained at least 85 g/L or , in patients with clinical ly significant cardiovascular disease , in the event of a 20-g/L or greater decrease in hemoglobin during any 4-week interval . Ribavirin therapy was to be discontinued if the hemoglobin concentration decreased to less than 85 g/L , or if it remained less than 120 g/L despite 4 weeks of treatment at a reduced dose in patients with clinical ly significant cardiovascular disease . On resolution of the precipitating event , the investigator could adjust the dosage of either study drug upward at his or her discretion . Outcomes and Follow-up We determined serum HCV RNA level by quantitative ( Cobas Amplicor HCV Monitor Test , version 2.0 ) and qualitative ( Cobas Amplicor HCV Test , version 2.0 ; limit of detection , 50 IU/mL ) assays at baseline and at weeks 12 , 24 , and 48 during treatment in all patients ; at week 72 of treatment in patients r and omly assigned to 72 weeks of treatment ( groups A and C ) ; and after 12 and 24 weeks of untreated follow-up . Discontinuation of treatment was allowed in patients with detectable HCV RNA at or after week 24 . Virologic end points were early virologic response at week 12 , defined as nondetectable HCV RNA ( < 50 IU/mL , qualitative assay ) in serum or a 2-log10 decrease or greater in serum HCV RNA by quantitative assay , and SVR , defined as nondetectable HCV RNA ( < 50 IU/mL ) in serum at the end of the 24-week untreated follow-up period ( week 96 for patients in groups A and C and week 72 for patients in groups B and D ) . The primary efficacy end point in the trial was SVR at the end of follow-up . The primary comparison was between patients treated with fixed-dose induction plus extended- duration combination therapy ( group A ) and those treated with the st and ard regimen ( group D ) . Study monitors verified and cross-checked study case report forms against investigators ' records . In addition , study sites , a central laboratory , and a contract research organization were audited as part of the clinical quality assurance program . Assessment of Adverse Events At each scheduled visit ( Figure 1 ) , we assessed adverse events by physical examination , laboratory tests , and adverse event reports . Investigators elicited information from patients regarding adverse events that occurred since the last visit by asking open-ended questions . Information collected for each adverse event included a description of the event , date of onset , duration , intensity , relationship to study drugs , required treatment , dosage adjustments to study treatment , and outcome . Statistical Analysis We estimated that a total of 592 patients would be required to detect a 10 % difference The objectives of this study were to assess the safety , pharmacokinetics , and efficacy of pegylated interferon alfa-2b ( PEG-Intron ) plus ribavirin in patients with chronic hepatitis C. A total of 72 patients ( 35 men/37 women , age range 20 - 68 years ) with clinical ly compensated chronic hepatitis C virus ( HCV ) were enrolled into this open-label , r and omized , active controlled study . Patients received either PEG-Intron 0.35 , 0.7 , or 1.4 microg/kg subcutaneously weekly for 24 weeks alone , or in combination with ribavirin 600 , 800 , or 1,000 to 1,200 mg orally daily . Patients were evaluated during treatment and after a 24-week follow-up period for safety and efficacy . Detailed pharmacokinetic assessment s were performed at weeks 1 and 4 . PEG-Intron alone produced expected dose-related reductions in white cells , neutrophils and platelets . Addition of ribavirin reduced hemoglobin levels in a dose-related manner , did not further reduce PEG-Intron-induced decreases in neutrophil or white cell count , and increased platelet counts . Neutrophil function tests ( C5a and FMLP migration , killing curves ) were unaltered . Reported adverse events ( flu-like symptoms , asthenia ) were qualitatively similar in all dose groups . Anti-HCV activity , as measured by loss of detectable serum HCV RNA ( i.e. < 100 copies/mL ) at the end of treatment ( week 24 ) and after 24 weeks of follow-up ( week 48 ) showed dose-response trends for PEG-Intron . At each PEG-Intron dose level , anti-HCV activity was higher in patients coadministered ribavirin than in patients treated with PEG-Intron monotherapy . There was no evidence of pharmacokinetic interactions with either drug . We conclude that the safety and tolerability of combined PEG-Intron/ribavirin and PEG-Intron alone were comparable . Combined PEG-Intron/ribavirin showed dose-related synergistic anti-HCV effects , which were numerically superior to those obtained with PEG-Intron monotherapy The two available pegylated interferon formulations , peginterferon alpha-2a and peginterferon alpha-2b , have different pharmacokinetic profiles ; as a result they may have differing abilities to suppress the hepatitis C virus . A recently reported study by Formann and colleagues assessing early viral kinetics among 20 patients receiving peginterferon alpha-2b either once or twice weekly suggests that once-weekly administration of peginterferon alpha-2b is not sufficient for continuous exposure to interferon over 160 h. Twice-weekly administration is recommended to avoid increases in viral load as interferon levels decline prior to the end of the one-week dosing period . The objective of this study was to compare viral dynamics and pharmacokinetics between peginterferon alpha-2a and peginterferon alpha-2b in interferon-naive chronic hepatitis C patients . Patients were r and omized to receive peginterferon alpha-2a 180 microg ( n=10 ) or peginterferon alpha-2b 1.0 microg/kg ( n=12 ) once weekly . Serum peginterferon concentrations were measured at baseline , 24 , 48 , 120 and 168h . Hepatitis C virus ( HCV ) RNA was measured at baseline , 24 , 48 , 120 and 168 h during week 1 and then at 4 and 12 weeks . Peginterferon alpha-2b achieved maximal serum levels at 24 h , and then decreased rapidly . Of the 12 patients who received peginterferon alpha-2b , no drug was detectable in seven ( 58 % ) patients at 120 h and in 11 ( 92 % ) at 168 h. In contrast , peginterferon alpha-2a concentrations increased continuously over time , reaching maximal serum levels from 48 to 168 h. Drug was detectable in all 10 patients at 168 h. At weeks 1 and 4 no significant difference was observed in mean HCV RNA between the groups . However , at week 12 , mean HCV RNA was significantly lower in the peginterferon alpha-2a group versus the peginterferon alpha-2b group ( 2.8126 vs 3.8726 ; P<0.01 ) . The differences in mean HCV RNA values at 12 weeks may be related to the different absorption and distribution profiles of the two drugs . In conclusion , once-weekly administration of peginterferon alpha-2b ( 1.0 microg/kg/wk ) may be insufficient for continuous interferon exposure ; twice-weekly administration may help avoid increases in viral replication as interferon levels decline . Larger-scale studies assessing both viral kinetics and sustained virological responses are needed to confirm these observations BACKGROUND Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus ( HCV ) infection . However , these regimens have not been adequately compared . METHODS At 118 sites , patients who had HCV genotype 1 infection and who had not previously been treated were r and omly assigned to undergo 48 weeks of treatment with one of three regimens : peginterferon alfa-2b at a st and ard dose of 1.5 microg per kilogram of body weight per week or a low dose of 1.0 microg per kilogram per week , plus ribavirin at a dose of 800 to 1400 mg per day , or peginterferon alfa-2a at a dose of 180 microg per week plus ribavirin at a dose of 1000 to 1200 mg per day . We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the st and ard-dose peginterferon alfa-2b regimen and the peginterferon alfa-2a regimen . RESULTS Among 3070 patients , rates of sustained virologic response were similar among the regimens : 39.8 % with st and ard-dose peginterferon alfa-2b , 38.0 % with low-dose peginterferon alfa-2b , and 40.9 % with peginterferon alfa-2a ( P=0.20 for st and ard-dose vs. low-dose peginterferon alfa-2b ; P=0.57 for st and ard-dose peginterferon alfa-2b vs. peginterferon alfa-2a ) . Estimated differences in response rates were 1.8 % ( 95 % confidence interval [ CI ] , -2.3 to 6.0 ) between st and ard-dose and low-dose peginterferon alfa-2b and -1.1 % ( 95 % CI , -5.3 to 3.0 ) between st and ard-dose peginterferon alfa-2b and peginterferon alfa-2a . Relapse rates were 23.5 % ( 95 % CI , 19.9 to 27.2 ) for st and ard-dose peginterferon alfa-2b , 20.0 % ( 95 % CI , 16.4 to 23.6 ) for low-dose peginterferon alfa-2b , and 31.5 % ( 95 % CI , 27.9 to 35.2 ) for peginterferon alfa-2a . The safety profile was similar among the three groups ; serious adverse events were observed in 8.6 to 11.7 % of patients . Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12 , a sustained virologic response was achieved in 86.2 % and 78.7 % , respectively . CONCLUSIONS In patients infected with HCV genotype 1 , the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon-ribavirin regimens or between the two doses of peginterferon alfa-2b . ( Clinical Trials.gov number , NCT00081770 . Health regulatory approval of the 1.5 microg/kg body weight dose of pegylated interferon ( PEG-I ) alpha-2b in combination with ribavirin for the treatment of chronic hepatitis C was based on a study using PEG-I alpha-2b at doses of only 0.5 and 1.5 microg/kg body weight ( BW ) , in spite of the previously shown flat dose-response curve at doses of > or = 1.0 microg/kg . Our aim was to compare PEG-I alpha-2b 1.0 microg/kg with 1.5 microg/kg , both in combination with ribavirin . Open-label , r and omized study in 227 patients with biopsy-proven chronic hepatitis C ( Metavir < or = F2 ) , receiving oral ribavirin ( 400 mg , twice daily ) in combination with subcutaneous PEG-I alpha-2b ( 1.0 or 1.5 microg/kg , once weekly ) for 24 weeks ( genotype 2 or 3 ) , or 48 weeks ( other genotypes ) , followed by a 24-week drug-free period . Virologic response rates did not differ between the two doses of PEG-I alpha-2b : in patients infected with hepatitis C virus ( HCV ) genotype 1 or 4 treated with PEG-I 1.0 microg/kg BW , 38 % ( 22/58 ) had a sustained virologic response compared with 39 % ( 27/70 ) in the PEG-I 1.5 microg/kg BW dose group ( P = ns ) . The corresponding values in patients infected with HCV genotype 2 or 3 were 71 % ( 39/55 ) and 81 % ( 29/36 ) respectively ( P = ns ) . Adverse events led to transient or permanent dose reductions in fewer patients in the 1.0 microg/kg BW dose group ( 48/113 patients ; 42 % ) than in the 1.5 microg/kg BW dose group ( 63/106 patients ; 59 % , P = 0.015 ) . Furthermore , 89 % of patients treated for 24 weeks but only 58 % of patients treated for 48 weeks ( P < 0.001 ) tolerated the treatment without relevant dose reduction or premature termination . In combination with ribavirin , PEG-I alpha-2b 1.0 microg/kg was as effective as 1.5 microg/kg but was better tolerated in patients with chronic hepatitis C and up to moderate fibrosis Guidelines for the treatment of patients infected with hepatitis C virus of genotypes 2 and 3 ( HCV-2 and HCV-3 , respectively ) recommend a 24-week course of Peg-interferon ( Peg-IFN ) alpha-2a combined with ribavirin , despite 50 % of patients in registration trials attaining a sustained virologic response ( SVR ) following Peg-IFN alpha-2a monotherapy . The aim of this study was to delineate patient characteristics that might help to identify individuals likely to benefit from ribavirin discontinuation . One hundred and forty-four HCV-2- and HCV-3-infected patients initiated Peg-IFN alpha-2a ( 180 microg/week ) and ribavirin ( 1000 or 1200 mg/day ) ; those with viral clearance at week 4 were r and omized to either Peg-IFN alpha-2a monotherapy ( n = 59 ) or continuing combination therapy ( n = 61 ) until week 12 . Overall , all but one patient with a rapid virologic response ( RVR ) responded by the end of therapy and the overall SVR rates were lower after discontinuation of ribavirin ( 54%vs 82 % ; P < 0.001 ) . In RVR patients who discontinued ribavirin , low baseline viraemia helped predict SVR ( odds ratio 11.2 , 95 % CI 2.7 - 47.1 ) . SVR rates were similar in patients receiving mono- or combination therapy with low ( < or = 300,000 IU/mL ) and intermediate viraemia ( 86%vs 81 % and 70%vs 71 % , 86 % refers to low viraemic patients receiving monotherapy and 81 % to those receiving combination therapy . Similarly , 70 % refers to patients with intermediate viraemic levels receiving monotherapy and 71 % to those receiving combination therapy ) , but different in those with high ( > 700,000 IU/mL ) viraemia ( 37%vs 88 % ; P = 0.004 ) . Thus in HCV-2- and HCV-3-infected patients , withdrawal of ribavirin and continuation of Peg-IFN alpha-2a monotherapy may be appropriate to attain an SVR , providing viraemia is cleared early during therapy and associated with low baseline viral load . These results warrant future investigations , as discontinuing ribavirin could lead to considerable savings in cost and quality of life related to over-treatment BACKGROUND It remains unclear how we can shorten the treatment duration of antiviral combination therapy with peginterferon and ribavirin for patients with chronic hepatitis C virus ( HCV ) genotype 2 infection who achieved a rapid virological response ( RVR ) . AIM We compared the efficacy of antiviral combination therapy with peginterferon and ribavirin for 8 vs. 24 weeks for the treatment of patients with HCV genotype 2 infection and with RVR . METHODS Sixty-one patients were enrolled . Serum HCV RNA was not detected at 4 weeks after the start of treatment in 32 patients with an RVR . These 32 patients were r and omly assigned to 8-week ( n=15 ) or 24-week ( n=17 ) treatment regimens . Patients in the 8-week group who relapsed underwent a 24-week retreatment . RESULTS No significant difference in patient characteristics was observed between the 8- and the 24-week treatment groups . A sustained virological response ( SVR ) was seen in five of 15 patients ( 33.3 % ) in the 8-week treatment group and 14 of 17 ( 82.4 % ) in the 24-week treatment group ; the rate was significantly higher in the 24-week treatment group ( P=0.0140 ) . Nine of 10 relapsed patients in the 8-week treatment group underwent a 24-week retreatment , and seven achieved an SVR . CONCLUSION An 8-week regimen of combination antiviral therapy with peginterferon and ribavirin yielded an increase in the relapse rate , indicating the limitation of a reduction of treatment below 12 weeks in patients with genotype 2 , after RVR UNLABELLED Treatment response remains suboptimal for many patients with chronic hepatitis C , particularly those with genotype 1 and high levels of viremia . The efficacy of high-dose regimens of peginterferon alfa-2a and ribavirin was compared with conventional dose regimens in patients with features predicting poor treatment responses . Eligible treatment-naïve adults with genotype 1 infection , hepatitis C virus ( HCV ) RNA > 800,000 IU/mL and body weight > 85 kg were r and omized to double-blind treatment with peginterferon alfa-2a at 180 or 270 microg/week plus ribavirin at 1200 or 1600 mg/day for 48 weeks ( four regimens were evaluated ) . The primary endpoint was viral kinetics during the first 24 weeks of therapy . Among patients receiving peginterferon alfa-2a ( 270 microg/week ) the magnitude of HCV RNA reduction was significantly greater than for patients r and omized to the conventional dose of peginterferon alfa-2a ( 180 microg/week ) for the pairwise comparison for ribavirin at 1600 mg/day ( P = 0.036 ) and numerically greater for the pairwise comparison for ribavirin at 1200 mg/day ( P = 0.060 ) . Patients r and omized to the highest doses of peginterferon alfa-2a ( 270 microg/week ) and ribavirin ( 1600 mg/day ) experienced the numerically highest rates of sustained virologic response ( HCV RNA < 50 IU/mL ) and the lowest relapse rate ( 47 % and 19 % , respectively ) . The arm with the higher doses of both drugs was less well-tolerated than the other regimens . CONCLUSION Higher fixed doses of peginterferon alfa-2a ( 270 microg/week ) and ribavirin ( 1600 mg/day ) may increase sustained virologic response rates compared with lower doses of both drugs in patients with a cluster of difficult-to-treat characteristics BACKGROUND AND AIMS In chronic hepatitis C virus ( HCV ) infection with genotype 3 , therapy with pegylated interferon ( peg-IFN ) alfa-2b in a dose of 1.5 mug/kg/week and ribavirin ( 800 - 1000 mg/day ) is recommended for 24 weeks . Reduced doses of peg-IFN may increase compliance and decrease cost and adverse events . This study aim ed to assess the safety and efficacy of two different regimens of peg-IFN alfa-2b , in combination with ribavirin , in genotype 3 patients . METHODS A total of 103 liver biopsy-proven chronic HCV patients with genotype 3 , having alanine aminotransferase levels > 1.2 x ULN and positive HCV-RNA were r and omized into two groups : group I ( n = 76 ; age , 43.1 + /- 11.4 years ; male/female , 67/9 ) received peg-IFN 1.0 mug/kg/week + ribavirin 10.6 mg/kg/day , while group II ( n = 27 ; age , 37.3 + /- 11.6 years ; male/female , 21/6 ) received peg-IFN 1.5 microg/kg/week + ribavirin 10.6 mg/kg/day . Patients in both groups were treated for 24 weeks . End of treatment viral response ( ETVR ) and sustained viral response ( SVR ) after a 6-month follow-up period were assessed . RESULTS In both groups I and II , one patient was lost to follow-up , while one patient in group II withdrew due to side-effects . ETVR was seen in 72/76 ( 94.7 % ) of patients in the low dose group and 24/27 ( 88.9 % ) of patients in the high dose group ( P = 0.375 ) . SVR was seen in 60/76 ( 78.9 % ) of patients in the low dose group and 25/27 ( 92.6 % ) of patients in the high dose group ( P = 0.145 ) . Age ( Pearson correlation coefficient = 0.263 ; P = 0.008 ) and fibrosis ( correlation coefficient , 0.263 ; P = 0.008 ) showed a significant correlation with the SVR . CONCLUSION In patients with genotype 3 , peg-IFN at 1.0 microg/kg/week with ribavirin is as effective as peg-IFN at 1.5 mug/kg/week with ribavirin BACKGROUND & AIMS Patients with chronic hepatitis C who do not respond rapidly to therapy have a low chance of developing a sustained virologic response ( SVR ) when treated for 48 weeks . This study investigated whether treatment for 72 weeks increases the rate of SVR in patients with detectable hepatitis C virus (HCV)-RNA levels at week 4 of treatment . METHODS A total of 510 treatment-naive patients were treated with peginterferon-alfa2a ( 180 microg/wk ) plus ribavirin ( 800 mg/day ) . Patients with detectable HCV-RNA levels at week 4 ( n = 326 ) were r and omized to complete 48 ( group A , n = 165 ) or 72 weeks ( group B , n = 161 ) of treatment . Patients with undetectable HCV-RNA levels at week 4 ( n = 184 ) were allocated into group C ( n = 148 ) or group D ( n = 36 ) , according to HCV genotype and baseline viremia , and treated for 24 or 48 weeks , respectively . All patients were followed-up for 24 weeks after the end of treatment . RESULTS The end-of-treatment response rate ( 61 % ) was similar in groups A and B , but the SVR rate was higher in group B ( 45 % vs 32 % in A ; P = .01 ) . In genotype 1-infected patients r and omized to group A ( n = 149 ) or B ( n = 142 ) , SVR rates were 28 % and 44 % , respectively ( P = .003 ) . The incidence of adverse events was similar in all groups . Treatment discontinuation was more frequent in group B ( 36 % ) than in group A ( 18 % ) ( P = .0004 ) . SVR rates in groups C and D were 79 % and 64 % , respectively . CONCLUSIONS Extension of treatment with peginterferon-alfa2a plus ribavirin from 48 to 72 weeks significantly increases the rate of SVR in patients with detectable viremia at week 4 of treatment In hepatitis C virus ( HCV ) genotype 1 infection , the duration of interferon‐based therapy is a critical determinant in achieving sustained virologic response ( SVR ) . Slow or late responders to peginterferon and ribavirin may benefit from an extended treatment course . We sought to determine if therapy extension could improve response rates in a United States population of slow responders . Slow response was defined by achieving at least a 2‐log decrement in HCV RNA from baseline , yet having detectable HCV RNA at 12 weeks and undetectable HCV RNA at 24 weeks ( polymerase chain reaction , TaqMan , Roche ; detection limit 10 IU/mL ) . Patients were treatment‐naïve , chronically infected genotype 1–infected slow responders to 1.5 μg/kg/week of peginterferon‐α2b and 800‐1400 mg/day of ribavirin and were r and omly assigned 1:1 to complete a total of 48 or 72 weeks of therapy . Dose reductions and treatment discontinuations for adverse events or laboratory abnormalities were similar between the 2 treatment arms . End‐of‐treatment response rates were similar in the 72‐week group compared with those in the 48‐week group ( 48 % versus 45 % ; P value not significant ) . Overall , the rate of SVR was superior in patients treated for 72 weeks versus 48 weeks ( 38 % versus 18 % , respectively ; P = 0.026 ) . Conclusion : Extending the treatment duration from 48 weeks to 72 weeks in genotype 1–infected patients with slow virologic response to peginterferon‐α2b and weight‐based ribavirin significantly improves SVR rates . Treatment extension does not seem to increase the rate of dose reduction or therapy discontinuation . ( HEPATOLOGY 2007;46:1688–1694 . Treatment with polyethylene glycol-modified interferon alfa-2a ( peginterferon ) alone produces significantly higher sustained antiviral responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus ( HCV ) infection . We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin , interferon alfa-2b plus ribavirin , and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. Thirty-two patients were r and omly assigned to treatment , and received at least one dose of medication consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin ( 1,000 or 1,200 mg , depending on body weight ) ( n = 14 ) , weekly peginterferon alfa-2a plus daily placebo ( n = 6 ) , or three million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks ( n = 12 ) . More patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response ( defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy ) than patients who received interferon alfa-2b plus ribavirin ( 7/14 vs. 4/12 ) or peginterferon alfa-2a plus placebo ( 0/6 ) . The overall safety profiles of the three treatment regimens were similar . In conclusion , for patients with chronic hepatitis C , once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained viral reduction compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone AIM Comparing the efficacy of peginterferon alpha-2b plus ribavirin with interferon alpha -2b plus ribavirin in Saudi patients with chronic hepatitis C virus ( HCV ) commonly infected with genotype 4 . METHODS A total of 96 patients with chronic HCV infection were r and omly assigned to two treatment groups . Forty-eight patients received once weekly 100 microg of peginterferon alpha-2b plus ribavirin given orally 800 mg/day ( peginterferon group ) . Another 48 patients received thrice weekly 3 million units of interferon alpha-2b plus ribavirin 800 mg/day ( interferon group ) . At the end of treatment ( 48 weeks ) and sustained ( 72 weeks ) biochemical and virologic responses were determined . RESULTS In the peginterferon group , 70.8 % ( 34/48 ) patients attained both biochemical and virologic responses at the end of the treatment as against 52.1 % ( 25/48 ) patients in the interferon group . ( P=0.09 for both ) . Similarly , sustained biochemical and virologic responses in the peginterferon group were attained in 52.1 % ( 25/48 ) and 43.8 % ( 21/48 ) patients as against 43.8 % ( 21/48 ) and 29.2 % ( 14/48 ) patients in the interferon group , respectively ( P=0.54 and 0.20 , respectively ) . The sustained virologic response rates in patients with genotype 4 were 42.9 % ( 12/28 ) in the peginterferon group and 32.3 % ( 10/31 ) in the interferon group ( P=0.43 ) . Patients in peginterferon group had higher , although statistically not significant adverse reactions . CONCLUSIONS Saudi patients with chronic HCV attained a higher , although statistically not significant sustained virologic response with pegylated interferon plus ribavirin compared with interferon plus ribavirin BACKGROUND Treatment with pegylated interferon ( peginterferon ) and ribavirin for 48 weeks is more effective than conventional interferon and ribavirin in patients with chronic hepatitis C. OBJECTIVE To assess the efficacy and safety of 24 or 48 weeks of treatment with peginterferon-alpha2a plus a low or st and ard dose of ribavirin . DESIGN R and omized , double-blind trial . SETTING 99 international centers . PATIENTS 1311 patients with chronic hepatitis C. INTERVENTION Peginterferon-alpha2a , 180 microg/wk , for 24 or 48 weeks plus a low-dose ( 800 mg/d ) or st and ard weight-based dose ( 1000 or 1200 mg/d ) of ribavirin . MEASUREMENT Sustained virologic response : undetectable HCV RNA concentration at the end of treatment and during 12 to 24 weeks of follow-up . RESULTS Overall and in patients infected with HCV genotype 1 , 48 weeks of treatment was statistically superior to 24 weeks and st and ard-dose ribavirin was statistically superior to low-dose ribavirin . In patients with HCV genotype 1 , absolute differences in sustained virologic response rates between 48 and 24 weeks of treatment were 11.2 % ( 95 % CI , 3.6 % to 18.9 % ) and 11.9 % ( CI , 4.7 % to 18.9 % ) , respectively , between st and ard- and low-dose ribavirin . Sustained virologic response rates for peginterferon-alpha2a and st and ard-dose ribavirin for 48 weeks were 63 % ( CI , 59 % to 68 % ) overall and 52 % ( CI , 46 % to 58 % ) in patients with HCV genotype 1 . In patients with HCV genotypes 2 or 3 , the sustained virologic response rates in the 4 treatment groups were not statistically significantly different . CONCLUSION Treatment with peginterferon-alpha2a and ribavirin may be individualized by genotype . Patients with HCV genotype 1 require treatment for 48 weeks and a st and ard dose of ribavirin ; those with HCV genotypes 2 or 3 seem to be adequately treated with a low dose of ribavirin for 24 weeks Previous studies in Caucasian patients showed treatment of chronic hepatitis C with pegylated interferon/ribavirin was well tolerated , and produced a higher response rate especially in genotype 1 infections . However , it is unknown whether this conclusion can be extrapolated to patients with Chinese ethnic origin . A total of 153 patients with biopsy-proven chronic hepatitis C were r and omly assigned to receive either weekly injection of peginterferon alpha-2b 1.5 mcg/kg plus oral ribavirin ( 1000 or 1200 mg/day , depending on body weight ) ( PEG group , n = 76 ) or 3 MU of interferon alpha-2b t.i.w . plus ribavirin ( IFN group , n = 77 ) for 24 weeks . Sustained virological response ( SVR ) was defined as the sustained disappearance of serum hepatitis C virus ( HCV ) RNA at 24 weeks after the end of treatment by polymerase chain reaction assay . Baseline demographic , viral and histological characteristics were comparable between the two groups . Using an intent-to-treat analysis , HCV genotype 1 patients showed a significantly higher SVR in patients receiving PEG-IFN rather than IFN ( 65.8%vs 41.0 % , P = 0.019 ) , but no difference was found in genotype non-1 patients ( PEG vs IFN : 68.4%vs 86.8 % , P = 0.060 ) . Genotype 1 patients ( 28.6 % ) in the PEG-IFN group relapsed , as compared with 52.9 % in the IFN group ( P = 0.040 ) . Multivariate analyses showed early virological response at week 12 of therapy and genotype non-1 were significant predictors to SVR . As compared with the IFN group , patients receiving PEG-IFN had a significantly higher rate of discontinuation , dose reduction , fever , headache , insomnia , leucopenia and thrombocytopenia . In genotype 1 chronic hepatitis C Chinese patient , PEG-IFNalpha2b ribavirin had significantly better SVR and lower relapse rate when compared to IFN/ribavirin . Both regimens can be recommended for genotype non-1 chronic hepatitis C Chinese patients . However , a higher rate of adverse events and discontinuance of therapy were noted in patients treated with PEG-IFNalpha2b ribavirin BACKGROUND / AIMS While combination of peginterferon-alpha ( PEG-IFN ) and ribavirin ( RBV ) therapy is the current st and ard of care for chronic hepatitis C ( CHC ) , only 44 - 51 % of genotype-1 patients achieve a sustained virological response ( SVR ) , and both agents produce treatment-limiting toxicities . In the hepatitis C virus ( HCV ) replicon system , merimepodib ( MMPD ) , a novel , selective inhibitor of inosine monophosphate dehydrogenase , has shown potent antiviral effects . METHODS This r and omized , placebo-controlled , double-blind study evaluated the safety and antiviral activity of PEG-IFN-alpha2b and RBV combined with either placebo , 25 mg MMPD every 12h ( q12h ) , or 50 mg MMPD q12h in interferon-alpha ( IFN ) and RBV nonresponders . After 24 weeks of treatment , subjects with undetectable HCV RNA were proposed to continue assigned treatment for up to 24 additional weeks . RESULTS The PEG-IFN-alpha , RBV , and MMPD combination was well tolerated at both doses . After 24 weeks , the proportion of HCV RNA undetectable subjects was 8/11 ( 73 % ) in the 50-mg MMPD group , 2/10 ( 20 % ) in the 25-mg MMPD group , and 3/10 ( 30 % ) in the placebo group ( P=0.02 , Jonckheere-Terpstra test for increasing dose response ) . Ten subjects entered and completed an extension study , at Week 48 , 2 of 2 ( 100 % ) of the 25-mg and 3 of 5 ( 60 % ) of the 50-mg subjects remained HCV RNA undetectable , compared with 3 of 3 ( 100 % ) of the placebo subjects . At Follow-up Week 24 , 2 ( 100 % ) of the 25-mg , and 1 ( 25 % ) of the 50-mg subjects remained undetectable , compared with 1 ( 33 % ) of the placebo subjects . Pharmacokinetic and pharmacodynamic analyses showed a correlation between MMPD exposure and early virological response at week 12 , but not with hemoglobin decreases often associated with RBV . CONCLUSIONS In conclusion , PEG-IFN-alpha2b and RBV combined with 50 mg MMPD q12h was well tolerated and induced virological response with undetectable HCV RNA in IFN-alpha and RBV nonresponders BACKGROUND To assess the efficacy of 24- or 48-week peginterferon/ribavirin treatment of Taiwanese patients with chronic hepatitis C virus genotype-1b ( HCV-1b ) infection , and to identify subgroups of patients in whom the 48-week treatment has benefits . METHODS We assigned 60 patients receiving peginterferon-alpha-2b ( 80 - 100 mcg/week ) plus ribavirin ( 1000 - 1200 mg/day ) , depending on body weight , for 24 or 48 weeks , with a 3:1 r and omization ratio . RESULTS The sustained virological response ( SVR ) rate was significantly higher in the 48-week ( 80.0 % , 12/15 ) than in the 24-week group ( 48.9 % , 22/45 , P < 0.05 ) . The 60 patients were classified into two subgroups according to the presence of unfavorable baseline predictors : viral loads > or = 400,000 IU/ml or a hepatic fibrosis score of 3 - 4 . In 19 patients without an unfavorable predictor , the SVR rate was comparable in the 24-week ( 78.6 % ) and 48-week ( 75.0 % ) groups ; in patients with either unfavorable predictors , the SVR rate was significantly higher in the 48-week ( 81.1 % , 9/11 ) than in the 24-week group ( 36.7 % , 11/30 , P = 0.015 ) . The discontinuation rate was significantly higher in the 48-week ( 20.0 % , 3/15 ) than in the 24-week group ( 2.2 % , 1/45 , P < 0.05 ) . CONCLUSION A 48-week course of peginterferon-alpha-2b/ribavirin was more effective than a 24-week course in Taiwanese HCV-1b patients , mainly in those with high viral loads and /or advanced hepatic fibrosis BACKGROUND Little is known about the efficacy , safety and tolerability of pegylated interferon plus ribavirin treatment in patients with chronic hepatitis Cvirus ( HCV ) infection and histologically proven fully established cirrhosis . We aim ed here to evaluate the safety of this regimen in such patients and to identify baseline and on-treatment predictors of a sustained virological response ( SVR ) . METHODS Patients with histologically proven , HCV-induced cirrhosis were r and omized to receive pegylated interferon-alpha2b ( PEG-IFN-alpha2b ; 1.0 microg/kg/week , n=56 ; group A ) or recombinant interferon-alpha2b ( IFN-alpha2b ; 3 million IU three times/week , n=36 ; group B ) , each in combination with a weight-based dose of ribavirin ( 800 - 1,200 mg/day ) for up to 48 weeks . The primary endpoint of the study was the assessment of SVR , defined as undetectable HCV RNA 24 weeks after treatment cessation . RESULTS Overall , 40 % ( 37/93 ) of patients attained SVR : 44 % ( 25/57 ) in group A and 33 % ( 12/36 ) in group B ( P=0.31 ) . SVR rates were significantly higher in genotype 2/3 patients than in genotype 1 patients ( 69 % versus 25 % ; P<0.0001 ) . Platelet count at baseline , rapid virological response , and early virological response were predictors of SVR . Twelve patients discontinued treatment because of an adverse event and 20 patients required ribavirin dose reduction for the management of anaemia . CONCLUSIONS PEG-IFN-alpha2b plus ribavirin for 48 weeks is an efficacious and well-tolerated treatment regimen for patients with HCV-induced cirrhosis . Although SVR rates were more satisfactory in genotype 2/3 than in genotype 1 patients , our study identified additional predictors of response that could allow physicians to better manage treatment in this ' difficult-to-cure ' subset of patients BACKGROUND / AIMS Previous studies using st and ard interferon and ribavirin combination therapy suggested that patients infected with HCV-1 and a low pretreatment HCV-RNA level can be treated for 24 weeks without compromising sustained virologic response rates . The aim of the present study was to investigate this schedule in the era of pegylated interferon-alpha plus ribavirin . METHODS Patients chronically infected with HCV-1 ( n=235 ) and a screening viremia < or = 600,000 IU/mL ( real-time PCR ) were treated with peginterferon alfa-2b 1.5 microg/kg subcutaneously once weekly plus ribavirin 800 - 1400 mg/day based on body weight for 24 weeks . RESULTS End-of-treatment and sustained virologic response rates were 80 and 50 % , respectively . The 48-week historical control ( Manns et al. , Lancet 2001;358:958 - 65 ) had similar end-of-treatment ( 74 % ) but higher sustained virologic response rates ( 71 % ) . This difference was due to a high virologic relapse rate after 24 weeks of therapy ( 37 % ) compared with the historical control ( 4 % ) . A subset of patients who had undetectable serum HCV-RNA at treatment week 4 , however , achieved similar sustained virologic response rate ( 89 % ) as in the control group ( 85 % ) . CONCLUSIONS HCV-1 infected patients with a low baseline HCV-RNA concentration who become HCV-RNA negative at week 4 may be treated for 24 weeks without compromising sustained virologic response rates Objective The objective of this study was to compare the efficacy of anti-hepatitis C virus ( anti-HCV ) treatment schedules on the basis of an early virological response ( EVR ) , defined as undetectable serum HCV-RNA ( < 50 IU/ml ) after a 12-week induction course of peginterferon & agr;-2a ( PEG-IFN ) 180 mcg/week . Methods A total of 210 interferon-naïve patients ( 69 % male ; median age , 42 years ) with histologically proven chronic hepatitis C infection ( genotype 1 : 62 % ) received PEG-IFN 180 mcg/week for 12 weeks . Patients with EVR ( 58 % ) were r and omized to continue PEG-IFN monotherapy ( n=64 ) or to add ribavirin ( RBV ) , 800 mg/day ( n=57 ) , for 36 additional weeks . Patients without EVR ( 42 % ) were r and omized to add RBV ( n=42 ) , or RBV plus amantadine , 200 mg/day ( n=47 ) , for 36 additional weeks . Sustained virological response ( SVR , undetectable HCV-RNA 24 weeks after treatment completion ) was compared among treatment groups . Results Patients with EVR : SVR rate was 60.3 % in the PEG-IFN group versus 67.2 % in the PEG-IFN+RBV group ( NS ) . In genotypes 2/3 , SVR rates were 66.7 versus 73.1 % ( NS ) ; in genotypes 1/4 , SVR rates were 51.6 versus 61.3 % , respectively ( NS ) . Patients without EVR : SVR was 16.7 % in the PEG-IFN+RBV group versus 31.9 % in the triple therapy group ( P=0.07 ) . In patients with genotypes 1/4 , SVR rates were 9.4 versus 29.7 % ( P=0.041 ) . Conclusion In genotypes 1/4 patients without EVR , triple therapy results in higher SVR rates than st and ard dual therapy . This study confirms that addition of amantadine is beneficial in early-recognized ‘ difficult-to-treat ’ patients UNLABELLED We compared the efficacy and tolerability of 24 weeks of treatment with ribavirin 800 mg/day ( group A ) or 400 mg/day ( group B ) plus peginterferon alfa-2a 180 mug/week in treatment-naive patients infected with hepatitis C virus ( HCV ) genotype 2 or 3 . A total of 97 of 141 patients r and omized to group A ( 68.8 % , 95 % confidence interval [ CI ] 60.5%-76.3 % ) and 90 of 141 patients r and omized to group B ( 63.8 ; 95 % CI 55.3%-71.7 % ) achieved a sustained virological response , defined as undetectable serum HCV RNA at the end of untreated follow-up ( week 48 ) . Among patients infected with genotype 3 , the rate of sustained virological response was 67.5 % ( 95 % CI 58.4%-75.6 % ) in group A and 63.9 % ( 95 % CI 54.7%-72.4 % ) in group B , and among patients infected with genotype 2 , the rate of sustained virological response was 77.8 % ( 95 % CI 54.2%-93.6 % ) in group A and 55.6 % ( 95 % CI 38.4%-83.7 % ) in group B. Relapse rates in the 2 treatment groups were similar ( 17 % in group A and 20 % in group B ) . The incidence of adverse events , laboratory abnormalities , and dose reductions was similar in the 2 treatment groups . CONCLUSION The results suggest that when administered for 24 weeks with peginterferon alfa-2a , ribavirin doses of 400 and 800 mg/day produce equivalent outcomes in patients infected with HCV genotype 3 UNLABELLED Individualized treatment on the basis of early viral kinetics has been discussed to optimize antiviral therapy in chronic hepatitis C virus ( HCV ) infection . Individually tailored reduction in treatment duration in HCV type 1-infected patients represents one possible strategy . Four hundred thirty-three patients were r and omly assigned to receive either 1.5 microg/kg peginterferon alfa-2b weekly plus 800 - 1,400 mg ribavirin daily for 48 weeks ( n = 225 , group A ) or an individually tailored treatment duration ( 18 - 48 weeks ; n = 208 , group B ) . In the latter group , treatment duration was calculated using the time required to induce HCV RNA negativity ( branched DNA [ bDNA ] assay ; sensitivity limit , 615 IU/mL ) multiplied by the factor 6 . All bDNA negative sample s were retested with the more sensitive transcription-mediated amplification ( TMA ) assay ( sensitivity limit , 5.3 IU/mL ) . Sustained virologic response ( SVR ) rates were significantly lower in group B ( 34.6 % versus 48.0 % [ P = 0.005 ] ) due to higher relapse rates ( 32.7 % versus 14.2 % [ P < 0.0005 ] ) . Important predictors of response were the levels of baseline viremia as well as the time to TMA negativity on treatment . Taking the simultaneous presence of low baseline viral load ( < 800,000 IU/mL ) and a negative TMA test within the first 4 weeks as predictors for treatment response , SVR rates were comparable between both treatment schedules with an SVR probability of > 80 % obtained in patients treated for only 18 or 24 weeks . CONCLUSION The individualized treatment strategy according to time to bDNA negativity failed to provide comparable efficacy compared with the st and ard of care . The inferiority of the individualized protocol may be explained by the use of a less sensitive HCV RNA assay , and also by underestimation of the importance of baseline viremia BACKGROUND & AIMS Pegylated interferon ( peg-IFN ) plus ribavirin ( st and ard of care for chronic hepatitis C virus [ HCV ] ) , can cause dose-limiting anemia in up to 22 % of patients . Viramidine is associated with a lower incidence of anemia because of its liver-targeting properties . METHODS The efficacy and safety of viramidine versus ribavirin plus peg-IFN alfa-2a was assessed in patients with HCV . R and omized patients received peg-IFN alfa-2a 180 mcg with viramidine 600 mg twice daily or weight-based doses of ribavirin 1000 or 1200 mg/day . Treatment duration was based on HCV ribonucleic acid ( RNA ) genotype : genotype 2/3 and non-2/3 patients were treated for 24 and 48 weeks , respectively . The primary efficacy end point was the non-inferiority of viramidine versus ribavirin ( proportion of patients achieving sustained virologic response at week 24 ) . The primary safety end point was the proportion of patients experiencing a hemoglobin event . RESULTS In total , 962 patients received peg-IFN alfa-2a with viramidine ( n=644 ) or ribavirin ( n=318 ) . Sustained virologic response was achieved in 40 % of viramidine-treated patients and 55 % of ribavirin-treated patients ( difference of proportions 0.150 [ 95 % CI , 0.09 , 0.21 ] ) . Improved efficacy was seen with higher viramidine exposure on a mg/kg basis . Viramidine was significantly superior to ribavirin in hemoglobin event rates ( 54 % vs. 80 % ; p<0.001 ) . Adverse event rates were similar between groups except for diarrhea ( viramidine 29.5 % ; ribavirin 15.7 % ; p<0.0001 ) . CONCLUSIONS Viramidine 600 mg BID did not meet the primary efficacy non-inferiority end point but met the safety end point . Determination of a viramidine dosage that would yield superior efficacy over ribavirin is needed |
13,202 | 27,322,710 | The findings of this systematic review and meta- analysis show that iCBT is an effective treatment for individuals with PTSD and comorbid depressive symptoms . | BACKGROUND Internet-delivered cognitive behavioral therapy ( iCBT ) is a relatively novel treatment method that may improve the accessibility of mental health care for individuals with posttraumatic stress disorder ( PTSD ) .
The aim of this meta- analysis was to evaluate the effectiveness of iCBT compared to inactive ( waitlist control and treatment-as-usual ( TAU ) ) and active other interventions in reducing PTSD symptoms . | OBJECTIVE Veterans who served in Operation Enduring Freedom ( OEF ) and Operation Iraqi Freedom ( OIF ) commonly experience alcohol misuse and symptoms of posttraumatic stress disorder ( PTSD ) following their return from deployment to a war zone . We conducted a r and omized clinical trial to evaluate the efficacy of a newly developed , 8-module , self-management web intervention ( VetChange ) based on motivational and cognitive-behavioral principles to reduce alcohol consumption , alcohol-related problems , and PTSD symptoms in returning combat veterans . METHOD Six hundred participants , recruited through targeted Facebook ads , were r and omized to either an Initial Intervention Group ( IIG ; n = 404 ) or a Delayed Intervention Group ( DIG ; n = 196 ) that waited 8 weeks for access to VetChange . Primary outcome measures were Drinks per Drinking Day , Average Weekly Drinks , Percent Heavy Drinking Days , and PTSD symptoms . Intent-to-treat analyses compared changes in outcome measures over time between IIG and DIG as well as within-group changes . RESULTS IIG participants demonstrated greater reductions in drinking ( p < .001 for each measure ) and PTSD symptoms ( p = .009 ) between baseline and end-of-intervention than did DIG participants between baseline and the end of the waiting period . DIG participants showed similar improvements to those in IIG following participation in VetChange . Alcohol problems were also reduced within each group between baseline and 3-month follow-up . CONCLUSIONS Results indicate that VetChange is effective in reducing drinking and PTSD symptoms in OIF/OEF veterans . Further studies of VetChange are needed to assess web-based recruitment and retention methods and to determine VetChange 's effectiveness in demographic and clinical sub- population s of returning veterans Background Guided self-help interventions for PTSD ( post-traumatic stress disorder ) are a promising tool for the dissemination of contemporary psychological treatment . Objective This study investigated the efficacy of the Chinese version of the My Trauma Recovery ( CMTR ) website . Methods In an urban context , 90 survivors of different trauma types were recruited via Internet advertisements and allocated to a r and omized controlled trial ( RCT ) with a waiting list control condition . In addition , in a rural context , 93 survivors mainly of the 2008 Sichuan earthquake were recruited in-person for a parallel RCT in which the website intervention was conducted in a counseling center and guided by volunteers . Assessment was completed online on a professional Chinese survey website . The primary outcome measure was the Post-traumatic Diagnostic Scale ( PDS ) ; secondary outcome measures were Symptom Checklist 90-Depression ( SCL-D ) , Trauma Coping Self-Efficacy Scale ( CSE ) , Post-traumatic Cognitive Changes ( PCC ) , and Social Functioning Impairment ( SFI ) question naires adopted from the My Trauma Recovery website . Results For the urban sample , findings indicated a significant group × time interaction in post-traumatic symptom severity ( F 1,88=7.65 , P=.007 ) . CMTR reduced post-traumatic symptoms significantly with high effect size after one month of treatment ( F 1,45=15.13 , Cohen ’s d=0.81 , P<.001 ) and the reduction was sustained over a 3-month follow-up ( F 1,45=17.29 , Cohen ’s d=0.87 , P<.001 ) . In the rural sample , the group × time interaction was also significant in post-traumatic symptom severity ( F 1,91=5.35 , P=.02 ) . Post-traumatic symptoms decreased significantly after treatment ( F 1,48=43.97 , Cohen ’s d=1.34 , P<.001 ) and during the follow-up period ( F 1,48=24.22 , Cohen ’s d=0.99 , P<.001 ) . Additional outcome measures ( post-traumatic cognitive changes , depression ) indicated a range of positive effects , in particular in the urban sample ( group × time interactions : F 1,88=5.32 - 8.37 , all Ps<.03 ) , contributing to the positive evidence for self-help interventions . Differences in the effects in the two RCTs are exploratorily explained by sociodemographic , motivational , and setting feature differences between the two sample s. Conclusions These findings give support for the short-term efficacy of CMTR in the two Chinese population s and contribute to the literature that self-help Web-based programs can be used to provide mental health help for traumatized persons . Trial Registration Australia New Zeal and Clinical Trials Registry ( ANZCTR ) : ACTRN12611000951954 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?ACTRN=12611000951954 ( Archived by WebCite at http://www.webcitation.org/6G7WyNODk ) Online therapy offers many advantages over face-to-face therapy . Interapy includes psychoeducation , screening , effect measures , and a protocol -driven treatment via the Internet for people suffering from posttraumatic stress . The present article reports the results of a controlled trial on the Internet-driven treatment of posttraumatic stress and grief in a group of people who manifested mild to relatively severe trauma symptoms . Participants in the treatment condition ( n=69 ) improved significantly more than participants in the waiting-list control condition ( n=32 ) on trauma-related symptoms and general psychopathology . The effect sizes were large . On most subscales , more than 50 % of the treated participants showed reliable change and clinical ly significant improvement , with the highest percentages being found for depression and avoidance Background Posttraumatic stress disorder ( PTSD ) develops in 10 - 20 % of injury patients . We developed a novel , self-guided Internet-based intervention ( called Trauma TIPS ) based on techniques from cognitive behavioral therapy ( CBT ) to prevent the onset of PTSD symptoms . Objective To determine whether Trauma TIPS is effective in preventing the onset of PTSD symptoms in injury patients . Methods Adult , level 1 trauma center patients were r and omly assigned to receive the fully automated Trauma TIPS Internet intervention ( n=151 ) or to receive no early intervention ( n=149 ) . Trauma TIPS consisted of psychoeducation , in vivo exposure , and stress management techniques . Both groups were free to use care as usual ( non protocol ized talks with hospital staff ) . PTSD symptom severity was assessed at 1 , 3 , 6 , and 12 months post injury with a clinical interview ( Clinician-Administered PTSD Scale ) by blinded trained interviewers and self-report instrument ( Impact of Event Scale — Revised ) . Secondary outcomes were acute anxiety and arousal ( assessed online ) , self-reported depressive and anxiety symptoms ( Hospital Anxiety and Depression Scale ) , and mental health care utilization . Intervention usage was documented . Results The mean number of intervention logins was 1.7 , SD 2.5 , median 1 , interquartile range ( IQR ) 1 - 2 . Thirty-four patients in the intervention group did not log in ( 22.5 % ) , 63 ( 41.7 % ) logged in once , and 54 ( 35.8 % ) logged in multiple times ( mean 3.6 , SD 3.5 , median 3 , IQR 2 - 4 ) . On clinician-assessed and self-reported PTSD symptoms , both the intervention and control group showed a significant decrease over time ( P<.001 ) without significant differences in trend . PTSD at 12 months was diagnosed in 4.7 % of controls and 4.4 % of intervention group patients . There were no group differences on anxiety or depressive symptoms over time . Post hoc analyses using latent growth mixture modeling showed a significant decrease in PTSD symptoms in a subgroup of patients with severe initial symptoms ( n=20 ) ( P<.001 ) . Conclusions Our results do not support the efficacy of the Trauma TIPS Internet-based early intervention in the prevention of PTSD symptoms for an unselected population of injury patients . Moreover , uptake was relatively low since one-fifth of individuals did not log in to the intervention . Future research should therefore focus on innovative strategies to increase intervention usage , for example , adding gameplay , embedding it in a blended care context , and targeting high-risk individuals who are more likely to benefit from the intervention . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 57754429 ; http://www.controlled-trials.com/IS RCT N57754429 ( Archived by WebCite at http://webcitation.org/6FeJtJJyD ) A total of 117 depressed clients , stratified for severity , completed 8 or 16 sessions of manualized treatment , either cognitive-behavioral psychotherapy ( CB ) or psychodynamic-interpersonal psychotherapy ( PI ) . Each of 5 clinician-investigators treated clients in all 4 treatment conditions . On most measures , CB and PI were equally effective , irrespective of the severity of depression or the duration of treatment . However , there was evidence of some advantage to CB on the Beck Depression Inventory ( Beck , Ward , Mendelson , Mock , & Erbaugh , 1961 ) . There was no evidence that CB 's effects were more rapid than those of PI , nor did the effects of each treatment method vary according to the severity of depression . There was no overall advantage to 16-session treatment over 8-session treatment . However , those presenting with relatively severe depression improved substantially more after 16 than after 8 sessions On-line therapy offers many advantages over face-to-face setting s. Interapy includes psycho-education , screening , effect measures and protocol -driven treatment via the Internet for clients . The present paper reports the results of a controlled trial on the Interapy treatment of posttraumatic stress and grief in students , gaining course credits . The participants in the experimental condition ( n = 13 ) improved significantly than the participants in the waiting-list control condition ( n = 12 ) , on trauma-related symptoms and general psychopathology . The effect sizes were large . Eighty percent of the treated participants showed clinical ly significant improvement after treatment . The possibilities for future research with Interapy , including studies into moderating variables , are discussed BACKGROUND Posttraumatic stress disorder ( PTSD ) is a severe and disabling condition and few receive appropriate care . Internet-based treatment of PTSD shows promise in reducing barriers to care and preliminary evidence suggests it is efficacious in treating symptoms of PTSD . METHODOLOGY Forty-two individuals with a diagnosis of PTSD confirmed by clinician interview completed a r and omized controlled comparison of Internet-based cognitive behavioral therapy ( CBT ) with a waitlist control condition . PRINCIPLE FINDINGS Large pre- to posttreatment effect sizes ( ESs ) were found for the Treatment group on measures of PTSD symptoms , depression , anxiety , and disability . A small between-group ES was found for PTSD symptoms and moderate between-group ESs were found for depression , anxiety , and disability . CONCLUSIONS Results provide preliminary support for Internet-based CBT as an efficacious treatment for individuals with a confirmed primary diagnosis of PTSD This study was an open trial evaluation of a 10-week therapist-assisted cognitive behavior therapy ( CBT ) internet intervention ( PTSD Online ) undertaken with people with a primary clinical diagnosis of posttraumatic stress disorder ( PTSD ) ( n=22 ) at pre- assessment . Participants were re-assessed at post- assessment and 3-month follow-up . Significant improvements on PTSD severity ratings and related PTSD symptomatology were observed at post- assessment and maintained at 3-month follow-up . At post- assessment , 69.2 % of the sample showed clinical ly significant improvement and 77 % of the sample at follow-up assessment . Non-significant , yet improved , change was observed on all other general psychological measures . Overall , treatment satisfaction was good ( 69 % ) , participant therapeutic alliance ratings were high ( 87.5 % ) , and the average total therapist time required was 194.5 min . PTSD Online appears to be an efficacious treatment option for people with PTSD that can be provided entirely remotely , with far less therapist time than traditional face-to-face treatment , and without compromising therapeutic alliance BACKGROUND Compared to those with depression alone , depressed patients with posttraumatic stress disorder ( PTSD ) experience more severe psychiatric symptomatology and factors that complicate treatment . OBJECTIVE To estimate PTSD prevalence among depressed military veteran primary care patients and compare demographic/illness characteristics of PTSD screen-positive depressed patients ( MDD-PTSD+ ) to those with depression alone ( MDD ) . DESIGN Cross-sectional comparison of MDD patients versus MDD-PTSD+ patients . PARTICIPANTS Six hundred seventy-seven r and omly sample d depressed patients with at least 1 primary care visit in the previous 12 months . Participants composed the baseline sample of a group r and omized trial of collaborative care for depression in 10 VA primary care practice s in 5 states . MEASUREMENTS The Patient Health Question naire-9 assessed MDD . Probable PTSD was defined as a Primary Care PTSD Screen ≥ 3 . Regression-based techniques compared MDD and MDD-PTSD+ patients on demographic/illness characteristics . RESULTS Thirty-six percent of depressed patients screened positive for PTSD . Adjusting for sociodemographic differences and physical illness comorbidity , MDD-PTSD+ patients reported more severe depression ( P < .001 ) , lower social support ( P < .001 ) , more frequent outpatient health care visits ( P < .001 ) , and were more likely to report suicidal ideation ( P < .001 ) than MDD patients . No differences were observed in alcohol consumption , self-reported general health , and physical illness comorbidity . CONCLUSIONS PTSD is more common among depressed primary care patients than previously thought . Comorbid PTSD among depressed patients is associated with increased illness burden , poorer prognosis , and delayed response to depression treatment . Providers should consider recommending psychotherapeutic interventions for depressed patients with PTSD OBJECTIVE To demonstrate the noninferiority of a telemedicine modality , videoteleconferencing , compared to traditional in-person service delivery of a group psychotherapy intervention for rural combat veterans with posttraumatic stress disorder ( PTSD ) . METHOD A r and omized controlled noninferiority trial of 125 male veterans with PTSD ( according to DSM criteria on the Clinician-Administered PTSD Scale ) and anger difficulties was conducted at 3 Veterans Affairs outpatient clinics . Participants were r and omly assigned to receive anger management therapy delivered in a group setting with the therapist either in-person ( n = 64 ) or via videoteleconferencing ( n = 61 ) . Participants were assessed at baseline , midtreatment ( 3 weeks ) , posttreatment ( 6 weeks ) , and 3 and 6 months posttreatment . The primary clinical outcome was reduction of anger difficulties , as measured by the anger expression and trait anger subscales of the State-Trait Anger Expression Inventory-2 ( STAXI-2 ) and by the Novaco Anger Scale total score ( NAS-T ) . Data were collected from August 2005 to October 2008 . RESULTS Participants in both groups showed significant and clinical ly meaningful reductions in anger symptoms , with posttreatment and 3 and 6 months posttreatment effect sizes ranging from .12 to .63 . Using a noninferiority margin of 2 points for STAXI-2 subscales anger expression and trait anger and 4 points for NAS-T outcomes , participants in the videoteleconferencing condition demonstrated a reduction in anger symptoms similar ( " non-inferior " ) to symptom reductions in the in-person groups . Additionally , no significant between-group differences were found on process variables , including attrition , adherence , satisfaction , and treatment expectancy . Participants in the in-person condition reported significantly higher group therapy alliance . CONCLUSIONS Clinical and process outcomes indicate delivering cognitive-behavioral group treatment for PTSD-related anger problems via videoteleconferencing is an effective and feasible way to increase access to evidence -based care for veterans residing in rural or remote locations Abstract This pilot study tested the efficacy of the My Disaster Recovery ( MDR ) website to decrease negative affect and increase coping self-efficacy . Fifty-six survivors of Hurricane Ike were recruited from a larger study being conducted at the University of Texas Medical Branch at the first anniversary of the storm . Restricted r and omization was used to assign participants to the MDR website , an information-only website , or a usual care condition . Group × time interactions indicated that MDR reduced participant worry more than the other conditions . A similar trend was also identified for depression . Both websites were accessed a small to moderate amount and participants reported mixed satisfaction for both websites . Although the effect sizes for worry and depression were in the moderate to large range , small sample size and timing of the intervention qualify the findings . These preliminary findings encourage further evaluation of MDR with a larger , demographically diverse sample and indicate that the MDR website might be helpful in reducing worry and depression This study retested effects of a Memory Structuring Intervention ( MSI ) and the moderating role of gender in relation to posttraumatic stress disorder ( PTSD ) symptoms . Thirty-four traffic accident victims with high pulse rates were r and omly assigned to MSI or supportive listening ( control ) phone conversations soon after accidents . Based on converging clinical and neuroscience research , the MSI taught chronological organization , labeling emotions/sensations , and describing causality . PTSD symptoms were assessed 3 months later . No overall group differences were found . However , a group by gender interaction revealed that , for women , the MSI was associated with less PTSD symptoms than the control treatment , while the opposite pattern was seen in men . Limitations and possible explanations for these findings are discussed Background : The loss of a child during pregnancy causes significant psychological distress for many women and their partners , and may lead to long-lasting psychiatric disorders . Internet-based interventions using exposure techniques and cognitive restructuring have proved effective for posttraumatic stress disorder ( PTSD ) and prolonged grief . This study compared the effects of an Internet-based intervention for parents after prenatal loss with a waiting list condition ( WLC ) . Methods : The Impact of Event Scale - Revised assessed symptoms of PTSD ; the Inventory of Complicated Grief and the Brief Symptom Inventory assessed depression , anxiety , and general mental health . The 228 participants ( 92 % female ) were r and omly allocated to a treatment group ( TG ; n = 115 ) or a WLC group ( n = 113 ) . The TG received a 5-week cognitive behavioral intervention including ( 1 ) self-confrontation , ( 2 ) cognitive restructuring , and ( 3 ) social sharing . Results : The TG showed significantly reduced symptoms of posttraumatic stress , prolonged grief , depression , and anxiety relative to the WLC control group . Intention-to-treat analysis revealed treatment effects of between d = 0.84 and d = 1.02 for posttraumatic stress and prolonged grief from pre- to posttreatment time points . Further significant improvement in all symptoms of PTSD and prolonged grief was found from the posttreatment evaluation to the 12-month follow-up . The attrition rate of 14 % was relatively low . Conclusions : The Internet-based intervention proved to be a feasible and cost-effective treatment , reducing symptoms of posttraumatic stress , grief , depression , anxiety , and general mental health after pregnancy loss . Low-threshold e-health interventions should be further evaluated and implemented routinely to improve psychological support after pregnancy loss |
13,203 | 11,034,770 | There was no effect on objective measures of disease activity ( including inflammation , pain and x-ray measured joint destruction ) of either ice versus control or heat versus control .
There was no difference in patient preference for heat or ice .
No harmful effects of ice or heat were reported .
REVIEW ER 'S CONCLUSIONS Since patients enjoy thermotherapy , and there are no harmful effects , thermotherapy should be recommended as a therapy which can be applied at home as needed to relieve pain .
There is no need for further research on the effects of heat or cold for RA | BACKGROUND Heat and cold therapy are often used as adjuncts in the treatment of rheumatoid arthritis by rehabilitation specialists .
OBJECTIVES To evaluate the effects of heat and cold on objective and subjective measures of disease activity in patients with rheumatoid arthritis . | Therapeutic trials often attempt to “ blind ” patient and investigator to the true nature of treatments received , reducing the influences of conscious or subconscious prejudices . In drug trials , this is accomplished with placebo tablets , but blinding in trials of physical treatments is more problematic . This issue arose in a clinical trial of transcutaneous electrical nerve stimulation ( TENS ) for patients with chronic low back pain . Several study design features were incorporated to promote blinding : use of sham TENS units visually identical with real units , exclusion of potential subjects with previous TENS experience , avoidance of a crossover design and use of identical visit frequency , instructions and modifications in electrode placement . Subjects were asked not to discuss treatments with the clinicians who performed outcome assessment s. Both patients and clinicians were asked to guess actual treatment assignments at the trial 's end . Every patient in the true TENS group believed the unit was functioning properly , but the degree of certainty varied . In the sham TENS group , 84 % also believed they had functioning units , but their certainty was significantly less than in the active treatment group . Differences in patient perceptions did not affect compliance , as the two groups had similar dropout rates , appointment compliance , days of TENS use and daily duration of TENS use . Clinicians guessed treatments correctly 61 % of the time ( as opposed to 50 % expected by chance ) , again suggesting partial success in blinding . These efforts at blinding may partly explain the negative trial results for TENS efficacy . We conclude that complete blinding is difficult to achieve because of sensory difference in treatment and unintended communication between patient and examiner . Nonetheless , trials of physical treatments can achieve partial blinding with the techniques described here , and the success of blinding can be assessed with simple questions at study completion The effect of active h and exercise and warm wax treatment was evaluated in 52 rheumatoid arthritis patients r and omized into four groups : ( 1 ) both exercise and wax bath , ( 2 ) exercise only , ( 3 ) wax bath only , and ( 4 ) controls . Treatment was given three times a week for 4 weeks . Deficits in flexion and extension in digits II-V bilaterally , grip function , grip strength , pain , and stiffness were measured before and after the treatment period . The control group was measured at corresponding times . Wax bath treatment followed by active h and exercise result ed in significant improvements of range of motion ( ROM ) and grip function . Active h and exercise alone reduced stiffness and pain with nonresisted motion and increased ROM . Wax bath alone had no significant effect OBJECTIVE To evaluate the effects of local application of ice chips , ligno-paraffin , short-wave diathermy , and nitrogen-cold air on skin and intraarticular temperature . METHODS Forty-two healthy subjects were divided into 4 treatment groups . A temperature probe was inserted into the knee joint cavity and another placed on the overlying skin , and changes in temperature over 3 hours , by treatment group , were recorded . RESULTS The mean skin surface temperature dropped from 27.9 degrees C to 11.5 degrees C after application of ice chips , and from 28.8 degrees C to 13.8 degrees C after application of cold air . The mean intraarticular temperature decreased from 31.9 degrees C to 22.5 degrees C and from 32.9 degrees C to 28.8 degrees C , respectively , after these 2 treatments . Shortwave diathermy increased skin temperature by 2.4 degrees C ; intraarticular temperature was increased only 1.4 degrees C by short-wave diathermy . Treatment with ligno-paraffin increased the skin surface temperature 8.9 degrees C ; the temperature in the joint cavity was increased 3.5 degrees C. CONCLUSION The use of short-wave diathermy and superficial heat packs in the treatment of patients with arthritis may potentially cause harm by increasing intraarticular temperature . This may have major implication s regarding treatment policy for patients with arthritis OBJECTIVE To evaluate and compare the effects of locally applied heat and cold treatments on skin and intraarticular temperature in patients with arthritis . METHODS Thirty-nine patients with arthritis of the knee were divided at r and om into 4 treatment groups ( ice chips , nitrogen cold air , ligno-paraffin , and placebo short wave ) . A temperature probe was inserted into the knee joint cavity and another placed on the overlying skin , and changes in temperature over 3 hours were recorded for each treatment group . RESULTS The mean temperature of the surface of the skin dropped from 32.2 degrees C to 16.0 degrees C after application of ice chips and from 32.6 degrees C to 9.8 degrees C after application of nitrogen cold air ; the mean intraarticular temperature decreased from 35.5 degrees C to 29.1 degrees C and from 35.8 degrees C to 32.5 degrees C , respectively , after these treatments . Treatment with ligno-paraffin increased the surface temperature by 7.5 degrees C and the temperature in the joint cavity by 1.7 degrees C. No significant changes were observed with placebo short wave diathermy . CONCLUSION The traditional model , that intraarticular temperature is decreased by superficial heat and increased by superficial cold , must be discarded . In arthritis patients , intraarticular temperature is increased by superficial heat and decreased by superficial cold . This has clear consequences for treatment policy Ninety consecutive patients undergoing primary knee arthroplasty received local cryotherapy 72 hours after surgery for pain relief . Thermal-pad circulating temperatures were r and omly assigned to 50 degrees , 60 degrees , or 70 degrees F ( room temperature ) . Pain relief was monitored using patient-controlled analgesia machines . The amount of morphine received and number of attempts per hour were statistically analyzed with relation to temperature group , age , sex , weight , side , and diagnosis . The amount of morphine injected was positively correlated to the number of attempts per hour and moderately correlated to body weight . There was no correlation between thermal-pad temperature or any other parameter and the amount of morphine injected after surgery Superficial heat and cold are commonly used therapeutic methods in patients with rheumatoid arthritis . Both procedures have analgesic effect . In 30 in patients with rheumatoid arthritis the pain threshold was measured before and after warm bath and ice massage . Rheumatoid patients had significantly lower pain threshold compared to the healthy subjects in normal circumstances . Heat and cold remarkably raise the pain threshold right after the application . The pain threshold is also raised 10 and 30 min after cryotherapy , but not after the warm bath . Between investigated groups there were no statistically significant differences in the pain threshold values in any observed time . We consider that both methods have a reasonable place in the therapy of rheumatoid arthritis |
13,204 | 25,539,893 | With regard to associated factors , age has an inverse association with hyperopia .
The frequency of hyperopia is higher among White children and those who live in rural areas .
There is no consensus about the association between hyperopia and gender , family income and parental schooling . | Background Studies show great variability in the prevalence of hyperopia among children .
This study aim ed to synthesize the existing knowledge about hyperopia prevalence and its associated factors in school children and to explore the reasons for this variability . | PURPOSE To describe the prevalence of hyperopia and associated factors in a representative sample of Australian schoolchildren 6 and 12 years old . DESIGN Population -based cross-sectional study . PARTICIPANTS Schoolchildren ages 6 ( n = 1765 ) and 12 ( n = 2353 ) from 55 r and omly selected schools across Sydney . METHODS Detailed eye examinations included cycloplegic autorefraction , ocular biometry , cover testing , and dilated fundus examination . Information on birth and medical history were obtained from a parent question naire . MAIN OUTCOME MEASURES Moderate hyperopia defined as spherical equivalent ( SE ) refraction of > or = + 2.00 diopters ( D ) , and eye conditions including amblyopia , strabismus , astigmatism , and anisometropia . RESULTS Prevalences of moderate hyperopia among children ages 6 and 12 were 13.2 % and 5.0 % , respectively ; it was more frequent in children of Caucasian ethnicity ( 15.7 % and 6.8 % , respectively ) than in children of other ethnic groups . Compared with children without significant ametropia ( -0.49 < or = SE refraction < or = + 1.99 D ) , the prevalence of eye conditions including amblyopia , strabismus , abnormal convergence , and reduced stereoacuity was significantly greater in children with moderate hyperopia ( all Ps < 0.01 ) . Maternal smoking was significantly associated with moderate hyperopia among 6-year-olds ( P = 0.03 ) , but this association was borderline among 12-year-olds ( P = 0.055 ) . Early gestational age ( < 37 weeks ) and low birth weight ( < 2500 g ) were not statistically significant predictors of moderate hyperopia in childhood . CONCLUSIONS Moderate hyperopia was strongly associated with many common eye conditions , particularly amblyopia and strabismus , in older children . Birth parameters did not predict moderate hyperopia PURPOSE To determine the prevalence of refractive error types in Singaporean Chinese children aged 6 to 72 months . METHODS The Strabismus , Amblyopia and Refractive Error in Singaporean Children ( STARS ) is a population -based study in southwest Singapore . Door-to-door recruitment of participants was used , with disproportionate r and om sampling in 6-month increments . Parental question naires were administered . Participant eye examinations included logMAR visual acuity , cycloplegic autorefraction , and ocular biometry . Overall and age-specific prevalences of myopia ( spherical equivalence [ SE ] < or= -0.50 D ) , high myopia ( SE < or= -6.00 D ) , hyperopia ( SE > or= + 3.00 D ) , astigmatism ( cylinder > or= + 1.50 D ) , and anisometropia ( SE difference between each eye > or=2.00 D ) were calculated . RESULTS A total of 3009 children were examined ( participation rate , 72.3 % ) . Right eye ( OD ) cycloplegia data were available for 1375 boys and 1264 girls ( mean age , 41 months ) . Mean OD SE was + 0.69 D ( SD 1.15 ) . Overall myopia prevalence was 11.0 % with no variance between the sexes ( P = 0.91 ) . The prevalence of high myopia ( at least -6.00 D ) was 0.2 % . The prevalences of hyperopia , astigmatism , and anisometropia were 1.4 % , 8.6 % , and 0.6 % , respectively . Most astigmatism ( > 95 % ) was with-the-rule ( cylinder axes between 1 degrees and 15 degrees or 165 degrees and 180 degrees ) . Myopia was present in 15.8 % , 14.9 % , 20.2 % , 8.6 % , 7.6 % , and 6.4 % of children aged 6 to 11 , 12 to 23 , 24 to 35 , 36 to 47 , 48 to 59 , and 60 to 72 months , respectively . Prevalence increased with age for astigmatism ( P < 0.001 ) , but not for hyperopia or anisometropia ( P = 0.55 and P = 0.37 ) , respectively . CONCLUSIONS The prevalences of myopia and astigmatism in young Singaporean Chinese children are high , but that of hyperopia is low . Age effects were observed for each refractive error category , but differences between the sexes were not significant . Age-related variation in myopia prevalence may be influenced by ocular development , environment , and /or testability PURPOSE To describe the methodology , sampling strategy and preliminary results for the Aston Eye Study ( AES ) , a cross-sectional study to determine the prevalence of refractive error and its associated ocular biometry in a large multi-racial sample of school children from the metropolitan area of Birmingham , Engl and . METHODS A target sample of 1700 children aged 6 - 7 years and 1200 aged 12 - 13 years is being selected from Birmingham schools selected r and omly with stratification by area deprivation index ( a measure of socio-economic status ) . Schools with pupils predominantly ( > 70 % ) from a single race are excluded . Sample size calculations account for the likely participation rate and the clustering of individuals within schools . Procedures involve st and ardised protocol s to allow for comparison with international population -based data . Visual acuity , non-contact ocular biometry ( axial length , corneal radius of curvature and anterior chamber depth ) and cycloplegic autorefraction are measured in both eyes . Distance and near oculomotor balance , height and weight are also assessed . Question naires for parents and older children will allow the influence of environmental factors on refractive error to be examined . RESULTS Recruitment and data collection are ongoing ( currently N=655 ) . Preliminary cross-sectional data on 213 South Asian , 44 black African Caribbean and 70 white European children aged 6 - 7 years and 114 South Asian , 40 black African Caribbean and 115 white European children aged 12 - 13 years found myopia prevalence of 9.4 % and 29.4 % for the two age groups respectively . A more negative mean spherical equivalent refraction ( SER ) was observed in older children ( -0.21 D vs + 0.87 D ) . Ethnic differences in myopia prevalence are emerging with South Asian children having higher levels than white European children 36.8 % vs 18.6 % ( for the older children ) . Axial length , corneal radius of curvature and anterior chamber depth were normally distributed , while SER was leptokurtic ( p<0.001 ) with a slight negative skew . CONCLUSIONS The AES will allow ethnic differences in the ocular characteristics of children from a large metropolitan area of the UK to be examined . The findings to date indicate the emergence of higher levels of myopia by early adolescence in second and third generation British South Asians , compared to white European children . The continuation of the AES will allow the early determinants of these ethnic differences to be studied PURPOSE To assess the prevalence of refractive errors and vision impairment in school-age children in Shunyi District , northeast of Beijing , the Peoples Republic of China . METHODS R and om selection of village-based clusters was used to identify a sample of children 5 to 15 years of age . Resident registration books were used to enumerate eligible children in the selected villages and identify their current school . Ophthalmic examinations were conducted in 132 schools on children from 29 clusters during May 1988 to July 1998 , including visual acuity measurements , cycloplegic retinoscopy , cycloplegic autorefraction , ocular motility evaluation , and examination of the external eye , anterior segment , media , and fundus . Independent replicate measurements of all children with reduced vision and a sample of those with normal vision were done for quality assurance monitoring in three schools . RESULTS A total of 6,134 children from 4,338 households were enumerated , and 5,884 children ( 95.9 % ) were examined . The prevalence of uncorrected , presenting , and best visual acuity 0.5 ( 20/40 ) or worse in at least one eye was 12.8 % , 10.9 % , and 1.8 % , respectively ; 0.4 % had best visual acuity 0.5 or worse in both eyes . Refractive error was the cause in 89.5 % of the 1,236 eyes with reduced vision , amblyopia in 5 % , other causes in 1.5 % , with unexplained causes in the remaining 4 % . Myopia -0.5 diopter or less in either eye was essentially absent in 5-year-old children , but increased to 36.7 % in males and 55.0 % in females by age 15 . Over this same age range , hyperopia 2 diopters or greater decreased from 8.8 % in males and 19.6 % in females to less than 2 % in both . Females had a significantly higher risk of both myopia and hyperopia . CONCLUSIONS Reduced vision because of myopia is an important public health problem in school-age children in Shunyi District . More than 9 % of children could benefit from prescription glasses . Further studies are needed to determine whether the upward trend in the prevalence of myopia continues far beyond age 15 and whether the development of myopia is changing for more recent birth cohorts purpose To determine the age- and gender-specific prevalences of refractive errors in Tehran through a population -based study . methods A total of 6497 citizens representing a cross-section of the population of Tehran were sample d from 160 clusters using a stratified , r and om , cluster sampling strategy . Eligible people were enumerated through a door-to-door household survey in the selected clusters and were invited to participate . All participants were transferred to a clinic for an extensive eye examination and interview . Refractive error was determined using manifest and cycloplegic refraction . Myopia was defined as the spherical equivalent of −0.5 diopters ( D ) or more and hyperopia was defined as the spherical equivalent of more than + 0.5 D. results Of those sample d , 4565 ( 70.3 % ) people participated in the study . Refraction data for 4354 participants aged five years and over are presented . The age- and gender-st and ardized prevalence of myopia based on manifest refraction was 21.8 % ( 95 % confidence interval [ CI ] , 20.1 to 23.5 ) and that for hyperopia was 26.0 % ( 95 % CI , 24.5 to 27.6 ) . The prevalences based on cycloplegic refraction were 17.2 % ( 95 % CI , 15.6 to 18.8 ) and 56.6 % ( 95 % CI , 54.7 to 58.6 ) , respectively . Prevalences of myopia and hyperopia differed significantly among the age and gender groups ( P < 0.001 ) . Astigmatism of 0.75 cylinder diopter or greater was present in 29.6 % ( 95 % CI , 28.0 to 31.3 ) of right eyes with manifest refraction and in 30.3 % ( 95 % CI , 28.5 to 32.1 ) with cycloplegic refraction . Among the study population , 6.1 % ( 95 % CI , 5.3 to 6.8 % ) had anisometropia of 1 D or more . conclusions This report has provided details of the refractive status in the population . We have documented prevalences of myopia , hyperopia , astigmatism and anisometropia by age and gender , identifying more affected age- and gender-groups for prevention programs in the community Objective : This study investigated the distribution pattern of refractive status and prevalence of refractive errors in school-age children in Western China to determine the possible environmental factors . Methods : A r and om sampling strategy in geographically defined clusters was used to identify children aged 6 - 15 years in Yongchuan , a socio-economically representative area in Western China . We carried out a door-to-door survey and actual eye examinations , including visual acuity measurements , stereopsis examination , anterior segment and eyeball movements , fundus examinations , and cycloplegic retinoscopy with 1 % cyclopentolate . Results : A total of 3469 children living in 2552 households were selected , and 3070 were examined . The distributions of refractive status were positively-skewed for 6 - 8-year-olds , and negatively-skewed for 9 - 12 and 13 - 15-year-olds . The prevalence of hyperopia ( ≥+2.00 D spherical equivalent [ SE ] ) , myopia ( ≤-0.50 D SE ) , and astigmatism ( ≥1.00 diopter of cylinder [ DC ] ) were 3.26 % , 13.75 % , and 3.75 % , respectively . As children 's ages increased , the prevalence rate of hyperopia decreased ( P<0.001 ) and that of myopia increased significantly ( P<0.001 ) . Children in academically challenging schools had a higher risk of myopia ( P<0.001 ) and astigmatism ( ≥1.00DC , P = 0.04 ) than those in regular schools . Conclusion : The distribution of refractive status changes gradually from positively-skewed to negatively-skewed distributions as age increases , with 9-year-old being the critical age for the changes . Environmental factors and study intensity influence the occurrence and development of myopia OBJECTIVE To assess the relationship of near , midworking distance , and outdoor activities with prevalence of myopia in school-aged children . DESIGN Cross-sectional study of 2 age sample s from 51 Sydney schools , selected using a r and om cluster design . PARTICIPANTS One thous and seven hundred sixty-five 6-year-olds ( year 1 ) and 2367 12-year-olds ( year 7 ) participated in the Sydney Myopia Study from 2003 to 2005 . METHODS Children had a comprehensive eye examination , including cycloplegic refraction . Parents and children completed detailed question naires on activity . MAIN OUTCOME MEASURES Myopia prevalence and mean spherical equivalent ( SE ) in relation to patterns of near , midworking distance , and outdoor activities . Myopia was defined as SE refraction < or = -0.5 diopters ( D ) . RESULTS Higher levels of outdoor activity ( sport and leisure activities ) were associated with more hyperopic refractions and lower myopia prevalence in the 12-year-old students . Students who combined high levels of near work with low levels of outdoor activity had the least hyperopic mean refraction ( + 0.27 D ; 95 % confidence interval [ CI ] , 0.02 - 0.52 ) , whereas students who combined low levels of near work with high levels of outdoor activity had the most hyperopic mean refraction ( + 0.56 D ; 95 % CI , 0.38 - 0.75 ) . Significant protective associations with increased outdoor activity were seen for the lowest ( P = 0.04 ) and middle ( P = 0.02 ) tertiles of near-work activity . The lowest odds ratios for myopia , after adjusting for confounders , were found in groups reporting the highest levels of outdoor activity . There were no associations between indoor sport and myopia . No consistent associations between refraction and measures of activity were seen in the 6-year-old sample . CONCLUSIONS Higher levels of total time spent outdoors , rather than sport per se , were associated with less myopia and a more hyperopic mean refraction , after adjusting for near work , parental myopia , and ethnicity PURPOSE To report the biometry data of pediatric cataractous eyes ( r and omly selected single eye in bilateral cases ; cataractous eye in unilateral cases ) and to compare the biometry data of the unilateral cataractous eye with the data of the corresponding noncataractous fellow eye . METHODS The study was a chart review / analysis of immersion A-scan biometry measurements , excluding traumatic cataract or lens subluxation . RESULTS Three hundred ten eyes were examined at surgery . The mean age was 45.30 + /- 48.10 months ; globe axial length ( AL ) , 20.52 + /- 2.87 mm ; anterior chamber depth ( ACD ) , 3.29 + /- 0.60 mm ; and lens thickness ( LT ) , 3.62 + /- 0.86 mm . During the first 6 months of life , AL increased 0.62 mm/mo , 0.19 mm/mo from 6 to 18 months , and 0.01 mm/mo during 18 months to 18 years of age . The girls had shorter ALs than did the boys ( P = 0.090 ) , and the African-American subjects had longer ALs than did the Caucasians ( P < 0.001 ) . Eyes with unilateral cataract had shorter ALs than those with bilateral cataracts before 60 months of age , but had longer ALs than the eyes with bilateral cataracts after 60 months of age . Eyes of the female subjects had shallower ACDs than those of male subjects ( P = 0.026 ) . Eyes with unilateral cataract had shallower ACDs than those of eyes with bilateral cataracts ( P = 0.001 ) . In the children > 5 years of age , LT was significantly greater in eyes with unilateral cataract than in those with bilateral cataract . AL of the unilateral cataractous eye was significantly shorter than that of the fellow noncataractous eye before 6 months of age ( P = 0.001 ) . CONCLUSIONS This study begins to lay the groundwork for calculating pediatric IOL power in cataractous eyes by using pediatric ocular measurements PURPOSE To study the distribution of spherical equivalent refraction and ocular biometric parameters in a young Australian population . METHODS Noncontact methods were used to examine ocular dimensions and cycloplegic autorefraction in a stratified r and om cluster sample of year 1 Sydney school students ( n = 1765 ) , mean age 6.7 years ( range , 5.5 - 8.4 years ) . Repeated measures of axial length , anterior chamber depth , and greatest and least corneal radius of curvature ( CR1 , CR2 , respectively ) were taken in each eye . Refraction was measured as the spherical equivalent . RESULTS Mean spherical equivalent refraction in right eyes was + 1.26 + /- 0.03 D ( SEM ; range , -4.88 to + 8.58 ) . The distribution was peaked ( kurtosis 14.4 ) and slightly skewed to the right ( skewness , 1.7 ) . Prevalence of myopia , defined as spherical equivalent refraction < or = -0.5 D , was 1.43 % ( 95 % CI , 0.94 - 2.18 ) in the overall population . Axial length , anterior chamber depth , and corneal radii of curvature were normally distributed . The mean axial length in right eyes was 22.61 + /- 0.02 mm ( SEM ; range , 19.64 - 25.35 ) . The mean anterior chamber depth was 3.34 + /- 0.01 mm ( SEM ; range , 2.14 - 4.06 ) . Mean CR1 was 7.85 + /- 0.01 mm ( SEM ) and mean CR2 was 7.71 + /- 0.01 mm ( SEM ) . The distribution of axial length/mean corneal radius ratio was peaked ( leptokurtic ) with a mean of 2.906 . Mean axial length was longer , anterior chambers were deeper , and corneas were flatter in the boys . CONCLUSIONS A peaked ( leptokurtic ) distribution of spherical equivalent refraction was present in this predominantly hyperopic 6-year-old population . The results also showed that ocular biometric measures were normally distributed , with statistically significant gender differences found in measurements PURPOSE To assess the prevalence of refractive error and visual impairment in school-age children in Gombak District , a suburban area near Kuala Lumpur city . DESIGN Population -based , cross-sectional survey . PARTICIPANTS Four thous and six hundred thirty-four children 7 to 15 years of age living in 3004 households . METHODS R and om selection of geographically defined clusters was used to identify the study sample . Children in 34 clusters were enumerated through a door-to-door survey and examined in 140 schools between March and July 2003 . The examination included visual acuity measurements ; ocular motility evaluation ; retinoscopy and autorefraction under cycloplegia ; and examination of the external eye , anterior segment , media , and fundus . MAIN OUTCOME MEASURES Distance visual acuity and cycloplegic refraction . RESULTS The examined population was 70.3 % Malay , 16.5 % Chinese , 8.9 % Indian , and 4.3 % of other ethnicity . The prevalence of uncorrected ( unaided ) , presenting , and best-corrected visual impairment ( visual acuity < or = 20/40 in the better eye ) was 17.1 % , 10.1 % , and 1.4 % , respectively . More than half of those in need of corrective spectacles were without them . In eyes with reduced vision , refractive error was the cause in 87.0 % , amblyopia in 2.0 % , other causes in 0.6 % , and unexplained causes in 10.4 % , mainly suspected amblyopia . Myopia ( spherical equivalent of at least -0.50 diopter [ D ] in either eye ) measured with retinoscopy was present in 9.8 % of children 7 years of age , increasing to 34.4 % in 15-year-olds ; and in 10.0 % and 32.5 % , respectively , with autorefraction . Myopia was associated with older age , female gender , higher parental education , and Chinese ethnicity . Hyperopia ( > or = 2.00 D ) with retinoscopy varied from 3.8 % in 7-year-olds , 5.0 % with autorefraction , to less than 1 % by age 15 , with either measurement method . Hyperopia was associated with younger age and " other " ethnicity . Astigmatism ( > or = 0.75 D ) was present in 15.7 % of children with retinoscopy and in 21.3 % with autorefraction . CONCLUSIONS Visual impairment in school-age children in urban Gombak District is overwhelmingly caused by myopia , with a particularly high prevalence among children of Chinese ethnicity . Eye health education and screening may help address the unmet need for refractive correction PURPOSE To assess the prevalence of refractive error and related visual impairment in school-aged children in the rural population of the Mahabubnagar district in the southern Indian state of And hra Pradesh . METHODS R and om selection of village-based clusters was used to identify a sample of children 7 to 15 years of age . From April 2000 through February 2001 , children in the 25 selected clusters were enumerated in a door-to-door survey and examined at a rural eye center in the district . The examination included visual acuity measurements , ocular motility evaluation , retinoscopy and autorefraction under cycloplegia , and examination of the anterior segment , media , and fundus . Myopia was defined as spherical equivalent refractive error of at least -0.50 D and hyperopia as + 2.00 D or more . Children with reduced vision and a sample of those with normal vision underwent independent replicate examinations for quality assurance in seven clusters . RESULTS A total of 4414 children from 4876 households was enumerated , and 4074 ( 92.3 % ) were examined . The prevalence of uncorrected , baseline ( presenting ) , and best corrected visual acuity of 20/40 or worse in the better eye was 2.7 % , 2.6 % , and 0.78 % , respectively . Refractive error was the cause in 61 % of eyes with vision impairment , amblyopia in 12 % , other causes in 15 % , and unexplained causes in the remaining 13 % . A gradual shift toward less-positive values of refractive error occurred with increasing age in both boys and girls . Myopia in one or both eyes was present in 4.1 % of the children . Myopia risk was associated with female gender and having a father with a higher level of schooling . Higher risk of myopia in children of older age was of borderline statistical significance ( P = 0.069 ) . Hyperopia in at least one eye was present in 0.8 % of children , with no significant predictors . CONCLUSIONS Refractive error was the main cause of visual impairment in children aged between 7 and 15 years in rural India . There was a benefit of spectacles in 70 % of those who had visual acuity of 20/40 or worse in the better eye at baseline examination . Because visual impairment can have a significant impact on a child 's life in terms of education and development , it is important that effective strategies be developed to eliminate this easily treated cause of visual impairment PURPOSE To assess the prevalence of refractive error and related visual impairment in school-aged children in an urban population in New Delhi , India . METHODS R and om selection of geographically defined clusters was used to identify a sample of children 5 to 15 years of age . From December 2000 through March 2001 , children in 22 selected clusters were enumerated through a door-to-door survey and examined at a local facility . The examination included visual acuity measurements , ocular motility evaluation , retinoscopy and autorefraction under cycloplegia , and examination of the anterior segment , media , and fundus . Myopia was defined as spherical equivalent refractive error of at least -0.50 D and hyperopia as + 2.00 D or more . Children with reduced vision and a sample of those with normal vision underwent independent replicate examinations for quality assurance in four of the clusters . RESULTS A total of 7008 children from 3426 households were enumerated , and 6447 ( 92.0 % ) examined . The prevalence of uncorrected , baseline ( presenting ) , and best corrected visual acuity of 20/40 or worse in the better eye was 6.4 % , 4.9 % , and 0.81 % , respectively . Refractive error was the cause in 81.7 % of eyes with vision impairment , amblyopia in 4.4 % , retinal disorders in 4.7 % , other causes in 3.3 % , and unexplained causes in the remaining 5.9 % . There was an age-related shift in refractive error from hyperopia in young children ( 15.6 % in 5-year-olds ) toward myopia in older children ( 10.8 % in 15-year-olds ) . Overall , hyperopia was present in 7.7 % of children and myopia in 7.4 % . Hyperopia was associated with female gender . Myopia was more common in children of fathers with higher levels of education . CONCLUSIONS Reduced vision because of uncorrected refractive error is a major public health problem in urban school-aged children in India . Cost-effective strategies are needed to eliminate this easily treated cause of vision impairment PURPOSE To determine the prevalence of refractive errors among schoolchildren in Northeastern Iran by age and gender . METHODS Using multistage r and om cluster sampling , 2020 schoolchildren 6 - 17 years of age were selected for this cross-sectional study . The participants totalled 1551 ( response rate 76.8 % ) elementary and junior high school children ( 41.5 % boys and 58.5 % girls ) from the northeast of Iran . Cycloplegic autorefraction was used to determine refractive error . Myopia was defined as a spherical equivalent ( SE ) of -0.50 dioptre ( D ) or worse , hyperopia as a SE of + 2.00 D or more , and astigmatism as cylinder equal to or worse than -0.75 D. RESULTS The prevalence of uncorrected , habitual and optimal visual acuity of 6/12 ( 0.30 logMAR ) or worse in the better eye was 2.2 % , 1.0 % , and 0.2 % respectively . The prevalence rates of myopia , hyperopia and astigmatism were 4.3 % ( 95%CI : 3.3 - 5.3 ) , 5.4 % ( 95%CI : 4.3 - 6.5 ) and 11.5 % ( 95%CI : 9.9 - 13.1 ) respectively and were not related to gender . The prevalence of myopia and against-the-rule astigmatism increased significantly with age ( p < 0.0001 ) . The prevalence of hyperopia significantly decreased with age ( p < 0.0001 ) . CONCLUSIONS The prevalence of myopia in schoolchildren in Northeastern Iran is considerably lower than that of East Asian population s , but similar to many other population s , including South Africa , Chile and other countries of the Middle East . Whilst comparisons with other studies show that the prevalence of hyperopia and astigmatism in Northeastern Iran is higher than that of some countries , it is lower compared with others Purpose To examine the prevalence of refractive error and distribution of ocular biometric parameters among major ethnic groups in a population -based sample of 11–15-year-old Australian children . Methods The Sydney Myopia Study examined 2353 students ( 75.3 % response ) from a r and om cluster- sample of 21 secondary schools across Sydney . Examinations included cycloplegic autorefraction , and measures of corneal radius of curvature , anterior chamber depth , and axial length . Results Participants mean age was 12.7 years ( range 11.1–14.4 ) ; 49.4 % were female . Overall , 60.0 % of children had European Caucasian ethnicity , 15.0 % East Asian , 7.1 % Middle Eastern , and 5.5 % South Asian . The most frequent refractive error was mild hyperopia ( 59.4 % , 95 % confidence interval ( CI ) , 53.2–65.6 ) , defined as spherical equivalent ( SE ) + 0.50 to + 1.99 D. Myopia ( SE−0.50 D or less ) was found in 11.9 % , 95 % ( CI 6.6–17.2 ) , and moderate hyperopia ( SE⩾+2.00 D ) in 3.5 % , 95 % ( CI 2.8–4.1 ) . Myopia prevalence was lower among European Caucasian children ( 4.6 % , 95 % CI 3.1–6.1 ) and Middle Eastern children ( 6.1 % , 95 % CI 1.3–11.0 ) than among East Asian ( 39.5 % , 95 % , CI 25.6–53.5 ) and South Asian ( 31.5 % , 95 % , CI 21.6–41.4 ) children . European Caucasian children had the most hyperopic mean SE ( + 0.82 D ) and shortest mean axial length ( 23.23 mm ) . East Asian children had the most myopic mean SE ( −0.69 D ) and greatest mean axial length ( 23.86 mm ) . Conclusion The overall myopia prevalence in this sample was lower than in recent similar-aged European Caucasian population sample s. East Asian children in our sample had both a higher prevalence of myopia and longer mean axial length PURPOSE To assess the prevalence of refractive error and vision impairment in school age children in the terai area of the Mechi zone in Eastern Nepal . METHODS R and om selection of village-based clusters was used to identify a sample of children 5 to 15 years of age . Children in the 25 selected clusters were enumerated through a door-to-door household survey and invited to village sites for examination . Visual acuity measurements , cycloplegic retinoscopy , cycloplegic autorefraction , ocular motility evaluation , and anterior segment , media , and fundus examinations were done from May 1998 through July 1998 . Independent replicate examinations for quality assurance monitoring took place in all children with reduced vision and in a sample of those with normal vision in seven villages . RESULTS A total of 5,526 children from 3,724 households were enumerated , and 5,067 children ( 91.7 % ) were examined . The prevalence of uncorrected , presenting , and best visual acuity 0.5 ( 20/40 ) or worse in at least one eye was 2.9 % , 2.8 % , and 1.4 % , respectively ; 0.4 % had best visual acuity 0.5 or worse in both eyes . Refractive error was the cause in 56 % of the 200 eyes with reduced uncorrected vision , amblyopia in 9 % , other causes in 19 % , with unexplained causes in the remaining 16 % . Myopia -0.5 diopter or less in either eye or hyperopia 2 diopters or greater was observed in less than 3 % of children . Hyperopia risk was associated with female gender and myopia risk with older age . CONCLUSIONS The prevalence of reduced vision is very low in school-age children in Nepal , most of it because of correctable refractive error . Further studies are needed to determine whether the prevalence of myopia will be higher for more recent birth cohorts PURPOSE In order to underst and and up date the prevalence of myopia in Taiwan , a nationwide survey was performed in 1995 . METHODS We stratified the cluster sampling by developmental grading of the city , using a size proportional to the population . Two cities were r and omly selected from each city grading . The total number of students enrolled was 11,178 , including 5,676 boys and 5,502 girls . The refractive status and corneal radius of each student were measured with an autorefractometer under cycloplegia and checked with retinoscopy . Axial length was measured with biometric ultrasound . RESULTS The myopic rate was from 12 % at the age of 6 , it increased to 56 % at the age of 12 , and then to 76 % at the age of 15 . A myopic rate of 84 % was found for the age range of 16 to 18 . The prevalence of high myopia ( over -6.0 D ) at the age of 18 was 20 % in girls and 12 % in boys . The mean refractive status became myopic at the age of 9 , then increased to -3.92 D in girls and -2.71 D in boys at the age of 18 . The increase of axial length is correspondent with the progression of myopia . The anterior chamber depth ( ACD ) was deeper with age and the severity of myopia , whereas the corneal curvature remained unchanged . The lens thickness became thinner from age 7 to 13 , then it became thicker with age and the severity of myopia after age 15 . The prevalence and degree of myopia in girls was more severe than in boys . CONCLUSIONS The prevalence of myopia in Taiwan increased year by year . The increase in severity and prevalence of high myopia may be due to earlier onset PURPOSE To assess the prevalence of refractive error and visual impairment in school-aged African children in South Africa . METHODS R and om selection of geographically defined clusters was used to identify a sample of children 5 to 15 years of age in the Durban area . From January to August 2002 , children in 35 clusters were enumerated through a door-to-door survey and examined in temporary facilities . The examination included visual acuity measurements , ocular motility evaluation , retinoscopy and autorefraction under cycloplegia , and examination of the anterior segment , media , and fundus . In nine clusters , children with reduced vision and a sample of those with normal vision underwent independent replicate examinations for quality assurance . RESULTS A total of 5599 children living in 2712 households were enumerated , and 4890 ( 87.3 % ) were examined . The prevalence of uncorrected , presenting , and best-corrected visual acuity of 20/40 or worse in the better eye was 1.4 % , 1.2 % , and 0.32 % , respectively . Refractive error was the cause in 63.6 % of the 191 eyes with reduced vision , amblyopia in 7.3 % , retinal disorders in 9.9 % , corneal opacity in 3.7 % , other causes in 3.1 % , and unexplained causes in the remaining 12.0 % . Exterior and anterior segment abnormalities were observed in 528 ( 10.8 % ) children , mainly corneal and conjunctival . Myopia ( at least -0.50 D ) in one or both eyes was present in 2.9 % of children when measured with retinoscopy and in 4.0 % measured with autorefraction . Beginning with an upward trend at age 14 , myopia prevalence with autorefraction reached 9.6 % at age 15 . Myopia was also associated with increased parental education . Hyperopia ( + 2.00 D or more ) in at least one eye was present in 1.8 % of children when measured with retinoscopy and in 2.6 % measured with autorefraction , with no significant predictors of hyperopia risk . CONCLUSIONS The prevalence of reduced vision is low in school-age African children , most of it because of uncorrected refractive error . The high prevalence of corneal and other anterior segment abnormalities is a reflection of the inadequacy of primary eye care services in this area OBJECTIVE Vientiane Province is an urbanizing region in Southeast Asia . We aim ed to determine the prevalence of refractive error and visual impairment in primary school-aged children in this region . DESIGN Prospect i ve , cross-sectional survey . PARTICIPANTS A total of 2899 schoolchildren from Vientiane Province , Lao People 's Democratic Republic ( Lao PDR ) . METHODS Ten districts from Vientiane were r and omly selected and 2 primary schools were r and omly selected from each district . All children aged 6 to 11 years at selected schools were eligible to participate . The examination included visual acuity ( VA ) testing , cycloplegic retinoscopy with subjective refinement if indicated , ocular motility testing , and anterior segment and fundus examinations in visually impaired children . MAIN OUTCOME MEASURES Cycloplegic refraction and VA . RESULTS There was an estimated total of 3330 children who were eligible to participate , and data were recorded from 2899 ( 87 % ) of these children . Complete refractive data were available on 2842 children ( 85 % of eligible population ) . The mean spherical equivalent ( SE ) in the right eyes was + 0.60 diopter ( D ) ( 95 % confidence interval [ CI ] , 0.49 - 0.72 ) , and the mean SE in the left eyes was + 0.59 ( 95 % CI , 0.50 - 0.68 ) . The prevalence of hyperopia was 2.8 % ( 95 % CI , 1.9 - 3.7 ; 88 subjects ) , and the prevalence of myopia was 0.8 % ( 95 % CI , 0.3 - 1.4 ; 24 subjects ) . The majority of children ( 98 % ; 95 % CI , 97.0 - 99.0 ) had normal unaided binocular VA ( at least 20/32 in their better eye ) . The overall prevalence of any visual impairment ( presenting VA < 20/32 in the better eye ) was 1.9 % ( 95 % CI , 1.0 - 2.9 ; 55 subjects ) . In multivariate logistic regression analysis , age ( P = 0.001 ) was a significant predictor , and female gender ( P = 0.08 ) and Yao ethnicity ( P = 0.09 ) were borderline significant predictors of the presence of any visual impairment . CONCLUSIONS Visual impairment is not a public health concern in this primary school-aged population ; however , visually impaired children in the community were not studied . From this baseline , future surveys could determine the effect of increasing urbanization on myopia prevalence in this population Aim : To determine the trend in the prevalence of hyperopia in Tehran , Iran . Methods : Using a stratified r and om cluster sample of the population of Tehran , all participants 5 years of age and older were studied with cycloplegic autorefraction 30 min after instilling two drops of cyclopentolate 1 % . Prevalence rates of cycloplegic hyperopia for different cut points were determined , stratified by age . Results : The prevalence rates of hyperopia as a spherical equivalent equal to or more than + 0.5 , + 1.0 , + 2.0 and + 3.0 D were 56.6 % , 28.1 % , 6.3 % and 2.2 % , respectively . With all these definitions , the prevalence of cycloplegic hyperopia reached a minimum in the 25–35-year age group , and then significantly increased until the age of 70 . Multivariable regression analysis with variables such as age , gender , diabetes and cataract showed that only age was significantly correlated with hyperopia . Conclusions : Although an age-cohort effect can not be ruled out , these results provide the first population -based evidence of increasing hyperopia with age using cycloplegic refraction . The results obtained suggest that the contribution of decreasing accommodation to observed hyperopic shifts in distance refraction in longitudinal studies is small , raising the question of the underlying causes of the hyperopic shift in refraction with age PURPOSE To assess the prevalence of refractive errors and vision impairment in school-age children in a suburban area ( La Florida ) of Santiago , Chile . METHODS R and om selection of geographically defined clusters was used to identify a representative sample of children 5 to 15 years of age . Children in the 26 selected clusters were enumerated through a door-to-door survey and invited to report to a community health clinic for examination . Visual acuity measurements , cycloplegic retinoscopy , cycloplegic autorefraction , ocular motility evaluation , and examination of the external eye , anterior segment , media , and fundus were done from April through August 1998 . Independent replicate examinations of all children with reduced vision and a sample of those with normal vision were done for quality assurance monitoring in six clusters . RESULTS A total of 6,998 children from 3,830 households were enumerated , and 5,303 children ( 75.8 % ) were examined . The prevalence of uncorrected , presenting , and best visual acuity 0.50 ( 20/40 ) or worse in at least one eye was 15.8 % , 14.7 % , and 7.4 % , respectively ; 3.3 % had best visual acuity 0.50 or worse in both eyes . Refractive error was the cause in 56.3 % of the 1,285 eyes with reduced vision , amblyopia in 6.5 % , other causes in 4.3 % , with unexplained causes in the remaining 32.9 % . Myopia -0.50 diopter or less in either eye was present in 3.4 % of 5-year-old children , increasing to 19.4 % in males and 14.7 % in females by age 15 . Over this same age range , hyperopia 2.00 diopters or greater decreased from 22.7 % to 7.1 % in males and from 26.3 % to 8.9 % in females . Females had a significantly higher risk of hyperopia than males . CONCLUSIONS Refractive error , associated primarily with myopia , is a major cause of reduced vision in school-age children in La Florida . More than 7 % of children could benefit from the provision of proper spectacles . Efforts are needed to make existing programs that provide free spectacles for school children more effective . Further studies are needed to determine whether the upward trend in myopia continues far beyond 15 years of age Aim : To determine the prevalence of refractive errors among schoolchildren in urban and rural areas of Dezful County , Iran . Methods : In a cross-sectional study , using r and om cluster sampling , 5721 Dezful schoolchildren were selected from 39 clusters . The participants in the study totalled 5544 ; 3673 elementary and middle school students and 1871 high school students . For the former group , cycloplegic refraction and for the latter , non-cycloplegic refraction was tested . In all participants , uncorrected visual acuity and best corrected visual acuity were determined , and those with a visual acuity of 20/40 or worse , underwent a complete ophthalmic examination to determine the cause of visual impairment . A spherical equivalent of −0.5 diopter ( D ) or worse was defined as myopia , + 2.0 D or more was defined as hyperopia , and a cylinder refraction greater than 0.75 D was considered astigmatism . Results : The uncorrected visual acuity was 20/40 or worse in the better eye of 224 schoolchildren ( 3.8 % of participants ) . This figure ( percentage ) was 14 ( 0.03 % ) based on their best corrected visual acuity and 96 ( 1.7 % ) with their presenting vision . According to results of cycloplegic refraction , 3.4 % ( 95 % confidence interval ( CI ) , 2.5 to 4.4 ) of the primary and middle school students were myopic and 16.6 % ( 95 % CI , 13.6 to 19.7 ) were hyperopic . For high school students , these rates were 2.1 % ( 95 % CI , 0.7 to 3.5 ) and 33.0 % ( 95 % CI , 24.9 to 41.1 ) , respectively , with non-cycloplegic refraction . In the multivariate logistic regression for primary and middle school students , myopia was correlated with age ( p = 0.030 ) , and hyperopia was correlated with age ( p<0.001 ) and area of residence ( p = 0.007 ) . In high school students , hyperopia again showed a correlation with their area of residence ( p = 0.029 ) . Conclusion : The present study reveals the considerable prevalence rates of refractive errors among schoolchildren in Dezful County and the high rate of an unmet need for their correction . Although myopia is not very prevalent , the high rate of hyperopia in the studied population emphasises its need for attention PURPOSE The Refractive Error Study in Children was design ed to assess the prevalence of refractive error and vision impairment in children of different ethnic origins and cultural setting s. METHODS Population -based cross-sectional sample s of children 5 to 15 years of age were obtained through cluster sampling . Presenting , uncorrected , and best-corrected visual acuity , along with refractive error under cycloplegia , were the main outcome measures . Amblyopia and other causes of uncorrectable vision impairment were determined . RESULTS Study design and sample size calculations , survey enumeration and ophthalmic examination methods , quality assurance monitoring , and da ta analyses and statistical methods are described . CONCLUSIONS The study design , sample size , and measurement methods ensure that the prevalence of age-specific and sex-specific refractive error can be estimated with reasonable accuracy in the target population s. With commonality of methods , a comparison of findings between studies in different ethnic origins and cultural setting s is possible AIMS To characterize ophthalmological findings in a sample of Swedish children aged 4 - 15 years . METHODS A prospect i ve cross-sectional comprehensive ophthalmological investigation was performed on a sample of 143 children ( 67 girls , 76 boys ) aged 4 - 15 years . RESULTS Visual acuity ( VA ) in the better eye > or=1.0 ( < or=0.0 logMAR ) was found in 79 % of subjects . None of the children had VA in the better eye < 0.5 ( > 0.3 logMAR ) . Amblyopia was found in 0.7 % of subjects . A total of 68 % of the children had no refractive errors . Hyperopia ( > or=2.0 dioptres [ D ] in spherical equivalent [ SE ] ) was found in 9 % and myopia ( > or=0.5 D SE ) in 6 % of children . Astigmatism ( > or=0.75 D ) was recorded in 22 % and anisometropia ( > or=1.0 D SE ) in 3 % . A total of 8 % were optically corrected . Strabismus was recorded in 3.5 % . Signs of visuoperceptual problems were reported in 3 % of the children . CONCLUSION This sample of Swedish children may serve as a comparison group regarding ophthalmological findings in children aged 4 - 15 years Aim : To compare the prevalences of refractive errors in Malay , Chinese and Indian children in Malaysia and Singapore . Methods : Children aged 7–9 years from three schools in the Singapore Cohort study of the Risk factors for Myopia ( n = 1962 ) and similarly aged children from a r and om cluster sample in the metropolitan Kuala Lumpur area in the Malaysia Refractive Error Study in Children ( n = 1752 ) were compared . Cycloplegic autorefraction was conducted in both countries . Results : The prevalence of myopia ( spherical equivalent of at least −0.5 diopters ( D ) in either eye ) was higher in Singapore Malays ( 22.1 % ) than in Malays in Malaysia ( 9.2 % ; 95 % confidence interval ( CI ) 11.2 to 14.7 ; p<0.001 ) . Similarly , Singapore Chinese ( 40.1 % ) had higher prevalences than Malaysian Chinese ( 30.9 % ; 95 % CI 1.5 to 16.9 ) . Singapore Indians had a higher prevalence ( 34.1 % ) than Malaysian Indians ( 12.5 % ; 95 % CI 17.4 to 25.9 ) . The multivariate odds ratio of astigmatism ( cylinder at least 0.75 D in either eye ) in Singapore Malays compared with Malaysian Malays was 3.47 ( 95 % CI 2.79 to 4.32 ) . Ethnicity-specific hyperopia rates did not differ in Singapore and Malaysia . Conclusion : The ethnicity-specific prevalences of myopia in Singapore Malays , Chinese and Indians are higher than those in Malaysian Malays , Chinese and Indians . As Malays , Chinese and Indians in Malaysia have genetic make-up similar to that of Malays , Chinese and Indians in Singapore , environmental factors may contribute to the higher myopia rates Purpose : To assess the prevalence of refractive error in schoolchildren aged 12–14 years in urban and rural setting s in Cambodia ’s Phnom Penh and K and al provinces . Methods : Ten schools from Phnom Penh Province and 26 schools from K and al Province were r and omly selected and surveyed in October 2010 . Children were examined by teams of Australian and Cambodian optometrists , ophthalmic nurses and ophthalmologists who performed visual acuity ( VA ) testing and cycloplegic refraction . Results : A total of 5527 children were included in the study . The prevalence of uncorrected , presenting and best-corrected VA ≤ 6/12 in the better eye were 2.48 % ( 95 % confidence interval [ CI ] 2.02–2.83 % ) , 1.90 % ( 95 % CI 1.52–2.24 % ) and 0.36 % ( 95 % CI 0.20–0.52 % ) , respectively ; 43 children presented with glasses whilst a total of 315 glasses were dispensed . The total prevalence of refractive error was 6.57 % ( 95 % CI 5.91–7.22 % ) , but there was a significant difference between urban ( 13.7 % , 95 % CI 12.2–15.2 % ) and rural ( 2.5 % , 95 % CI 2.03–3.07 % ) schools ( P < 0.0001 ) . Refractive error accounted for 91.2 % of visually impaired eyes , cataract for 1.7 % , and other causes for 7.1 % . Myopia ( spherical equivalent ≤ −0.50 diopters [ D ] in either eye ) was associated with increased age , female gender and urban schooling . Conclusions : The prevalence of refractive error was significantly higher in urban Phnom Penh schools than rural schools in K and al Province . The prevalence of refractive error , particularly myopia was relatively low compared to previous reports in Asia . The majority of children did not have appropriate correction with spectacles , highlighting the need for more effective screening and optical intervention PURPOSE To assess the prevalence of refractive error and visual impairment in school children in a rural area of southern China . DESIGN Prospect i ve cross-sectional survey . PARTICIPANTS Two thous and four hundred children from junior high schools in Yangxi County . METHODS R and om selection of classes from the 3 junior high school grade levels was used to identify the study sample . Children from 36 classes in 13 schools were examined in April 2005 . The examination included visual acuity ( VA ) testing ; ocular motility evaluation ; cycloplegic autorefraction ; and examination of the external eye , anterior segment , media , and fundus . MAIN OUTCOME MEASURES Distance VA and cycloplegic refraction . RESULTS Among 2515 enumerated children , 2454 ( 97.6 % ) were examined . The study population consisted of the 2400 children between 13 and 17 years old . Prevalences of uncorrected , presenting , and best-corrected VA < or = 20/40 in the better eye were 27.0 % , 16.6 % , and 0.46 % , respectively . Sixty percent of those who could achieve acuity > or = 20/32 in at least one eye with best correction were without the necessary spectacles . Refractive error was the cause in 97.1 % of eyes with reduced vision ; amblyopia , 0.81 % ; other causes , 0.67 % ; and unexplained causes , 1.4 % . Myopia ( spherical equivalent , -0.50 diopters [ D ] or more in either eye ) affected 36.8 % of 13-year-olds , increasing to 53.9 % of 17-year-olds . Myopia was associated with higher grade level , female gender , schooling in the county urban center , and higher parental education . Hyperopia ( + 2.00 D or more ) affected approximately 1.0 % in all age groups . Astigmatism ( > or = 0.75 D ) was present in 25.3 % of all children . CONCLUSIONS Reduced vision because of uncorrected myopia is a public health problem among school-age children in rural China . Effective VA screening strategies are needed to eliminate this easily treated cause of visual impairment PURPOSE To assess the prevalence of refractive error and visual impairment in school-age children in a metropolitan area of southern China . METHODS R and om selection of geographically defined clusters was used to identify children 5 to 15 years of age in Guangzhou . Children in 22 clusters were enumerated through a door-to-door survey and examined in 71 schools and 19 community facilities from October 2002 to January 2003 . The examination included visual acuity measurements , ocular motility evaluation , retinoscopy , and autorefraction under cycloplegia and examination of the external eye , anterior segment , media , and fundus . RESULTS A total of 5053 children living in 4814 households were enumerated , and 4364 ( 86.4 % ) were examined . The prevalence of uncorrected , presenting , and best-corrected visual acuity 20/40 or worse in the better eye was 22.3 % , 10.3 % , and 0.62 % , respectively . Refractive error was the cause in 94.9 % of the 2335 eyes with reduced vision , amblyopia in 1.9 % , other causes in 0.4 % , and unexplained causes in the remaining 2.8 % . External and anterior segment abnormalities were seen in 1496 ( 34.3 % ) children , mainly minor conjunctival abnormalities . Media and fundus abnormalities were observed in 32 ( 0.73 % ) children . Myopia ( spherical equivalent of at least -0.50 D in either eye ) measured with retinoscopy affected 73.1 % of children 15 years of age , 78.4 % with autorefraction . The prevalence of myopia was 3.3 % in 5-year-olds with retinoscopy and 5.7 % with autorefraction . Females had a significantly higher risk of myopia . Hyperopia ( + 2.00 D or more ) measured with retinoscopy was present in 16.7 % of 5-year-olds , 17.0 % with autorefraction . The prevalence of hyperopia was below 1 % in 15-year-olds , with both methods . Astigmatism ( cylinder of > or = 0.75 D ) was present in 33.6 % of children with retinoscopy and in 42.7 % with autorefraction . CONCLUSIONS The prevalence of reduced vision because of myopia is high in school-age children living in metropolitan Guangzhou , representing an important public health problem . One third of these children do not have the necessary corrective spectacles . Effective strategies are needed to eliminate this easily treated cause of significant visual impairment |
13,205 | 29,637,593 | Haloperidol appeared less efficacious than nearly all comparators .
Most treatments had noninferior treatment continuation compared to placebo , except oxcarbazepine , which was inferior .
CONCLUSIONS Risperidone , serotonin reuptake inhibitors as a class and dextromethorphan/quinidine demonstrated evidence of efficacy for agitation in dementia , although findings for dextromethorphan/quinidine were based on a single RCT .
Our findings do not support prescribing haloperidol due to lack of efficacy , or oxcarbazepine due to lack of acceptability . | AIMS To determine the most efficacious and acceptable treatments of agitation in dementia . | OBJECTIVES The objectives of this study were to evaluate the efficacy , safety , and tolerability of quetiapine for treating psychosis in patients with probable/possible Alzheimer disease and assess its impact on other psychopathology and social and daily functioning . METHOD The authors conducted a multicenter , double-blind , placebo-controlled , r and omized trial of flexibly dosed quetiapine and haloperidol . Primary outcomes were change in total Brief Psychiatric Rating Scale ( BPRS ) and Clinical Global Impressions-Severity of Illness ( CGI-S ) scores at week 10 . Secondary outcomes included BPRS factors , Neuropsychiatric Inventory ( NPI ) , Multidimensional Observation Scale for Elderly Subjects ( MOSES ) , and Physical Self-Maintenance Scale ( PSMS ) . RESULTS Two hundred eighty-four participants ( mean age : 83.2 years ) were r and omized ; 63.4 % completed ; and mean Mini-Mental State Examination score was 12.8 . Median of the mean daily dose was 96.9 mg for quetiapine and 1.9 mg for haloperidol . No differential benefit was seen on any psychosis measure . BPRS agitation factor scores improved with quetiapine versus placebo and not quetiapine versus haloperidol . BPRS anergia scores worsened with haloperidol versus quetiapine but not quetiapine versus placebo . No NPI factors showed change , including the agitation factor . MOSES Withdrawal Subscale and PSMS total scores worsened with haloperidol versus quetiapine . Somnolence occurred in 25.3 % , 36.2 % , and 4.1 % of the quetiapine , haloperidol , and placebo groups , respectively ; parkinsonism was most prevalent in the haloperidol group ; other safety and tolerability measures differed little among groups . CONCLUSION All treatment groups showed improvement in measures of psychosis without significant differences between them when planned comparisons were performed . Participants treated with quetiapine or haloperidol showed inconsistent evidence of improvement in agitation . Tolerability was better with quetiapine compared with haloperidol SETTING Treating elderly patients with Alzheimer 's disease ( AD ) and behavioral and psychological symptoms of dementia ( BPSD ) is challenging due to the increased risk of iatrogenic movement disorders with old neuroleptics and the seemingly increasing risk of cardiovascular events with newer atypical agents . Quetiapine is an atypical antipsychotic agent that warrants further investigation . OBJECTIVES To assess tolerability , safety , and clinical benefit of quetiapine in AD patients with BPSD . PARTICIPANTS AND DESIGN AD patients with BPSD participated in a 6-week r and omized , double-blind , placebo-controlled trial . Quetiapine was increased on the basis of clinical response and tolerability . Primary efficacy assessment s included the Neuropsychiatric Inventory ( NPI ) and Clinical Global Impression of Change ( CGI-C ) . Secondary efficacy measures included the Mini-Mental State Examination ( MMSE ) , the Simpson-Angus Scale ( SAS ) and the Abnormal Involuntary Movement Scale ( AIMS ) . RESULTS Forty patients ( 26 women ) , mean age 82.2 ( SD 6.4 ) years were enrolled , 27 completed treatment . Median dose of quetiapine was 200 mg/day . Significant NPI total scores reductions ( 79 % for placebo and 68.5 % for quetiapine ) were observed . The CGI-C score decreased significantly in the quetiapine group ( p = 0.009 at 6 weeks ) and did not change significantly in the placebo group ( p = 0.48 ) . The MMSE , AIMS , SAS scores and adverse events did not differ significantly between the two arms . CONCLUSIONS Quetiapine did not significantly improve psychosis scores . It did not cause cognitive and motor deterioration . These results might possibly be due to small sample size OBJECTIVE To compare citalopram and risperidone for the treatment of psychotic symptoms and agitation associated with dementia , with a priori hypotheses that risperidone would be more efficacious for psychosis and citalopram for agitation . METHODS A 12-week r and omized , controlled trial in nondepressed patients with dementia hospitalized because of behavioral symptoms ( N = 103 ) was conducted at the University of Pittsburgh Medical Center . Participants were consecutively recruited on an inpatient unit if they had at least one moderate to severe target symptom ( aggression , agitation , hostility , suspiciousness , hallucinations , or delusions ) . Once they improved sufficiently , they were discharged to nursing homes , personal care homes , or residential homes for continued treatment . Planned pre-post and mixed model analyses of the main outcome measures of Neurobehavioral Rating Scale and Side Effect Rating Scale at baseline and at weekly/biweekly intervals were conducted . RESULTS Completion rates did not differ for citalopram and risperidone ( overall completion rate : 44 % ) . Agitation symptoms ( aggression , agitation , or hostility ) and psychotic symptoms ( suspiciousness , hallucinations , or delusions ) decreased in both treatment groups but the improvement did not differ significantly between the two groups . There was a significant increase in side effect burden with risperidone but not with citalopram such that the two groups differed significantly . CONCLUSION No statistical difference was found in the efficacy of citalopram and risperidone for the treatment of either agitation or psychotic symptoms in patients with dementia . These findings need to be replicated before citalopram or other serotonergic antidepressants can be recommended as alternatives to antipsychotics for the treatment of agitation or psychotic symptoms associated with dementia Yokukansan ( YKS ) , a traditional herbal medicine , has been used to treat behavioral and psychological symptoms of dementia ( BPSD ) . The present study is the first double‐blind , r and omized , placebo‐controlled trial to determine the efficacy and safety of YKS for the treatment of BPSD in Alzheimer 's disease ( AD ) Background Agitation in Alzheimer ’s disease ( AD ) is common and associated with poor patient life- quality and carer distress . The best evidence -based pharmacological treatments are antipsychotics which have limited benefits with increased morbidity and mortality . There are no memantine trials in clinical ly significant agitation but post-hoc analyses in other population s found reduced agitation . We tested the primary hypothesis , memantine is superior to placebo for clinical ly significant agitation , in patients with moderate-to-severe AD . Methods and Findings We recruited 153 participants with AD and clinical ly significant agitation from care-homes or hospitals for a double-blind r and omised-controlled trial and 149 people started the trial of memantine versus placebo . The primary outcome was 6 weeks mixed model autoregressive analysis of Cohen-Mansfield Agitation Inventory ( CMAI ) . Secondary outcomes were : 12 weeks CMAI ; 6 and 12 weeks Neuropsychiatric symptoms ( NPI ) , Clinical Global Impression Change ( CGI-C ) , St and ardised Mini Mental State Examination , Severe Impairment Battery . Using a mixed effects model we found no significant differences in the primary outcome , 6 weeks CMAI , between memantine and placebo ( memantine lower −3.0 ; −8.3 to 2.2 , p = 0.26 ) ; or 12 weeks CMAI ; or CGI-C or adverse events at 6 or 12 weeks . NPI mean difference favoured memantine at weeks 6 ( −6.9 ; −12.2 to −1.6 ; p = 0.012 ) and 12 ( −9.6 ; −15.0 to −4.3 p = 0.0005 ) . Memantine was significantly better than placebo for cognition . The main study limitation is that it still remains to be determined whether memantine has a role in milder agitation in AD . Conclusions Memantine did not improve significant agitation in people with in moderate-to-severe AD . Future studies are urgently needed to test other pharmacological c and i date s in this group and memantine for neuropsychiatric symptoms . Trial Registration Clinical Trials.gov NCT00371059 Trial Registration International St and ard R and omised Controlled Trial BACKGROUND Second-generation ( atypical ) antipsychotic drugs are widely used to treat psychosis , aggression , and agitation in patients with Alzheimer 's disease , but their benefits are uncertain and concerns about safety have emerged . We assessed the effectiveness of atypical antipsychotic drugs in out patients with Alzheimer 's disease . METHODS In this 42-site , double-blind , placebo-controlled trial , 421 out patients with Alzheimer 's disease and psychosis , aggression , or agitation were r and omly assigned to receive olanzapine ( mean dose , 5.5 mg per day ) , quetiapine ( mean dose , 56.5 mg per day ) , risperidone ( mean dose , 1.0 mg per day ) , or placebo . Doses were adjusted as needed , and patients were followed for up to 36 weeks . The main outcomes were the time from initial treatment to the discontinuation of treatment for any reason and the number of patients with at least minimal improvement on the Clinical Global Impression of Change ( CGIC ) scale at 12 weeks . RESULTS There were no significant differences among treatments with regard to the time to the discontinuation of treatment for any reason : olanzapine ( median , 8.1 weeks ) , quetiapine ( median , 5.3 weeks ) , risperidone ( median , 7.4 weeks ) , and placebo ( median , 8.0 weeks ) ( P=0.52 ) . The median time to the discontinuation of treatment due to a lack of efficacy favored olanzapine ( 22.1 weeks ) and risperidone ( 26.7 weeks ) as compared with quetiapine ( 9.1 weeks ) and placebo ( 9.0 weeks ) ( P=0.002 ) . The time to the discontinuation of treatment due to adverse events or intolerability favored placebo . Overall , 24 % of patients who received olanzapine , 16 % of patients who received quetiapine , 18 % of patients who received risperidone , and 5 % of patients who received placebo discontinued their assigned treatment owing to intolerability ( P=0.009 ) . No significant differences were noted among the groups with regard to improvement on the CGIC scale . Improvement was observed in 32 % of patients assigned to olanzapine , 26 % of patients assigned to quetiapine , 29 % of patients assigned to risperidone , and 21 % of patients assigned to placebo ( P=0.22 ) . CONCLUSIONS Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis , aggression , or agitation in patients with Alzheimer 's disease . ( Clinical Trials.gov number , NCT00015548 [ Clinical Trials.gov ] . ) CONTEXT Cognitive decline , mood , behavioral and sleep disturbances , and limitations of activities of daily living commonly burden elderly patients with dementia and their caregivers . Circadian rhythm disturbances have been associated with these symptoms . OBJECTIVE To determine whether the progression of cognitive and noncognitive symptoms may be ameliorated by individual or combined long-term application of the 2 major synchronizers of the circadian timing system : bright light and melatonin . DESIGN , SETTING , AND PARTICIPANTS A long-term , double-blind , placebo-controlled , 2 x 2 factorial r and omized trial performed from 1999 to 2004 with 189 residents of 12 group care facilities in the Netherl and s ; mean ( SD ) age , 85.8 ( 5.5 ) years ; 90 % were female and 87 % had dementia . INTERVENTIONS R and om assignment by facility to long-term daily treatment with whole-day bright ( + /- 1000 lux ) or dim ( + /- 300 lux ) light and by participant to evening melatonin ( 2.5 mg ) or placebo for a mean ( SD ) of 15 ( 12 ) months ( maximum period of 3.5 years ) . MAIN OUTCOME MEASURES St and ardized scales for cognitive and noncognitive symptoms , limitations of activities of daily living , and adverse effects assessed every 6 months . RESULTS Light attenuated cognitive deterioration by a mean of 0.9 points ( 95 % confidence interval [ CI ] , 0.04 - 1.71 ) on the Mini-Mental State Examination or a relative 5 % . Light also ameliorated depressive symptoms by 1.5 points ( 95 % CI , 0.24 - 2.70 ) on the Cornell Scale for Depression in Dementia or a relative 19 % , and attenuated the increase in functional limitations over time by 1.8 points per year ( 95 % CI , 0.61 - 2.92 ) on the nurse-informant activities of daily living scale or a relative 53 % difference . Melatonin shortened sleep onset latency by 8.2 minutes ( 95 % CI , 1.08 - 15.38 ) or 19 % and increased sleep duration by 27 minutes ( 95 % CI , 9 - 46 ) or 6 % . However , melatonin adversely affected scores on the Philadelphia Geriatric Centre Affect Rating Scale , both for positive affect ( -0.5 points ; 95 % CI , -0.10 to -1.00 ) and negative affect ( 0.8 points ; 95 % CI , 0.20 - 1.44 ) . Melatonin also increased withdrawn behavior by 1.02 points ( 95 % CI , 0.18 - 1.86 ) on the Multi Observational Scale for Elderly Subjects scale , although this effect was not seen if given in combination with light . Combined treatment also attenuated aggressive behavior by 3.9 points ( 95 % CI , 0.88 - 6.92 ) on the Cohen-Mansfield Agitation Index or 9 % , increased sleep efficiency by 3.5 % ( 95 % CI , 0.8%-6.1 % ) , and improved nocturnal restlessness by 1.00 minute per hour each year ( 95 % CI , 0.26 - 1.78 ) or 9 % ( treatment x time effect ) . CONCLUSIONS Light has a modest benefit in improving some cognitive and noncognitive symptoms of dementia . To counteract the adverse effect of melatonin on mood , it is recommended only in combination with light . TRIAL REGISTRATION controlled-trials.com/is rct n Identifier : IS RCT N93133646 OBJECTIVE To evaluate the efficacy and safety of aripiprazole treatment for psychotic symptoms associated with Alzheimer disease ( AD ) . METHODS In this parallel group , r and omized , double-blind , placebo-controlled , flexible-dose trial , institutionalized subjects with AD and psychotic symptoms were r and omized to aripiprazole ( n = 131 ) or placebo ( n = 125 ) for 10 weeks . The aripiprazole starting dose was 2 mg/day , and could be titrated to higher doses ( 5 , 10 , and 15 mg/day ) based on efficacy and tolerability . RESULTS No significant differences in mean change [ 2 x SD ] from baseline between aripiprazole ( mean dose approximately 9 mg/day at endpoint ; range = 0.7 - 15.0 mg ) and placebo were detected in the co primary efficacy endpoints of Neuropsychiatric Inventory-Nursing Home Version ( NPI-NH ) Psychosis score ( aripiprazole , -4.53 [ 9.23 ] ; placebo , -4.62 [ 9.56 ] ; F = 0.02 , df = 1 , 222 , p = 0.883 [ ANCOVA ] ) and Clinical Global Impression (CGI)-Severity score ( aripiprazole , -0.57 [ 1.63 ] ; placebo , -0.43 [ 1.65 ] ; F = 1.67 , df = 1 , 220 , p = 0.198 [ ANCOVA ] ) at endpoint . However , improvements in several secondary efficacy measures ( NPI-NH Total , Brief Psychiatric Rating Scale Total , CGI - improvement , Cohen-Mansfield Agitation Inventory and Cornell Depression Scale scores ) indicated that aripiprazole may confer clinical benefits beyond the primary outcome measures . Treatment-emergent adverse events ( AEs ) were similar in both groups , except for somnolence ( aripiprazole , 14 % ; placebo , 4 % ) . Somnolence with aripiprazole was of mild or moderate intensity , and not associated with accidental injury . Incidence of AEs related to extrapyramidal symptoms was low with aripiprazole ( 5 % ) and placebo ( 4 % ) . CONCLUSIONS In nursing home residents with AD and psychosis , aripiprazole did not confer specific benefits for the treatment of psychotic symptoms ; but psychological and behavioral symptoms , including agitation , anxiety , and depression , were improved with aripiprazole , with a low risk of AEs OBJECTIVE In this study we directly compared the efficacy and tolerability of the atypical antipsychotics quetiapine and risperidone in elderly patients with dementia and symptoms of disturbed perception , thought content , mood or behaviour ( behavioural and psychological symptoms of dementia-BPSD ) . METHODS We conducted an 8-week , rater-blinded , r and omised study of 72 out patients ( 55 - 85 years ) with BPSD ( assessed by NPI baseline score ) , who received flexibly-dosed quetiapine ( 50 - 400 mg/day ) or risperidone ( 0.5 - 2 mg/day ) . Primary efficacy measure : Neuropsychiatric Inventory ( NPI ) Parts 1 and 2 ; secondary efficacy measures : Clinical Global Impression ( CGI ) , Cohen-Mansfield Agitation Inventory ( CMAI ) , Mini-Mental State Examination ( MMSE ) , Age-adjusted concentration test ( AKT ) . Safety evaluations included the incidence of extrapyramidal symptoms ( EPS ) and adverse events ( AEs ) . RESULTS Sixty-nine of 72 patients were evaluable for efficacy ( 72 were evaluated for safety ) , 4 patients discontinued ( 3 due to AEs : quetiapine 2 , risperidone 1 ; 1 lost to follow-up ) . Sixty-five patients received quetiapine ( n=34 ; mean dose 77+/-40 mg/day ) or risperidone ( n=31 ; mean dose 0.9+/-0.3 mg/day ) . There was no significant difference between treatments on NPI scores ; within treatment groups , NPI scores decreased significantly from baseline to Week 8 ( P < or=0.05 vs. baseline ) . Most patients ( quetiapine arm 67.6 % , risperidone arm 71.0 % ) experienced clinical improvement ( CGI-Improvement scores ) ; both agents reduced agitation ( CMAI scores ) ; and there was no cognitive impairment ( MMSE and AKT scores ) . There were no significant differences between treatments in any safety measures , including EPS . Four patients experienced serious AEs ( quetiapine arm 3 ; risperidone arm 1 ) ; none were considered treatment-related by the study investigator . There were no cerebrovascular AEs or deaths . CONCLUSIONS Quetiapine or risperidone , at low doses , were equally effective and generally well tolerated ( including no cognitive impairment ) in the treatment of BPSD in elderly patients Abstract Objectives To determine the respective efficacy of quetiapine and rivastigmine for agitation in people with dementia in institutional care and to evaluate these treatments with respect to change in cognitive performance . Design R and omised double blind ( clinician , patient , outcomes assessor ) placebo controlled trial . Setting Care facilities in the north east of Engl and . Participants 93 patients with Alzheimer 's disease , dementia , and clinical ly significant agitation . Intervention Atypical antipsychotic ( quetiapine ) , cholinesterase inhibitor ( rivastigmine ) , or placebo ( double dummy ) . Main outcome measures Agitation ( Cohen-Mansfield agitation inventory ) and cognition ( severe impairment battery ) at baseline and at six weeks and 26 weeks . The primary outcome was agitation inventory at six weeks . Results 31 patients were r and omised to each group , and 80 ( 86 % ) started treatment ( 25 rivastigmine , 26 quetiapine , 29 placebo ) , of whom 71 ( 89 % ) tolerated the maximum protocol dose ( 22 rivastigmine , 23 quetiapine , 26 placebo ) . Compared with placebo , neither group showed significant differences in improvement on the agitation inventory either at six weeks or 26 weeks . Fifty six patients scored > 10 on the severe impairment battery at baseline , 46 ( 82 % ) of whom were included in the analysis at six week follow up ( 14 rivastigmine , 14 quetiapine , 18 placebo ) . For quetiapine the change in severe impairment battery score from baseline was estimated as an average of -14.6 points ( 95 % confidence interval -25.3 to -4.0 ) lower ( that is , worse ) than in the placebo group at six weeks ( P = 0.009 ) and -15.4 points ( -27.0 to -3.8 ) lower at 26 weeks ( P = 0.01 ) . The corresponding changes with rivastigmine were -3.5 points ( -13.1 to 6.2 ) lower at six weeks ( P = 0.5 ) and -7.5 points ( -21.0 to 6.0 ) lower at 26 weeks ( P = 0.3 ) . Conclusions Neither quetiapine nor rivastigmine are effective in the treatment of agitation in people with dementia in institutional care . Compared with placebo , quetiapine is associated with significantly greater cognitive decline Background / Aims : To evaluate the efficacy of oxcarbazepine ( OXC ) in the treatment of agitation and aggression in patients with Alzheimer ’s disease , vascular dementia or both . Methods : This is an 8-week , multicenter , r and omized , double-blind , placebo-controlled trial carried out independently of the pharmaceutical industry . Changes in the agitation and aggression subscore of the Neuropsychiatric Inventory ( NPI ) were the primary outcomes . The secondary out- comes were the changes in the caregivers ’ total burden scores ( measured by the NPI ) and changes in the Brief Agitation Rating Scale ( BARS ) . Results : In total , 103 institutionalized patients at 35 sites were r and omized to the trial . After 8 weeks , no statistically significant differences were found between the 2 groups for all outcomes . A trend was observed in favor of the OXC group in the reduction in the scores on the BARS ( p = 0.07 ) . Conclusion : This study found no significant effect of OXC in treatment of agitation and aggression in patients with dementia IMPORTANCE Agitation is common among patients with Alzheimer disease ; safe , effective treatments are lacking . OBJECTIVE To assess the efficacy , safety , and tolerability of dextromethorphan hydrobromide-quinidine sulfate for Alzheimer disease-related agitation . DESIGN , SETTING , AND PARTICIPANTS Phase 2 r and omized , multicenter , double-blind , placebo-controlled trial using a sequential parallel comparison design with 2 consecutive 5-week treatment stages conducted August 2012-August 2014 . Patients with probable Alzheimer disease , clinical ly significant agitation ( Clinical Global Impressions-Severity agitation score ≥4 ) , and a Mini-Mental State Examination score of 8 to 28 participated at 42 US study sites . Stable dosages of antidepressants , antipsychotics , hypnotics , and antidementia medications were allowed . INTERVENTIONS In stage 1 , 220 patients were r and omized in a 3:4 ratio to receive dextromethorphan-quinidine ( n = 93 ) or placebo ( n = 127 ) . In stage 2 , patients receiving dextromethorphan-quinidine continued ; those receiving placebo were stratified by response and rer and omized in a 1:1 ratio to dextromethorphan-quinidine ( n = 59 ) or placebo ( n = 60 ) . MAIN OUTCOMES AND MEASURES The primary end point was change from baseline on the Neuropsychiatric Inventory ( NPI ) Agitation/Aggression domain ( scale range , 0 [ absence of symptoms ] to 12 [ symptoms occur daily and with marked severity ] ) . RESULTS A total of 194 patients ( 88.2 % ) completed the study . With the sequential parallel comparison design , 152 patients received dextromethorphan-quinidine and 127 received placebo during the study . Analysis combining stages 1 ( all patients ) and 2 ( rer and omized placebo nonresponders ) showed significantly reduced NPI Agitation/Aggression scores for dextromethorphan-quinidine vs placebo ( ordinary least squares z statistic , -3.95 ; P < .001 ) . In stage 1 , mean NPI Agitation/Aggression scores were reduced from 7.1 to 3.8 with dextromethorphan-quinidine and from 7.0 to 5.3 with placebo . Between-group treatment differences were significant in stage 1 ( least squares mean , -1.5 ; 95 % CI , -2.3 to -0.7 ; P<.001 ) . In stage 2 , NPI Agitation/Aggression scores were reduced from 5.8 to 3.8 with dextromethorphan-quinidine and from 6.7 to 5.8 with placebo . Between-group treatment differences were also significant in stage 2 ( least squares mean , -1.6 ; 95 % CI , -2.9 to -0.3 ; P=.02 ) . Adverse events included falls ( 8.6 % for dextromethorphan-quinidine vs 3.9 % for placebo ) , diarrhea ( 5.9 % vs 3.1 % respectively ) , and urinary tract infection ( 5.3 % vs 3.9 % respectively ) . Serious adverse events occurred in 7.9 % with dextromethorphan-quinidine vs 4.7 % with placebo . Dextromethorphan-quinidine was not associated with cognitive impairment , sedation , or clinical ly significant QTc prolongation . CONCLUSIONS AND RELEVANCE In this preliminary 10-week phase 2 r and omized clinical trial of patients with probable Alzheimer disease , combination dextromethorphan-quinidine demonstrated clinical ly relevant efficacy for agitation and was generally well tolerated . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01584440 BACKGROUND This r and omized , double-blind , placebo-controlled trial examined the efficacy and safety of risperidone in the treatment of aggression , agitation , and psychosis in elderly nursing-home patients with dementia . METHOD Elderly patients with a DSM-IV diagnosis of dementia of the Alzheimer 's type , vascular dementia , or a combination of the 2 ( i.e. , mixed dementia ) and significant aggressive behaviors were r and omized to receive , for a period of 12 weeks , a flexible dose of either placebo or risperidone solution up to a maximum of 2 mg/day . Outcome measures were the Cohen-Mansfield Agitation Inventory ( CMAI ) , the Behavioral Pathology in Alzheimer 's Disease ( BEHAVE-AD ) rating scale , and the Clinical Global Impression of Severity ( CGI-S ) and of Change ( CGI-C ) scales . RESULTS A total of 345 patients were r and omized to treatment with risperidone or placebo , and 337 patients received at least one dose of study drug . The trial was completed by 67 % of patients in the placebo group and 73 % of patients in the risperidone group . The mean + /- SE dose of risperidone was 0.95 + /- 0.03 mg/day . The primary endpoint of the study , the difference from baseline to endpoint in CMAI total aggression score , showed a significant reduction in aggressive behavior for risperidone versus placebo ( p < .001 ) . A similar improvement was also seen for the CMAI total non-aggression subscale ( p < .002 ) and for the BEHAVE-AD total ( p < .001 ) and psychotic symptoms subscale ( p = .004 ) . At endpoint , the CGI-S and the CGI-C scores indicated a significantly greater improvement with risperidone compared with placebo ( p < .001 ) . Overall , 94 % and 92 % of the risperidone and placebo groups , respectively , reported at least 1 adverse event . Somnolence and urinary tract infection were more common with risperidone treatment , whereas agitation was more common with placebo . There was no significant difference in the number of patients who reported extrapyramidal symptoms between the risperidone ( 23 % ) and placebo ( 16 % ) groups . CONCLUSION Treatment with low-dose ( mean = 0.95 mg/day ) risperidone result ed in significant improvement in aggression , agitation , and psychosis associated with dementia CONTEXT The decision to institutionalize a patient with dementia is complex and is based on patient and caregiver characteristics and the sociocultural context of patients and caregivers . Most studies have determined predictors of nursing home placement primarily according to patient or caregiver characteristics alone . OBJECTIVE To develop and vali date a prognostic model to determine the comprehensive predictors of placement among an ethnically diverse population of patients with dementia . DESIGN , SETTING , AND PARTICIPANTS The Medicare Alzheimer 's Disease Demonstration and Evaluation study , a prospect i ve study at 8 sites in the United States , with enrollment between December 1989 and December 1994 of 5788 community-living persons with advanced dementia . MAIN OUTCOME MEASURES Time to nursing home placement throughout a 36-month follow-up period , assessed by interview and review of Medicare records , and its association with patient and caregiver characteristics , obtained by interview at enrollment . RESULTS Patients were divided into a development ( n = 3859 ) and validation ( n = 1929 ) cohort . In the development cohort , the Kaplan-Meier estimates of nursing home placement throughout 1 , 2 , and 3 years were 22 % , 40 % , and 52 % , respectively . After multivariate adjustment , patient characteristics that were associated with nursing home placement were as follows : black ethnicity ( hazard ratio , 0.60 ; 95 % confidence interval [ CI ] , 0.48 - 0.74 ) , Hispanic ethnicity ( HR , 0.40 ; 95 % CI , 0.28 - 0.56 ) ( both ethnicities were inversely associated with placement ) , living alone ( HR , 1.74 ; 95 % CI , 1.49 - 2.02 ) , 1 or more dependencies in activities of daily living ( HR , 1.38 ; 95 % CI , 1.20 - 1.60 ) , high cognitive impairment ( for Mini-Mental Status Examination score < or = 20 : HR , 1.52 ; 95 % CI , 1.33 - 1.73 ) , and 1 or more difficult behaviors ( HR , 1.30 ; 95 % CI , 1.11 - 1.52 ) . Caregiver characteristics associated with patient placement were age 65 to 74 years ( HR , 1.17 ; 95 % CI , 1.01 - 1.37 ) , age 75 years or older ( HR , 1.55 ; 95 % CI , 1.31 - 1.84 ) , and high Zarit Burden Scale score ( for highest quartile : HR , 1.73 ; 95 % CI , 1.49 - 2.00 ) . Patients were assigned to quartiles of risk based on this model . In the development cohort , patients in the first , second , third , and fourth quartile had a 25 % , 42 % , 64 % , and 91 % rate of nursing home placement at 3 years , respectively . In the validation cohort , the respective rates were 21 % , 50 % , 64 % , and 89 % . The C statistic for 3-year nursing home placement was 0.66 in the development cohort and 0.63 in the validation cohort . CONCLUSIONS Patient and caregiver characteristics are both important determinants of long-term care placement for patients with dementia . Interventions directed at delaying placement , such as reduction of caregiver burden or difficult patient behaviors , need to take into account the patient and caregiver as a unit BACKGROUND Agitation is a common and distressing symptom in patients with Alzheimer 's disease . Cholinesterase inhibitors improve cognitive outcomes in such patients , but the benefits of these drugs for behavioral disturbances are unclear . METHODS We r and omly assigned 272 patients with Alzheimer 's disease who had clinical ly significant agitation and no response to a brief psychosocial treatment program to receive 10 mg of donepezil per day ( 128 patients ) or placebo ( 131 patients ) for 12 weeks . The primary outcome was a change in the score on the Cohen-Mansfield Agitation Inventory ( CMAI ) ( on a scale of 29 to 203 , with higher scores indicating more agitation ) at 12 weeks . RESULTS There was no significant difference between the effects of donepezil and those of placebo on the basis of the change in CMAI scores from baseline to 12 weeks ( estimated mean difference in change [ the value for donepezil minus that for placebo ] , -0.06 ; 95 % confidence interval [ CI ] , -4.35 to 4.22 ) . Twenty-two of 108 patients ( 20.4 % ) in the placebo group and 22 of 113 ( 19.5 % ) in the donepezil group had a reduction of 30 % or greater in the CMAI score ( the value for donepezil minus that for placebo , -0.9 percentage point ; 95 % CI , -11.4 to 9.6 ) . There were also no significant differences between the placebo and donepezil groups in scores for the Neuropsychiatric Inventory , the Neuropsychiatric Inventory Caregiver Distress Scale , or the Clinician 's Global Impression of Change . CONCLUSIONS In this 12-week trial , donepezil was not more effective than placebo in treating agitation in patients with Alzheimer 's disease . ( Clinical Trials.gov number , NCT00142324 [ Clinical Trials.gov ] . ) BACKGROUND We report the findings from the first large , double-blind , placebo-controlled study conducted to evaluate the efficacy and safety of risperidone in the treatment of psychotic and behavioral symptoms in institutionalized elderly patients with dementia . METHOD 625 patients ( 67.8 % women ; mean age = 82.7 years ) with DSM-IV diagnoses of Alzheimer 's disease ( 73 % ) , vascular dementia ( 15 % ) , or mixed dementia ( 12 % ) and significant psychotic and behavioral symptoms were included . Each patient was r and omly assigned to receive placebo or 0.5 mg/day , 1 mg/day , or 2 mg/day of risperidone for 12 weeks . The primary outcome measure was the Behavioral Pathology in Alzheimer 's Disease rating scale ( BEHAVE-AD ) . RESULTS The study was completed by 70 % of the patients . Baseline Functional Assessment Staging scores were 6 or 7 in more than 95 % of the patients , indicating severe dementia . At endpoint , significantly greater reductions in BEHAVE-AD total scores and psychosis and aggressiveness subscale scores were seen in patients receiving 1 and 2 mg/day of risperidone than in placebo patients ( p = .005 and p < .001 , respectively ) . At week 12 , 0.5 mg/day of risperidone was superior to placebo in reducing BEHAVE-AD aggression scores ( p = .02 ) . More adverse events were reported by patients receiving 2 mg/day of risperidone than 1 mg/day . The most common dose-related adverse events were extrapyramidal symptoms , somnolence , and mild peripheral edema . The frequency of extrapyramidal symptoms in patients receiving 1 mg/day of risperidone was not significantly greater than in placebo patients . CONCLUSION Risperidone significantly improved symptoms of psychosis and aggressive behavior in patients with severe dementia . Results show that 1 mg/day of risperidone is an appropriate dose for most elderly patients with dementia OBJECTIVES To evaluate the safety and efficacy of donepezil in the management of patients with Alzheimer 's disease ( AD ) residing in nursing home facilities . DESIGN Twenty-four-week , r and omized , multicenter , parallel-group , double-blind , placebo-controlled trial . SETTING Twenty-seven nursing homes across the United States . PARTICIPANTS Two hundred eight nursing home patients with a diagnosis of probable or possible AD , or AD with cerebrovascular disease ; mean Mini-Mental State Examination ( MMSE ) score 14.4 ; mean age 85.7 . MEASUREMENTS The primary outcome measure was the Neuropsychiatric Inventory-Nursing Home Version ( NPI-NH ) . Secondary efficacy measures were the Clinical Dementia Rating ( Nursing Home Version)-Sum of the Boxes ( CDR-SB ) , MMSE , and the Physical Self-Maintenance Scale ( PSMS ) . Safety was monitored by physical examinations , vital signs , clinical laboratory tests , electrocardiograms ( ECGs ) , and treatment-emergent adverse events ( AEs ) . RESULTS Eighty-two percent of donepezil- and 74 % of placebo-treated patients completed the trial . Eleven percent of donepezil- and 18 % of placebo-treated patients withdrew because of AEs . Mean NPI-NH 12-item total scores improved relative to baseline for both groups , with no significant differences observed between the groups at any assessment . Mean change from baseline CDR-SB total score improved significantly with donepezil compared with placebo at Week 24 ( P < .05 ) . The change in CDR-SB total score was not influenced by age . Differences in mean change from baseline on the MMSE favored donepezil over placebo at Weeks 8 , 16 , and 20 ( P < .05 ) . No significant differences were observed between the groups on the PSMS . Overall rates of occurrence and severity of AEs were similar between the two groups ( 97 % placebo , 96 % donepezil ) . Gastrointestinal AEs occurred more frequently in donepezil-treated patients . In general , AEs were similar in older and younger donepezil-treated patients , with the majority of patients experiencing only AEs that were transient and mild or moderate in severity . Weight loss was reported as an AE more frequently in older patients , although a loss at last visit of > or=7 % of screening weight occurred at the same rate in older and younger patients ( 9 % of donepezil- and 6 % of placebo-treated patients ) . No significant differences between groups in vital sign changes , bradycardia , or rates of clinical ly significant laboratory or ECG abnormalities were observed . CONCLUSION Patients treated with donepezil maintained or improved in cognition and overall dementia severity in contrast to placebo-treated patients who declined during the 6-month treatment period . The safety and tolerability profile was comparable with that reported in outpatient studies of donepezil . These findings also suggest that advanced age , comorbid illnesses , and high concomitant medication usage should not be barriers to donepezil treatment . Given the apparent improvement in behavior in the placebo group , and the high use of concomitant medications in both groups , the impact of donepezil on behavior in the nursing home setting is unresolved and merits further investigation . In summary , effects on cognition , overall dementia severity , and safety and tolerability findings are consistent with previous findings in out patients and support the use of donepezil in patients with AD who reside in nursing homes Objective : Enhanced behavioral responsiveness to central nervous system ( CNS ) norepinephrine ( NE ) in Alzheimer disease ( AD ) may contribute to the pathophysiology of disruptive behaviors such as aggression , uncooperativeness with necessary care , irritability , and pressured pacing . We evaluated the efficacy of the beta-adrenergic antagonist propranolol for treatment-resistant disruptive behaviors and overall behavioral status in nursing home residents with probable or possible AD . Methods : Thirty-one subjects ( age 85 ± 8 [ SD ] ) with probable or possible AD and persistent disruptive behaviors that interfered with necessary care were r and omized to propranolol ( n = 17 ) or placebo ( n = 14 ) in a double-blind study . Stable doses of previously prescribed psychotropics were maintained at pre- study dose during the study . Following a propranolol or placebo dose titration period of up to 9 days ( per a dosing algorithm ) , subjects were maintained on maximum achieved dose for 6 weeks . Primary outcome measures were the Neuropsychiatric Inventory ( NPI ) and the Clinical Global Impression of Change ( CGIC ) . Results : Propranolol augmentation ( mean achieved dose 106 ± 38 mg/d ) was significantly more effective than placebo for improving overall behavioral status on the total NPI score and CGIC . Improvement in individual NPI items within propranolol subjects was significant only for “ agitation/aggression ” and “ anxiety , ” and reached borderline statistical significance favoring propranolol over placebo only for “ agitation/aggression . ” Pressured pacing and irritability did not appear responsive to propranolol . In propranolol subjects rated “ moderately improved ” or “ markedly improved ” on the CGIC at the end of the double-blind study phase , improvement of overall behavioral status had diminished substantially after 6 months of open-label propranolol treatment . Conclusion : Short-term propranolol augmentation treatment appeared modestly effective and well tolerated for overall behavioral status in nursing home residents with probable or possible AD complicated by disruptive behaviors . Propranolol may be helpful specifically for aggression and uncooperativeness ( the behaviors assessed by the NPI “ agitation/aggressiveness ” item ) . However , the usefulness of propranolol in this very old and frail population was limited by the high frequency of relative contraindications to beta-adrenergic antagonist treatment and diminution of initial behavioral improvements over time OBJECTIVE To examine the safety and efficacy of sertraline augmentation therapy in the treatment of behavioral manifestations of Alzheimer 's disease ( AD ) in out patients treated with donepezil . METHODS AND MATERIAL S Patients with probable or possible AD , and a Neuropsychiatric Inventory ( NPI ) total score > 5 ( with a severity score > or = 2 in at least one domain ) , were treated with donepezil ( 5 - 10 mg ) for 8 weeks , then r and omly assigned to 12 weeks of double-blind augmentation therapy with either sertraline ( 50 - 200 mg ) or placebo . Primary efficacy measures were the 12-item Neuropsychiatric Inventory ( NPI ) and the Clinical Global Impression Improvement ( CGI-I ) and Severity ( CGI-S ) scales . RESULTS 24 patients were treated with donepezil+sertraline and 120 patients with donepezil+placebo . There were no statistically significant differences at endpoint on any of the three primary efficacy measures . However , a linear mixed model analysis found modest but statistically significantly greater improvements in the CGI-I score on donepezil+sertraline . Moreover , in a sub-group of patients with moderate-to-severe behavioral and psychological symptoms of dementia , 60 % of patients on sertraline vs 40 % on placebo ( p = 0.006 ) achieved a response ( defined as > or = 50 % reduction in a four-item NPI-behavioral subscale ) . One adverse event ( diarrhea ) was significantly ( p < 0.05 ) more common in the donepezil+sertraline group compared to the donepezil+placebo group . CONCLUSION Sertraline augmentation was well-tolerated in this sample of AD out patients . In addition , post hoc analyses demonstrated a modest but statistically significant advantage of sertraline over placebo augmentation in mixed model analyses and a clinical ly and statistically significant advantage in a subgroup of patients with moderate-to-severe behavioral and psychological symptoms of dementia The authors assessed the efficacy , tolerability , and safety of divalproex sodium for the treatment of agitation associated with dementia in a 6-week , r and omized study of 56 nursing home patients with agitation and dementia treated with either placebo or individualized doses of divalproex sodium . Participants were blinded to treatment except for a physician-monitor and a pharmacist . When several covariates were taken into account , the drug/placebo difference in Brief Psychiatric Rating Scale Agitation scores became statistically significant ( P=0.05 ) . Sixty-eight percent of patients on divalproex were rated as showing reduced agitation on the Clinical Global Impression scale , vs. 52 % on placebo ( P=0.06 in the adjusted analysis ) . Side effects occurred in 68 % of the divalproex group vs. 33 % of the placebo group ( P=0.03 ) and were generally rated as mild . This placebo-controlled study , despite some limitations , suggests possible short-term efficacy , tolerability , and safety of divalproex for agitation in dementia and supports further placebo-controlled studies Yokukansan ( YKS ) is used frequently against behavioral and psychological symptoms of dementia ( BPSD ) together with donepezil in patients with Alzheimer 's disease ( AD ) . Here , we investigated the efficacy and safety of YKS in patients with AD in a non-blinded , r and omized , parallel-group comparison study . Patients who had at least one symptom score of four or more on the Neuropsychiatric Inventory ( NPI ) subscales were enrolled in the study . The subjects were r and omly assigned to the YKS-treated group ( YKS/donepezil combination therapy group ) and the non-YKS-treated group ( donepezil monotherapy group ) . TSUMURA Yokukansan ( TJ-54 , 7.5 g , t.i.d . ) was administered in a four-week study treatment period . The subjects were evaluated twice at the start ( Week 0 ) and completion ( Week 4 ) of the study treatment in terms of NPI , Mini-Mental Status Examination ( MMSE ) , Disability Assessment for Dementia ( DAD ) , Zarit Burden Interview , and Self-rating Depression Scale ( SDS ) . The efficacy analysis was performed in 29 patients ( YKS-treated group ) and 32 patients ( non-YKS-treated group ) . The NPI total score improved significantly more in the YKS-treated group than in the non-YKS-treated group . In the NPI subscales of agitation/aggression and irritability/lability , the YKS-treated group showed significantly greater improvement than the non-YKS-treated group , but no statistically significant improvement was seen with YKS in the other subscales . There were no significant differences between the YKS-treated group and the non-YKS-treated group in MMSE , DAD , Zarit Burden Interview and SDS . No adverse reactions were noted in either group . The results of this study showed that YKS is safe and effective in the treatment of BPSD in AD patients OBJECTIVES Agitation/aggression in Alzheimer disease ( AD ) is a major cause of patient distress , caregiver burden , and institutionalization . Enhanced behavioral responsiveness to central nervous system norepinephrine ( NE ) release may contribute to the pathophysiology of agitation/aggression in AD . Prazosin , a nonsedating generic medication used for hypertension and benign prostatic hypertrophy , antagonizes NE effects at brain postsynaptic alpha-1 adrenoreceptors . This pilot study examined the efficacy and tolerability of prazosin for behavioral symptoms in patients with agitation/aggression in AD . DESIGN Double-blind , placebo controlled , parallel group study . SETTING A university AD center and a nursing home in Seattle , WA . PARTICIPANTS Twenty-two nursing home and community-dwelling participants with agitation/aggression and probable or possible AD ( mean age : 80.6 + /- 11.2 ) . INTERVENTION R and omization to placebo ( N = 11 ) or prazosin ( N = 11 ) . Medication was initiated at 1 mg/day and increased up to 6 mg/day using a flexible dosing algorithm . MEASUREMENTS The Brief Psychiatric Rating Scale ( BPRS ) and Neuropsychiatric Inventory ( NPI ) at Weeks 1 , 2 , 4 , 6 , and 8 . The Clinical Global Impression of Change ( CGIC ) at Week 8 . RESULTS Participants taking prazosin ( mean dose : 5.7 + /- 0.9 mg/day ) had greater improvements than those taking placebo ( mean dose : 5.6 + /- 1.2 mg/day ) on the NPI ( mean change : -19 + /- 21 versus -2 + /- 15 , chi = 6.32 , df = 1 , p = 0.012 ) and BPRS ( mean change : -9 + /- 9 versus -3 + /- 5 , chi = 4.42 , df = 1 , p = 0.036 ) based on linear mixed effects models and the CGIC ( mean : 2.6 + /- 1.0 versus 4.5 + /- 1.6 , z = 2.57 , p = 0.011 [ Mann-Whitney test ] ) . Adverse effects and blood pressure changes were similar between prazosin and placebo groups . CONCLUSION Prazosin was well tolerated and improved behavioral symptoms in patients with agitation/aggression in AD Objective : To assess the efficacy and tolerability of quetiapine for agitation or psychosis in patients with dementia and parkinsonism . Methods : Multicenter r and omized , double-blind , placebo-controlled parallel groups clinical trial involving 40 patients with dementia with Lewy bodies ( n = 23 ) , Parkinson disease ( PD ) with dementia ( n = 9 ) , or Alzheimer disease with parkinsonian features ( n = 8) . The main outcome measure for efficacy was change in the Brief Psychiatric Rating Scale ( BPRS ) from baseline to 10 weeks of therapy . For tolerability it was change in the Unified PD Rating Scale ( UPDRS ) motor section over the same time period . The trial was confounded by the need for a design change and incomplete recruitment . Results : No significant differences in the primary or secondary outcome measures of efficacy were observed . An unexpectedly large placebo effect , inadequate dosage ( mean 120 mg/day ) , and inadequate power may have contributed to lack of demonstrable benefit . Quetiapine was generally well-tolerated and did not worsen parkinsonism , but was associated with a trend toward a decline on a measure of daily functioning . Conclusions : Quetiapine was well-tolerated and did not worsen parkinsonism . Although conclusions about efficacy may be limited , the drug in the dosages used did not show demonstrable benefit for treating agitation or psychosis in patients with dementia and parkinsonism . These findings are in keeping with prior studies reporting limited efficacy of various medications for reducing behavioral problems in demented patients Abstract The descriptive term behavioral and psychological symptoms of dementia ( BPSD ) is used to cover a range of noncognitive disturbances including anxiety , depression , irritability , aggression , agitation , eating disorders , and inappropriate social or sexual behaviors . Behavioral and psychological symptoms of dementia are seen in about 90 % of patients with dementia . We aim ed to compare the efficacy and tolerability of risperidone , yokukansan , and fluvoxamine used for BPSD in elderly patients with dementia . Ninety in patients with dementia according to the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria were investigated in Sato Hospital , Koutokukai . We conducted an 8-week , rater-blinded , r and omized trial , administering flexibly dosed risperidone , yokukansan , or fluvoxamine . Primary outcome measures were Neuropsychiatric Inventory in Nursing Home Version total score and its items . Secondary outcome measures were cognitive function measured by Mini-Mental State Examination and daily life function measured by Functional Independence Measure ( FIM ) . Neurological adverse effects were measured by the Drug-Induced Extra-Pyramidal Symptoms Scale . At the end of the study , we analyzed 76 patients ( 92.7 % ) . Mean Neuropsychiatric Inventory in Nursing Home Version total score decreased in all 3 drug groups , with no significant between-group differences . Mini-Mental State Examination and Functional Independence Measure scores did not change significantly . Drug-Induced Extra-Pyramidal Symptoms Scale scores did not change in the yokukansan and fluvoxamine groups , but increased significantly in the risperidone group . Risperidone , yokukansan , and fluvoxamine were equally effective in the treatment of BPSD in elderly patients . However , yokukansan or fluvoxamine for BPSD showed a more favorable profile in tolerability compared with risperidone . This trial is registered at UMIN Clinical Trials Registry ( identifier : UMIN000006146 ) BACKGROUND Patients with Alzheimer disease ( AD ) commonly exhibit psychosis and behavioral disturbances that impair patient functioning , create caregiver distress , and lead to institutionalization . This study was conducted to assess the efficacy and safety of olanzapine in treating psychosis and /or agitation/aggression in patients with AD . METHODS A multicenter , double-blind , placebo-controlled , 6-week study was conducted in 206 elderly US nursing home residents with AD who exhibited psychotic and /or behavioral symptoms . Patients were r and omly assigned to placebo or a fixed dose of 5 , 10 , or 15 mg/d of olanzapine . The primary efficacy measure was the sum of the Agitation/Aggression , Hallucinations , and Delusions items ( Core Total ) of the Neuropsychiatric Inventory-Nursing Home version . RESULTS Low-dose olanzapine ( 5 and 10 mg/d ) produced significant improvement compared with placebo on the Core Total ( -7.6 vs -3.7 [ P<.001 ] and -6.1 vs -3 . 7 [ P = .006 ] , respectively ) . Core Total improvement with olanzapine , 15 mg/d , was not significantly greater than placebo . The Occupational Disruptiveness score , reflecting the impact of patients ' psychosis and behavioral disturbances on the caregiver , was significantly reduced in the 5-mg/d olanzapine group compared with placebo ( -2.7 vs -1.5 ; P = .008 ) . Somnolence was significantly more common among patients receiving olanzapine ( 25.0%-35.8 % ) , and gait disturbance occurred in those receiving 5 or 15 mg/d ( 19.6 % and 17.0 % , respectively ) . No significant cognitive impairment , increase in extrapyramidal symptoms , or central anticholinergic effects were found at any olanzapine dose relative to placebo . CONCLUSION Low-dose olanzapine ( 5 and 10 mg/d ) was significantly superior to placebo and well tolerated in treating agitation/aggression and psychosis in this population of patients with AD ABSTRACT Background : The management of disruptive neuropsychiatric symptom ( NPS ) such as agitation and aggression ( A/A ) is a major priority in caring for people with Alzheimer 's disease ( AD ) . Few effective pharmacological or non-pharmacological options are available . Results of r and omized clinical trials ( RCTs ) of drugs for A/A have been disappointing . This may result from the absence of biological efficacy for medications tested in treating A/A. It may also be related to method ological issues such as the choice of outcomes . The aim of this review was to highlight key method ological issues pertaining to RCTs of current and emerging medications for the treatment of A/A in AD . Methods : We search ed PubMed / Medline , Cochrane Central Register of Controlled Trials , and Clinical Trials.gov for RCTs comparing medications with either placebo or other drugs in the treatment of A/A in AD , between January 2008 and December 2013 . Results : We identified a total of 18 RCTs ; of these , 11 were completed and 7 ongoing . Of the ongoing RCTs , only one is in Phase III . Seven of 10 completed RCTs with reported results did not report greater benefit from drug than placebo . Each of the completed RCTs used a different definition of " clinical ly significant A/A. " There was considerable heterogeneity in study design . The primary endpoints were largely proxy-based but a variety of scales were used . The definition of caregiver and scales used to assess caregiver outcomes were similarly heterogeneous . Placebo response was notable in all trials . Conclusions : This review highlights a great heterogeneity in RCTs design of drugs for A/A in AD and some key method ological issues such as definition of A/A , choice of outcome measures and caregiver participation that could be addressed by an expert consensus to optimize future trials design Background / Aims : To assess the efficacy and tolerability of valproate for the treatment of agitation and aggression in moderate-to-severe Alzheimer ’s disease ( AD ) . Methods : This was a r and omized , double-blind , placebo-controlled crossover trial of valproate in institutionalized AD patients . Patients were assessed with the Neuropsychiatric Inventory ( NPI ) and Cohen-Mansfield Agitation Inventory at baseline and after 6 weeks of treatment with valproate and placebo , with 2 weeks between phases to allow for placebo washout and tapering . Results : Fourteen patients ( 8 male/6 female ) aged 85.6 ± 4.5 years with baseline Mini Mental State Examination scores of 4.5 ± 4.6 and NPI agitation/aggression scores of 6.4 ± 3.5 were r and omized to treatment . NPI agitation/aggression treatment change scores significantly worsened during valproate treatment compared with placebo ( Z = –2.03 , p = 0.04 ) . Tolerability of valproate was also poor , with patients experiencing a significantly greater mean number of adverse events during valproate therapy compared to placebo ( Z = –2.82 , p = 0.005 ) . Conclusion : Valproate is not effective for the management of agitation in moderate-to-severe AD , and may be poorly tolerated in this population Introduction : Behavioral disturbances are determining factors in h and ling patients with Alzheimer dementia . The current pharmacotherapy for behavioral symptoms associated with dementia is not satisfactory . Our goal was to compare a new anticonvulsant , topiramate , with a usually used medication , risperidone , for controlling behavioral disturbances of patients with Alzheimer dementia . Method : Elderly patients with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition diagnosis of Alzheimer disease and significant behavioral disturbances were r and omized to receive , for a period of 8 weeks , a flexible dose of either topiramate ( 25 - 50 mg/d ) or risperidone ( 0.5 - 2 mg/d ) . Outcome measures were the Cohen-Mansfield Agitation Inventory , Neuropsychiatry Inventory parts 1 and 2 , and the Clinical Global Impression . Result : Forty-eight patients were r and omized to treatment with either topiramate or risperidone , and 41 patients ( 21 of 25 in topiramate group and 20 of 23 in risperidone group ) completed the trial . Both groups showed significant improvement in all outcome measures without important difference ( Neuropsychiatry Inventory total score P < 0.531 , Z = 0.62 ; Cohen-Mansfield Agitation Inventory P < 0.927 , Z = 0.09 ; Clinical Global Impression , P < 0.654 , Z = 0.48 ) . There were no significant changes in the cognitive status of patients ( assessed by Mini-Mental Status Examination ) taking topiramate or risperidone during the trial . Conclusion : Treatment with a low dose of topiramate ( 25 - 50 mg/d ) demonstrated a comparable efficacy with risperidone in controlling behavioral disturbances of patients with Alzheimer dementia The goal of this study was to compare the efficacy and safety of olanzapine versus haloperidol in the treatment of agitation and aggression in patients with dementia . The subjects were 58 out- patients with dementia and agitation . After baseline assessment s and , if necessary , a period of wash-out of a previous antipsychotic drug , they were r and omly assigned to 5 weeks of double-blind treatment with either olanzapine or haloperidol . The first 2 weeks were used for dose titration . Subsequently , the patients received a fixed dose of either olanzapine ( average dose 4.71 mg ) or haloperidol ( average dose 1.75 mg ) from day 14 to day 35 . Both olanzapine and haloperidol decreased agitation significantly ( decrease in Cohen-Mansfield Agitation Inventory scores ) , but there was no significant difference between the two drugs . The two drugs had comparable effects on all secondary outcome measures . They were well tolerated and had a similar side-effect pattern . Our study could not demonstrate the superiority of olanzapine , compared to haloperidol , for the treatment of agitation in patients with dementia OBJECTIVE Three placebo-controlled clinical trials have suggested the benefit of valproate for treatment of agitation associated with dementia ; one was used as the basis for this multicenter trial , conducted by the Alzheimer 's Disease ( AD ) Cooperative Study . It addresses the efficacy , safety , and tolerability of divalproex sodium for the treatment of agitation associated with dementia . METHODS This was a r and omized , double-blind , placebo-controlled clinical trial in 153 nursing home residents with probable or possible AD complicated by agitation ; 110 ( 72 % ) completed the trial . Participants were r and omized to treatment with divalproex sodium at a target dose of 750 mg/day ( N = 75 ) or placebo ( N = 78 ) for 6 weeks . The primary outcome measure was change from baseline on the Brief Psychiatric Rating Scale ( BPRS ) Agitation factor . Secondary outcomes included total BPRS , Clinical Global Impression of Change , Cohen-Mansfield Agitation Inventory score , and measures of safety and tolerability . RESULTS Compliance averaged 88 % . Participants receiving divalproex achieved a mean dose of 800 mg/day . Change in mean BPRS Agitation factor scores did not differ between patients treated with divalproex and placebo , nor did secondary behavioral measures . Measures of safety and tolerability did not reveal clinical ly important drug/placebo differences . CONCLUSIONS This multicenter trial showed no benefit of divalproex sodium for treatment for agitation in dementia at a mean dose of 800 mg/day over 6 weeks . The results do not support findings from previous trials indicating possible benefit Aims : To examine the effects of galantamine and risperidone on agitation in patients with dementia . Methods : A total of 100 patients with dementia and neuropsychiatric symptoms ( mean age ± SD : 78.6 ± 7.5 years ; 67 % female ) were included in this 12-week , r and omized , parallel-group , controlled , single-center trial . The participants received galantamine ( n = 50 ; target dose : 24 mg ) or risperidone ( n = 50 ; target dose : 1.5 mg ) for 12 weeks . Results : Both galantamine and risperidone treatment result ed in reduced agitation . However , risperidone showed a significant advantage over galantamine both at week 3 ( mean difference in total Cohen-Mansfield Agitation Inventory score : 3.7 points ; p = 0.03 ) and at week 12 ( 4.3 points ; p = 0.01 ) . Conclusions : Agitation improved in both groups , even if the treatment effects were more pronounced in the risperidone group ; however , the effects on cognition and other aspects of tolerability were stronger with galantamine IMPORTANCE Agitation is common , persistent , and associated with adverse consequences for patients with Alzheimer disease . Pharmacological treatment options , including antipsychotics are not satisfactory . OBJECTIVE The primary objective was to evaluate the efficacy of citalopram for agitation in patients with Alzheimer disease . Key secondary objectives examined effects of citalopram on function , caregiver distress , safety , cognitive safety , and tolerability . DESIGN , SETTING , AND PARTICIPANTS The Citalopram for Agitation in Alzheimer Disease Study ( CitAD ) was a r and omized , placebo-controlled , double-blind , parallel group trial that enrolled 186 patients with probable Alzheimer disease and clinical ly significant agitation from 8 academic centers in the United States and Canada from August 2009 to January 2013 . INTERVENTIONS Participants ( n = 186 ) were r and omized to receive a psychosocial intervention plus either citalopram ( n = 94 ) or placebo ( n = 92 ) for 9 weeks . Dosage began at 10 mg per day with planned titration to 30 mg per day over 3 weeks based on response and tolerability . MAIN OUTCOMES AND MEASURES Primary outcome measures were based on scores from the 18-point Neurobehavioral Rating Scale agitation subscale ( NBRS-A ) and the modified Alzheimer Disease Cooperative Study - Clinical Global Impression of Change ( mADCS-CGIC ) . Other outcomes were based on scores from the Cohen-Mansfield Agitation Inventory ( CMAI ) and the Neuropsychiatric Inventory ( NPI ) , ability to complete activities of daily living ( ADLs ) , caregiver distress , cognitive safety ( based on scores from the 30-point Mini Mental State Examination [ MMSE ] ) , and adverse events . RESULTS Participants who received citalopram showed significant improvement compared with those who received placebo on both primary outcome measures . The NBRS-A estimated treatment difference at week 9 ( citalopram minus placebo ) was -0.93 ( 95 % CI , -1.80 to -0.06 ) , P = .04 . Results from the mADCS-CGIC showed 40 % of citalopram participants having moderate or marked improvement from baseline compared with 26 % of placebo recipients , with estimated treatment effect ( odds ratio [ OR ] of being at or better than a given CGIC category ) of 2.13 ( 95 % CI , 1.23 - 3.69 ) , P = .01 . Participants who received citalopram showed significant improvement on the CMAI , total NPI , and caregiver distress scores but not on the NPI agitation subscale , ADLs , or in less use of rescue lorazepam . Worsening of cognition ( -1.05 points ; 95 % CI , -1.97 to -0.13 ; P = .03 ) and QT interval prolongation ( 18.1 ms ; 95 % CI , 6.1 - 30.1 ; P = .01 ) were seen in the citalopram group . CONCLUSIONS AND RELEVANCE Among patients with probable Alzheimer disease and agitation who were receiving psychosocial intervention , the addition of citalopram compared with placebo significantly reduced agitation and caregiver distress ; however , cognitive and cardiac adverse effects of citalopram may limit its practical application at the dosage of 30 mg per day . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00898807 The authors compared the efficacy and side effects of trazodone and haloperidol for treating agitated behaviors associated with dementia . Twenty-eight elderly patients with dementia and agitated behaviors were r and omly assigned to double-blind treatment with either trazodone ( 50 - 250 mg/day ) or haloperidol ( 1 - 5 mg/day ) for 9 weeks . There was no significant difference in improvement between the medication groups . Adverse effects , however , were more common in the group treated with haloperidol . Improvement in individual areas suggested that repetitive , verbally aggressive , and oppositional behaviors responded preferentially to trazodone , whereas symptoms of excessive motor activity and unwarranted accusations responded preferentially to haloperidol . These results indicate that moderate doses of trazodone and haloperidol are equally effective for treatment of overall agitated behaviors in patients with dementia , but specific symptoms may respond preferentially to a particular agent Objective : To compare effects of risperidone with placebo ( efficacy and tolerability ) and haloperidol ( tolerability ) for treating demented patients with aggression and other behavioral symptoms . Methods : A 13-week double-blind study involving 344 patients with dementia r and omly assigned to receive placebo or flexible doses ( 0.5 to 4 mg/d ) of risperidone or haloperidol . Behavioral symptoms were assessed by the Behavior Pathology in Alzheimer ’s Disease Rating Scale ( BEHAVE-AD ) , the Cohen-Mansfield Agitation Inventory ( CMAI ) , and the Clinical Global Impression ( CGI ) scale . Tolerability assessment s included the Extrapyramidal Symptom Rating Scale , sedation levels , Functional Assessment Staging , Mini-Mental State Examination , and incidence of adverse events . Results : The mean dose at endpoint was 1.1 mg/d of risperidone and 1.2 mg/d of haloperidol . Although not significant , a higher percentage of patients receiving risperidone than those receiving placebo showed clinical improvement ( ≥30 % reduction from baseline to endpoint in BEHAVE-AD total score ) at endpoint and week 12 . Reductions in the BEHAVE-AD total score were significantly greater with risperidone than with placebo at week 12 . In a further analysis of aggression , the most dominant symptom in these patients , BEHAVE-AD and CMAI aggression cluster scores were significantly reduced compared with placebo at endpoint and week 12 . CGI scores were also significantly reduced at endpoint and week 12 . Severity of extrapyramidal symptoms with risperidone did not differ significantly from that of placebo and was less than that of haloperidol . A post hoc analysis showed significantly greater reductions in the BEHAVE-AD aggressiveness score with risperidone than haloperidol at week 12 . Conclusion : Low-dose risperidone ( mean 1.1 mg/d ) was well tolerated and associated with reductions in the severity and frequency of behavioral symptoms , particularly aggression , in elderly patients with dementia Behavioural troubles due to frontotemporal dementia ( FTD ) are difficult to treat . The serotonergic system is associated with frontal lobes , the degeneration of which contributes to FTD . Trazodone increases the extracellular 5-HT levels in the frontal cortex . In a r and omised , double-blind , placebo-controlled cross-over study , we investigated the effect of trazodone . There was a significant decrease in the Neuropsychiatry Inventory ( NPI ) total score with trazodone ( p = 0.028 ) in the 26 evaluable patients . A decrease of more than 50 % in the NPI score was observed in 10 patients with trazodone . This improvement was mainly based on the improvement of 4 items of the scale ( irritability , agitation , depressive symptoms and eating disorders ) . The Mini-Mental State Examination was not modified and trazodone was well tolerated . Results of this first placebo-controlled trial suggest that trazodone is an effective treatment for the behavioural symptoms of FTD OBJECTIVE To assess the efficacy and safety of aripiprazole for psychosis associated with Alzheimer dementia ( AD ) . METHODS In this double-blind , multicenter study , 487 institutionalized patients with psychosis associated with AD were r and omized to placebo or aripiprazole , 2 , 5 or 10 mg/day . Primary efficacy assessment was the mean change from baseline to week 10 on the Neuropsychiatric Inventory-Nursing Home ( NPI-NH ) version Psychosis Subscale score . Secondary measures included NPI-NH Total , Clinical Global Impression-Severity of Illness ( CGI-S ) , Brief Psychiatric Rating Scale ( BPRS ) Core and Total , and the Cohen-Mansfield Agitation Inventory ( CMAI ) scores . RESULTS Aripiprazole 10 mg/day showed significantly greater improvements ( mean change [ 2 x SD ] ) than placebo on the NPI-NH Psychosis Subscale ( -6.87 [ 8.6 ] versus -5.13 [ 10.0 ] ; F = 6.29 , df = 1 , 422 , p = 0.013 by analysis of covariance [ ANCOVA ] ) ; CGI-S ( -0.72 [ 1.8 ] versus -0.46 [ 1.6 ] ; F = 4.68 , df = 1 , 419 , p = 0.031 [ ANCOVA ] ) ; BPRS Total ( -7.12 [ 18.4 ] versus -4.17 [ 21.6 ] ; F = 4.72 , df = 1 , 399 , p = 0.030 [ ANCOVA ] ) ; BPRS Core ( -3.07 [ 6.9 ] versus -1.74 [ 7.8 ] ; F = 7.30 , df = 1 , 407 , p = 0.007 [ ANCOVA ] ) ; CMAI ( -10.96 [ 22.6 ] versus -6.64 [ 28.6 ] ; F = 5.23 , df = 1 , 410 , p = 0.023 [ ANCOVA ] ) , and NPI-NH Psychosis response rate ( 65 versus 50 % ; chi(2 ) = 5.52 , df = 1 , p = 0.019 [ CMH ] ) . Aripiprazole 5 mg/day showed significant improvements versus placebo on BPRS and CMAI scores . Aripiprazole 2 mg/day was not efficacious . Cerebrovascular adverse events were reported : aripiprazole 2 mg/day , N = 1 ; 5 mg/day , N = 2 ; 10 mg/day , N = 4 ; placebo , N = 0 . No deaths in any group ( aripiprazole 2 mg/day , 3 % ; 5 mg/day , 2 % ; 10 mg/day , 7 % ; placebo , 3 % ) were considered to be treatment-related . CONCLUSION Aripiprazole 10 mg/day was efficacious and safe for psychosis associated with AD , significantly improving psychotic symptoms , agitation , and clinical global impression . However , clinicians should be aware of the safety considerations of atypical antipsychotic uses in this population Purpose : People with dementia fall more often than cognitively healthy older adults , but their risk factors are not well understood . A review is needed to determine a fall risk profile for this population . The objective was to critically evaluate the literature and identify the factors associated with fall risk in older adults with dementia . Methods : Articles published between January 1988 and October 2014 in EMBASE , PubMed , PsycINFO , and CINAHL were search ed . Inclusion criteria were participants aged 55 years or older with dementia or cognitive impairment , prospect i ve cohort design , detailed fall definition , falls as the primary outcome , and multi-variable regression analysis . Two authors independently review ed and extracted data on study characteristics , quality assessment , and outcomes . Adjusted risk estimates were extracted from the articles . Results : A total of 17 studies met the inclusion criteria . Risk factors were categorized into demographic , balance , gait , vision , functional status , medications , psychosocial , severity of dementia , and other . Risk factors varied with living setting and were not consistent across all studies within a setting . Conclusion : Falls in older adults with dementia are associated with multiple intrinsic and extrinsic risk factors , some shared with older adults in general and others unique to the disease . Risk factors vary between community- and institution-dwelling sample s of adults with dementia or cognitive impairment OBJECTIVE Until recently , conventional antipsychotics were the st and ard pharmacotherapy for psychosis and behavioral disturbances associated with dementia . This double-blind , placebo-controlled study compared the acute efficacy of the selective serotonin reuptake inhibitor citalopram and the neuroleptic perphenazine with placebo for the treatment of psychosis and behavioral disturbances in nondepressed patients with dementia . METHOD Eighty-five hospitalized patients with at least one moderate to severe target symptom ( aggression , agitation , hostility , suspiciousness , hallucinations , or delusions ) were r and omly assigned to receive either citalopram , perphenazine , or placebo under double-blind conditions for up to 17 days . RESULTS Patients treated with citalopram or perphenazine showed statistically significant improvement on several Neurobehavioral Rating Scale factor scores . Compared to those receiving placebo , only patients treated with citalopram showed significantly greater improvement in their total Neurobehavioral Rating Scale score as well as in the scores for the agitation/aggression and lability/tension factors . Side effect scores were similar among the three treatment groups . CONCLUSIONS Citalopram was found to be more efficacious than placebo in the short-term hospital treatment of psychotic symptoms and behavioral disturbances in nondepressed , demented patients In this 10-week , double-blind , fixed-dose study , elderly institutionalized patients with dementia and agitation were r and omized ( 3:3:2 ) to quetiapine 200mg/day , 100mg/day , or placebo . The primary endpoint was change in Positive and Negative Syndrome Scale (PANSS)-Excitement Component ( EC ) scores at endpoint , analysed using last observation carried forward ( LOCF ) and observed cases ( OC ) approaches . Other efficacy measures were the Clinical Global Impression of Change ( CGI-C ) , and response rates ( percentage with > or = 40 % reduction [ PANSS-EC ] ; " much " or " very much improved " [ CGI-C ] ) , Neuropsychiatric Inventory-Nursing Home version ( NPI-NH ) , and Cohen-Mansfield Agitation Inventory ( CMAI ) . The key safety measure was incidence of adverse events ; change in Mini-Mental State Examination ( MMSE ) was also assessed . Baseline characteristics of 333 participants ( quetiapine 200mg/day , n=117 ; quetiapine 100mg/day , n=124 ; placebo , n=92 ) and completion rates ( 63 - 65 % ) were comparable among groups . Compared with placebo , quetiapine 200mg/day was associated with clinical ly greater improvements in PANSS-EC ( LOCF , p=0.065 ; OC , p=0.014 [ ANCOVA ] ) , CGI-C ( LOCF , p=0.017 ; OC , p=0.002 [ ANOVA ] ) , and CGI-C response rates ( LOCF , p=0.002 ; OC , p<0.001 [ Chi-square test ] ) . Quetiapine 100mg/day did not differentiate from placebo on these measures . There were no between-group differences in NPI-NH or CMAI . Incidences of cerebrovascular adverse events , postural hypotension , and falls were similar among groups . MMSE did not change in any group . Mortality was numerically higher in the quetiapine groups ; rates were not statistically different from placebo . The results of this study suggest that quetiapine 200mg/day was effective and well-tolerated for treating agitation associated with dementia . However , caution should be exercised given the concerns regarding increased mortality with atypical antipsychotics in this vulnerable patient population This pilot study compared haloperidol , fluoxetine , and placebo for reduction of agitation in 15 out patients with AD . The two drugs were no more effective than placebo at reducing agitation in these subjects ; however , both drugs produced more toxicity than did placebo BACKGROUND Behavioural and psychological symptoms ( BPSD ) are common during the course of dementia and present severe problems to patients and their caregivers . OBJECTIVES To assess the therapeutic efficacy and safety of haloperidol and risperidone in treating BPSD in Chinese dementia patients . METHODS A 12-week double-blind r and omised comparison of haloperidol and risperidone treatments was conducted in 58 patients with DSM-IV diagnosis of dementia of Alzheimer 's type or vascular dementia . They were r and omly assigned to receive flexible doses ( 0.5 to 2 mg/day ) of haloperidol or risperidone . Clinical response was evaluated using the Cohen-Mansfield Agitation Inventory ( CMAI ) , the Behavioral Pathology in Alzheimer 's Disease Rating Scale ( BEHAVE-AD ) , Simpson-Angus Scale , Functional Assessment Staging and Cantonese version of the Mini-Mental State Examination . RESULTS The mean doses at the last week were 0.90 mg/day of haloperidol and 0.85 mg/day of risperidone . Both haloperidol and risperidone significantly reduced the severity of BPSD ( scores on CMAI and BEHAVE-AD ) , with no significant between-group differences . Haloperidol-treated patients showed a worsening on Simpson-Angus scale while there was no significant change in this measure in risperidone-treated patients . CONCLUSIONS Low-dose haloperidol and risperidone were well tolerated and associated with reductions in the severity and frequency of behavioural symptoms in subjects with dementia . Risperidone may have a more favourable risk-benefit profile in view of its lower propensity to induce extrapyramidal symptoms OBJECTIVES The aim of this study is to compare the Empirical Behavioral Rating Scale ( E-BEHAVE-AD ) , Neurobehavioral Rating Scale ( NBRS ) , and Neuropsychiatric Interview ( NPI ) in detecting behavioral disturbance and psychotic symptoms in dementia and characterizing changes in response to treatment . DESIGN Eighty-seven subjects in the r and omized controlled trial " Continuation Pharmacotherapy for Agitation of Dementia " were included in this analysis . We compared the detection in , and changes of , both agitation and psychosis , using these three instruments . A receiver operating characteristic analysis was performed to compare the performance of the three instruments in detecting global improvement . RESULTS The instruments were equally likely to detect agitation . The NBRS was most likely to detect psychosis . Although the NPI best detected improvement in agitation , the instruments were equal for detecting improvement in psychosis . In the receiver operating characteristic analysis for overall clinical improvement in response to treatment , there were no differences in the areas under the correlated curves for the three instruments , but they demonstrated different sensitivity and specificity at different cutoff points for target symptom reduction . The E-BEHAVE-AD performed best at a cut point of 30 % target symptom reduction and the NBRS and NPI both performed best at 50 % . CONCLUSION The E-BEHAVE-AD , NBRS , and NPI were more similar than different in characterizing symptoms but differed in detecting response to treatment . Differences in sensitivity and specificity may lead clinicians to prefer a specific instrument , depending on their goal and the expected magnitude of response to any specific intervention |
13,206 | 22,675,226 | CONCLUSION Studies that monitored both subjective and objective outcome measures of relevance to both patients and parents tended to report the most favorable response to SMT , especially among children with asthma . | INTRODUCTION This study had two purpose s. These were : ( i ) to conduct a search of the literature between 2007 and 2011 investigating the use of spinal manipulative therapy ( SMT ) for pediatric health conditions and ( ii ) to perform a systematic review of eligible retrieved clinical trials . | Background Adolescent idiopathic scoliosis ( AIS ) remains the most common deforming orthopedic condition in children . Increasingly , both adults and children are seeking complementary and alternative therapy , including chiropractic treatment , for a wide variety of health concerns . The scientific evidence supporting the use chiropractic intervention is inadequate . The purpose of this study was to conduct a pilot study and explore issues of safety , patient recruitment and compliance , treatment st and ardization , sham treatment refinement , inter-professional cooperation , quality assurance , and outcome measure selection . Methods Six patients participated in this 6-month study , 5 of whom were female . One female was braced . The mean age of these patients was 14 years , and the mean Cobb angle was 22.2 degrees . The study design was a r and omized controlled clinical trial with two independent and blinded observers . Three patients were treated by st and ard medical care ( observation or brace treatment ) , two were treated with st and ard medical care plus chiropractic manipulation , and one was treated with st and ard medical care plus sham manipulation . The primary outcome measure was Cobb , and the psychosocial measure was Scoliosis Quality of Life Index . Results Orthopedic surgeons and chiropractors were easily recruited and worked cooperatively throughout the trial . Patient recruitment and compliance was good . Chiropractic treatments were safely employed , and research protocol s were successful . Conclusion Overall , our pilot study showed the viability for a larger r and omized trial . This pilot confirms the strength of existing protocol s with amendments for use in a full r and omized controlled trial . Trial registration This trial has been assigned an international st and ard r and omized controlled trial number by Current Controlled Trials , Ltd. http://www.controlled-trials.com/is rct n/. The number is IS RCT N41221647 OBJECTIVE To evaluate chiropractic management of primary nocturnal enuresis in children . DESIGN A controlled clinical trial for 10 wk preceded by and followed by a 2-wk nontreatment period . SETTING Chiropractic clinic of the Palmer Institute of Graduate Studies and Research . PARTICIPANTS Forty-six nocturnal enuretic children ( 31 treatment and 15 control group ) , from a group of 57 children initially included in the study , participated in the trial . INTERVENTION High velocity , short lever adjustments of the spine consistent with the Palmer Package Techniques ; or a sham adjustment using an Activator at a nontension setting administered to the examiner 's underlying contact point . Two 5th-year chiropractic students under the supervision of two clinic faculty performed the adjustments . MAIN OUTCOME MEASURES Frequency of wet nights . RESULTS The post-treatment mean wet night frequency of 7.6 nights/2 wk for the treatment group was significantly less than its baseline mean wet night frequency of 9.1 nights/2 wk ( p = 0.05 ) . For the control group , there was practically no change ( 12.1 to 12.2 nights/2 wk ) in the mean wet night frequency from the baseline to the post-treatment . The mean pre- to post-treatment change in the wet night frequency for the treatment group compared with the control group did not reach statistical significance ( p = 0.067 ) . Twenty-five percent of the treatment-group children had 50 % or more reduction in the wet night frequency from baseline to post-treatment while none among the control group had such reduction . CONCLUSIONS Results of the present study strongly suggest the effectiveness of chiropractic treatment for primary nocturnal enuresis . A larger study of longer duration with a 6-month follow-up is therefore warranted OBJECTIVE The purpose of this study was to describe Danish chiropractic patients younger than 18 years . METHODS Question naires were mailed to all chiropractic clinics in Denmark during a r and omly assigned month between September 2007 and September 2008 . All patients younger than 18 years or their parents were asked to complete a question naire collecting information on age , presenting complaint , duration and consequences of this complaint , referral mode , and use of pain medication . RESULTS Babies were the most common pediatric patients with about one third being between 0 and 4 months of age . Infantile colic was the most common presenting complaint in this age group . For the older children , musculoskeletal problems were the most dominant complaint , ranging from 33 % among the preschool children to 75 % among the teenagers . These complaints were often chronic and about a third of the children older than 2 years had experienced symptoms for more than 1 year before seeing the chiropractor . These health complaints were reported to restrict activity as well as alter mood , and 39 % of the 2- to 17-year olds used analgesics . There was limited referral of patients from other health care professionals . CONCLUSIONS Babies made up most of the Danish chiropractic patients younger than 18 years . Among the older children and the adolescents , musculoskeletal complaints were most common and mostly of a chronic nature . The large number of pediatric patients in chiropractic practice s and the paucity of evidence of treatment effectiveness indicate the need for further research in these age groups Objective . To compare supination at the wrist followed by flexion at the elbow ( the traditional reduction technique ) to hyperpronation at the wrist in the reduction of radial head subluxations ( nursemaid 's elbow ) . Material s and Methods . This prospect i ve , r and omized study involved a consecutive sampling of children younger than 6 years of age who presented to one of two urban pediatric emergency departments and two suburban pediatric ambulatory care centers with a clinical diagnosis of radial head subluxation . Patients were r and omized to undergo reduction by one of the two methods and were followed every 5 minutes for return of elbow function . The initial procedure was repeated if baseline functioning did not return 15 minutes after the initial reduction attempt . Failure of that technique 30 minutes after the initial reduction attempt result ed in a cross-over to the alternate method of reduction . The alternate procedure was repeated if baseline functioning did not return 15 minutes after the alternate procedure was attempted . If the patient failed both techniques , radio-graphy of the elbow was performed . Results . A total of 90 patients were enrolled in the study . Five patients were removed from further analysis secondary to a final diagnosis of fracture , 84 were reduced successfully , and 1 failed both techniques . Demographic characteristics of each group were similar . Thirty-nine of 41 patients ( 95 % ) r and omized to hyper-pronation were reduced successfully on the first attempt versus 34 of 44 patients ( 77 % ) r and omized to supination . Two patients in the hyperpronation group required two attempts versus 10 patients in the supination group . Hyperpronation was more successful ; 40 of 41 patients ( 97.5 % ) in the hyperpronation group were reduced successfully versus 38 of 44 patients ( 86 % ) in the supination group . Of the 6 patients who crossed over from supination to hyperpronation , 5 were reduced on the first attempt and 1 was reduced on the second attempt . Conclusions . In the reduction of radial head subluxations , the hyperpronation technique required fewer attempts at reduction compared with supination , was successful more often than supination , and was often successful when supination failed OBJECTIVE To provide a review of the literature and rate the quality of published studies regarding chiropractic care , including spinal manipulation , for asthmatic patients . METHODS A multimodal search strategy was conducted , including multiple data base search es , along with reference and journal h and - search ing . Studies were limited to those published in English and in peer- review ed journals or conference proceedings between January 1980 and March 2009 . All study design s were considered except personal narratives or review s. Retrieved articles that met the inclusion criteria were rated for quality by using the Downs and Black checklist . A brief summary was also written for each retrieved study . RESULTS Eight articles met the inclusion criteria of this review in the form of one case series , one case study , one survey , two r and omized controlled trials ( RCTs ) , one r and omized patient and observer blinded cross-over trial , one single blind cross study design , and one self-reported impairment question naire . Their quality scores ranged from 5 to 22 out of 27 . CONCLUSION Results of the eight retrieved studies indicated that chiropractic care showed improvements in subjective measures and , to a lesser degree objective measures , none of which were statistically significant . It is evident that some asthmatic patients may benefit from this treatment approach ; however , at this time , the evidence suggests chiropractic care should be used as an adjunct , not a replacement , to traditional medical therapy OBJECTIVE This study investigates the effect of chiropractic treatment on hip joint extension ability and running velocity . METHODS This was a prospect i ve , r and omized , controlled experimental pilot study . Seventeen healthy male junior athletes ( age , 17 - 20 years ) training in middle distance running were recruited from local Swedish athletic associations . Hip extension ability and running velocity were measured before and after the study period . Chiropractic investigations comprised motion palpation of the sacroiliac and hip joints and modified Thomas test of the ability to extend the leg . In the treatment group , findings of restrictive joint dysfunctions formed the basis for the choice of chiropractic treatment . The interventions were based on a pragmatic approach consisting of high-velocity , low-amplitude manipulations targeted toward , but not exclusively to , the sacroiliac joints . RESULTS The treatment group showed significantly greater hip extension ability after chiropractic treatment than did controls ( P < .05 ) . Participants in the treatment group did not show a significant decrease in time for running 30 m after treatment ( average , -0.065 seconds ; P = .0572 ) , whereas the difference was even smaller for the control subjects ( average , -0.003 ; P = .7344 ) . CONCLUSIONS The results imply that chiropractic treatment can improve hip extensibility in subjects with restriction as measured by the modified Thomas test . It could be speculated that the running step was amplified by increasing the angle of step through facilitated hip joint extension ability . The possible effect of chiropractic treatment to enhance the running velocity , by increasing the hip joint extension ability and thereby increasing the running step , remains unproven A prospect i ve , uncontrolled study of 316 infants suffering from infantile colic and selected according to well-defined criteria shows a satisfactory result of spinal manipulative therapy in 94 % of the cases . The median age of the infants was 5.7 wk at the beginning of the treatment . The results were evaluated by analysis of a diary continuously kept by the mother and an assessment file comprised by interview . The study was carried out as a multicenter study lasting 3 months and involving 73 chiropractors in 50 clinics . The results occurred within 2 wk and after an average of three treatments OBJECTIVE To review the biomedical literature up to and including 2003 , and determine the extent of the evidence related to the therapeutic application of chiropractic manipulation for paediatric health conditions . No critical appraisal of the evidence is undertaken . DATA SOURCES The indexed manual therapy sector including medical , chiropractic , physiotherapy , naturopathic and osteopathic literature was search ed . This included PubMed ; the Manual , Alternative , and Natural Therapy Index System ; the Cumulative Index to Nursing and Allied Health Literature ; the Index to Chiropractic Literature ; the Paediatric Economic Data base Evaluation Project ; the Cochrane Library ; the Canadian Coordinating Office for Health Technology Assessment data base ; and the Agency for Healthcare Research and Quality data base . Other re sources included research conference and symposium proceedings , and the references of identified studies . RESULT The search identified 1731 articles , of which 166 met the eligibility criteria . Two review ers determined by consensus each citation 's appropriate level on the strength of evidence scale . There was one systematic review , nine r and omized controlled trials , one observational study , 141 descriptive case studies and 14 conference abstract s. SUMMARY Health cl aims made by practitioners regarding the application of chiropractic manipulation as a health care intervention for paediatric health conditions are , for the most part , supported by low levels of scientific evidence . Chiropractors , in particular , employ manipulation for the treatment of a wide variety of paediatric health conditions . The evidence rests primarily with clinical experience , descriptive case studies and a few r and omized controlled trials . There is a need for more rigorous scientific inquiry to examine the value of manipulative therapy in the treatment of paediatric conditions . To advance the health interests of paediatric patients , health care decisions made on the basis of expert opinion or clinical experience must integrate the best research evidence available from high- quality , scientific studies Background The purpose of this report is to provide a succinct but comprehensive summary of the scientific evidence regarding the effectiveness of manual treatment for the management of a variety of musculoskeletal and non-musculoskeletal conditions . Methods The conclusions are based on the results of systematic review s of r and omized clinical trials ( RCTs ) , widely accepted and primarily UK and United States evidence -based clinical guidelines , plus the results of all RCTs not yet included in the first three categories . The strength/ quality of the evidence regarding effectiveness was based on an adapted version of the grading system developed by the US Preventive Services Task Force and a study risk of bias assessment tool for the recent RCTs . Results By September 2009 , 26 categories of conditions were located containing RCT evidence for the use of manual therapy : 13 musculoskeletal conditions , four types of chronic headache and nine non-musculoskeletal conditions . We identified 49 recent relevant systematic review s and 16 evidence -based clinical guidelines plus an additional 46 RCTs not yet included in systematic review s and guidelines .Additionally , brief references are made to other effective non-pharmacological , non-invasive physical treatments . Conclusions Spinal manipulation/mobilization is effective in adults for : acute , subacute , and chronic low back pain ; migraine and cervicogenic headache ; cervicogenic dizziness ; manipulation/mobilization is effective for several extremity joint conditions ; and thoracic manipulation/mobilization is effective for acute/subacute neck pain . The evidence is inconclusive for cervical manipulation/mobilization alone for neck pain of any duration , and for manipulation/mobilization for mid back pain , sciatica , tension-type headache , coccydynia , temporom and ibular joint disorders , fibromyalgia , premenstrual syndrome , and pneumonia in older adults . Spinal manipulation is not effective for asthma and dysmenorrhea when compared to sham manipulation , or for Stage 1 hypertension when added to an antihypertensive diet . In children , the evidence is inconclusive regarding the effectiveness for otitis media and enuresis , and it is not effective for infantile colic and asthma when compared to sham manipulation . Massage is effective in adults for chronic low back pain and chronic neck pain . The evidence is inconclusive for knee osteoarthritis , fibromyalgia , myofascial pain syndrome , migraine headache , and premenstrual syndrome . In children , the evidence is inconclusive for asthma and infantile colic BACKGROUND Pediatric otitis media with effusion is a common and costly condition . Although chiropractors have anecdotally cl aim ed success in treating otitis media , there is little research to support their cl aims . OBJECTIVE A pilot study was undertaken for the purpose of assessing the feasibility of conducting a full-scale r and omized clinical trial investigating the efficacy of chiropractic spinal manipulative therapy ( SMT ) for children with chronic otitis media with effusion . METHODS This study was a prospect i ve , parallel-group , observer-blinded , r and omized feasibility study . Twenty-two patients , ages 6 months to 6 years , received either active chiropractic SMT or placebo chiropractic SMT . Otoscopy and tympanometry were used to create a middle ear status profile , and daily diaries were collected . RESULTS Five newspaper advertisements over 6 months generated 105 responses . Twenty patients subsequently qualified and were r and omized into the study . Collection of tympanometric and otoscopic data proved to be challenging . Compliance with the treatment and evaluation protocol s and daily diaries was excellent . There were no reports of serious side effects as a result of either the active or placebo chiropractic treatments . CONCLUSION Recruitment for a r and omized controlled trial is feasible and could be enhanced by medical collaboration . Patients and parents are able and willing to participate in a study comparing active SMT and placebo SMT . Parents were extremely compliant with the daily diaries , suggesting that similar quality -of-life and functional status measures can be successfully used in a larger trial . We found the objective outcomes assessment involving tympanometry and otoscopy extremely challenging and should be performed by experienced examiners in future studies OBJECTIVE To determine the effect of chiropractic care on jet lag in Finnish junior elite athletes . SUBJECTS Fifteen Finnish junior elite athletes . METHODS Through use of a table of r and om numbers , each athlete was assigned by sex to one of 3 groups : chiropractic adjustment , sham adjustment , or control . As needed , the chiropractic adjustment group athletes ( n = 5 ) were adjusted on a daily basis by licensed chiropractors using a toggle/recoil procedure . The sham adjustment group athletes ( n = 5 ) received sham adjustments on a daily basis by licensed chiropractors . The control group athletes ( n = 5 ) were not adjusted or sham-adjusted but participated in all test protocol s. Sleep , jet lag , chiropractic , and mood data ( the last acquired through use of the Profile of Mood States ) were collected on a daily basis for 18 consecutive days . RESULTS Repeated- measures analyses of variance ( 3 x 2 ) of total mood disturbance scores and heart rate variables indicated that there were no significant ( .05 level ) between-group differences . Sleep data were analyzed through use of a 3 x 2 , repeated- measures multivariate analysis of variance . Pillai 's trace indicated that there were no between-group differences . Self- assessment of jet lag by participants after traveling to Georgia and after returning to Finl and showed no between-group differences . CONCLUSIONS It was concluded that chiropractic care did not reduce the effects of jet lag |
13,207 | 21,445,251 | / SIGNIFICANCE Putative low EPHX1 enzyme activity may have a potential protective effect on tobacco-related carcinogenesis of lung and UADT cancers , whereas putative high EPHX1 activity may have a harmful effect .
Moreover , cigarette-smoking status may influence the association of EPHX1 enzyme activity and the related cancer risk | BACKGROUND EPHX1 is a key enzyme in metabolizing some exogenous carcinogens such as products of cigarette-smoking .
Two functional polymorphisms in the EPHX1 gene , Tyr113His and His139Arg can alter the enzyme activity , suggesting their possible association with carcinogenesis risk , particularly of some tobacco-related cancers . | Cigarette smoking is a risk factor for colorectal adenoma , a precursor of colorectal cancer . Microsomal epoxide hydrolase ( EPHX1 ) metabolizes polycyclic aromatic hydrocarbons , carcinogens found in cigarette smoke . Nonsynonymous variants of EPHX1 at Tyr(113)His ( exon 3 ) and His(139)Arg ( exon 4 ) are associated , respectively , with low ( (113)His ) and high ( (139)Arg ) predicted activity . Among participants r and omized to the screening arm of the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial , we evaluated risks for advanced adenoma in relation to cigarette use and these two EPHX1 variants . We compared 772 cases with advanced adenoma ( adenoma > /=1 cm or containing high- grade dysplasia or villous , including tubulovillous , elements ) of the distal colon ( left-sided , descending colon and sigmoid or rectum ) to 777 gender- and age-matched controls who were screen-negative for left-sided adenoma . Compared to those with homozygous genotypes predicting low EPHX1 activity , advanced adenoma risks tended to be elevated for carriers of (113)TyrTyr [ odds ratios ( OR ) , 1.5 ; 95 % confidence intervals ( CI ) , 1.0 - 2.2 ] and (139)ArgArg ( OR , 1.4 ; 95 % CI , 0.8 - 2.5 ) and for subjects who carried a greater number of the alleles ( (113)Tyr or (139)Arg ) associated with high predicted enzymatic activity ( P(trend ) = 0.03 ) . The increased risk associated with the increasing number of putative high-activity alleles was most apparent among current and recent ( quit < 10 years ) cigarette smokers ( P(trend ) = 0.02 ) . In conclusion , EPHX1 variants at codon 113 and 139 associated with high predicted enzymatic activity appear to increase risk for colorectal adenoma , particularly among recent and current smokers Microsomal epoxide hydrolase ( mEH ) is involved in the metabolism of environmental and tobacco carcinogens . Smaller studies found inconsistent results in the relationship between mEH polymorphisms and lung cancer risk . We investigated the two polymorphisms of mEH in 974 Caucasian lung cancer patients and 1142 controls using PCR-RFLP techniques . The results were analyzed using generalized additive models and logistic regression , adjusting for relevant covariates . There was no overall relationship between mEH genotypes and lung cancer risk . The adjusted odds ratio ( OR ) of the very low activity genotype versus that of other genotypes combined was 1.00 [ 95 % confidence interval ( CI ) , 0.74 - 1.34 ] . However , gene-environment interaction analyses revealed that the ORs decreased as cumulative smoking ( defined as square root of pack-years ) increased . When pack-years = 0 , the OR was 1.89 ( 95 % CI , 1.08 - 3.28 ) . When pack-years = 28.5 , the OR was 1.00 ( 95 % CI , 0.76 - 1.32 ) , and when pack-years = 80 , the OR decreased to 0.65 ( 95 % CI , 0.42 - 1.00 ) . When cases were stratified according to histological subtypes , the interaction between mEH genotype and cumulative smoking was statistically significant ( P < 0.01 ) for the 222 squamous cell carcinoma cases , whereas it was not significant ( P = 0.18 ) for the 432 adenocarcinoma cases . In conclusion , cumulative cigarette smoking plays a pivotal role in the association between mEH polymorphisms and lung cancer risk , altering the direction of risk ( in the case of the very low activity genotype ) from a risk factor in nonsmokers to a relatively protective factor in heavy smokers |
13,208 | 29,284,713 | CONCLUSIONS Interventions offered to at-risk families in the first year of the child 's life appear to improve child behaviour , parent-child relationship and maternal sensitivity post-intervention , but not child cognitive development and internalising or externalising behaviour . | OBJECTIVES Infancy is a critical stage of life , and a secure relationship with caring and responsive caregivers is crucial for healthy infant development .
Early parenting interventions aim to support families in which infants are at risk of developmental harm .
Our objective is to systematic ally review the effects of parenting interventions on child development and on parent-child relationship for at-risk families with infants aged 0 - 12 months . | Child development literature suggests a relationship between mother-child interaction and enhanced infant development . We conducted a r and omized clinical trial to determine if a pediatrician 's guidance improves the mother-infant relationship and the infant 's development . Thirty-two normal mothers and their healthy first-born infants were followed by one pediatrician at 2 , 4 , 8 , 15 , and 21 weeks of age . These dyads were r and omly assigned to a control group , who received customary care , or to an intervention group , who also received guidance based on the infant 's developmental status at each age . Just prior to a 27-week visit , the mother-infant relationship was assessed by a person blind to group assignment . Infant development was assessed with the Bayley Mental Scales of Infant Development and two of the Uzguris-Hunt Ordinal Scales . Intervention group mothers were rated significantly higher on sensitivity , cooperation , appropriateness of interaction , and appropriateness of play ( P less than .05 ) . Experimental infants were advanced on the Vocal Imitation ordinal scale . This study shows the effectiveness of this intervention on both the mother-infant relationship and infant development and supports pediatric involvement in this biosocial approach to well child care OBJECTIVES We evaluated Legacy for Children , a public health strategy to improve child health and development among low-income families . METHODS Mothers were recruited prenatally or at the birth of a child to participate in Legacy parenting groups for 3 to 5 years . A set of 2 r and omized trials in Miami , Florida , and Los Angeles , California , between 2001 and 2009 assessed 574 mother-child pairs when the children were 6 , 12 , 24 , 36 , 48 , and 60 months old . Intent-to-treat analyses from 12 to 60 months compared groups on child behavioral and socioemotional outcomes . RESULTS Children of mothers in the intervention group were at lower risk for behavioral concerns at 24 months and socioemotional problems at 48 months in Miami , and lower risk for hyperactive behavior at 60 months in Los Angeles . Longitudinal analyses indicated that children of intervention mothers in Miami were at lower risk for behavior problems from 24 to 60 months of age . CONCLUSIONS R and omized controlled trials documented effectiveness of the Legacy model over time while allowing for implementation adaptations by 2 different sites . Broadly disseminable , parent-focused prevention models such as Legacy have potential for public health impact . These investments in prevention might reduce the need for later intervention strategies Background For the first time to our knowledge , short- and long-term effects of a multi-site r and omized-controlled trial ( RCT ) of video feedback of infant – parent interaction ( VIPI ) intervention in naturalistic setting s are published . The intervention targets families with children younger than 2 years old and parent – child interactions problems . Outcome variables were 1 ) observed parent – child interactions and 2 ) parent-reported child social and emotional development . Between-group differences of the moderating effects of parental symptoms of depression , personality disorders traits , and demographic variables were investigated . Method The study had a parallel-group , consecutively r and omized , single-blinded design ; participants were recruited by health- and social workers . Seventy-five families received VIPI , and 57 families received treatment as usual ( TAU ) . Videotapes of each parent – child interactions were obtained before treatment , right after treatment , and at a 6-month follow-up and coded according to Biringen ’s Emotional Availability Scales . Parental symptoms of depression and personality disorder traits were included as possible moderators . Results Evidence of a short-term effect of VIPI treatment on parent – child interactions was established , especially among depressed parents and parents with problematic interactions– and , to some extent , among parents with dependent and paranoid personality disorder traits . A long-term positive effect of VIPI compared with TAU on child social/emotional development was also evident . In a secondary analysis , VIPI had a direct positive effect on the depressive symptoms of parents compared with TAU . Conclusion The findings of the study support the use of VIPI as an intervention in families with interaction difficulties . Trial registration Current Controlled Trials IS RCT N99793905 Based on the US Nurse-Family Partnership ( NFP ) program , the German home visiting program “ Pro Kind ” offered support for socially and financially disadvantaged first-time mothers from pregnancy until the children ’s second birthday . A multi-centered , longitudinal r and omized controlled trial ( RCT ) was conducted to assess its effectiveness on mothers and children . A total of 755 women with multiple risk factors were recruited , 394 received regular home visits ( treatment group ) , while 361 only had access to st and ard community services ( control group ) . Program influences on family environment ( e.g. , quality of home , social support ) , maternal competencies ( e.g. , maternal self-efficacy , empathy , parenting style ) , and child development ( e.g. , cognitive and motor development ) were assessed from mothers ’ program intake in pregnancy to children ’s second birthday based on self-reports in regular interviews and developmental tests . Generalized estimating equations ( GEE ) models showed small , but significant positive treatment effects on parental self-efficacy , and marginally significant effects on social support , and knowledge on child rearing . Maternal stress , self-efficacy , and feelings of attachment in the TG tend to show a more positive development over time . Subgroup effects were found for high-risk mothers in the TG , who reported more social support over time and , generally , had children with higher developmental scores compared to their CG counterparts . Post hoc analyses of implementation variables revealed the quality of the helping relationship as a significant indicator of treatment effects . Results are discussed in terms of implementation and public policy differences between NFP and Pro Kind Objective . To evaluate the extent to which a program of home visitation ( Early Start ) , targeted at families who are facing stress and difficulty , had beneficial consequences for child health , preschool education , service utilization , parenting , child abuse and neglect , and behavioral adjustment . Methods . The study used a r and omized , controlled trial design in which 220 families who were participating in the Early Start program were contrasted with a control series of 223 families who were not participating in the program . Families were enrolled in the program after population screening that was conducted by community health nurses . Families were enrolled in the program for up to 36 months . Outcomes were assessed at 6 , 12 , 24 , and 36 months after trial entry . Results . Families in the Early Start series received a mean of 24 months of service . Comparisons between the Early Start and control series over the 36-month follow-up period revealed that families in the Early Start program showed significant benefits in the areas of improved utilization of child health services , reduced rates of hospital attendance for injury/poisoning , increased preschool education , increased positive and nonpunitive parenting , reduced rates of severe parent/child assaults , and reduced rates of early problem behaviors . Effect sizes ( Cohen 's “ d ” ) were found to be in the small to moderate range , with d ranging from .03 to .31 ( median : .22 ) . Conclusions . The Early Start program was associated with small to moderate benefits in a wide range of areas relating to child health , preschool education , parenting , child abuse , and early behavioral adjustment . Comparisons with other studies are made , and threats to validity are considered Background Psychopathology in women after childbirth represents a significant risk factor for parenting and infant mental health . Regarding child development , these infants are at increased risk for developing unfavorable attachment strategies to their mothers and for subsequent behavioral , emotional and cognitive impairments throughout childhood . To date , the specific efficacy of an early attachment-based parenting group intervention under st and ard clinical outpatient conditions , and the moderators and mediators that promote attachment security in infants of mentally ill mothers , have been poorly evaluated . Methods / Design This r and omized controlled clinical trial tests whether promoting attachment security in infancy with the Circle of Security ( COS ) Intervention will result in a higher rate of securely attached children compared to treatment as usual ( TAU ) . Furthermore , we will determine whether the distributions of securely attached children are moderated or mediated by variations in maternal sensitivity , mentalizing , attachment representations , and psychopathology obtained at baseline and at follow-up . We plan to recruit 80 mother-infant dyads when infants are aged 4 - 9 months with 40 dyads being r and omized to each treatment arm . Infants and mothers will be reassessed when the children are 16 - 18 months of age . Method ological aspects of the study are systematic recruitment and r and omization , explicit inclusion and exclusion criteria , research assessors and coders blinded to treatment allocation , advanced statistical analysis , manualized treatment protocol s and assessment s of treatment adherence and integrity . Discussion The aim of this clinical trial is to determine whether there are specific effects of an attachment-based intervention that promotes attachment security in infants . Additionally , we anticipate being able to utilize data on maternal and child outcome measures to obtain preliminary indications about potential moderators of the intervention and inform hypotheses about which intervention may be most suitable when offered in a clinical psychiatric outpatient context .Trial registration Current Controlled Trials IS RCT The Parents as Teachers ( PAT ) program is a parent-education program that includes home visiting and is design ed to begin prenatally or at birth . Through home visits , visitors called parent educators help parents to strengthen their parenting skills and knowledge of child development and to prepare young children for school . This article describes the PAT program and reports the results of evaluations of two r and omized trials of PAT : ( 1 ) the Northern California ( Salinas Valley ) Parents as Teachers Demonstration , which served primarily Latino parents in the Salinas Valley of California 's Monterey County ; and ( 2 ) the Teen Parents as Teachers Demonstration , which served adolescent parents in four counties in Southern California . The two evaluations revealed small and inconsistent positive effects on parent knowledge , attitudes , and behavior , and no gains in child development or health , when analyses compared the experimental and control groups overall . However , subgroup analyses in the Salinas Valley program indicated that children in primarily Spanish-speaking Latino families benefitted more than either non-Latino or English-speaking Latino families , with significant gains in cognitive , communication , social , and self-help development . Subgroup analyses in the Teen PAT Demonstration indicated that families that received both PAT services and comprehensive case management services design ed to help mothers improve their life course benefitted most . Subgroup analyses in the Salinas Valley study suggested that children in families that received more intensive services benefitted more than children whose families received less intensive services . Results from that study suggested that home visits produced about a one-month developmental advantage per 10 visits for participating children OBJECTIVE : To evaluate the extent to which a home-visitation program ( Early Start ) had benefits for child abuse , child behavior , and parental- and family-level benefits to the 9-year follow-up . METHODS : A r and omized controlled trial in which 220 families receiving Early Start were contrasted with a control series of 223 families not receiving the program . Families were enrolled in the program for up to 5 years . Outcomes were assessed at 6 months , annually from 1 year to 6 years , and at 9 years after trial entry . RESULTS : Comparisons between the Early Start and control series showed that families in the Early Start program showed significant ( P < .05 ) benefits in reduced risk of hospital attendance for unintentional injury , lower risk of parent-reported harsh punishment , lower levels of physical punishment , higher parenting competence scores , and more positive child behavioral adjustment scores . Effect sizes ( Cohen ’s “ d ” ) ranged from 0.13 to 0.29 ( median = 0.25 ) . There were no significant differences ( all P values > .05 ) between the Early Start and control series on a range of measures of parental behavior and family outcomes , including maternal depression , parental substance use , intimate partner violence , adverse economic outcomes , and life stress . CONCLUSIONS : The Early Start program was associated with small to moderate benefits in a range of areas relating to child abuse , physical punishment , child behavior , and parenting competence . There was little evidence to suggest that the Early Start program had benefits that extended to the level of parents or family overall Objectives From a developmental perspective , infancy is a critical stage of life . Early childhood interventions aim to support caretakers , but the effects of universal interventions for parents with infants are unknown . The objective is to determine the effects of universal parenting interventions offered to parents with infants 0–12 months on measures of child development and parent – child relationship . Design A systematic review using the Preferred Reporting Items for Systematic Review s and Meta- Analysis . We extracted publications from 10 data bases in June 2013 , January 2015 and June 2016 and supplemented with grey and h and search . Risk of bias was assessed , and effect sizes were calculated . Participants Inclusion criteria are : ( 1 ) r and omised controlled trials of structured , psychosocial interventions offered to a universal population of parents with infants 0–12 months old in western OECD countries , ( 2 ) interventions that include a minimum of 3 sessions with at least half of the sessions delivered postnatally and ( 3 ) programme outcomes reported for child development or parent – child relationship . Results 14 papers representing 7 studies are included . There were no statistically significant effects of the intervention for the majority of the primary outcomes across the studies . Conclusions The findings of this review are mixed . No clear conclusions can be drawn regarding the effects of universally offered parenting interventions on child development and parent – child relationship for this age group BACKGROUND The Copenhagen Child Cohort , CCC 2000 , was established to investigate developmental psychopathology prospect ively from birth in a general population . METHODS A r and om sample of 211 children from the CCC 2000 was investigated when the children were 1(1/2 ) years of age . The prevalence and associates of mental health problems and psychopathology were studied by clinical and st and ardised strategies , including videotape recordings , parent interviews and the following instruments : The Child Behavior Check List 1(1/2)-5 ( CBCL 1(1/2)-5 ) , The Infant Toddler Symptom Check List ( ITSCL ) , Checklist for Autism in Toddlers ( CHAT ) , Bayley Scales of Infant Development II ( BSID II ) , The Parent Child Early Relationship Assessment ( PC ERA ) and Parent Infant Relationship Global Assessment Scale ( PIR-GAS ) . RESULTS Mental health problems according to International Classification of Diseases ( ICD-10 ) and Diagnostic Classification Zero to Three ( DC 0 - 3 ) diagnoses were found in 16 - 18 % of 1(1/2)-year-old children . Most common were disturbances of emotion , behaviour and eating and the DC 0 - 3 diagnosis of regulatory disorder . Parent-child relationship disturbances were found in 8 % . High psychosocial risk was significantly associated with emotional and behavioural disorders ( OR 3.1 95 % ( 1.2 - 8.1 ) ) and disturbed parent-child relationship ( OR 5.0 95 % ( 1.6 - 16.0 ) ) . The strongest association of risk was found between relationship disorders and emotional and behavioural disorders ( OR 11.6 95 % ( 3.8 - 37.5 ) ) . CONCLUSIONS The prevalence and distribution of psychopathology in 1(1/2)-year-old children seem to correspond to the distributions among older children . Disturbances in parent-child relationship have a key position in the risk mechanisms in early child psychopathology OBJECTIVE To determine if group well child care ( GWCC ) for high-risk children affects maternal-child interaction and development as compared to these outcomes in children receiving traditional individual well child care ( IWCC ) . STUDY DESIGN R and omized controlled trial . PARTICIPANTS Infants less than 4 months old at the initiation of the study who came from high-risk families . Families were classified as high risk , and eligible for study participation , if the mother had one or more of the following characteristics : poverty , single marital status , less than a high school education , age less than 20 years at delivery , previous substance abuse , or a history of abuse as a child . SETTING Two urban , university pediatric clinics in Seattle , Washington . INTERVENTIONS Study children were r and omized to receive GWCC or IWCC prior to the first study visit at the age of 4 months . Study health supervision visits were scheduled at 4 , 5 , 6 , 8 , 10 , 12 , and 15 months of age . For children r and omized to receive GWCC , study visits consisted of an age-matched group discussion of child rearing issues , either preceding or following a brief physical examination . After the 15-month visit , development of study patients was assessed by the use of Bayley Scales of Infant Development ( Bayley ) . Maternal-child interaction and the home environment were evaluated by the use of the Nursing Child Assessment Teaching Scale ( NCATS ) and the Home Observation for Measurement of the Environment ( HOME ) , respectively . RESULTS At least one outcome measure was obtained on 114 children ; 86 patients completed all three outcome measures . Bayley psychomotor mean scores were 103.6 + /- 11.5 for GWCC patients versus 100.0 + /- 12.4 for those receiving IWCC ( P = .14 ) ; mean scores for the mental section were 99.3 + /- 14.8 and 100.4 + /- 14.3 , respectively ( P = .71 ) . The prevalence of high-risk maternal-child interactions was 10 % in both the GWCC and IWCC groups . A high-risk home environment was found in 16 % of IWCC patients versus 4 % of those r and omized to GWCC ( odds ratio comparing IWCC to GWCC 4.6 , 95 % confidence interval 0.78 , 26.0 , after controlling for confounding variables ) . Provider time was similar among groups ( mean number of minutes/patient/ study visit : 19.8 + /- 5.6 and 20.4 + /- 6.7 for GWCC and IWCC , respectively , P = .66 ) . CONCLUSION GWCC is a viable alternative to IWCC for high-risk children . Developmental outcomes and maternal-child interaction are at least as good for children who received GWCC as compared to traditional IWCC , without any increase in provider time required This study evaluated the enduring effectiveness of a skill-based training program to enhance maternal sensitivity between 6 and 9 months of age . 82 mothers and their toddlers were evaluated at 18 and 24 months , and 79 at 31/2 years on the bases of observations of free play , everyday interaction , problem solving , and peer interaction . Most of the significant behavioral changes noted in the second year pertain to attachment security , indices of maternal sensitivity across situations , and child cooperation . Some enduring effects on indices of sensitivity appear to be attachment-mediated . In the third year , results revealed direct enduring intervention effects on parental responsiveness and child cooperation . Attachment-mediated effects were evident for maternal assistance , child security , and positive peer contact . Attachment pattern also predicted differences in attractiveness of the focal child as an interactive partner This r and omized controlled trial examined ( a ) the efficacy of a brief intervention design ed to increase the rate of secure infant attachment , ( b ) the differential susceptibility hypothesis , and ( c ) whether maternal attachment styles moderated the expected Treatment x Irritability interaction in predicting infant attachment outcomes . Although there was no main effect of treatment , a significant Treatment x Irritability interaction revealed intervention effects for the highly irritable infants only , thus supporting one of two predictions of the differential susceptibility hypothesis : highly irritable infants would have disproportionately better outcomes than moderately irritable infants in better conditions ( i.e. , with intervention ) . When separate analyses were conducted with maternal attachment styles , we found significant three-way interactions among treatment , irritability , and each of the examined maternal attachment style dimensions ( i.e. , secure-fearful and dismissing-preoccupied ) . Specifically , with more secure mothers , beneficial effects of intervention emerged for highly irritable infants . For more dismissing mothers , the results revealed support for both predictions of the differential susceptibility hypothesis : highly irritable infants , compared to moderately irritable infants , were both more likely to be secure with intervention and less likely to be secure when in the control group . It is interesting that , for more preoccupied mothers , a treatment effect emerged only for moderately irritable infants . We discuss the implication s of these findings for the differential susceptibility hypothesis as well as for early intervention 65 families with children at risk for cognitive difficulties were r and omly assigned at the time of the child 's birth to 1 of 3 groups , 2 intervention and 1 control . For the most intensive intervention group , family education was combined with a center-based educational day-care program ; the less intensive intervention group received the home-based family education program only . To assess the cognitive performance of children , The Bayley Scales of Infant Development were administered at 6 , 12 , and 18 months ; the Stanford-Binet Intelligence Test at 24 , 36 , and 48 months ; and the McCarthy Scales of Children 's Abilities at 30 , 42 , and 54 months . On each test after the 6-month assessment , scores of children in the educational day-care plus family support group were greater than those in the other 2 groups . No cognitive intervention effects were obtained for the family education group . Group effects were not obtained for measures of either the quality of the home environment or parent attention The current intervention study aim ed at breaking the potential intergenerational cycle of insecure attachment . The authors r and omly assigned 81 first-time mothers to one of two intervention groups or a control group . The interventions involved four home visits when the infants were between 7 and 10 months old . The first intervention , VIPP , consisted of video-feedback and brochures to enhance sensitive parenting . The second intervention , VIPP-R , involved additional discussion s of mothers ' childhood attachment experiences in relation to their current caregiving . After the intervention , intervention mothers were more sensitive than control mothers . The interventions were most effective for highly reactive children and their mothers , providing experimental support for Belsky 's ( 1997 ) hypothesis of highly reactive versus less reactive children 's evolutionary based differential susceptibility to rearing influences An earlier r and omized controlled trial ( RCT ) compared 80 mother-infant dyads in a Stockholm sample . One had received mother-infant psychoanalytic treatment [ mother-infant psychoanalytic therapies ( MIP ) group ] , and the other received Child Health Center care ( CHCC group ) . Effects were found on mother-reported depression and expert-rated mother-infant relationship qualities and maternal sensitivity . When the children were 412 years , the dyads were followed up with assessment s of the children 's attachment representations , social and emotional development , and global functioning , and the mothers ' psychological well-being and representations of the child as well as the mother-child interactions . We gathered data from 66 cases approximately 312 years ' posttreatment . All scores involving the mothers had now approached community levels . We found effects on maternal depression in favor of MIP , but no other between-group differences . The MIP treatments seemed to have helped the mothers to recover more quickly on personal well-being , to become more sensitive to their babies ' suffering , and to better support and appreciate their children throughout infancy and toddlerhood . If so , this would explain why the MIP children had a better global functioning and were more often " OK " and less often " Troubled " at 412 years The purpose of the study was to analyze the efficacy of early home-visiting intervention in enhancing the quality of mother – infant interaction in psychosocial risk and depressive risk mother – infant dyads . Thirty depressive risk , 28 psychosocial risk , and 33 low-depressed and low-risk mothers were r and omly distributed between the Home Visiting Program and control groups . Attachment ( Adult Attachment Interview ; Main & Goldwyn , 1997 ) and maternal representations during pregnancy ( Interview of Maternal Representations During Pregnancy ; Ammaniti , C and elori , Pola , & Tambelli , 1999 ) and after the birth of the infant ( Interview of Maternal Representations After the Birth ; Ammaniti et al. , 1999 ) were evaluated as well as depressive symptoms ( Center for Epidemiological Studies -Depression Scale ; Radloff , 1977 ) during the first year . Ratings of sensitivity , interference , affective state of the mother , cooperation , and infant self-regulation during mother – infant interactions were assessed at 3 , 6 , and 12 months . Results showed the efficacy of the home-visiting program in improving sensitive maternal behaviors toward the child after 6 months of intervention A r and omized controlled trial ( RCT ) compared two groups of mother-infant dyads in a Stockholm sample . One had received mother-infant psychoanalytic treatment ( MIP group ) and the other Child Health Center care ( CHCC group ) . Effects were found on mother-reported depression and expert-rated mother-infant relationship qualities and maternal sensitivity . When the children were 4½ years old , they were followed up with assessment s of attachment representations , socioemotional development , and global functioning . They also were divided into two types according to individual characteristics and psychological well-being : the " OK " and the " Troubled " children . Of 80 dyads in the mother-infant RCT , data were gathered from 66 cases approximately 3½ years after treatment . The children in the MIP group had better results on global functioning . There were more OK children in the MIP group and more Troubled children in the CHCC group . No other between-group differences were found . A relatively brief mother-infant psychotherapy seemed to help the children function better and be less troubled 3½ years after therapy Intervention strategies are needed to improve maternal and infant outcomes in minority population s living in poverty . Home visiting by nurses has improved outcomes for mothers and young children , but use of professional staff makes these programs expensive . Pride in Parenting was a r and omized controlled trial of paraprofessional home visitation to provide health and developmental intervention for high-risk African American mothers in Washington , DC . This study proposed to test whether paraprofessional visitors drawn from the community could effectively influence health and mothers ’ parenting behaviors and attitudes . African American mothers with inadequate prenatal care were recruited at delivery and r and omized to intervention or usual care groups . The intervention curriculum was delivered through both home visitation and parent-infant groups for 1 year . The intervention curriculum was design ed to improve knowledge , influence attitudes , and promote life skills that would assist low-income mothers in offering better health oversight and development for their infants . Both intervention and usual care groups received monthly social work contact over the one-year study period to provide referrals for identified needs . The intervention participants improved their home environments , a characteristic important for promoting good child development . Mothers ’ perceptions of available social support improved and child-rearing attitudes associated with child maltreatment were reduced . Paraprofessional home visitors can be successful in improving the child-rearing environments and parenting attitudes for infants at risk , perhaps offering a less costly option to professional home visitors Seven hundred thirty-one income-eligible families in 3 geographical regions who were enrolled in a national food supplement program were screened and r and omized to a brief family intervention . At child ages 2 and 3 , the intervention group caregivers were offered the Family Check-Up and linked parenting support services . Latent growth models on caregiver reports at child ages 2 , 3 , and 4 revealed decreased behavior problems when compared with the control group . Intervention effects occurred predominantly among families reporting high levels of problem behavior at child age 2 . Families in the intervention condition improved on direct observation measures of caregivers ' positive behavior support at child ages 2 and 3 ; improvements in positive behavior support mediated improvements in children 's early problem behavior Mother-infant relationship disturbances occur in three domains : maternal distress , infant functional problems , and relationship difficulties . They constitute common clinical problems . In Sweden , they are usually h and led by nurses as part of public Child Health Centre care . Severe cases are referred to child psychiatry services . This r and omized controlled trial compared two groups of mother-infant dyads in a Stockholm sample . One received only Child Health Centre care ( the " CHCC " group ) while the other received mother-infant psychoanalytic treatment plus CHCC ( the " MIP " group ) . Eighty dyads of mothers and infants under 1½ years of age where the mothers had serious concerns about themselves in their role as mothers , their infants ' well-being , or the mother-baby relationship were r and omly selected for either the MIP or the CHCC group . The primary outcomes were mother-reported depression , mother-reported infant functional problems , and interviewer-based relationship assessment s , all at 6 months after joining the project . Secondary outcomes were mother-reported stress and general psychic distress , externally rated video-recorded interactions , and the consumption of healthcare at the CHC , again all after 6 months . Intent-to-treat analyses of Treatment × Time effects significantly favored MIP treatment for maternal depression , mother-infant relationships , and maternal sensitivity . Effects were nearly significant on maternal stress , but nonsignificant on mother-reported infant functional problems , general psychic distress , maternal interactive structuring and nonintrusiveness , infant responsiveness and involvement , and healthcare consumption . MIP treatment improved mother-infant relationships and maternal sensitivity and depression , all of which are known to influence child development . If effects persist and are reproduced , MIP treatment holds promise for more widespread use Objective : We performed a r and omized , controlled trial to assess the impact of the Video Interaction Project ( VIP ) , a program based in pediatric primary care in which videotaped interactions are used by child development specialists to promote early child development . Method : Ninety-nine Latino children ( 52 VIP , 47 controls ) at risk of developmental delay based on poverty and low maternal education were assessed at age 33 months . VIP was associated with improved parenting practice s including increased teaching behaviors . Results : VIP was associated with lower levels of parenting stress . VIP children were more likely to have normal cognitive development and less likely to have developmental delays . Conclusion : This study provides evidence that a pediatric primary care – based intervention program can have an impact on the developmental trajectories of at-risk young preschool children 6-month-old infants selected on irritability shortly after birth and their mothers were r and omly assigned to 2 intervention and 2 control groups to test the hypothesis that enhancing maternal sensitive responsiveness will improve quality of mother-infant interaction , infant exploration , and attachment . The intervention lasted 3 months and ended when the child was 9 months of age . When infants were 9 months of age , intervention group mothers were significantly more responsive , stimulating , visually attentive , and controlling of their infant 's behavior than control group mothers . Intervention infants had higher scores than control infants on sociability , self-soothing , and exploration , and they cried less . Quality of exploration also improved , with intervention infants engaged in cognitively sophisticated kinds of exploration more than control infants . At 12 months of age , significantly more intervention group dyads were securely attached than control group dyads In great dem and are efficient mechanisms for delivery of evidence -based interventions for promoting social-emotional development and early positive behavior of all children , and especially for those with or at risk for disabilities . The rise of Internet use has created potentially new avenues for intervention delivery , which , when paired with the many recent advances in computer networking and multimedia technology , is fueling this dem and . This article describes the development of an Internet-based , computer-delivered parent-training intervention , Infant Net , with infants at risk for poor social-emotional outcomes . Results of a r and omized control trial of the Infant Net intervention with 40 parent-infant dyads showed significant increase , reflecting a medium to large effect size , in infant social engagement and engagement with the environment for infants in the intervention group as compared to the control group . Implication s are discussed with regard to future research BACKGROUND Epidemiological studies of mental health problems in the first years of life are few . This study aims to investigate infancy predictors of psychopathology in the second year of life . METHODS A r and om general population sample of 210 children from the Copenhagen Child Birth Cohort CCC 2000 was investigated by data from National Danish registers and data collected prospect ively from birth in a general child health surveillance programme . Mental health outcome at 1(1/2 ) years was assessed by clinical and st and ardised measures including the Child Behavior Check List 1(1/2)-5 ( CBCL 1(1/2)-5 ) , Infant Toddler Symptom Check List ( ITSCL ) , Checklist for Autism in Toddlers ( CHAT ) , Bayley Scales of Infant Development ( BSID II ) , Mannheim Eltern Interview ( MEI ) , Parent Child Early Relational Assessment ( PC ERA ) and Parent Infant Relationship Global Assessment Scale ( PIR-GAS ) , and disordered children were diagnosed according to the International Classification of Diseases ( ICD-10 ) and Diagnostic Classification Zero to Three ( DC : 0 - 3 ) . RESULTS Deviant language development in the first 10 months of life predicted the child having any disorder at 1(1/2 ) years , OR 3.3 ( 1.4 - 8.0 ) . Neuro-developmental disorders were predicted by deviant neuro-cognitive functioning , OR 6.8 ( 2.2 - 21.4 ) , deviant language development , OR 5.9 ( 1.9 - 18.7 ) and impaired social interaction and communication , OR 3.8 ( 1.3 - 11.4 ) . Unwanted pregnancy and parents ' negative expectations of the child recorded in the first months of the child 's life were significant predictors of relationship disturbances at 1(1/2 ) years . CONCLUSIONS Predictors of neuro-developmental disorders and parent-child relationship disturbances can be identified in the first 10 months of life in children from the general population |
13,209 | 19,278,981 | These promising results suggest that SDF is more effective than fluoride varnish , and may be a valuable caries-preventive intervention .
As well , the availability of a safe , effective , efficient , and equitable caries-preventive agent appears to meet the criteria of both the WHO Millennium Goals and the US Institute of Medicine ’s criteria for 21st century medical care | The antimicrobial use of silver compounds pivots on the 100-year-old application of silver nitrate , silver foil , and silver sutures for the prevention and treatment of ocular , surgical , and dental infections .
Ag+ kills pathogenic organisms at concentrations of < 50 ppm , and current/potential anti-infective applications include : acute burn coverings , catheter linings , water purification systems , hospital gowns , and caries prevention .
To distill the current best evidence relative to caries , this systematic review asked : Will silver diamine fluoride ( SDF ) more effectively prevent caries than fluoride varnish ? | PURPOSE This study compares four chemotherapeutic regimens used for inhibiting carious lesion progression : silver nitrate ( AgNO3 ) ; silver fluoride/stannous fluoride ( AgF/SnF2 ) ; silver diammine fluoride ( SDF ) ; and chlorhexidine ( CHX ) . METHODS For this study , a bacterial model system containing Mutans streptococci ( MS ) and Lactobacilli casei ( L ) was used to generate carious lesions on 85 extracted sound permanent third molars which were r and omly assigned to four test groups and one control group . At week two , the four treatment regimens were applied to the lesions ( one treatment per test group ) . RESULTS Six weeks later , lesions treated with a single AgF/SnF2 or AgNO3 application demonstrated 29 % and 19 % less lesion progression , respectively , than did the control group ( P < 0.05 ) . SDF and CHX did not differ significantly from the control . CONCLUSION AgF/SnF2 and AgNO3 may be useful in slowing down carious lesion depth progression The recording of multiple interval-censored failure times is common in dental research . Modeling multilevel data has been a difficult task . This paper aims to use the Bayesian approach to analyze a set of multilevel clustered interval-censored data from a clinical study to investigate the effectiveness of silver diamine fluoride and sodium fluoride varnish in arresting active dentin caries in Chinese pre-school children . The time to arrest dentin caries on a surface was measured . A three-level r and om-effects Weibull regression model was used . Analysis was performed with WinBUGS . Results revealed a strong positive correlation ( 0.596 ) among the caries lesions ’ arrest times on different surfaces from the same child . The software WinBUGS made the above complicated estimation simple . In conclusion , the annual application of silver diamine fluoride on caries lesions , and caries removal before the application , were found to shorten the arrest time We hypothesized that the six-monthly application of silver diamine fluoride ( SDF ) can arrest the development of caries in the deciduous dentition of six-year-old schoolchildren and prevent caries in their first permanent molars . A prospect i ve controlled clinical trial was conducted on the efficacy of a 38 % SDF solution for caries reduction . Four hundred and twenty-five six-year-old children were divided into two groups : One group received SDF solution in primary canines and molars and first permanent molars every 6 mos for 36 mos . The second group served as controls . The 36-month follow-up was completed by 373 children . The mean number of new decayed surfaces appearing in primary teeth during the study was 0.29 in the SDF group vs. 1.43 in controls . The mean of new decayed surfaces in first permanent molars was 0.37 in the SDF group vs. 1.06 in controls . The SDF solution was found to be effective for caries reduction in primary teeth and first permanent molars in schoolchildren Over a period of 18 months the following non-traumatic methods of treating dental caries in deciduous teeth were compared : application of stannous fluoride ( SnF2 ) ; application of SnF2 and silver diamine fluoride ( SDF ) ; application of SnF2 , SDF , minimal cavity preparation and use of composite resin ; minimal cavity preparation and composite resin only ; no treatment . Caries progressed in only 5 per cent of the SDF/SnF2 group and 11 per cent of the composite resin group . The results indicate that it may be possible to treat carious lesions in a non-traumatic way using minimally prepared cavities and composite resin . This could significantly alter the restorative care of deciduous molars and it may be reasonable to speculate that the technique could also have important implication s for use in the permanent dentition This study aim ed to evaluate the risk-benefit balance of several fluoride exposures . Fluoride exposure history of r and omly selected children was collected for calculation of exposure to fluori date d water , toothpaste , and other fluoride sources . We evaluated the risk-benefit balance of fluoride exposure by comparing dental fluorosis on maxillary central incisors , recorded at the time of the study with the use of the Thylstrup and Fejerskov Index , and deciduous caries experience , recorded at age six years , of the same group of South Australian children who were from 8 to 13 years old in 2002–03 . Population Attributable Risk for fluorosis and Population Prevented Fraction for caries were estimated . Fluorosis prevalence was found to be 11.3 % ; caries prevalence , 32.3 % ; mean dmfs , 1.57 ( SD 3.3 ) . Exposure to fluori date d water was positively associated with fluorosis , but was negatively associated with caries . Using 1000-ppm-F toothpaste ( compared with 400- to 550-ppm-F toothpaste ) and eating/licking toothpaste were associated with higher risk of fluorosis without additional benefit in caries protection . Evaluation of the risk-benefit balance of fluoride exposure provides evidence to assist in the formulation of appropriate guidelines for fluoride use Dental caries in Chinese pre-school children is common , and restorative treatment is not readily available . This prospect i ve controlled clinical trial investigated the effectiveness of topical fluoride applications in arresting dentin caries . We divided 375 children ( aged 3 - 5 yrs ) with carious upper anterior teeth into five groups . Children in the first and second groups received annual applications of silver diamine fluoride solution ( 44,800 ppm F ) . NaF varnish ( 22,600 ppm F ) was applied every three months onto the lesions of children in the third and fourth groups . For children in the first and third groups , soft carious tissues were removed prior to fluoride application . The fifth group was the control . We followed 341 children for 18 months . The mean numbers of new caries surfaces in the five groups were 0.4 , 0.4 , 0.8 , 0.6 , and 1.2 , respectively ( p = 0.001 ) . The respective mean numbers of arrested carious tooth surfaces were 2.8 , 3.0 , 1.7 , 1.5 , and 1.0 ( p < 0.001 ) |
13,210 | 20,091,666 | Vitamin D therapy significantly reduced PTH levels compared with placebo or no treatment .
Bone disease , assessed by changes in PTH levels , is improved by all vitamin D preparations .
However no consistent differences between routes of administration , frequencies of dosing or vitamin D preparations have been demonstrated .
Though fewer episodes of high calcium levels occurred with the non calcium-containing binder , sevelamer , compared with calcium-containing binders , there were no differences in serum phosphorus and calcium overall and phosphorus values were reduced to similar extents .
All RCTs were small with few data available on patient-centred outcomes ( growth , bone deformities ) and limited data on biochemical parameters result ing in considerable imprecision of results thus limiting the applicability to care of children with CKD | BACKGROUND Bone disease is common in children with chronic kidney disease ( CKD ) and when untreated may result in bone deformities , bone pain , fractures and reduced growth rates .
OBJECTIVES To investigate the benefits and harms of interventions for preventing and treating bone disease in children with CKD . | BACKGROUND Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat secondary hyperparathyroidism ( secondary HPT ) . This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal ( i.p . ) versus oral doses of calcitriol in children with secondary HPT undergoing peritoneal dialysis ( CCPD ) . METHODS Forty-six patients aged 12.5+/-4.8 years on CCPD for 22+/-25 months were r and omly assigned to treatment with oral ( p.o . ) or i.p . calcitriol for 12 months ; 17 subjects given p.o . calcitriol and 16 subjects given i.p . calcitriol completed the study . Bone biopsies were performed at the beginning and at the end of the study , while determinations of serum and total ionized calcium , phosphorus , alkaline phosphatase , parathyroid hormone ( PTH ) and calcitriol levels were done monthly . RESULTS Serum total and ionized calcium levels were higher in subjects treated with i.p . calcitriol , P < 0.0001 , whereas serum phosphorus levels were higher in those given p.o . calcitriol , P < 0.0001 . For the i.p . group , serum PTH levels decreased from pre-treatment values of 648+/-125 pg/ml to a nadir of 169+/-57 pg/ml after nine months . In contrast , serum PTH levels did not change from baseline values of 670+/-97 pg/ml in subjects given p.o . calcitriol , P < 0.0001 by multiple regression analysis . Serum alkaline phosphatase levels were also lower in patients treated with i.p . calcitriol , P < 0.0001 , but there was no difference between groups in the average dose of calcitriol given thrice weekly . The skeletal lesions of secondary HPT improved in both groups , 33 % of patients developed adynamic bone lesion . CONCLUSION Differences in the bioavailability of calcitriol and /or in phosphorus metabolism may account for the divergent biochemical response to p.o . and i.p . calcitriol BACKGROUND Oral and intravenous calcitriol bolus therapy are both recommended for the treatment of secondary hyperparathyroidism , but it has been cl aim ed that the latter is less likely to induce absorptive hypercalcemia . The present study was undertaken to verify whether intravenous calcitriol actually stimulates intestinal calcium absorption less than oral calcitriol and whether it is superior in suppressing parathyroid hormone ( PTH ) secretion . METHODS Twenty children ( 16 males , age range of 5.1 to 16.9 years , mean creatinine clearance 21.9 + /- 11.5 mL/min/1.73 m2 , range of 7.4 to 52.7 ) with chronic renal failure ( CRF ) and secondary hyperparathyroidism [ median intact PTH ( iPTH ) , 327 pg/mL ; range 143 to 1323 ] received two single calcitriol boli ( 1.5 mg/m2 body surface area ) orally and intravenously using a r and omized crossover design . iPTH and 1,25(OH)2D3 levels were measured over 72 hours , and intestinal calcium absorption was measured 24 hours after the calcitriol bolus using stable strontium ( Sr ) as a surrogate marker . Baseline control values for Sr absorption were obtained in a separate group of children with CRF of similar severity . RESULTS The peak serum level of 1,25(OH)2D3 and area under the curve baseline to 72 hours ( AUC0 - 72h ) were significantly higher after intravenous ( IV ) calcitriol ( AUC0 - 72h oral , 1399 + /- 979 pg/mL. hour vs. IV 2793 + /- 1102 pg/mL. hour , P < 0.01 ) , but the mean intestinal Sr absorption was not different [ SrAUC0 - 240min during the 4 hours after Sr administration 2867 + /- 1101 FAD% ( fraction of the absorbed dose ) vs. 3117 + /- 1581 FAD% with oral and IV calcitriol , respectively ] . The calcitriol-stimulated Sr absorption was more then 30 % higher compared with control values ( 2165 + /- 176 FAD% ) . A significant decrease in plasma iPTH was noted 12 hours after the administration of the calcitriol bolus , which was maintained for up to 72 hours without any differences regarding the two routes of administration . CONCLUSIONS These results demonstrate that under acute conditions , intravenous and oral calcitriol boli equally stimulate calcium absorption and had a similar efficacy in suppressing PTH secretion Secondary hyperparathyroidism was suppressed over a period of one year in 12 children with chronic renal failure by using a regimen of mild dietary phosphate restriction and high dose phosphate binders . The patients were r and omised to receive either aluminium hydroxide or calcium carbonate by mouth for six months and then crossed over to the other medication . Vitamin D ( dihydrotachysterol ) dosage was unchanged . Serum parathyroid hormone concentrations were reduced to within the normal range , urinary cyclic adenosine monophosphate values fell , plasma phosphate concentrations decreased , and the theoretical renal phosphate threshold increased significantly . Transiliac bone biopsy findings improved in four patients with adequate suppression of parathyroid hormone concentrations , deteriorated in two patients who were not compliant , and did not change in five patients in whom initial bone disease was mild . Growth velocity improved significantly . There was no difference in the clinical response , biochemical changes , or incidence of complications during treatment with the two agents . In view of the risk of aluminium toxicity the use of high dose calcium carbonate with dietary phosphate restriction and vitamin D supplementation is recommended in the control of secondary hyperparathyroidism in children with chronic renal failure Recent studies in adults have suggested that parenteral 1,25-dihydroxyvitamin D3 ( 1,25[OH]2D3 ) may have advantages over oral therapy in the management of renal osteodystrophy . The purpose of this study was to determine whether there were clear differences between oral and IP 1,25(OH)2D3 treatments in children who did not pose a treatment problem . Seven children ( 5 males , 2 females , aged 1.8 to 16 years , median 4.8 years ) undergoing peritoneal dialysis were initially treated with oral 1,25(OH)2D3 for a one month equilibration period They were r and omly assigned to 3 months of either oral or intraperitoneal ( IP ) therapy with 1,25(OH)2D3 followed by 3-months-treatment using the alternative route . No significant differences in serum creatinine , phosphate , or parathyroid hormone concentrations were found between the different routes of administration in the patients . No significant differences in height st and ard deviation scores or renal osteodystrophy scores were found over the six-month study . Paired oral and IP pharmacokinetic studies were performed on these 7 patients and 2 other children who had been treated for at least 2 months using either oral or IP 1,25(OH)2D3 . Serum was taken prior to one of the usual 1,25(OH)2D3 doses and 0.5 , 1.5 , 3 , 6 , and 24 h afterward . The highest measured concentrations of 1,25(OH)2D3 were found at 1.5 h for both oral and IP treatments ( mean Cmax [ SD ] : oral 116 [ 23 ] pmol/l , IP 121 [ 24 ] pmol/l , p > 0.05 ) . The AUC 's for oral and IP therapy were similar ( 1701 [ 276 ] and 1645 [ 301 ] pmol/h/l , respectively ) . In the paired pharmacokinetic studies no significant differences were found between oral and IP treatments for the serum half life ( 27.4 [ 11.6 ] h and 19.2 [ 8.1 ] h , respectively ) and total body clearance ( 15.3 [ 2.1 ] h and 18.4 [ 3.3 ] h , respectively ) of 1,25(OH)2D3 . In children who respond appropriately to oral 1,25(OH)2D3 there is no biological advantage to the use of IP 1,25(OH)2D3 ABSTRACT . Ten children with end stage renal disease on chronic hemofiltration ( HF ) were studied for a 1-yr period to evaluate the efficacy of l,25-dihydroxyvitamin-D3 ( 1,25(OH)2D3 ) therapy on biohumoral parameters of renal osteodystrophy and bone mineral content . In six of these children an acute study was done of the direct effect of the HF procedure on calcium and phosphate balance during 12 HF sessions . During the first 6 months of the study all children were treated with 1,25(OH)2D3 ( 0.25 - 0.50 µg/day ) to maintain plasma calcium at 9.5 - 11.0 mg/dl . There was a significant increase in plasma calcium ( p<0.05 ) and a significant decrease in plasma phosphate ( p<0.01 ) and alkaline phosphatase concentrations ( p<0.05 ) . The circulating levels of NH2 immunoreactive parathyroid hormone did not change , remaining at the upper limits of reference values . Immunoreactive parathyroid hormone- COOH terminal fragment levels decreased significantly ( p<0.05 ) . Bone mineral content rose significantly ( p<0.01 ) . During the last 6 months of the study , to evaluate the possibility that HF alone might control secondary hyperparathyroidism , 1,25(OH)2D3 treatment was discontinued in five children ; plasma calcium and phosphate were well controlled whereas hyperparathyroidism worsened in all five , and one also developed intense pruritus and hypertension . The other five children remained on 1,25(OH)2D3 treatment ; two of these were transplanted , and the other three continued to show an improvement of mineral balance . The results of the acute study showed that calcium balance was positive with a mean Ca++ gain of 140 mg/HF session . The mean total phosphate removed per HF run was 574 mg . We conclude that even though a calcium gain and a high phosphate removal was obtained with our HF prescription , secondary hyperparathyroidism in children on chronic HF may be maintainued under control if 1,25(OH)2D3 supplementation is provided Little is known about the impact of various phosphate binders on the skeletal lesions of secondary hyperparathyroidism ( 2 degrees HPT ) . The effects of calcium carbonate ( CaCO3 ) and sevelamer were compared in pediatric peritoneal dialysis patients with bone biopsy-proven 2 degrees HPT . Twenty-nine patients were r and omly assigned to CaCO3 ( n = 14 ) or sevelamer ( n = 15 ) , concomitant with either intermittent doses of oral calcitriol or doxercalciferol for 8 mo , when bone biopsies were repeated . Serum phosphorus , calcium , parathyroid hormone ( PTH ) , and alkaline phosphatase were measured monthly . The skeletal lesions of 2 degrees HPT improved with both binders , and bone formation rates reached the normal range in approximately 75 % of the patients . Overall , serum phosphorus levels were 5.5 + /- 0.1 and 5.6 + /- 0.3 mg/dl ( NS ) with CaCO3 and sevelamer , respectively . Serum calcium levels and the Ca x P ion product increased with CaCO3 ; in contrast , values remained unchanged with sevelamer ( 9.6 + /- 01 versus 8.9 + /- 0.2 mg/dl ; P < 0.001 , respectively ) . Hypercalcemic episodes ( > 10.2 mg/dl ) occurred more frequently with CaCO3 ( P < 0.01 ) . Baseline PTH levels were 980 + /- 112 and 975 + /- 174 pg/ml ( NS ) ; these values decreased to 369 + /- 92 ( P < 0.01 ) and 562 + /- 164 pg/ml ( P < 0.01 ) in the CaCO3 and the sevelamer groups , respectively ( NS between groups ) . Serum alkaline phosphatase levels also diminished in both groups ( P < 0.01 ) . Thus , treatment with either CaCO3 or sevelamer result ed in equivalent control of the biochemical and skeletal lesions of 2 degrees HPT . Sevelamer , however , maintained serum calcium concentrations closer to the lower end of the normal physiologic range , thereby increasing the safety of treatment with active vitamin D sterols BACKGROUND Prior studies of dialysis practice s and outcomes have included children with varied duration of end-stage renal disease ( ESRD ) . This study evaluated dialysis characteristics , complications , practice s , and outcomes in an incident pediatric cohort . METHODS The cohort was limited to 1992 subjects enrolled in the North American Pediatric Renal Transplant Cooperative Study registry , starting hemodialysis ( HD ) or peritoneal dialysis ( PD ) between 1992 and 1998 , without prior dialysis or transplantation . RESULTS At dialysis initiation , the median glomerular filtration rate ( GFR ; Schwartz formula ) was 6 to 11 mL/min/1.73 m2 , and 90th percentile was 14 to 25 mL/min/1.73 m2 . GFR was not associated with age or race . PD was used in 97 % of infants , 70 to 80 % of children and 59 % of adolescents . Blacks were significantly less likely to be started on PD than whites . Twenty percent of patients switched dialysis modality , largely due to infection , inadequate access or family choice . Younger children received HD almost exclusively through percutaneous catheters , while 57 % of children more than six years old were dialyzed with fistula or graft after six months on HD . The prevalence of anemia ( Hct < 33 % ) still exceeded 40 % after six months of dialysis . The median interval to transplantation was 1.4 years , and was significantly greater in non-white , young , and female patients . Mortality rates ( deaths/1000 patient-years ) varied with age , from 13.6 in infants to 2.2 in adolescents . CONCLUSION These data demonstrate considerable variability in patient management across pediatric centers . Prospect i ve studies are needed to determine the optimum adequacy of care among children on dialysis and to identify population s at risk The efficacy of 1 alpha-hydroxycholecalciferol in the prevention of renal osteodystrophy in children commencing continuous ambulatory peritoneal dialysis was studied in 12 patients , 0.8 - 17 years of age , who were r and omly assigned to either group I receiving st and ard therapy or to group II receiving in addition 10 - 20 ng/kg body weight/day of 1 alpha-hydroxycholecalciferol . Calcium carbonate compounds were used to control hyperphosphataemia . Mean plasma calcium ( total and ionised ) and phosphate levels were not significantly different between the two groups . All group I patients continued to have elevated plasma immunoreactive parathyroid hormone levels at 6 months compared to only 1 patient in group II ( p less than 0.05 ) . Four patients in group I developed subperiosteal erosions on radiography compared to the healing of mild lesions in 2 patients in group II . Bone histomorphometry on iliac crest needle biopsy specimens revealed a significant reduction in osteoid index and seam width in group II . Serum aluminum levels decreased during the course of continuous ambulatory peritoneal dialysis , and the significant staining for bone aluminum in 6 patients at the beginning of the study was no longer present in 5 patients at 6 months . Our data demonstrate that 1 alpha-hydroxycholecalciferol is beneficial in the prevention and treatment of bone disease in children on continuous ambulatory peritoneal dialysis Successful renal transplantation corrects many of the metabolic abnormalities associated with the development of renal osteodystrophy , but despite a well-functioning graft osteopenia , growth failure , spontaneous fractures , and avascular necrosis remain prevalent in adult and pediatric kidney recipients . A paucity of information exists regarding the effects of different therapies to prevent and treat bone loss in the renal transplant recipients . We constructed a design to study the effect of different modalities of treatment on bone mass in our renal transplant children . Among 93 patients who underwent renal transplantation at the age of 17 yr or less and were subjected to dual-energy X-ray absorptiometry ( DEXA ) , we blindly r and omized 60 patients who had osteopenia or osteoporosis ( T-score = -1 by DEXA ) in a prospect i ve study . Their mean age at time of transplantation was 13.4 + /- 4.3 yr . The mean duration after transplantation was 48 + /- 34 months . The patients were classified r and omly into four groups . Each group consisted of 15 patients : group 1 was the control group , group 2 received oral alfacalcidol 0.25 microg daily , group 3 received oral alendronate 5 mg daily , and group 4 received 200 IU/day nasal spray calcitonin . Parameters of bone turnover , calcium metabolism , and DEXA were measured before and after 12 months of treatment duration . The characteristics of all groups were comparable at the beginning of the study . At the lumber spine , bone mass density decreased from -2.4 to -2.8 in group 1 , increased from -2.3 to -0.5 in group 2 , from -2.3 to -1.9 in group 3 , and from -2.3 to -1.0 in group 4 . The four groups had similar patient profiles , serum creatinine , intact parathyroid hormone , osteocalcin , and deoxypyridinoline . This study confirmed the value of alfacalcidol and antiresorptive agents in the treatment of osteopenia and osteoporosis in young renal transplant recipients . These therapies were safe , tolerable , simple to administer and potentially applicable to other renal transplant patients Metabolic effects of deflazacort vs. methylprednisone were studied in prepubertal patients after kidney transplantation . Thirty-one patients participated : 15 received deflazacort and 16 remained on methylprednisone . The study started at a mean of 2.1 years after transplantation , when patients were r and omized to either continue with methylprednisone or switch to deflazacort . Height velocity increased more in the deflazacort than in the methylprednisone group only during the first 2 years : 5.4 ± 0.5 vs. 3.5 ± 0.3 cm/year , and 4.2 ± 0.8 vs. 2.2 ± 0.4 cm/year p = 0.007 , [ by two-way analysis of variance ( ANOVA ) ] . After 2 and 3 years , the number of patients who were overweight increased in the methylprednisone group and decreased in the deflazacort group ; p < 0.01 . Lean body mass increased more in the deflazacort than in the methylprednisone group ( p = 0.003 ) . Fat body mass increased only in the methylprednisone group ( p < 0.01 ) . Total cholesterol and low-density-lipoprotein ( LDL ) cholesterol increased in the methylprednisone group ( p < 0.05 and p < 0.01 , respectively ) . Total and LDL cholesterol were reduced ( p < 0.01 and p < 0.001 , respectively ) , whereas high-density-lipoprotein ( HDL ) cholesterol increased ( p < 0.001 ) during deflazacort therapy . Lumbar spine bone mineral density ( BMD ) decreased in both groups , but total skeleton BMD decreased only in the methylprednisone group ( p < 0.001 ) . Finally , normal glucose/insulin ratio , defined as > 7 , was associated ( p < 0.05 ) with the deflazacort group . Our data suggest that deflazacort therapy might improve linear growth and lean body mass and prevent excessive bone loss and fat accumulation . It also leads to an improvement in lipoprotein profile without reduction in insulin sensitivity BACKGROUND A multicenter , r and omized , open-label , crossover study was performed to compare the efficacy and safety of sevelamer , a calcium-free phosphate binder , with calcium acetate in pediatric patients with chronic kidney disease ( CKD ) . METHODS Children ( age , 0.9 to 18 years ) with CKD undergoing hemodialysis or peritoneal dialysis or with a glomerular filtration rate of 20 or greater and less than 60 mL/min/1.73 m2 ( > or = 0.33 and < 1.00 mL/s/1.73 m2 ) were r and omly assigned to the following treatment scheme : 2 weeks of washout followed by 8 weeks of treatment with either sevelamer or calcium acetate in a crossover fashion . Phosphorus , calcium , and intact parathyroid hormone in serum were measured every 2 weeks , and phosphate binder dosages were adjusted , if needed . Serum lipid and vitamin concentrations were measured at the beginning and end of each treatment period . The primary end point was the decrease in serum phosphorus levels after 8 weeks of treatment . RESULTS Forty-four patients were screened . Altogether , data for 18 patients ( 5 girls ) aged 12.4 + /- 4.1 years were used for the crossover analysis . There was no significant difference in serum phosphorus levels at 8 weeks after the start of treatment in both groups . Total cholesterol ( -27 % ) and low-density lipoprotein cholesterol ( -34 % ) levels decreased significantly with sevelamer treatment ( P < 0.02 and P < 0.005 ) . An increased incidence of hypercalcemia ( P < 0.0005 ) was observed with calcium acetate treatment , whereas metabolic acidosis was more frequent with sevelamer treatment ( P < 0.005 ) . CONCLUSION Treatment of children with CKD with sevelamer and calcium acetate provides similar phosphorus level control . The marked decrease in lipid levels and lower rate of hypercalcemia may augment the long-term benefit of sevelamer Calcitriol ( C ) treatment strategies for secondary hyperparathyroidism remain controversial regarding efficacy and safety . In children , intermittent C administration has been suspected of impairing body growth . In a prospect i ve , r and omized multicenter study , we compared the effect of daily versus twice weekly C on plasma intact parathyroid hormone ( iPTH ) levels and growth in 24 prepubertal children with chronic renal insufficiency ( mean creatinine clearance 20±9 ml/min per 1.73 m2 ) . After a 3-week washout period , the patients were r and omly assigned to 10 ng/kg per day or 35 ng/kg twice a week oral C. The C dose was kept constant for 2 months and could then be adapted to maintain an iPTH target range of 140–280 pg/ml . Median ( range ) baseline iPTH levels were 567 ( 114–1209 ) pg/ml in the daily and 332 ( 93–614 ) pg/ml in the intermittent treatment group ( P = NS ) . After 12 months , iPTH had decreased to 255 ( 85–710 ) and 179 ( 51–443 ) pg/ml ( P<0.01 ) . The average weekly dose of C was 76±34 and 62±34 ng/kg ( P = NS ) . Five episodes of calcium phosphate product≥70 occurred in the daily group and four in the intermittent group . The change in height st and ard deviation score during the study period was not affected by either treatment modality ( −0.18±0.34 vs. −0.05±0.52 , P = NS ) . Daily and intermittent C do not differentially affect growth rate and are equally effective in controlling secondary hyperparathyroidism in children with chronic renal failure This double-blind , placebo-controlled study evaluated the safety and efficacy of intravenous ( IV ) calcitriol ( Calcijex ) for treatment of secondary hyperparathyroidism ( 2 ° HPT ) in pediatric end-stage renal disease ( ESRD ) patients on hemodialysis ( HD ) . After a 2 to 6-week washout period of all vitamin D compounds , patients with two consecutive PTH values > 400 pg mL−1 , calcium levels ≤10.5 mg dL−1 and calcium × phosphorus product values ≤70 mg2 dL−2 were eligible for the treatment phase . Patients received a bolus injection of calcitriol or placebo three times a week , immediately after dialysis for up to 12 weeks . Initial doses ( 0.5–1.5 μg ) were based on the severity of 2ºHPT . The dose was increased every two weeks by 0.25 μg until there was at least a 30 % decrease in PTH from baseline , or Ca>11.0 mg dL−1 , or Ca × P>75 mg2 dL−2 . Overall , 11/21 ( 52 % ) patients in the calcitriol group had two consecutive ≥30 % decreases from baseline in serum PTH compared with 5/26 ( 19 % ) patients in the placebo group ( P=0.03 ) . The mean total alkaline phosphatase decreased from 274 to 232 IU L−1 in the calcitriol group and increased from 547 to 669 IU L−1 in the placebo group ( P=0.002 ) . The mean bone-specific alkaline phosphatase decreased from 72.5 to 68 μg L−1 in the calcitriol group and increased from 105.3 to 148.5 μg L−1 in the placebo group ( P=0.03 ) . The incidence of two consecutive occurrences of elevated calcium × phosphorus ( Ca × P>75 mg2 dL−2 ) product was higher in the calcitriol group than in the placebo group ( P=0.01 ) . Two consecutive occurrences of phosphorus > 6.5 mg dL−1 occurred in 71 % of the calcitriol group and 46 % of the placebo group ( P=0.14 ) . Calcium levels > 10.5 mg dL−1 were more common in the calcitriol group than in the placebo group ( P=0.01 ) . There was a direct relationship between serum phosphorus concentration and the percentage change in PTH from baseline in both the calcitriol group ( r=0.46 ; P<0.0001 ) and the placebo group ( r=0.21 ; P=0.0005 ) . This study demonstrates that IV calcitriol , at initial doses of 0.5–1.5 μg , effectively reduces PTH levels in pediatric HD patients and that patients should be closely monitored for hyperphosphatemia and elevated Ca × P product Daily calcitriol therapy has been reported to improve linear growth in children with renal bone disease , and 1,25-dihydroxyvitamin D is a key regultor of chondrocyte proliferation and differentiation . Whereas large intermittent doses of calcitriol can lower serum parathyroid hormone ( PTH ) levels and reverse the skeletal changes of secondary hyperparathyroidism , the impact of intermittent calcitriol therapy on linear growth in children is not known . Thus , we studied 16 pre-pubertal patients with bone biopsy-proven secondary hyperparathyroidism who completed a 12-month prospect i ve clinical trial of intermittent calcitriol therapy . Biochemical results and growth data obtained during intermittent calcitriol therapy were compared to values determined during the preceding 12 months of daily calcitriol therapy in each study subject ; changes in bone histology were assessed after one year of intermittent calcitriol therapy . Z-scores for height did not change during 12 months of daily calcitriol therapy . Although the skeletal lesions of secondary hyperparathyroidism improved in most patients , Z-scores for height decreased from -1.8 + /- 0.32 to -2.0 + /- 0.33 , P < 0.01 , during intermittent calcitriol therapy . The largest reductions were seen in patients who developed adynamic bone lesions after 12 months of treatment . Delta Z-scores for height correlated with serum PTH , r = 0.71 , P < 0.01 , and alkaline phosphatase levels , r = 0.67 , P < 0.01 , during intermittent calcitriol therapy but not during daily calcitriol therapy . The data suggest that high dose intermittent calcitriol therapy adversely affects linear growth , particularly in patients with the adynamic lesion . The higher doses of calcitriol or the intermittent schedule of calcitriol administration may directly inhibit chondrocyte activity within growth plate cartilage of children with end-stage renal disease Abstract Calcitriol oral pulse therapy has been suggested as the treatment of choice for secondary hyperparathyroidism , but its efficacy and safety are still under discussion . The present r and omized multicenter study compares the effect of an 8-week course of daily versus intermittent ( twice weekly ) calcitriol therapy on parathyroid hormone ( PTH ) suppression in 59 children ( mean age 8.4±4.7 years ) with chronic renal insufficiency ( mean Ccr 22.4±11.6 ml/min per 1.73 m2 ) and secondary hyperparathyroidism . After a 3-week washout period , the patients were r and omly assigned to treatment with daily oral calcitriol ( 10 ng/kg per day ) or intermittent oral calcitriol ( 35 ng/kg given twice a week ) . The calcitriol dose was not changed throughout the study period of 8 weeks . At start of the study , the median intact PTH ( iPTH ) level was 485 pg/ml ( range 83–2032 ) in the daily group ( n=29 ) and 315 pg/ml ( range 93–1638 ) in the intermittent group ( n=30 ) . After 8 weeks , the respective median iPTH concentrations were 232 pg/ml ( range 63–1614 ) and 218 pg/ml ( range 2–1785 ) ( ns ) . The mean iPTH decrease from baseline was 19.2±57.8 % and 13.7±46.7 % respectively ( not significant ) . Calcitriol reduced the iPTH concentration in 23/29 patients in the daily group and in 21/30 in the intermittent group . One episode of hypercalcemia ( > 11.5 mg/dl ) was observed in both groups and a single episode of hyperphosphatemia ( > 7.5 mg/dl ) was observed in the daily group . It is concluded that oral calcitriol pulse therapy does not control secondary hyperparathyroidism more effectively than the daily administration of calcitriol in children with chronic renal failure prior to dialysis Serial measurements of 51Cr edetic acid clearance were made over a period of one year in two groups of 8 children , in a double blind trial of 1 alpha-hydroxycholecalciferol ( 10 ng/kg/day ) and calciferol ( 670 ng/kg/day ) . Glomerular filtration rate ( GFR ) at the beginning of the trial was 20 - 50 ml/min/1.73 m2 ; it rose in the children given 1 alpha-hydroxycholecalciferol ( group A ) after 6 months but was not appreciably different from the pretreatment value after 12 months . The GFR in the children given calciferol ( group B ) showed no significant difference at 6 or 12 months . Parathyroid hormone values fell markedly in group A after 6 months but not in group B. Quantitative bone histology improved considerably in group A but not in group B at 12 months . Low dose 1 alpha-hydroxycholecalciferol may be used effectively for renal osteodystrophy in children with moderate but stable renal failure without jeopardising renal function During the control period of the Growth Failure in Children With Renal Diseases Study , investigators at 23 centers were able to observe and characterize growth and to make anthropometric and nutritional measurements in 82 children with mild to moderate renal insufficiency . As a multicenter , controlled clinical trial design ed to study the relative efficacy of 1,25-dihydroxyvitamin D3 and dihydrotachysterol in the treatment of renal osteodystrophy , no prior vitamin D exposure and a creatinine clearance of 25 to 75 ml/min/1.73 m2 were criteria for entrance into the clinical trial . Ages ranged from 18 months to 11 years ( mean 5.6 + /- 3.1 years ) , and distribution by age category was as follows : 38 % , 1 to 3 years ; 28 % , 4 to 6 years ; and 34 % , 7 to 10 years . There was a 3:1 male/female ratio ; 72 % of the patients had congenital disease by the International Classification of Diseases ( ninth revision ) . Mean creatinine clearance was 49.5 + /- 20 ml/min/1.73 m2 . The C-terminal parathyroid hormone values ( 1121 + /- 1562 pg/ml ) were well above 2 SD of the mean of a normal growing population of similar age . Parathyroid hormone values correlated with degree of renal insufficiency ( r = -0.57 ) and with height by bone age but not with chronologic height or growth velocity . The bone age/height age ratio , a predictor of growth potential in normal children , was low for the entire series of patients ( 0.88 + /- 0.35 ) but failed to correlate with growth velocity and was negatively correlated with rising parathyroid hormone levels . Average values for height , weight , triceps skin fold , mid-arm muscle circumference , and body mass index were within 2 SD of the mean of the normal population , although measurements for the 1- to 3-year age group were significantly less than those of the older patients . Total energy intake averaged less than 86 % of the recommended dietary allowances ; total protein intake was more than 161 % of the allowance . Nitrogen balance in 23 patients was positive and correlated most significantly with increasing energy intake ( r = 0.6 ) . Growth velocity , calculated from the interval gain during the month control period , averaged + 0.3 SD , with the highest growth velocity z scores recorded for those with acquired disease . A growth velocity index , expressed as the slope of the regression between change in height SD and growth velocity z score , was used to describe the growth accomplished in the control period by age category . ( ABSTRACT TRUNCATED AT 400 WORDS |
13,211 | 30,594,468 | DATA SYNTHESIS Antiretroviral therapy has significantly reduced morbidity and mortality in HIV-infected children and is clearly associated with recovery of weight and height-for-age Z-scores , especially when started early , in the asymptomatic child still without weight-height impairment .
CONCLUSIONS HIV-infected children show early weight-height impairment ; antiretroviral therapy improves the anthropometric profile of these children | OBJECTIVE Weight and height growth impairment is one of the most frequent manifestations in HIV-infected children and may be the first sign of disease , being considered a marker of disease progression and an independent risk factor for death .
The aim of this review is to evaluate the influence of antiretroviral therapy on the growth pattern of children and adolescents living with HIV/AIDS . | OBJECTIVE To describe the effects of age at antiretroviral therapy ( ART ) initiation on growth outcomes among children infected with HIV followed for 48 months after treatment initiation . STUDY DESIGN This secondary analysis describes anthropometric changes in children infected with HIV in Johannesburg , South Africa who initiated ritonavir-boosted lopinavir-based ART before 24 months of age and were r and omized to continue ritonavir-boosted lopinavir or to receive nevirapine after achieving and maintaining virologic suppression . Weight , height , and head circumference were measured at visits over 48 months post-ART initiation . Growth patterns including weight-for-age z-scores ( WAZs ) , height-for-age z-scores , body mass index-for-age z-scores , and head circumference for age z-score were compared between children initiating ART<6 months , 6 - 12 months , and 12 - 24 months of age . RESULTS A total of 195 children ( mean±SD age 10.7±5.9 months ) , including 54 (27.7%)<6 months , 69 ( 35.4 % ) 6 - 12 months , and 72 ( 36.9 % ) 12 - 24 months of age at ART initiation , were evaluated . In the first 12 months on treatment , children<6 months of age at ART initiation experienced more rapid improvement in WAZ ( 1.98 vs 1.44 , P=.084 ) and head circumference for age z-score ( 1.24 vs 0.45 , P=.004 ) than children who initiated ART between 12 - 24 months of age . By 48 months on ART , growth outcomes were similar , regardless of age at ART initiation . WAZ approached population norms by 12 months on ART . Although improving , height-for-age z-scores remained on average 1.0 z-score below population norms at 48 months of therapy . CONCLUSIONS Initiation of ART before 6 months of age results in more rapid growth recovery in children infected with HIV . These data provide further evidence for the importance of prompt diagnosis and early initiation of ART for infants infected with HIV Background : We assessed a nutritional support intervention in malnourished HIV-infected children in a HIV-care program of the University Hospital Gabriel Touré , Bamako , Mali . Methods : All HIV-infected children younger than 15 years were diagnosed for malnutrition between 07 and 12 , 2014 . Malnutrition was defined according to the WHO growth st and ards with Z-scores . Two types were studied : acute malnutrition ( AM ) and chronic malnutrition ( CM ) . All participants were enrolled in a 6-month prospect i ve interventional cohort , receiving Ready-To-Use Therapeutic Food , according to type of malnutrition . The nutritional intervention was offered until child growth reached −1.5 SD threshold . Six-month probability to catch up growth ( > −2 SD ) was assessed for AM using Kaplan-Meier curves and Cox model . Results : Among the 348 children screened , 198 ( 57 % ) were malnourished of whom 158 ( 80 % ) children were included : 97 ( 61 % ) for AM ( 35 with associated CM ) and 61 ( 39 % ) with CM . Fifty-nine percent were boys , 97 % were on antiretroviral therapy , median age was 9.5 years ( Interquartile Range : 6.7–12.3 ) . Among children with AM , 74 % catch-up their growth at 6-month ; probability to catch-up growth was greater for those without associated CM ( adjusted Hazard Ratio = 1.97 , CI 95 % : 1.13 to 3.44 ) . Anemia decreased significantly from 40 % to 12 % at the end of intervention ( P < 0.001 ) . Conclusions : This macronutrient intervention showed 6-month benefits for weight gain and reduced anemia among these children mainly on antiretroviral therapy for years and aged greater than 5 years at inclusion . Associated CM slows down AM recovery and needs longer support . Integration of nutritional screening and care in the pediatric HIV-care package is needed to optimize growth and prevent metabolic disorders Background Data on long-term toxicity of antiretroviral therapy ( ART ) in HIV-infected children are sparse . PENPACT-1 was an open-label trial in which HIV-infected children were assigned r and omly to receive protease inhibitor (PI)- or nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART . Methods We examined changes in clinical , immunologic , and inflammatory markers from baseline to year 4 in the subset of children in the PENPACT-1 study who experienced viral suppression between week 24 and year 4 of ART . Liver enzyme , creatinine , and cholesterol levels and hematologic parameters were assessed during the trial . Cystatin C , high-sensitivity C-reactive protein ( hs-CRP ) , interleukin 6 ( IL-6 ) , d-dimer , and soluble CD14 ( sCD14 ) were assayed from cryopreserved specimens . Results Ninety-nine children ( 52 on PI-based and 47 on NNRTI-based ART ) met inclusion criteria . The median age at initiation of ART was 6.5 years ( interquartile range [ IQR ] , 3.7 - 13.4 years ) , and 22 % were aged <3 years at ART initiation ; 56 % of the PI-treated children received lopinavir/ritonavir , and 70 % of NNRTI-treated children received efavirenz initially . We found no evidence of significant clinical toxicity in either group ; growth , liver , kidney , and hematologic parameters either remained unchanged or improved between baseline and year 4 . Total cholesterol levels increased modestly , but no difference between the groups was found . IL-6 and hs-CRP levels decreased more after 4 years in the NNRTI-based ART group . The median change in IL-6 level was -0.35 pg/ml in the PI-based ART group and -1.0 in the NNRTI-based ART group ( P = .05 ) , and the median change in hs-CRP level was 0.25 µg/ml in the PI-based ART group and -0.95 µg/ml in the NNRTI-based ART group ( P = .005 ) . Conclusion These results support the safety of prolonged ART use in HIV-infected children and suggest that suppressive NNRTI-based regimens can be associated with lower levels of systemic inflammation INTRODUCTION Growth failure is a common feature of children with human immunodeficiency virus type 1 ( HIV-1 ) infection . Children who are treated with mono or dual nucleoside analogue reverse transcriptase inhibitor ( NRTI ) therapy show a temporary increase in weight gain and linear growth rate . In adults , protease-inhibitor-containing antiretroviral therapy is associated with a sustained weight gain and increased body mass index ( BMI ) . Experience with protease inhibitors and growth in children is still limited . The data mainly deal with short-term effects on growth . OBJECTIVE To evaluate the effect of highly active antiretroviral therapy ( HAART ) on growth in children with HIV-1 infection . DESIGN AND METHODS We analyzed selected growth parameters , clinical data , and laboratory results as part of a prospect i ve , open , uncontrolled , multicenter study to evaluate the clinical , immunologic , and virologic response to HAART consisting of indinavir , zidovudine , and lamivudine in children with HIV-1 infection . Height and weight were measured at 0 , 12 , 24 , 36 , 48 , 60 , 72 , 84 , and 96 weeks after initiation of HAART . Information about the children 's growth before enrollment in the study was retrieved from the hospital medical records and /or the school doctor or health center . BMI was calculated . z Scores were used to express the st and ard deviation ( SD ) in SD units from the Dutch reference curves for age and gender . Viral loads and CD4 + T-cell counts were examined prospect ively and related to these growth parameters . z Scores were also calculated for CD4 + T-cell counts to correct for age-related differences . A z score of 0 represents the P50 , which is exactly the age/sex-appropriate median . A height z score of -1 indicates that a child 's height is 1 SD below the age- and gender-specific median height for the normal population . Virologic responders were defined as those who either reached an undetectable viral load ( < 500 copies/mL ) or had a > 1.5 log reduction in viral load compared with baseline at week 12 after the initiation of HAART , which was maintained during the follow-up period . RESULTS . PATIENTS Twenty-four patients were included ( age : 0.4 - 16.3 years at baseline ) , with a median HIV-1 RNA load of 105 925 copies/mL ( 5.03 log ) , a median CD4 + T-cell count of 0.586 x 10(9)/L ( median z score : -2.28 SD ) , a median height z score of -1.22 , a median weight z score of -0.74 , and a median baseline BMI z score of -0.32 . Eleven patients were naive to antiretroviral therapy , and 13 patients had received previous treatment with NRTI monotherapy . Twenty children used indinavir and 4 children used nelfinavir as part of HAART . VIROLOGIC AND IMMUNOLOGIC RESPONSES TO HAART : Seventeen children were virologic responders , and 7 children were virologic nonresponders . In patients naive to NRTIs , median baseline viral loads were significantly higher than in pretreated patients . However , at weeks 48 and 96 , there was no significant difference between the viral loads of both groups . At baseline , there was no significant difference in CD4+a T-cell z scores between virologic responders and nonresponders or between naive and pretreated patients . During 96 weeks of HAART , the increase of CD4 + T-cell z score was significantly higher in responders than in nonresponders . The increase in CD4 + T-cell z score was not significantly different for naive and pretreated patients . HEIGHT , WEIGHT , AND BMI z SCORE CHANGES : We found that there was a trend toward a significantly increased z score change during 96 weeks of HAART compared with the z score change before HAART initiation for height and weight , but not for BMI . GROWTH AND VIROLOGIC RESPONSE TO HAART : When the data were analyzed separately for virologic responders and nonresponders , virologic responders showed significant increases in height and weight . The height and weight of virologic nonresponders did not change significantly . The BMI did not change significantly in responders or in nonresponders . GROWTH AND IMMUNOLOGIC RESPONSE TO HAART : The increase of weight and BMI z scores from baseline correlated positively with the CD4 + T-cell z score increase from baseline . It did not correlate with absolute CD4 + T-cell count increase . Height z score increase did not correlate with CD4 + T-cell z score or with absolute CD4 + T-cell counts . GROWTH AND PREVIOUS NRTI TREATMENT : The height z score decrease from week -48 to baseline was significantly larger in naive than in pretreated patients . The weight and BMI z score change from week -48 to baseline was not significantly different for pretreated and naive patients . From baseline to week 96 , the height and weight z score change increased significantly in naive patients but not in pretreated patients compared with the change from week -48 to baseline . The BMI z score did not change significantly over 96 weeks of HAART for naive or pretreated patients . GROWTH AND CLINICAL STAGE OF INFECTION : The clinical stage of infection according to the Centers for Disease Control and Prevention classification correlated negatively with the BMI z score and the weight z score at baseline but not with the height z score . Thus , children with the most severe clinical disease had the lowest BMI and weight z scores at baseline . The BMI z score increased more in children with more advanced clinical infection at baseline , who had lower BMI at baseline . The clinical stage of infection did not correlate with the change in weight z score from baseline to week 96 . CONCLUSIONS HAART has a positive influence effect on the growth of HIV-1-infected children . This effect is sustained for at least 96 weeks . Height and weight are favorably influenced in children in whom HAART leads to a reduction of the viral load of at least 1.5 log or to < 500 copies/mL and to an increase in the CD4 + T-cell z score . In contrast to the increase of the BMI in adults on HAART , BMI did not increase in all children effectively treated with HAART . BMI increased more in children with an advanced stage of infection and a poor nutritional status at baseline . Data from pretreated and naive patients were difficult to interpret , because the baseline characteristics of these 2 groups differed too much OBJECTIVE To evaluate the nature and magnitude of the effect of congenitally or perinatally acquired human immunodeficiency virus ( HIV ) infection on somatic growth from birth through 18 months of age . STUDY DESIGN Anthropometry was performed serially in 282 term infants born to HIV-infected women in a multicenter prospect i ve natural history cohort study . Repeated measures analysis was used to compare z-score anthropometric indexes of weight-for-age , length-for-age , weight-for-length , and head circumference-for-age between infected and uninfected infants , with adjustment for covariates including infant gender ; maternal education ; prenatal alcohol , tobacco , and /or illicit drug exposure ; and mean prenatal CD4 + T-lymphocyte count . A separate repeated measures model was used to assess the effect of infant zidovudine treatment on growth . RESULTS Infants infected with HIV were an estimated average 0.28 kg lighter and 1.64 cm shorter than uninfected infants at birth , were 0.71 kg lighter and 2.25 cm shorter by 18 months of age , and had a sustained estimated average decrement of 0.70 to 0.75 cm in head circumference . Patterns of growth were similar in male and female infants . Infected infants had a progressive decrement in body mass index from birth through 6 months of age . Infection with HIV was associated with significant decrements across all st and ardized growth outcome measures after adjustment for covariates . Mean z scores were lower for weight by 0.612 ( p < 0.001 ) , for length by 0.735 ( p < 0.001 ) , for weight-for-length by 0.255 ( p = 0.02 ) , and for head circumference by 0.563 ( p < 0.001 ) SD units compared with uninfected infants . Zidovudine treatment was not associated with improved growth . CONCLUSION The effect of congenitally or perinatally acquired HIV infection on infant growth is one of early and progressive decrements in attained linear growth and growth in mass , early and sustained decrements in head growth , and marked early decrements in body mass index Abstract . To determine the long-term impact of antiretroviral treatment ( ART ) including a protease inhibitor ( PI ) on growth in children infected with the human immunodeficiency virus type 1 ( HIV-1 ) , a prospect i ve multi-centre study was conducted in Switzerl and on HIV-1-infected children treated with ritonavir ( 350 mg/m2 twice a day ) or nelfinavir ( 20–30 mg/kg three times a day ) in addition to two nucleoside reverse transcriptase inhibitors . Length or height of HIV-1-infected children from before ( weeks –72 , –48 , –24 , and 0 ) and after ( weeks + 24 , + 48 , and + 72 ) introducing a PI to the ART were compared . To allow for age- and gender-independent assessment , values were expressed in st and ard deviations from the mean . Complete data sets on body length were available for 44 children after 72 weeks of treatment with a PI . Preceding initiation of a PI , there was an overall decline in growth to –0.3 SD . Following start of a PI , an increase in growth was noted from weeks 0 to + 24 ( + 0.33 SD , P=0.02 ) and from weeks + 48 to + 72 ( + 0.21 SD , P=0.03 ) . The increase in growth was restricted to children with stunting before a PI was introduced ( P=0.03 ) , and was more marked in children younger than 3 years of age . Conclusion : children infected with human immunodeficiency virus type 1showed catch-up growth after addition of a protease inhibitor to their antiretroviral treatment , but this phenomenon was observed almost exclusively in children under 3 years of age Background : Diminished growth is highly prevalent among HIV-infected children and might be improved by antiretroviral therapy ( ART ) . We examined growth recovery in a rural Ug and an cohort of HIV-infected children r and omized to lopinavir/ritonavir ( LPV/r ) or non nucleoside reverse transcription inhibitor-based ART . Methods : HIV-infected children 2 months to 6 years of age were r and omized to LPV/r- or non nucleoside reverse transcription inhibitor-based ART . Changes in weight-for-age ( WAZ ) , height-for-age ( HAZ ) and weight-for-height Z-scores for 24 months were evaluated using generalized linear repeated measures models . Recovery from being underweight ( WAZ<−2 ) , stunted ( HAZ<−2 ) and wasted ( weight-for-height < −2 ) to Z-scores greater than −2 was also compared by arm using Kaplan – Meier survival and Cox proportional hazard modeling . Results : A total of 129 children with median age of 3 years initiated therapy ; 64 received LPV/r-based and 65 non nucleoside reverse transcription inhibitor-based ART ( nevirapine : 36 and efavirenz : 29 ) . The median ( interquartile range ) difference in growth measures between baseline and 24 months for LPV/r ( n = 45 ) versus non nucleoside reverse transcription inhibitor-based therapy ( n = 40 ) were as follows : WAZ , 0.47 ( 0.10 , 1.62 ) versus 0.53 ( 0.03 , 1.14 ) ( P = 0.59 ) and HAZ , median 1.55 ( 0.78 , 1.86 ) versus 1.19 ( 0.62 , 1.65 ) ( P = 0.23 ) , respectively . ART regimen was not predictive of change in WAZ ( & bgr ; : −0.02 , 95 % confidence interval : −0.25 , 0.20 ) or HAZ ( & bgr ; : 0.05 , 95 % confidence interval : −0.10 , 0.19 ) . The presence of confirmed virologic failure was not associated with growth . Conclusions : Most ART-naive children experienced recovery of both WAZ and HAZ over the 24 months after ART initiation , with no significant difference between those receiving LPV/r versus non nucleoside reverse transcriptase inhibitor-based ART . However , the persistence of median Z-scores below 0 underscores the need for additional strategies to improve growth outcomes in HIV+ African children BACKGROUND In countries with a high seroprevalence of human immunodeficiency virus type 1 ( HIV-1 ) , HIV infection contributes significantly to infant mortality . We investigated antiretroviral-treatment strategies in the Children with HIV Early Antiretroviral Therapy ( CHER ) trial . METHODS HIV-infected infants 6 to 12 weeks of age with a CD4 lymphocyte percentage ( the CD4 percentage ) of 25 % or more were r and omly assigned to receive antiretroviral therapy ( lopinavir-ritonavir , zidovudine , and lamivudine ) when the CD4 percentage decreased to less than 20 % ( or 25 % if the child was younger than 1 year ) or clinical criteria were met ( the deferred antiretroviral-therapy group ) or to immediate initiation of limited antiretroviral therapy until 1 year of age or 2 years of age ( the early antiretroviral-therapy groups ) . We report the early outcomes for infants who received deferred antiretroviral therapy as compared with early antiretroviral therapy . RESULTS At a median age of 7.4 weeks ( interquartile range , 6.6 to 8.9 ) and a CD4 percentage of 35.2 % ( interquartile range , 29.1 to 41.2 ) , 125 infants were r and omly assigned to receive deferred therapy , and 252 infants were r and omly assigned to receive early therapy . After a median follow-up of 40 weeks ( interquartile range , 24 to 58 ) , antiretroviral therapy was initiated in 66 % of infants in the deferred-therapy group . Twenty infants in the deferred-therapy group ( 16 % ) died versus 10 infants in the early-therapy groups ( 4 % ) ( hazard ratio for death , 0.24 ; 95 % confidence interval [ CI ] , 0.11 to 0.51 ; P<0.001 ) . In 32 infants in the deferred-therapy group ( 26 % ) versus 16 infants in the early-therapy groups ( 6 % ) , disease progressed to Centers for Disease Control and Prevention stage C or severe stage B ( hazard ratio for disease progression , 0.25 ; 95 % CI , 0.15 to 0.41 ; P<0.001 ) . Stavudine was substituted for zidovudine in four infants in the early-therapy groups because of neutropenia in three infants and anemia in one infant ; no drugs were permanently discontinued . After a review by the data and safety monitoring board , the deferred-therapy group was modified , and infants in this group were all reassessed for initiation of antiretroviral therapy . CONCLUSIONS Early HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76 % and HIV progression by 75 % . ( Clinical Trials.gov number , NCT00102960 . Background . The relationships among weight and height growth , viral load and survival in HIV-infected children remain unclear . Objectives . To determine whether weight or height growth velocity independently predicts survival and to investigate associations of weight , height and head circumference growth velocities with viral loads in symptomatic HIV-infected children . Methods . We analyzed data from a prospect i ve antiretroviral study utilizing clinical endpoints ( PACTG 152 ) . Viral load [ log(RNA PCR ) ] and anthropometric measures 12 weeks before and after viral load measures were available in 494 of 831 children . Interval changes during 24 weeks in z-scores for weight-for-age ( & Dgr;WAZ ) , height-for-age ( & Dgr;HAZ ) and head circumference-for-age ( & Dgr;HCZ ) were used as growth velocity surrogates . Logistic regression determined whether & Dgr;WAZ and /or & Dgr;HAZ correlated with survival when age , viral load and CD4 + cell count were controlled . Bivariate analysis assessed correlation among viral load and & Dgr;WAZ , & Dgr;HAZ and /or & Dgr;HCZ . Results . Survival related significantly to height growth velocity ( P = 0.03 , n = 434 ) but not to weight growth velocity ( P = 0.84 , n = 446 ) or head circumference growth velocity ( P = 0.67 , n = 148 ) . Viral load was not significantly associated with changes in weight- , height- , or head circumference-for-age z scores ( P = 0.86 , n = 235 ; P = 0.07 , n = 226 ; and P = 0.09 , n = 165 , respectively ) in children < 30 months of age or with changes in weight- or height-for-age z scores ( P = 0.27 , n = 259 ; P = 0.11 , n = 251 ) in older children . Conclusions . Height growth velocity predicted survival independently of age , viral load and CD4 + cell count . Weight , height and head circumference growth velocities were not significantly associated with viral load in symptomatic HIV-infected children in this large prospect i ve trial of nucleoside reverse transcriptase therapy OBJECTIVE To evaluate the clinical , immunologic , and virologic response to indinavir , zidovudine , and lamivudine in children with human immunodeficiency virus-1 ( HIV-1 ) infection . STUDY DESIGN Twenty-eight HIV-1-infected children ( 3 months to 16 years of age ) with or without prior treatment with reverse-transcriptase inhibitors and a HIV-1 RNA > 5000 copies/mL and /or a CD4 cell count less than the lower limit of the age-specific reference value were treated with indinavir , zidovudine , and lamivudine . Pharmacokinetics of indinavir were determined in each child . RESULTS The combination treatment was well tolerated in the majority of patients . Clinical improvement was seen in all patients . After 6 months of therapy , 70 % of the patients had an HIV-1 RNA load below 500 copies/mL , whereas 48 % of the children had a viral load below 40 copies/mL. Relative CD4 cell counts in relation to the lower limit of the age-specific reference value increased significantly from a median value of 79 % at baseline to 106 % after 6 months of therapy . The doses of indinavir necessary to achieve area under the curve values comparable to adult values varied from 1250 mg/m(2)/d to 2450 mg/m(2)/d . CONCLUSIONS Highly active antiretroviral therapy consisting of indinavir , zidovudine , and lamivudine in children reduced HIV-1 RNA to less than 500 copies/mL in 70 % of the children within 6 months . Improved CD4 cell counts were observed in most patients , as was a better clinical condition ( no invasive or opportunistic infections , increased weight gain ) . Side effects of the triple therapy were mild . Highly active antiretroviral therapy can be used as successfully in children as in adults We assembled a prospect i ve cohort of 3144 human immunodeficiency virus ( HIV ) infected children aged < 15 years initiating antiretroviral therapy ( ART ) in Dar es Salaam , Tanzania . The prospect i ve relationships of baseline covariates with growth were examined using linear regression models . ART led to improvement in mean weight-for-age ( WAZ ) , height/length-for-age ( HAZ ) and weight-for-length or body mass index ( WLZ/ BMI Z ) scores . However , normal HAZ values were not attained over an average follow-up of 17.2 months . After 6 months of ART , underweight ( P < 0.001 ) , low CD4 count or percent ( P < 0.001 ) , stavudine containing regimens ( P = 0.05 ) and advanced WHO disease stage ( P < 0.001 ) at ART initiation were associated with better WAZ scores . Age > 5 years on the other h and was associated with less increase in WAZ score after 6 months of ART ( P < 0.001 ) . These findings suggest that although ART improved the growth of the HIV-infected children in Tanzania , adjunct nutritional interventions may be needed to ensure that the growth of these children is optimized to the greatest extent possible Objective : We evaluated morbidity and mortality during the first 2 years of life among children born to human immunodeficiency virus-(HIV ) type 1-infected women enrolled in the Women and Infants Transmission Study ( WITS ) during an 11-year period ( 1990–2001 ) . Design and Methods : As part of WITS , evaluations were performed at birth and at 1 , 2 , 4 , 6 , 9 , 12 , 18 and 24 months of age . Growth , hospitalization and the incidence of clinical disease were assessed regularly . Results : Data regarding 1118 children born to HIV-infected women ( 955 HIV-uninfected children and 163 HIV-infected children ) were analyzed . Fewer changes in the caretaker of the child and fewer in utero exposures to drugs , tobacco and alcohol occurred in the latter periods of the study ( all P values for time trend analyses < 0.01 ) . The percentages of HIV-uninfected children with poor weight gain ( 44 of 767 ; 5.7 % ) , short stature ( 32 of 703 ; 4.5 % ) and wasting ( 27 of 792 ; 3.4 % ) were higher than expected for the general population . Two or more changes in caretaker were associated with all growth deficiencies except wasting , and fetal exposure to tobacco was associated with height abnormalities . Anemia was common and was associated with receipt of zidovudine prophylaxis . Morbidity and mortality decreased during the study period . For the uninfected children , a decrease in class A events ( Kaplan-Meier rates : group 1 , 22.3 % ; group 2 , 6.8 % ; group 3 , 4.2 % ; P < 0.001 ) and class C events and death ( Kaplan- Meier event rates : group 1 , 2.0 % ; group 2 , 1.7 % ; group 3 , 0.2 % ; P = 0.062 ) during the first 2 years of life account for the differences in the curves over time . Conclusions : During an 11-year period , morbidity and mortality during the first 24 months of life decreased substantially for children born to HIV-infected women |
13,212 | 31,198,467 | : The use of oral hygiene products containing AmF/NaF/SnCl2 or NaF may be effective in the prevention of erosive tooth wear | BACKGROUND : The effectiveness of the application of topical fluorides in prevention of erosive tooth wear has been an issue of controversy in the literature . | Background : To compare the enamel protection efficacy of stannous-containing sodium fluoride and sodium monofluorophosphate (MFP)/triclosan dentifrices marketed in India in an in situ erosion model with acidic challenge . Material s and Methods : This r and omised and controlled , in situ , supervised , double-blind clinical trial employed a two-treatment , four-period crossover design , wherein subjects wore an appliance fitted with human enamel sample s 6 h/day during each 10 day treatment period and swished twice daily with their assigned dentifrice slurry : Oral-B ® Pro-Health ( maximum 1,000 ppm F as sodium fluoride with stannous chloride ) or Colgate ® Strong Teeth with Cavity Protection ( maximum 1,000 F as sodium MFP and triclosan ) . Subjects swished with 250 ml of orange juice over a 10 min period after each treatment and twice daily for the acidic erosive challenge . Enamel sample s were measured for tooth surface loss using contact profilometry at baseline and day 10 . Results : A total of 34 subjects were r and omised to treatment ; 32 subjects completed the final visit . Baseline profilometry measurements of the specimen surfaces were near zero within ± 0.3 μm , and no statistically significant difference ( P > 0.48 ) on average was observed between the two test dentifrices . At day 10 , the stannous-containing dentifrice demonstrated 88 % less erosion ( P < 0.0001 ) relative to the MFP/triclosan dentifrice . Estimated medians ( 95 % confidence intervals ) were 0.21 μm ( 0.17 , 0.25 ) for the stannous-containing dentifrice versus 1.66 μm ( 1.39 , 1.99 ) for the MFP/triclosan dentifrice . Both dentifrices were well-tolerated . Conclusions : Compared with MFP/triclosan toothpaste , a stabilised stannous-containing sodium fluoride dentifrice gave statistically significantly greater protection against tooth enamel surface loss in situ following repeated acid erosive challenge Objectives The aim of these investigations was to assess the ability of two fluoride dentifrices to protect against the initiation and progression of dental erosion using a predictive in vitro erosion cycling model and a human in situ erosion prevention clinical trial for verification of effectiveness . Material s and methods A stabilized stannous fluoride ( SnF2 ) dentifrice ( 0.454 % SnF2 + 0.077 % sodium fluoride [ NaF ] ; total F = 1450 ppm F ) [ dentifrice A ] and a sodium monofluorophosphate [SMFP]/arginine dentifrice ( 1.1 % SMFP + 1.5 % arginine ; total F = 1450 ppm F ) [ dentifrice B ] were tested in a 5-day in vitro erosion cycling model and a 10-day r and omized , controlled , double-blind , two-treatment , four-period crossover in situ clinical trial . In each study , human enamel specimens were exposed to repetitive product treatments using a st and ardized dilution of test products followed by erosive acid challenges in a systematic fashion . Results Both studies demonstrated statistically significant differences between the two products , with dentifrice A providing significantly better enamel protection in each study . In vitro , dentifrice A provided a 75.8 % benefit over dentifrice B ( p < 0.05 , ANOVA ) , while after 10 days in the in situ model , dentifrice A provided 93.9 % greater protection versus dentifrice B ( p < 0.0001 , general linear mixed model ) . Conclusion These results support the superiority of stabilized SnF2 dentifrices for protecting human teeth against the initiation and progression of dental erosion . Clinical relevance Stabilized SnF2 dentifrices may provide more significant benefits to consumers than conventional fluoride dentifrices OBJECTIVE To compare the enamel protection efficacy of a stabilized stannous fluoride ( SnF2 ) dentifrice to a sodium fluoride (NaF)/triclosan dentifrice following acidic erosive challenge . METHODS In this in situ , r and omized , controlled , double-blind , two-treatment , four-period crossover clinical trial , subjects wore an appliance fitted with human enamel sample s 6 h day-1 during each 15-day treatment period . Twice each treatment day they swished with their assigned dentifrice slurry : 0.454 % SnF2 /0.077 % NaF or 0.32 % NaF/0.3 % triclosan . After each treatment and two other times daily , subjects swished with 250 ml of orange juice over a 10-min period ( acidic erosive challenge ) . Enamel sample s were measured for tooth surface loss using contact profilometry at baseline and days 10 and 15 . RESULTS Thirty-six subjects ( mean age 44.8 years , range 23 - 65 years ) were r and omized to treatment ; 33 subjects completed the final study visit . There were no statistically significant baseline differences ( P > 0.44 ) in the specimen surfaces of the two dentifrice treatment groups via profilometry . At day 10 , the SnF2 dentifrice provided a statistically significant ( P < 0.0001 ) reduction in enamel loss by 67 % versus the NaF/triclosan dentifrice with estimated medians of 1.22 and 3.68 μm , respectively . At day 15 , the SnF2 dentifrice again provided a significantly greater benefit ( P < 0.0001 ) against tooth surface loss versus the NaF/triclosan dentifrice , with 68 % less erosion , and estimated medians of 1.60 and 5.03 μm , respectively . Both dentifrices were well tolerated . CONCLUSION A stabilized SnF2 dentifrice provided superior protection against the initiation and progression of tooth enamel surface loss in situ after erosive challenge compared to a NaF/triclosan dentifrice Background / Aims : Stannous fluoride ( SnF ) has been suggested as a dental erosion-preventive agent . The aim of this single-centre , r and omized , double-blind , in situ study was to evaluate the effect of toothpastes with SnF in the prevention of erosive enamel wear . Methods : A combined split-mouth ( extra-oral water or toothpaste brushing ) and crossover ( type of toothpaste ) set-up was used . Twelve volunteers wore palatal appliances containing human enamel sample s. Three toothpastes were used , in three consecutive runs , in r and omized order : two toothpastes containing SnF ( coded M and PE ) and one toothpaste containing only sodium fluoride ( coded C ) . On day 1 of each run the appliances were worn for pellicle formation . On days 2–5 the sample s were also brushed twice with a toothpaste-water slurry or only water ( control ) . Erosion took place on days 2–5 extra-orally 3 times a day ( 5 min ) in a citric acid solution ( pH 2.3 ) . Enamel wear depth was quantified by optical profilometry . The effect of toothpastes was tested using General Linear Modeling . Results : Average erosive wear depth of control sample s was 23 µm . Both SnF toothpastes significantly reduced erosive wear : M by 34 % ( SD 39 % ) and PE by 26 % ( SD 25 % ) . The control toothpaste reduced erosive wear non-significantly by 7 % ( SD 20 % ) . Both SnF-containing toothpastes significantly reduced erosive wear compared to the sodium fluoride toothpaste . Conclusion : We conclude that SnF-containing toothpastes are able to reduce erosive tooth wear in situ Although several studies have demonstrated the efficacy of AmF/NaF/SnCl2 solution in inhibiting dental erosion progression , measures for further improvement in its effectiveness are paramount . Thus , this in situ study evaluated whether the protective effect promoted by the AmF/NaF/SnCl2 solution would be enhanced by increasing its frequency of use . The study was conducted with 12 volunteers , a 4-phase ( 5 days each ) r and omized , crossover model . Extraoral erosive challenges ( 0.5 % citric acid , pH 2.6 , 6 × 2 min/day ) and rinsing protocol ( 1 or 2 × 2 min/day ) were performed . Before the in situ phase , human enamel sample s were subjected to an in vitro surface softening ( 1 % citric acid , pH 4.0 , for 3 min ) . Four treatment protocol s were tested using sample s in replicas ( n = 12 ) : group G1 - deionized water ( negative control ) ; G2 - NaF solution ( positive control , 500 ppm F- , pH 4.5 ) ; G3 - AmF/NaF/SnCl2 solution ( 500 ppm F- , 800 ppm Sn2 + , pH 4.5 ) once a day ; G4 - AmF/NaF/SnCl2 solution twice a day . Tissue loss and morphological changes were determined by optical profilometry ( n = 12 ) and scanning electron microscopy ( n = 3 ) analysis , respectively . Data were statistically analyzed by ANOVA with subsequent pairwise comparison of treatments . Tissue loss means ( ±SD in µm ) for each treatment protocol and statistical differences were found as follows : G1 4.55 ± 2.75 , G2 4.59 ± 2.13 , G3 2.64 ± 1.55 , and G4 1.34 ± 1.16 . Although there was no difference between the 2 AmF/NaF/SnCl2 solution application regimens ( once or twice a day ) , application of the product twice a day was the only treatment that was able to control erosion progression , differing from the control groups OBJECTIVES To determine if brushing dentine with 2 moderate RDA desensitising toothpastes , results in a significant dentine wear difference and whether this difference continues to be relevant when preceded with an erosive challenge . METHODS An in situ , single centre , single blind , r and omised , split mouth study , evaluated the difference in abrasion of 2 toothpastes ( SFM - Sensodyne Fresh Mint ( ® ) RDA 70 ; CPHM - Crest Pro-Health Clean Mint ( ® ) RDA 120 ) in 28 healthy volunteers . Two toothpaste treatments were administered 3 × /day , for each of the two 15 day periods , subjects wearing bi-lateral , lower buccal appliances each with 4 dentine sections . A 2 min extra-oral acidic challenge preceded toothbrushing for 2 study arms . Contact profilometry measured sample s at baseline , days 5 , 10 and 15 . RESULTS Brushing with SFM was significantly less abrasive than brushing with CPHM at all time points , with or without a preceding acidic challenge ( p<0.0001 ) . The additional dentine loss arising from the erosive challenge prior to brushing with each paste was linear with time and independent of abrasive effect . CONCLUSIONS The desensiting toothpastes ' RDA , directly related to dentine loss with toothbrushing . An acidic challenge prior to brushing did not negate the benefits of reduced wear from the lower RDA paste compared to the higher RDA paste . When brushing eroded dentine , the additional wear appeared independent of abrasive effect . Dentine hypersensitivity sufferers should be recommended to use a low-moderate RDA toothpaste , not to brush more than 2 × /day and not immediately following an acidic challenge OBJECTIVES To determine if a stabilised , stannous-containing sodium fluoride dentifrice provides greater enamel protection in situ against intraoral dietary erosive challenges compared with a sodium fluoride/potassium nitrate dentifrice . METHODS A single-centre , investigator blind , r and omised , supervised , two-treatment , non-brushing , four-period crossover in situ study was undertaken , with each test period being 15 days . Thirty-five healthy adult subjects were recruited to participate in the study , which included four erosive acid challenges per day . Subjects were r and omised to product treatment , which included either : ( 1 ) a stannous-containing sodium fluoride dentifrice ( Oral-B ( ® ) Pro-Expert Sensitive ) or ( 2 ) a sodium fluoride/potassium nitrate dentifrice ( Sensodyne ( ® ) Pronamel ( ® ) ) . Each study subject wore an intraoral appliance retaining two sterilised , polished human enamel sample s for 6 hours/day . Subjects swished with an allocated dentifrice slurry twice a day and with 250 ml of orange juice for 10 minutes ( 25 ml/minute over a 10-minute period ) four times per day . The primary and secondary outcomes for this study were enamel loss measured using contact profilometry at days 15 and 5 , respectively , using parametric analysis methods . RESULTS At day 15 , a 38 % lower enamel loss ( P < 0.0001 ) was observed , with estimated medians of 2.03 μm ( SE 0.247 ) and 3.30 μm ( SE 0.379 ) , in favour of the stannous-containing dentifrice . At day 5 , specimens treated with the stannous-containing sodium fluoride dentifrice demonstrated 25 % less enamel loss than those treated with the sodium fluoride/potassium nitrate dentifrice . Treatment differences at day 5 were also statistically significant ( P < 0.05 ) , with estimated medians of 1.37 μm ( SE 0.177 ) and 1.83 μm ( SE 0.223 ) , respectively . CONCLUSIONS Results of this in situ study suggest the stabilised , stannous-containing sodium fluoride dentifrice could be used to provide significantly greater protection to enamel from erosive acid challenge compared with that provided by conventional fluoride-containing products OBJECTIVES The aim of this investigation was to assess the erosion protection ability of a novel stabilized stannous fluoride ( SnF2 ) dentifrice and a control sodium fluoride dentifrice ( NaF ) using a well-credentialed human in situ model . METHODS A novel smooth texture 0.454 % stabilized SnF2 dentifrice ( Crest ® Pro-Health ™ smooth formula ) and a 0.23 % NaF marketed control dentifrice with 5 % potassium nitrate ( Sensodyne ® Pronamel ® ) were compared in a 10-day , single center , r and omized , controlled , double-blind , two-treatment , three-period crossover in situ clinical trial . Subjects wore a m and ibular buccal appliance fitted with eight enamel specimens for approximately six hours over the course of each study day . Twice daily , subjects brushed the lingual surfaces of their teeth for 30 seconds while wearing the appliance , then swished with their assigned treatment toothpaste slurry for 90 seconds under the supervision of clinic staff . Erosive acid challenges with a citric acid-containing beverage ( commercial orange juice ) were done four times each day . RESULTS The SnF2 dentifrice provided 26.9 % greater erosion protection relative to the NaF dentifrice at Day 10 ( p < 0.03 ) . Adjusted means of enamel surface loss at Day 10 were 9.117 µm for the SnF2 dentifrice and 12.471 µm for the NaF marketed control . CONCLUSIONS These results demonstrate the stabilized SnF2 dentifrice offered greater protection over the NaF dentifrice against the initiation and progression of dental erosion The aim of this study was to investigate the effectiveness of both waiting periods between acid exposure and tooth brushing and fluoride applications in preventing toothbrush abrasion of acid-softened enamel surfaces . The study , on 5 subjects , had an in situ crossover design with experimental periods of 5 days each . Human enamel sample s were recessed in mouth appliances and at the end of each experimental period , enamel loss was determined profilometrically . Specimens were eroded extraorally ( 2 × 20 min per day ; 0.05 M citric acid ) , st and ardized brushing ( 2 × 30 s per sample per day ; powered toothbrush ) was performed in situ . The groups were : ( 1 ) erosion only , ( 2 ) brushing with fluoride-free toothpaste directly after , ( 3 ) 2 h after , or ( 4 ) before erosion ; fluoride application was either ( 5 ) brushing with a fluoride toothpaste or ( 6 ) brushing with a fluoride toothpaste or gel , and rinsing with a fluoride mouth rinse . Enamel loss was ( 1 ) 45.2 ± 10.8 , ( 2 ) 79.3 ± 7.8 , ( 3 ) 81.7 ± 9.5 , ( 4 ) 69.7 ± 13.8 , ( 5 ) 51.5 ± 13.0 , and ( 6 ) 41.2 ± 1.8 µm . Brushing without fluoride increased the enamel loss significantly ( p ≤ 0.001 ) , waiting for 2 h had no protective effect , and brushing before erosion decreased enamel loss values only by 12 % ( n.s . ) . In the fluoride groups , enamel loss was significantly lower than after brushing with the fluoride-free toothpaste and comparable to values after erosion only ( n.s . ) . Waiting periods had only a minor effect , whilst the application of fluoride appeared promising OBJECTIVE This manuscript examined the prevalence and extrinsic risk factors for dental erosion ( DE ) in early and middle adolescents in Pasto , Colombia . STUDY DESIGN Dental erosion was evaluated in a r and om sample of 384 individuals aged 10 - 15 years attending three primary and high schools in this cross-sectional study . Clinical dental assessment for DE was done using O'Sullivan index . Data on general sociodemographic variables and extrinsic risks factors were obtained . Descriptive and univariate binary logistic regression analyses were performed . RESULTS Dental erosion was observed in 57.3 % of individuals . The univariate binary logistic regression analysis showed that frequency of drinking natural fruit juices ( OR 2.670 , 95 % CI 1.346 - 5.295 , P=0.004 ) and their pH ( OR 2.303 , 95 % CI 1.292 - 4.107 , P=0.004 ) were more associated with the odd of DE in early adolescence . However , a high SES ( OR 10.360 , 95 % CI 3.700 - 29.010 , P<0.001 ) and frequency of snacks with artificial lemon taste ( OR 3.659 , 95 % CI 1.506 - 8.891 , P=0.003 ) were highly associated with the risk of DE in middle adolescence . CONCLUSIONS The results suggest that DE is a prevalent condition in adolescents living in a city in southern Colombia . The transition from early to middle adolescence implies new bio-psychosocial changes , which increase the risk for DE Tin is a notable anti-erosive agent , and the biopolymer chitosan has also shown demineralisation-inhibiting properties . Therefore , the anti-erosive/anti-abrasive efficacy of the combination of both compounds was tested under in situ conditions . Twenty-seven volunteers were included in a r and omised , double-blind , three-cell crossover in situ trial . Enamel specimens were recessed on the buccal aspects of m and ibular appliances , extraorally demineralised ( 6 × 2 min/day ) and intraorally treated with toothpaste slurries ( 2 × 2 min/day ) . Within the slurry treatment time , one-half of the specimens received additional intraoral brushing ( 5 s , 2.5 N ) . The tested toothpastes included a placebo toothpaste , an experimental NaF toothpaste ( 1,400 ppm F- ) and an experimental F/Sn/chitosan toothpaste ( 1,400 ppm F- , 3,500 ppm Sn2 + , 0.5 % chitosan ) . The percentage reduction of tissue loss ( slurry exposure/slurry exposure + brushing ) compared to placebo was 19.0 ± 47.3/21.3 ± 22.4 after use of NaF and 52.5 ± 30.9/50.2 ± 34.3 after use of F/Sn/chitosan . F/Sn/chitosan was significantly more effective than NaF ( p ≤ 0.001 ) and showed good efficacy against erosive and erosive-abrasive tissue loss . This study suggests that the F/Sn/chitosan toothpaste could provide good protection for patients who frequently consume acidic foodstuffs OBJECTIVES To compare the erosion protection efficacy of a stabilised , stannous fluoride ( SnF2 ) dentifrice versus a sodium fluoride ( NaF ) dentifrice using a modified in situ clinical model . METHODS This study , a r and omised parallel group in situ design with in vivo product use and ex vivo acid challenge , compared : A , a dentifrice containing 1,450 ppm F as NaF ; B , a dentifrice containing 1,450 ppm F ( 1,100 ppm F as SnF2 + 350 ppm F as NaF ) ; and T , tap water . Sample size was n = 4 per group ( total of 12 subjects ) and within each subject appliances were placed on each side of the mouth ( left and right ) . Enamel specimens were placed in different positions of the mouth ( front , mid-front , mid-rear , rear ) in each appliance ( total = 8 specimens per subject ) . Product treatment was twice per day ( lingual brushing for 30 seconds followed by swishing for 90 seconds with the result ant product/saliva slurry ) in vivo for 15 days , and ex vivo acid treatment ( 0.02 m citric acid 5 minutes four times per day ; total exposure time = 300 minutes ) . Data were analysed using a general linear repeated measures model with treatment , side and position as fixed effects . Within subjects , correlations were modelled assuming a different correlation and variance for treatment B relative to the other groups . Pairwise treatment differences were performed using a 5 % two-sided significance level . RESULTS Enamel loss ( in μm ) was significantly lower ( P < 0.005 ) for treatment B versus treatments A and T. Treatment B reduced enamel surface loss by 86.9 % relative to treatment A. There was no statistical difference in mean enamel loss ( P = 0.51 ) between treatments A and T. Enamel loss was not statistically different for side ( left vs. right ; P = 0.44 ) or position ( front , mid-front , mid-rear , rear ; P = 0.36 ) . CONCLUSION This modified in situ erosion model confirmed the enhanced erosion protection benefits of a stabilised SnF2 dentifrice versus a conventional NaF dentifrice , validating the ability of the model to safely and effectively demonstrate differences in the erosion protection potential of oral care products OBJECTIVES To evaluate the progression of dental erosion in 13 - 14 year-olds after 4 years , and its association with lifestyle and oral health . METHODS 227 r and omly selected 13 - 14 year-olds from a Public Dental Clinic , Örebro , Sweden , were investigated . A clinical examination was performed which included dental caries/gingival/plaque status , as well as grading of dental erosion at the tooth surface and participant levels in " marker teeth " , including buccal/palatal surfaces of 6 maxillary anterior teeth ( 13 - 23 ) , and occlusal surfaces of first molars . An interview and a question naire regarding drinking habits and other lifestyle factors were completed . All investigations were repeated at follow-up . The participants were divided into high and low progression erosion groups and logistic regression statistics were applied . RESULTS 175 individuals participated at follow-up . Progression occurred in 35 % of the 2566 tooth surfaces . 32 % of the surfaces had deteriorated by one severity grade ( n=51 individuals ) and 3 % by two grade s ( n=2 individuals ) . Boys showed more severe erosion than girls at the follow-up . Among the variables predicting greater progression , a lower severity of erosive wear at baseline had the highest OR ( 13.3 ) , followed in descending order by a " retaining " drinking technique , more frequent intake of drinks between meals , low GBI and lesser sour milk intake , with reference to the baseline recording . Using these five variables , sensitivity and specificity were 87 % and 67 % respectively , for predicting progression of erosion . CONCLUSIONS Progression of erosive lesions in Swedish adolescents aged 13 - 14 years followed up to age 17 - 18 years was common and related to certain lifestyle factors . CLINICAL SIGNIFICANCE In permanent teeth , dental erosion may develop early in life and its progression is common . Dental health workers should be made aware of this fact and regular screenings for erosion and recording of associated lifestyle factors should be performed OBJECTIVE To evaluate the anti-erosive effect of solutions containing sodium fluoride ( F : 225ppm of fluoride ) , sodium fluoride+stannous chloride ( F+Sn : 225ppm of fluoride+800ppm of stannous ) , sodium fluoride+stannous chloride+sodium linear polyphosphate ( F+Sn+LPP : 225ppm of fluoride+800ppm of stannous+2 % of sodium linear polyphosphate ) , and deionized water ( C : control ) , using a four-phase , single-blind , crossover in situ clinical trial . METHODS In each phase , 12 volunteers wore appliances containing 4 enamel specimens , which were su bmi tted to a 5-day erosion-remineralization phase that consisted of 2h of salivary pellicle formation with the appliance in situ , followed by 2min extra-oral immersion in 1 % citric acid ( pH 2.4 ) , 6x/day , with 90min of exposure to saliva in situ between the challenges . Treatment with the test solutions was performed extra-orally for 2 min , 2x/day . At the end of the experiment , surface loss ( SL , in μm ) was evaluated by optical profilometry . Data were analyzed using ANOVA and Tukey tests ( α=0.05 ) . The surface of additional specimens was evaluated by x-ray diffraction after treatments ( n=3 ) . RESULTS C ( mean SL±st and ard-deviation : 5.97±1.70 ) and F ( 5.36±1.59 ) showed the highest SL , with no significant difference between them ( p>0.05 ) . F+Sn ( 2.68±1.62 ) and F+Sn+LPP ( 2.10±0.95 ) did not differ from each other ( p>0.05 ) , but presented lower SL than the other groups ( P<0.05 ) . Apatite and stannous deposits on specimen surfaces were identified in the x-ray analysis for F+Sn and F+Sn+LPP . CONCLUSIONS Sodium fluoride solution exhibited no significant anti-erosive effect . The combination between sodium fluoride and stannous chloride reduced enamel erosion , irrespective of the presence of linear sodium polyphosphate . CLINICAL SIGNIFICANCE Under highly erosive conditions , sodium fluoride rinse may not be a suitable alternative to prevent enamel erosion . A rinse containing sodium fluoride and stannous chloride was shown to be a better treatment option , which was not further improved by addition of the sodium linear polyphosphate Concentrated tin- and fluoride-containing mouthrinses are effective erosion inhibitors in enamel and dentin . To test whether this is also true for solutions with lower concentrations , we conducted a r and omized double-blind three-cell crossover in situ study with extra-orally performed erosive impacts ( citric acid , 6 x 5 min/day ) and an intra-oral rinsing protocol ( 1 x 30 sec/day ) in 24 volunteers . The mouthrinses were a placebo , a NaF ( 500 ppm F- ) , and an amine fluoride (AmF)/NaF/SnCl2 mouthrinse ( 500 ppm F- , 800 ppm Sn2 + ) . Compared with the placebo , the NaF mouthrinse reduced substance loss by 19 % in enamel and 23 % in dentin ( p ≤ 0.01 each ) ; the AmF/NaF/SnCl2 mouthrinse reduced this parameter by 67 % in enamel and 47 % in dentin ( p ≤ 0.001 each ) . AmF/NaF/SnCl2 was significantly more effective than NaF in both tissues ( p ≤ 0.01 ) . The mouthrinse containing Sn and F exhibited good efficacy , even under severe erosive conditions |
13,213 | 24,737,131 | In addition , there was a lack of long-term follow-up data for most studies .We found positive effects for some interventions for : body mass index ( BMI ) , physical activity , physical fitness , fruit and vegetable intake , tobacco use , and being bullied .
Intervention effects were generally small but have the potential to produce public health benefits at the population level .
We therefore can not draw any clear conclusions as to the effectiveness of this approach for improving academic achievement .
The results of this review provide evidence for the effectiveness of some interventions based on the HPS framework for improving certain health outcomes but not others . | BACKGROUND The World Health Organization 's ( WHO 's ) Health Promoting Schools ( HPS ) framework is an holistic , setting s-based approach to promoting health and educational attainment in school .
The effectiveness of this approach has not been previously rigorously review ed .
OBJECTIVES To assess the effectiveness of the Health Promoting Schools ( HPS ) framework in improving the health and well-being of students and their academic achievement . | Background The current academic literature suggests there is a potential for using gardening as a tool to improve children ’s fruit and vegetable intake . This study is two parallel r and omised controlled trials ( RCT ) devised to evaluate the school gardening programme of the Royal Horticultural Society ( RHS ) Campaign for School Gardening , to determine if it has an effect on children ’s fruit and vegetable intake . Method / Design Trial One will consist of 26 schools ; these schools will be r and omised into two groups , one to receive the intensive intervention as “ Partner Schools ” and the other to receive the less intensive intervention as “ Associate Schools ” . Trial Two will consist of 32 schools ; these schools will be r and omised into either the less intensive intervention “ Associate Schools ” or a comparison group with delayed intervention . Baseline data collection will be collected using a 24-hour food diary ( CADET ) to collect data on dietary intake and a question naire exploring children ’s knowledge and attitudes towards fruit and vegetables . A process measures question naire will be used to assess each school ’s gardening activities . Discussion The results from these trials will provide information on the impact of the RHS Campaign for School Gardening on children ’s fruit and vegetable intake . The evaluation will provide valuable information for design ing future research in primary school children ’s diets and school based interventions .Trial registration IS RCT The Fast Track prevention trial was used to test hypotheses from the Early-Starter Model of the development of chronic conduct problems . We r and omly assigned 891 high-risk first- grade boys and girls ( 51 % African American ) to receive the long-term Fast Track prevention or not . After 4 years , outcomes were assessed through teacher ratings , parent ratings , peer nominations , and child self-report . Positive effects of assignment to intervention were evident in teacher and parent ratings of conduct problems , peer social preference scores , and association with deviant peers . Assessment s of proximal goals of intervention ( e.g. , hostile attributional bias , problem-solving skill , harsh parental discipline , aggressive and prosocial behavior at home and school ) collected after grade 3 were found to partially mediate these effects . The findings are interpreted as consistent with developmental theory BACKGROUND Pathways , a multisite school-based study aim ed at promoting healthful eating and increasing physical activity , was a r and omized field trial including 1704 American Indian third to fifth grade students from 41 schools ( 21 intervention , 20 controls ) in seven American Indian communities . METHODS The intervention schools received four integrated components : a classroom curriculum , food service , physical activity , and family modules . The curriculum and family components were based on Social Learning Theory , American Indian concepts , and results from formative research . Process evaluation data were collected from teachers ( n=235 ) , students ( n=585 ) , and families . Knowledge , Attitudes , and Behavior Question naire data were collected from 1150 students including both intervention and controls . RESULTS There were significant increases in knowledge and cultural identity in children in intervention compared to control schools with a significant retention of knowledge over the 3 years , based on the results of repeating the third and fourth grade test items in the fifth grade . Family members participated in Family Events and take-home activities , with fewer participating each year . CONCLUSION A culturally appropriate school intervention can promote positive changes in knowledge , cultural identity , and self-reported healthful eating and physical activity in American Indian children and environmental change in school food service OBJECTIVE To evaluate the effect of the middle and junior high school Drug Abuse Resistance Education ( D.A.R.E. ) and D.A.R.E. Plus programs on drug use and violence . DESIGN R and omized controlled trial of 24 schools , with 3 conditions : D.A.R.E. only , D.A.R.E. Plus , and delayed program control . SETTING Schools and neighborhoods , primarily in Minneapolis-St Paul . PARTICIPANTS All seventh- grade students in 24 schools in the academic year 1999 - 2000 ( N = 6237 at baseline , 67.3 % were white , and there was 84.0 % retention at final follow-up ) . INTERVENTIONS The middle and junior high school D.A.R.E. curriculum in the 16 schools that received D.A.R.E. only and D.A.R.E. Plus . In the 8 schoolts that received D.A.R.E. Plus , additional components included a peer-led parental involvement classroom program called " On the VERGE , " youth-led extracurricular activities , community adult action teams , and postcard mailings to parents . The interventions were implemented during 2 school years , when the cohort was in the seventh and eighth grade s. MAIN OUTCOME MEASURES Self-reported tobacco , alcohol , and marijuana use ; multidrug use ; violence ; and victimization , assessed at the beginning and end of seventh grade and at the end of eighth grade . Growth curve analytic methods were used to assess changes over time by condition . RESULTS There were no significant differences between D.A.R.E. only and the controls ; significant differences among boys between D.A.R.E. Plus and controls for tobacco , alcohol , and multidrug use and victimization ; significant differences among boys between D.A.R.E. Plus and D.A.R.E. only in tobacco use and violence ; and no significant behavioral differences among girls . CONCLUSION D.A.R.E. Plus significantly enhanced the effectiveness of the D.A.R.E. curriculum among boys and was more effective than the delayed program controls , underscoring the potential for multiyear , multicomponent prevention programs and demonstrating sex differences in response to intervention programs Background Obesity has become a global public health problem , which also affects children . It has been proposed that the educational interventions during childhood could be a key strategy in the prevention of obesity . Objective To evaluate the efficacy of an intervention on food habits and physical activity in school children . Methods A 2-year cluster-r and omised prospect i ve study with two parallel arms was used to evaluate an intervention programme in children in their first year of primary schooling ( 5–6 years of age ) in schools in the city of Granollers . The intervention consisted of the promotion of healthy eating habits and physical activity by means of the educational methodology Investigation , Vision , Action and Change ( IVAC ) . At the beginning and at the end of the study ( 2006 and 2008 ) the weight and height of each child was measured in situ , while the families were given a self-report physical activity question naire and the Krece Plus quick test . Results Two years after the beginning of the study , the body mass index of the children in the control group was 0.89 kg/m2 higher than that of the intervention schools . The intervention reduced by 62 % the prevalence of overweight children . Similarly , the proportion of children that ate a second piece of fruit and took part in an after-school physical activity increased in the intervention group . In the control group , the weekly consumption of fish was reduced . Conclusions The educational intervention in healthy eating habits and physical activity in the school could contribute to lessen the current increase in child obesity This study examined the effectiveness of the universal component of the Fast Track prevention model : the PATHS ( Promoting Alternative THinking Strategies ) curriculum and teacher consultation . This r and omized clinical trial involved 198 intervention and 180 comparison classrooms from neighborhoods with greater than average crime in 4 U.S. locations . In the intervention schools , Grade 1 teachers delivered a 57-lesson social competence intervention focused on self-control , emotional awareness , peer relations , and problem solving . Findings indicated significant effects on peer ratings of aggression and hyperactive-disruptive behavior and observer ratings of classroom atmosphere . Quality of implementation predicted variation in assessment s of classroom functioning . The results are discussed in terms of both the efficacy of universal , school-based prevention models and the need to examine comprehensive , multiyear programs OBJECTIVE We evaluated the impact of an intervention promoting sun protection behavior among children 2 to 11 years of age through schools and day care centers , primary care practice s , and recreation areas . METHODS Ten towns in New Hampshire were paired , then assigned r and omly to intervention or control status . The multicomponent SunSafe intervention was provided to children and caregivers through primary care practice s , day care centers , schools , and beach recreation areas . Training support and material s were provided by the SunSafe project , but project staff had no direct contact with children or parents in providing the intervention . All intervention components promoted the same message : avoid the sun between 11 AM and 3 PM , cover up using hats and protective clothing , use sun block with a sun protection factor > /=15 , and encourage sun protection among family and friends . The impact of the intervention was determined by observing children 's sun protection behavior at the beach during baseline compared with 1 year later . The primary outcomes of interest were changes in the proportion of children per town using at least some sun protection and changes in the proportion of children fully protected . Children were clustered by town , with the town thus being the unit of analysis . The primary care practice component included one practice meeting for clinicians and staff at which project staff presented background on skin cancer and how to promote its prevention ; a sun protection office system manual based on our previous work , which provided specific direction on how to share responsibility among office staff and clinicians in carrying out routines that promote sun protection ; and educational posters , pamphlets , and self-adhesive reminder notes design ed to enhance sun protection counseling . SunSafe removable tattoos and stickers were offered to children at well-child and illness visits during the summer months . Schools each received three project staff visits : a brief visit with the principal to describe the intervention and to answer questions ; an in-service program to educate teachers about skin cancer and to introduce curricular material s ; and help with one parent outreach program . Larger day care centers each received one project staff visit . An additional six smaller day care centers received curricular material s through the mail but no visits . Two similar sets of curricular material s were used , one for grade schools and the other for preschools and day care centers . Both emphasized the importance of sun protection rather than the danger of skin cancer . Material s emphasized dynamic activities modeled after the " Slip , Slop , Slap " and " SunSmart " programs and included new material developed to suit regional needs . Both manuals offered structured plans but also provided a variety of activities from which teachers could choose . Teachers agreed to devote a minimum of two class periods to these material s. For recreation areas , lifeguards in each of the intervention communities attended an in-service meeting , during which background about skin cancer prevention was presented by project staff . The project also provided displays about the ultraviolet ( UV ) light index and about sun protection to be posted at each beach . Subsequently , project staff called beach staff in each community each morning with the predicted UV index for the day to post on the display . Educational pamphlets about the UV index and free sun-block sample s were available to beachgoers through the lifeguards . One brief follow-up visit by project staff was made to each beach area to provide reinforcement . RESULTS We observed 1930 children . Use of some sunscreen on at least one body area increased in all 5 intervention towns compared with paired control towns . In intervention towns , this mean proportion increased from 0.56 of those observed at baseline to 0.76 of those observed postintervention , with a minimal increase among control town children . ( ABSTRACT The primary aim of the Trial of Activity in Adolescent Girls ( TAAG ) is to test an intervention to reduce by half the age-related decline in moderate to vigorous physical activity ( MVPA ) in middle school girls . The intervention will be evaluated using a group-r and omized trial involving 36 middle schools . The primary endpoint is the mean difference in intensity-weighted minutes ( i.e. , MET-minutes ) of MVPA between intervention and comparison schools assessed using accelerometry . The TAAG study design calls for two cross-sectional sample s , one drawn from 6th grade rs at the beginning of the study and the second drawn from 8th grade rs at the end of the study following the 2-year implementation of the intervention . An important strength of this design over a cohort design is the consistency with the goals of TAAG , which focus on environmental-level rather than individual-level interventions to produce change . The study design specifies a recruitment rate of 80 % and a smaller sample of girls at baseline ( n=48 per school ) than at follow-up ( n=96 per school ) . A two-stage model will be used to test the primary hypothesis . In the first stage , MET-weighted minutes of MVPA will be regressed on school , time ( baseline or follow-up ) , their interaction , ethnicity and week of data collection . The second stage analysis will be conducted on the 72 adjusted means from the first stage . In the main-effects model , we will regress the follow-up school mean MET-weighted minutes of MVPA on study condition , adjusting for the baseline school mean . The TAAG study addresses an important health behavior , and also advances the field of group-r and omized trials through the use of a study design and analysis plan tailored to serve the main study hypothesis BACKGROUND Twenty-four-hour recalls were used to assess the change in nutrient intake among elementary-age school children exposed to the Child and Adolescent Trial for Cardiovascular Health ( CATCH ) . The purpose of this paper is to compare changes in nutrient intakes between treatment groups , sexes , ethnic groups , and the four CATCH sites . METHODS Twenty-four-hour recalls were administered to a sub sample of the CATCH cohort at baseline in third grade and following the intervention in fifth grade ( n = 1,182 ) . Changes in nutrient levels for total energy , dietary cholesterol , and dietary fiber and changes in the proportion of energy from fat , protein , carbohydrate , and fatty acids were studied looking at differences by treatment group , sex , ethnicity , and site . Mixed-model analysis of variance was used to examine the change in nutrient intake , defined as intake at follow-up minus intake at baseline . RESULTS Students in the intervention schools showed statistically significant differences in the changes in total energy and proportion of energy from total fat , saturated fat , protein , and monounsaturated fat compared with students in the control group . Students in the intervention group decreased their total fat intake from 32.7 % of energy to 30.3 % of energy and saturated fat from 12.8 % of energy to 11.4 % of energy . There were no significant differences in intervention effects by ethnic group , sex , or site . Differences in nutrient change between the school-only and the school-plus-family intervention groups were nonsignificant . CONCLUSION The results show that a school-based intervention can positively influence children 's intakes of total fat and saturated fat , suggesting that population -based approaches for reducing cardiovascular risk factors in children are feasible and effective . The results are also important in showing that the intervention was effective in Caucasian , African-American , and Hispanic students , in boys and girls , and across four regions of the United States OBJECTIVE : We tested the impact of the Fast Track conduct disorder prevention program on the use of pediatric , general health , and mental health services in adolescence . PATIENTS AND METHODS : Participants were 891 public kindergarten boys and girls screened from a population of 9594 children and found to be at risk for conduct disorder . They were assigned r and omly ( by school ) to intervention or control conditions and were followed for 12 years . Intervention lasted 10 years and included parent training , child social-cognitive skills training , reading tutoring , peer-relations enhancement , and classroom curricula and management . Service use was assessed through annual interviews of parents and youth . RESULTS : Youth assigned to preventive intervention had significantly reduced use of professional general health , pediatric , and emergency department services relative to control youth on the basis of parent-report data . For control-group youth , the odds of greater use of general health services for any reason and general health services use for mental health purpose s were roughly 30 % higher and 56 % higher , respectively . On the basis of self-report data , the intervention reduced the likelihood of outpatient mental health services among older adolescents for whom odds of services use were more than 90 % higher among control-group youth . No differences were found between intervention and control youth on the use of inpatient mental health services . Statistical models controlled for key study characteristics , and potential moderation of the intervention effect was assessed . CONCLUSIONS : R and om assignment to the Fast Track prevention program is associated with reduced use of general health and outpatient mental health services in adolescents . Future studies should examine the mechanism of this impact and service use patterns as subjects reach young adulthood In India , 57 % of men between 15 and 54 years and 10.8 % of women between 15 and 49 years use tobacco . A wide variety of tobacco gets used and the poor and the underprivileged are the dominant victims of tobacco and its adverse consequences . Project MYTRI ( Mobilizing Youth for Tobacco-Related Initiatives in India ) was a tobacco prevention intervention program , a cluster-r and omized trial in 32 Indian schools which aim ed to decrease susceptibility to tobacco use among sixth- to ninth- grade students in urban setting s in India . This culture-specific intervention , which addressed both smokeless and smoked forms of tobacco , was Indian in content and communication . We qualitatively developed indicators which would help accurately measure the dose of the intervention given , received and reached . A multi-staged process evaluation was done through both subjective and objective measures . Training the teachers critically contributed toward a rigorous implementation and also correlated with the outcomes , as did a higher proportion of students participating in the classroom discussion s and better peer-leader-student communication . A sizeable proportion of subjective responses were ' socially desirable ' , making objective assessment a preferred methodology even for ' dose received ' . The peer-led health activism was successful . Teachers ' manuals need to be concise Background : Population -based studies directed at promoting physical activity in youth have shown limited success in obesity prevention . Objective : To assess whether an intervention integrating environmental changes to induce sustained changes in physical activity , prevents overweight in adolescents . Design : Four-year r and omized trial started in 2002 in eight middle schools of Eastern France . The intervention , r and omized at school level , was design ed to promote physical activity by changing attitudes through debates and attractive activities , and by providing social support and environmental changes encouraging physical activity . Subjects : Nine hundred and fifty four 12-year-old six- grade rs . Measurements : Body mass index ( BMI ) , body composition , physical activity by question naire , plasma lipids and glucose , insulin resistance . Results : Intervention students had a lower increase in BMI ( P=0.01 ) and age- and gender-adjusted BMI ( P<0.02 ) over time than controls . The differences across groups of the age- and gender-adjusted BMI changes ( 95 % confidence interval ( CI ) ) were −0.29 ( −0.51 ; −0.07 ) kg/m2 at 3 years , −0.25 ( −0.51 ; 0.01 ) kg/m2 at 4 years . An interaction with baseline weight status was noted . The intervention had a significant effect throughout the study in initially non-overweight adolescents ( −0.36 ( −0.60;−0.11 ) kg/m2 for adjusted BMI at 4 years ) , corresponding to a lower increase in fat mass index ( P<0.001 ) . In initially overweight adolescents , the differences observed across groups at 2 years ( –0.40 ( −0.94 ; 0.13 ) kg/m2 for adjusted BMI ) did not persist over time . At 4 years , 4.2 % of the initially non-overweight adolescents were overweight in the intervention schools , 9.8 % in the controls ( odds ratio=0.41 ( 0.22 ; 0.75 ) ; P<0.01 ) . Independent of initial weight status , compared with controls , intervention adolescents had an increase in supervised physical activity ( P<0.0001 ) , a decrease of TV/video viewing ( P<0.01 ) and an increase of high-density cholesterol concentrations ( P<0.0001 ) . Conclusion : Enhancing physical activity with a multilevel program prevents excessive weight gain in non-overweight adolescents . Our study provides evidence that prevention of obesity in youth is feasible Background The School Fruit and Vegetable Scheme ( SFVS ) is an important public health intervention . The aim of this scheme is to provide a free piece of fruit and /or vegetable every day for children in Reception to Year 2 . When children are no longer eligible for the scheme ( from Year 3 ) their overall fruit and vegetable consumption decreases back to baseline levels . This proposed study aims to design a flexible multi-component intervention for schools to support the maintenance of fruit and vegetable consumption for Year 3 children who are no longer eligible for the scheme . Method This study is a cluster r and omised controlled trial of Year 2 classes from 54 primary schools across Engl and . The schools will be r and omly allocated into two groups to receive either an active intervention called Project Tomato , to support maintenance of fruit intake in Year 3 children , or a less active intervention ( control group ) , consisting of a 5 A DAY booklet . Children 's diets will be analysed using the Child And Diet Evaluation Tool ( CADET ) , and height and weight measurements collected , at baseline ( Year 2 ) and 18 month follow-up ( Year 4 ) . The primary outcome will be the ability of the intervention ( Project Tomato ) to maintain consumption of fruit and vegetable portions compared to the control group . Discussion A positive result will identify how fruit and vegetable consumption can be maintained in young children , and will be useful for policies supporting the SFVS . A negative result would be used to inform the research agenda and contribute to redefining future strategies for increasing children 's fruit and vegetable consumption . Trial registration Medical Research Council Registry code Abstract Objective : To assess if a school based intervention was effective in reducing risk factors for obesity . Design : Group r and omised controlled trial . Setting : 10 primary schools in Leeds . Participants : 634 children aged 7 - 11 years . Intervention : Teacher training , modification of school meals , and the development of school action plans targeting the curriculum , physical education , tuck shops , and playground activities . Main outcome measures : Body mass index , diet , physical activity , and psychological state . Results : Vegetable consumption by 24 hour recall was higher in children in the intervention group than the control group ( weighted mean difference 0.3 portions/day , 95 % confidence interval 0.2 to 0.4 ) , representing a difference equivalent to 50 % of baseline consumption . Fruit consumption was lower in obese children in the intervention group ( −1.0 , −1.8 to −0.2 ) than those in the control group . The three day diary showed higher consumption of high sugar foods ( 0.8 , 0.1 to 1.6 ) ) among overweight children in the intervention group than the control group . Sedentary behaviour was higher in overweight children in the intervention group ( 0.3 , 0.0 to 0.7 ) . Global self worth was higher in obese children in the intervention group ( 0.3 , 0.3 to 0.6 ) . There was no difference in body mass index , other psychological measures , or dieting behaviour between the groups . Focus groups indicated higher levels of self reported behaviour change , underst and ing , and knowledge among children who had received the intervention . Conclusion : Although it was successful in producing changes at school level , the programme had little effect on children 's behaviour other than a modest increase in consumption of vegetables . What is already known on this topic Obesity is increasing among school children and dem and s preventive strategies R and omised controlled trials of school based primary prevention programmes have all used a prescriptive approach What this study adds Behavioural changes were disappointing with this programme based on the health promoting schools philosophy , despite changes at school level The only positive outcome was a modest increase in vegetable consumption The discrepancy between changes achieved at the individual and school level raises issues regarding the problems inherent in such Objective : To examine whether smoking onset in young adolescents is predicted by peer or parental smoking . Design : Longitudinal design with one pretest and one follow-up at 12 months . Setting : Schools in Finl and , Denmark , the Netherl and s , the United Kingdom , Spain and Portugal . Participants : 7102 r and omly selected adolescents from six countries . Mean age was 12.78 years . Main outcome measures : Smoking behaviour of adolescents , peers and parents . Results : No support was found for peer smoking as an important predictor of smoking onset in most countries . Support was found for the selection paradigm , implying that adolescents choose friends with similar smoking behaviour . Support for the impact of parents on adolescent behaviour and the choice of friends was also found . Conclusions : Smoking uptake in this age cohort may be more strongly influenced by personal and parental influences than initially believed . Hence , social inoculation programmes teaching youngsters to resist the pressures to smoke may be less appropriate if youngsters have a positive attitude towards smoking , associate smoking with various advantages and look for peers with similar values . For this group attitudes towards smoking may thus guide future friend selection A population -based r and omized intervention trial for the prevention of conduct problems ( i.e. , oppositional defiant disorder and conduct disorder ) is described . The LIFT ( Linking the Interests of Families and Teachers ) intervention was design ed for all first- and fifth- grade elementary school boys and girls and their families living in at-risk neighborhoods characterized by high rates of juvenile delinquency . The 10-week intervention strategy was carefully targeted at proximal and malleable antecedents in three social domains that were identified by a developmental model of conduct problems . From 12 elementary schools , 671 first and fifth grade rs and their families participated either in the theory-based universal preventive intervention or in a control condition . The intervention consisted of parent training , a classroom-based social skills program , a playground behavioral program , and systematic communication between teachers and parents . A multiple measure assessment strategy was used to evaluate participant satisfaction and participation , fidelity of implementation , and the immediate impacts of the program on targeted antecedents This study reports the effect of the Fruits and Vegetables Make the Marks intervention , a school-based fruit and vegetable intervention consisting of a home economics classroom component and parental involvement and encouraged participation in the Norwegian School Fruit Programme , all delivered during the school year of 2001 - 02 . Nine r and omly chosen schools received the intervention and 10 schools served as control schools . Participating pupils completed question naires at baseline ( September 2001 ) , at Follow-up 1 ( May-June 2002 ) and at Follow-up 2 ( May 2003 ) . A total of 369 pupils ( 69 % ; mean age , 11.3 years at baseline ) participated in all three surveys . No effect of the intervention was found for intake of fruit and vegetables eaten at school or all day , neither at Follow-up 1 nor at Follow-up 2 . On analysing the effects on potential mediators , significant differences between intervention and control groups were found for Awareness of the five-a-day recommendations only . The intervention programme was rated as very good by the teachers , and the pupils reported that they enjoyed it . However , the intervention failed to change fruit and vegetable intake , probably because it did not succeed in changing the pupils ' preferences for or the accessibility of fruit and vegetables -- the two strongest correlates of children 's fruit and vegetable intake Reports of cluster r and omised trials require additional information to allow readers to interpret them accurately The effective reporting of r and omised controlled trials has received useful attention in recent years . Many journals now require that reports conform to the guidelines in the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement , first published in 1996 and revised in 2001 . The statement includes a checklist of items that should be included in the trial report . These items are evidence based whenever possible and are regularly review ed . The statement also recommends including a flow diagram to show the flow of participants from group assignment through to the final analysis . The CONSORT statement focused on reporting parallel group r and omised trials in which individual participants are r and omly assigned to study groups . However , in some situations it is preferable to r and omly assign groups of individuals ( such as families or medical practice s ) rather than individuals . Reasons include the threat of contamination of some interventions ( such as dietary interventions ) if individual r and omisation is used . 5 Also , in certain setting s r and omisation by group may be the only feasible method of conducting a trial . Trials with this design are variously known as field trials , community based trials , place based trials , or ( as in this paper ) cluster r and omised trials . In an earlier discussion paper we considered the implication s of the CONSORT statement for the reporting of cluster r and omised trials . Here we present up date d guidance , based on the 2001 revision of the CONSORT statement Background Krachtvoer is a Dutch healthy diet programme for prevocational schools , developed in 2001 and revised for a broader target group in 2007 , based on the findings of an evaluation of the first version . The goal of this study was to report on the short- and longer-term total and subgroup effects of the revised programme on students ’ fruit , fruit juice , breakfast , and snack consumption . Methods Schools were r and omized to the experimental condition , teaching the Krachtvoer programme , or to the control condition teaching the regular nutrition lessons . Self-reported consumption of fruit , fruit juice , breakfast and snacks was measured at baseline directly before programme implementation , one to four weeks after finishing programme implementation , and after six months . Mixed linear and logistic regression analyses were conducted . Results In total 1117 students of 13 experimental schools and 758 students of 11 control schools participated in the study . Short- and longer-term favourable intervention effects were found on fruit consumption ( mean difference between experimental and control group 0.15 servings at both posttests ) . Regarding fruit juice consumption , only short-term favourable effects were revealed ( mean difference between experimental and control group 0.05 glasses ) . Intervention effects on breakfast intakes were limited . No changes in snack frequency were reported , but students made healthier snack choices as a result of the programme . Some favourable as well as unfavourable effects occurred in subgroups of students . Conclusions The effects on fruit consumption and snack choices justify the current nationwide dissemination of the programme . Achieving changes in breakfast consumption may , however , require other strategies OBJECTIVE To evaluate the effectiveness of a program to increase walking to and from school . DESIGN A cluster r and omised controlled trial . SETTING 24 primary public schools in inner west Sydney , Australia . PARTICIPANTS 1996 students aged 10 - 12 years and their parents . INTERVENTION A two-year multi-component program included classroom activities , development of school Travel Access Guides , parent newsletters and improving environments with local councils . MEASURES Two measures were used : a survey completed by students on how they travelled to and from school over five days , and a survey completed by their parents on how their child travelled to and from school in a usual week . RESULTS The percentage of students who walked to and from school increased in both the intervention and control schools . Data from parent surveys found that 28.8 % of students in the intervention group increased their walking , compared with 19 % in the control group ( a net increase of 9.8 % , p=0.05 ) . However this effect was not evident in the student data . CONCLUSION The study produced a mixed result , with a high variation in travel patterns from school to school . Intervention research should address the complexity of multiple factors influencing student travel to school with a focus on changing local environments and parents ' travel to work OBJECTIVE To assess the impact of a school-based nutrition education intervention aim ed at increasing the consumption of fruits and vegetables . DESIGN The intervention programme increased the provision of fruits and vegetables in schools and provided a range of point-of-purchase marketing material s , newsletters for children and parents , and teacher information . Curriculum material s at age 6 - 7 and 10 - 11 years were also developed and utilised . Evaluation was undertaken with groups of younger ( aged 6 - 7 years ) and older ( aged 10 - 11 years ) children . Methods included 3-day dietary records with interview and cognitive and attitudinal measures at baseline , with follow-up at 9 months , in intervention and control schools . SETTING The work was undertaken in primary schools in Dundee , Scotl and . SUBJECTS Subjects comprised 511 children in two intervention schools with a further 464 children from two schools acting as controls . RESULTS Children ( n=64 ) in the intervention schools had an average increase in fruit intake ( 133+/-1.9 to 183+/-17.0 g day(-1 ) ) that was significantly ( P<0.05 ) greater than the increase ( 100+/-11.7 to 107+/-14.2 g day(-1 ) ) estimated in children ( n=65 ) in control schools . No other changes in food or nutrient intake were detected . Increases in scores for variables relating to knowledge about fruits and vegetables and subjective norms were also greater in the intervention than in the control group , although taste preferences for fruits and vegetables were unchanged . CONCLUSIONS It is concluded that a whole school approach to increasing intakes of fruits and vegetables has a modest but significant effect on cognitive and attitudinal variables and on fruit intake BACKGROUND The purpose of this study was to examine the impact of the Pathways intervention on pychosocial variables related to physical activity and diet in American Indian children . METHODS Schools serving American Indian children were r and omized to a multicomponent intervention or control condition . At baseline ( fall of third grade ) and in the spring semester of third , fourth , and fifth grade s 755 boys and 692 girls completed a classroom-administered question naire . The question naire assessed self-efficacy , knowledge , and behavioral intentions related to diet and physical activity , as well as weight loss behaviors and body image . RESULTS Knowledge of nutrition and physical activity messages increased in both boys and girls in the intervention group compared to controls ; however , knowledge of which foods contained more fat did not increase consistently . Compared to controls , self-efficacy to be physically active increased among girls in intervention schools , but not among boys , whereas self-efficacy to make more healthy food choices did not increase more than in controls in either gender . In the intervention group , compared to controls , healthy food intentions and participation in physically active behaviors increased in both boys and girls . Perception of healthy body size and weight loss attempts did not differ in the intervention and control groups . CONCLUSION The Pathways intervention program had a positive impact on several aspects of obesity-related knowledge , attitudes , and behaviors OBJECTIVE The purpose of the present study was to evaluate the effects of a school-based , 2-year , multi-component intervention on BMI , eating and physical activity behaviour in Fl and ers , Belgium , targeting children aged 3 - 6 years in communities of high and low socio-economic status ( SES ) . DESIGN Cluster-r and omized controlled trial . SETTING Thirty-one pre- primary and primary schools in three different intervention communities and three paired-matched ( on SES profile ) control communities in Fl and ers , Belgium . SUBJECTS BMI Z-scores at baseline and follow-up were calculated for 1102 children . Question naires with sociodemographic data and FFQ were available from 694 of these 1102 children . RESULTS No significant effects were found on BMI Z-scores for the total sample . However , there was a significant decrease in BMI Z-score of 0·11 in the low-SES intervention community compared with the low-SES control community , where the BMI Z-score increased by 0·04 ( F = 6·26 , P = 0·01 ) . No significant intervention effects could be found for eating behaviour , physical activity or screen-time . There were no significant interaction effects of age and gender of the children on the outcome variables . CONCLUSIONS Although no significant effects were found for BMI Z-scores in the total sample , this intervention had a promising effect in the low-SES community of reducing excess weight gain among young children Background Increasing prevalences of overweight and obesity in children are known problems in industrialized countries . Early prevention is important as overweight and obesity persist over time and are related with health problems later in adulthood . " Komm mit in das gesunde Boot - Grundschule " is a school-based program to promote a healthier lifestyle . Main goals of the intervention are to increase physical activity , decrease the consumption of sugar-sweetened beverages , and to decrease time spent sedentary by promoting active choices for healthy lifestyle . The program to date is distributed by 34 project delivery consultants in the state of Baden-Württemberg and is currently implemented in 427 primary schools . The efficacy of this large scale intervention is examined via the Baden-Württemberg Study . Methods / Design The Baden-Württemberg Study is a prospect i ve , stratified , cluster-r and omized , and longitudinal study with two groups ( intervention group and control group ) . Measurements were taken at the beginning of the academic years 2010/2011 and 2011/2012 . Efficacy of the intervention is being assessed using three main outcomes : changes in waist circumference , skinfold thickness and 6 minutes run . Stratified cluster-r and omization ( according to class grade level ) was performed for primary schools ; pupils , teachers/principals , and parents were investigated . An approximately balanced number of classes in intervention group and control group could be reached by stratified r and omization and was maintained at follow-up . Discussion At present , " Komm mit in das Gesunde Boot - Grundschule " is the largest school-based health promotion program in Germany . Comparative objective main outcomes are used for the evaluation of efficacy . Simulations showed sufficient power with the existing sample size . Therefore , the results will show whether the promotion of a healthier lifestyle in primary school children is possible using a relatively low effort within a school-based program involving children , teachers and parents . The research team anticipates that not only efficacy will be proven in this study but also expects many other positive effects of the program . Trial registration German Clinical Trials Register ( DRKS ) , DRKS-ID : This study demonstrates the effectiveness of the KiVa antibullying program using a large sample of 8,237 youth from Grade s 4 - 6 ( 10 - 12 years ) . Altogether , 78 schools were r and omly assigned to intervention ( 39 schools , 4,207 students ) and control conditions ( 39 schools , 4,030 students ) . Multilevel regression analyses revealed that after 9 months of implementation , the intervention had consistent beneficial effects on 7 of the 11 dependent variables , including self- and peer-reported victimization and self-reported bullying . The results indicate that the KiVa program is effective in reducing school bullying and victimization in Grade s 4 - 6 . Despite some evidence against school-based interventions , the results suggest that well-conceived school-based programs can reduce victimization Background Although it is important to investigate how interventions work , no formal mediation analyses have been conducted to explain behavioral outcomes in school-based fat intake interventions in adolescents . The aim of the present study was to examine mediation effects of changes in psychosocial determinants of dietary fat intake ( attitude , social support , self-efficacy , perceived benefits and barriers ) on changes in fat intake in adolescent girls . Methods Data from a 1-year prospect i ve intervention study were used . A r and om sample of 804 adolescent girls was included in the study . Girls in the intervention group ( n = 415 ) were exposed to a multi-component school-based intervention program , combining environmental changes with a computer tailored fat intake intervention and parental support . Fat intake and psychosocial determinants of fat intake were measured with vali date d self-administered question naires . To assess mediating effects , a product-of-coefficient test , appropriate for cluster r and omized controlled trials , was used . Results None of the examined psychosocial factors showed a reliable mediating effect on changes in fat intake . The single-mediator model revealed a statistically significant suppression effect of perceived barriers on changes in fat intake ( p = 0.011 ) . In the multiple-mediator model , this effect was no longer significant , which was most likely due to changes in perceived barriers being moderately related to changes in self-efficacy ( -0.30 ) and attitude ( -0.25 ) . The overall mediated-suppressed effect of the examined psychosocial factors was virtually zero ( total mediated effect = 0.001 ; SE = 7.22 ; p = 0.992 ) . Conclusion Given the lack of intervention effects on attitudes , social support , self-efficacy and perceived benefits and barriers , it is suggested that future interventions should focus on the identification of effective strategies for changing these theoretical mediators in the desired direction . Alternatively , it could be argued that these constructs need not be targeted in interventions aim ed at adolescents , as they may not be responsible for the intervention effects on fat intake . To draw any conclusions regarding mediators of fat-intake change in adolescent ' girls and regarding optimal future intervention strategies , more systematic research on the mediating properties of psychosocial variables is needed Formative research uses qualitative and quantitative methods to provide information for research ers to plan intervention programs . Gaps in the formative research literature include how to define goals , implementation plans , and research questions ; select methods ; analyze data ; and develop interventions . The National Heart , Lung , and Blood Institute funded the Trial of Activity for Adolescent Girls ( TAAG ) , a r and omized , multicenter field trial , to reduce the decline in physical activity in adolescent girls . The goals of the TAAG formative research are to ( a ) describe study communities and schools , ( b ) help design the trial ’s interventions , ( c ) develop effective recruitment and retention strategies , and ( d ) design evaluation instruments . To meet these goals , a variety of methods , including telephone interviews , surveys and checklists , semistructured interviews , and focus group discussion s , are employed . The purpose , method of development , and analyses are explained for each method BACKGROUND The ability of specific behaviour-change interventions to reduce HIV infection in young people remains question able . Since January 1999 , an adolescent sexual and reproductive health ( SRH ) intervention has been implemented in ten r and omly chosen intervention communities in rural Tanzania , within a community r and omised trial ( see below ; NCT00248469 ) . The intervention consisted of teacher-led , peer-assisted in-school education , youth-friendly health services , community activities , and youth condom promotion and distribution . Process evaluation in 1999 - 2002 showed high intervention quality and coverage . A 2001/2 intervention impact evaluation showed no impact on the primary outcomes of HIV seroincidence and herpes simplex virus type 2 ( HSV-2 ) seroprevalence but found substantial improvements in SRH knowledge , reported attitudes , and some reported sexual behaviours . It was postulated that the impact on " upstream " knowledge , attitude , and reported behaviour outcomes seen at the 3-year follow-up would , in the longer term , lead to a reduction in HIV and HSV-2 infection rates and other biological outcomes . A further impact evaluation survey in 2007/8 ( approximately 9 years post-intervention ) tested this hypothesis . METHODS AND FINDINGS This is a cross-sectional survey ( June 2007 through July 2008 ) of 13,814 young people aged 15 - 30 y who had attended trial schools during the first phase of the MEMA kwa Vijana intervention trial ( 1999 - 2002 ) . Prevalences of the primary outcomes HIV and HSV-2 were 1.8 % and 25.9 % in males and 4.0 % and 41.4 % in females , respectively . The intervention did not significantly reduce risk of HIV ( males adjusted prevalence ratio [ aPR ] 0.91 , 95%CI 0.50 - 1.65 ; females aPR 1.07 , 95%CI 0.68 - 1.67 ) or HSV-2 ( males aPR 0.94 , 95%CI 0.77 - 1.15 ; females aPR 0.96 , 95%CI 0.87 - 1.06 ) . The intervention was associated with a reduction in the proportion of males reporting more than four sexual partners in their lifetime ( aPR 0.87 , 95%CI 0.78 - 0.97 ) and an increase in reported condom use at last sex with a non-regular partner among females ( aPR 1.34 , 95%CI 1.07 - 1.69 ) . There was a clear and consistent beneficial impact on knowledge , but no significant impact on reported attitudes to sexual risk , reported pregnancies , or other reported sexual behaviours . The study population was likely to have been , on average , at lower risk of HIV and other sexually transmitted infections compared to other rural population s , as only youth who had reached year five of primary school were eligible . CONCLUSIONS SRH knowledge can be improved and retained long-term , but this intervention had only a limited effect on reported behaviour and no significant effect on HIV/STI prevalence . Youth interventions integrated within intensive , community-wide risk reduction programmes may be more successful and should be evaluated . TRIAL REGISTRATION Clinical Trials.gov OBJECTIVE To decrease the intake of sucrose , increase the intake of fibre and the consumption of fruit and vegetables among secondary -school pupils . DESIGN Intervention study among eighth grade pupils during one school year . Data were collected by question naires and from a subgroup of pupils by 48 h dietary recall at baseline in spring 2007 and after the intervention in 2008 . SETTING Twelve secondary schools were r and omly allocated to intervention ( IS ) and control schools ( CS ) within three cities . Intervention included nutrition education and improvement of the food environment focusing particularly on the quality of snacks at school . SUBJECTS A total of 659 pupils completed the question naires and the dietary recall was obtained from 287 pupils both at baseline and follow-up . RESULTS The frequency of consumption of rye bread increased ( P = 0.03 ) and that of sweets decreased ( P = 0.006 ) among girls in the IS . The intake of sucrose fell among IS pupils , from 12.8 % to 10.5 % of the total energy intake ( P = 0.01 ) . Intake of fruit ( g/MJ ) remained the same in IS , whereas it decreased in CS ( P = 0.04 ) . CONCLUSIONS Sugar intake can be lowered by improving the quality of snacks , but it is more difficult to increase fibre intake and fruit and vegetable consumption unless the content of school lunches can be modified . It is the responsibility of the adults working in schools to create a healthy environment and to make healthy choices easy for pupils BACKGROUND Childhood obesity is a major public health problem in the United States , particularly among American Indian communities . OBJECTIVE The objective was to evaluate the effectiveness of a school-based , multicomponent intervention for reducing percentage body fat in American Indian schoolchildren . DESIGN This study was a r and omized , controlled , school-based trial involving 1704 children in 41 schools and was conducted over 3 consecutive years , from 3rd to 5th grade s , in schools serving American Indian communities in Arizona , New Mexico , and South Dakota . The intervention had 4 components : 1 ) change in dietary intake , 2 ) increase in physical activity , 3 ) a classroom curriculum focused on healthy eating and lifestyle , and 4 ) a family-involvement program . The main outcome was percentage body fat ; other outcomes included dietary intake , physical activity , and knowledge , attitudes , and behaviors . RESULTS The intervention result ed in no significant reduction in percentage body fat . However , a significant reduction in the percentage of energy from fat was observed in the intervention schools . Total energy intake ( by 24-h dietary recall ) was significantly reduced in the intervention schools but energy intake ( by direct observation ) was not . Motion sensor data showed similar activity levels in both the intervention and control schools . Several components of knowledge , attitudes , and behaviors were also positively and significantly changed by the intervention . CONCLUSIONS These results document the feasibility of implementing a multicomponent program for obesity prevention in elementary schools serving American Indian communities . The program produced significant positive changes in fat intake and in food- and health-related knowledge and behaviors . More intense or longer interventions may be needed to significantly reduce adiposity in this population BACKGROUND Nationwide data on obesity prevalence in American Indian communities are limited . OBJECTIVE We describe the body composition and anthropometric characteristics of schoolchildren from 7 American Indian communities enrolled in the Pathways study , a r and omized field trial evaluating a program for the primary prevention of obesity . DESIGN A total of 1704 children in 41 schools were enrolled in the study . Basic anthropometric measurements included weight , height , and triceps and subscapular skinfold thicknesses . Percentage body fat was estimated from bioelectrical impedance and anthropometric variables with the use of an equation developed and vali date d for this population . RESULTS The children 's mean ( + /- SD ) age was 7.6 + /- 0.6 y , and their mean weight and height were 32.1 + /- 8.9 kg and 129.8 + /- 6.3 cm , respectively . Mean body mass index ( BMI ; in kg/m(2 ) ) was 18.8 + /- 3.9 , and mean percentage body fat was 32.6 + /- 6.8 % . With the use of current Centers for Disease Control and Prevention reference values , 30.5 % of girls and 26.8 % of boys were above the 95th percentiles for BMI -for-age , and 21 % of girls and 19.6 % of boys were between the 85th and 95th percentiles . Although there was a wide range in BMI across study sites and for both sexes , the percentage of children with a BMI above the 95th percentile was consistently higher than the national averages in all communities studied and in both girls and boys . CONCLUSIONS Overweight can be documented in a substantial number of American Indian children by the time they reach elementary school . Despite differences in the prevalence of overweight observed among communities , rates are uniformly high relative to national all-race averages Background Adolescence is an established period of physical activity decline . Multi-component school-based interventions have the potential to slow the decline in adolescents ’ physical activity ; however , few interventions have been conducted in schools located in low-income or disadvantaged communities . This study aims to assess the effectiveness of a multi-component school-based intervention in reducing the decline in physical activity among students attending secondary schools located in disadvantaged communities . Methods / Design The cluster r and omised trial will be conducted with 10 secondary schools located in selected regions of New South Wales , Australia . The schools will be selected from areas that have a level of socio-economic status that is below the state average . Five schools will be allocated to receive an intervention based on the Health Promoting Schools framework , and will be supported by a part-time physical activity consultant placed in intervention schools who will implement a range of intervention adoption strategies . Study measures will be taken at baseline when students are in Year 7 ( 12–13 years ) and again after 12- and 24-months . The primary outcome , minutes of moderate- to-vigorous- intensity physical activity per day and percentage of time in moderate- to vigorous-intensity physical activity ( MVPA ) , will be objective ly assessed using accelerometers ( Actigraph GT3x+ ) . Group allocation and intervention delivery will commence after baseline data collection . The intervention will continue during school terms through to 24-month follow-up . Discussion The study will provide evidence regarding the effectiveness of a multi-component school-based intervention that includes an in-school physical activity consultant targeting the physical activity levels of adolescents in disadvantaged Australian secondary schools . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12612000382875 The central aim of this study was to evaluate Project PRIDE , a school-based affective education program offered in select schools since 1970 and throughout the entire Philadelphia Public School System since 1981 . The primary purpose of the program is to increase youth 's resistance to drug use and abuse through weekly small group counseling sessions . The 12 weekly student sessions focused on developing self-awareness , life skills , knowledge , and appropriate attitudes about drugs . Project PRIDE also developed training modules for teachers and parents . Evaluation was by means of a true experimental pretest-posttest design , with r and om assignment to treatment and control groups . Measures of attitudes , self-reported drug use , and behavioral intentions were administered to students , teachers , and parents ; process evaluation measures of the student component were collected throughout the treatment period as well . Data analyses indicate that , while a few of the broad aims of the prevention program were not met , there were reliable changes in the intended direction in many of the students ' attitudes and intentions . Student attitudes toward drug use and knowledge about drugs both improved . Project PRIDE participation was associated with a relative decrease in willingness to experiment with drugs , even though all groups showed strongly negative attitudes toward drug use . Treatment interacted with sex of student and /or SES on a number of items . Generally , effects were more pronounced for girls and for low SES students . All groups of participants felt they gained significant knowledge and skills from the program . Other effects for parents and teachers were infrequent and inconsistent The HEALTHY study was a multi-site r and omized trial design ed to determine whether a 3-year school-based intervention targeting nutrition and physical activity behaviors could effectively reduce risk factors associated with type 2 diabetes in middle school children . Pilot and formative studies were conducted to inform the development of the intervention components and the process evaluation methods for the main trial . During the main trial , both qualitative and quantitative assessment s monitored the fidelity of the intervention and motivated modifications to improve intervention delivery . Structured observations of physical education classes , total school food environments , classroom-based educational modules , and communications and promotional campaigns provided verification that the intervention was delivered as intended . Interviews and focus groups yielded a multidimensional assessment of how the intervention was delivered and received , as well as identifying the barriers to and facilitators of the intervention across and within participating schools . Interim summaries of process evaluation data were presented to the study group as a means of ensuring st and ardization and quality of the intervention across the seven participating centers . Process evaluation methods and procedures documented the fidelity with which the HEALTHY study was implemented across 21 intervention schools and identified ways in which the intervention delivery might be enhanced throughout the study OBJECTIVE . Rising rates of skin cancer associated with early-life sun exposure make it important to improve adolescent sun-protection practice s. Our study objective was to determine if a multicomponent community-wide intervention could alter the decline in sun protection that begins in early adolescence . METHODS . A r and omized , controlled trial was conducted in 10 communities to assess the impact of the SunSafe in the Middle School Years program . The intervention sought to ( 1 ) educate and activate adults and peers to role model and actively promote sun-protection practice s and ( 2 ) create a pro – sun protection community environment . It targeted school personnel , athletic coaches , lifeguards , and clinicians and enlisted teens as peer advocates . Annual observations of cross-sectional sample s of teens at community beach/pool sites were used to assess the impact of 1 and 2 years of intervention exposure compared to grade -matched controls . The outcome was percent of body surface protected by sunscreen , clothing , or shade . RESULTS . Observers determined the sun protection level of 1927 adolescents entering 6th to 8th grade s. After 2 years of intervention exposure , adolescents at the beach/pool in intervention communities were significantly better protected than those in control communities . Over 2 years , the percent of body surface area protected declined by 23 % in the control arm but only 8 % in intervention arm . After intervention , the average percent of body surface protected at intervention sites ( 66.1 % ) was significantly greater than control sites ( 56.8 % ) . Teens in intervention communities reported sun-protection advice from more adult sources , were more likely to use sunscreen , and applied it more thoroughly than control-site teens . CONCLUSIONS . Our multicomponent model addressing adolescent sun protection shows the power of engaging teens and adults from across the community as role models and educators . This new ecological approach shows promise in changing adolescent sun protection behaviors and reducing skin cancer risks OBJECTIVE To assess differences through grade 8 in diet , physical activity , and related health indicators of students who participated in the Child and Adolescent Trial for Cardiovascular Health ( CATCH ) school and family intervention from grade s 3 through 5 . DESIGN Follow-up of the 4-center , r and omized , controlled field trial with 56 intervention and 40 control elementary schools . PARTICIPANTS We studied 3714 ( 73 % ) of the initial CATCH cohort of 5106 students from ethnically diverse background s in California , Louisiana , Minnesota , and Texas at grade s 6 , 7 , and 8 . RESULTS Self-reported daily energy intake from fat at baseline was virtually identical in the control ( 32.7 % ) and intervention ( 32.6 % ) groups . At grade 5 , the intake for controls remained at 32.2 % , while the intake for the intervention group declined to 30.3 % ( P<.001 ) . At grade 8 , the between-group differential was maintained ( 31.6 % vs 30.6 % , P = .01 ) . Intervention students maintained significantly higher self-reported daily vigorous activity than control students ( P = .001 ) , although the difference declined from 13.6 minutes in grade 5 to 11.2 , 10.8 , and 8.8 minutes in grade s 6 , 7 , and 8 , respectively . Significant differences in favor of the intervention students also persisted at grade 8 for dietary knowledge and dietary intentions , but not for social support for physical activity . No impact on smoking behavior or stages of contemplating smoking was detected at grade 8 . No significant differences were noted among physiologic indicators of body mass index , blood pressure , or serum lipid and cholesterol levels . CONCLUSION The original CATCH results demonstrated that school-level interventions could modify school lunch and school physical education programs as well as influence student behaviors . This 3-year follow-up without further intervention suggests that the behavioral changes initiated during the elementary school years persisted to early adolescence for self-reported dietary and physical activity behaviors The purpose of the present study was to investigate if the effects of the parental component of a school-based intervention on dietary fat intake from snacking were mediated by changes in home-related factors . A r and om sample of 10 schools with 2232 pupils aged 11 - 15 years was r and omly assigned to one of two intervention groups [ one with ( n = 1226 ) and one without a parental component ( n = 1006 ) ] . Fat intake , home availability of low-fat foods and parental encouragement and support to eat a low-fat diet were assessed with vali date d self-administered question naires . Mediation was assessed with the product-of-coefficient test . Changes in home-related determinants were significantly related to changes in fat intake from snacks ; therefore , school-based obesity programmes on adolescents should try to address these determinants . In the present study , one of the three investigated home-related factors , namely parental support , was affected by the parental component intervention . Decreases in parental support were prevented . These changes in parental support were found to mediate the parental intervention effects on changes in fat intake from snacks . Home-related factors appear to be related to changes in adolescents ' snacking behaviours , therefore , school-based obesity programmes should target them . Nevertheless , more research is needed concerning effectively addressing the other determinants Background School-based interventions that target prevention of overweight and obesity in children have been tested with mixed results . Thus , successful interventions are still called for . The aim of the present study was to investigate effects of a multicomponent school-based intervention programme targeting physical activity , sedentary and dietary behaviours on anthropometric outcomes . Methods A 20-month intervention was evaluated in a cluster r and omised , controlled study of 1324 11-year-olds . Outcome variables were body mass index ( BMI ) , BMI -for-age z-score ( BMI z ) , waist circumference ( WC ) , waist-to-height ratio ( WTHR ) and weight status ( International Obesity Task Force 's cut-offs ) . Weight , height and WC were measured objective ly ; pubertal status was self-reported and parental education was self-reported by the parents . Intervention effects were determined by one-way analysis of covariance and logistic regression , after checking for clustering effects of school , and moderating effects of gender , pubertal status and parental education . Results Beneficial effects were found for BMI ( p=0.02 ) and BMI z ( p=0.003 ) in girls , but not in boys . While a beneficial effect was found for BMI ( p=0.03 ) in participants of parents reporting a high level of education , a negative effect was found for WTHR in participants with parents reporting a low level of education ( p=0.003 ) . There were no intervention effects for WC and weight status . Conclusions A multicomponent 20-month school-based intervention had a beneficial effect on BMI and BMI z in adolescent girls , but not in boys . Furthermore , children of higher educated parents seemed to benefit more from the intervention , and this needs attention in future interventions to avoid further increase in social inequalities in overweight and obesity PURPOSE OBJECTIVES The purpose of this study is to report the impact of the three-year middle school-based HEALTHY study on intervention school vending machine offerings . There were two goals for the vending machines : serve only dessert/snack foods with 200 kilocalories or less per single serving package , and eliminate 100 % fruit juice and beverages with added sugar . METHODS Six schools in each of seven cities ( Houston , TX , San Antonio , TX , Irvine , CA , Portl and , OR , Pittsburg , PA , Philadelphia , PA , and Chapel Hill , NC ) were r and omized into intervention ( n=21 schools ) or control ( n=21 schools ) groups , with three intervention and three control schools per city . All items in vending machine slots were tallied twice in the fall of 2006 for baseline data and twice at the end of the study , in 2009 . The percentage of total slots for each food/beverage category was calculated and compared between intervention and control schools at the end of study , using the Pearson chi-square test statistic . RESULTS At baseline , 15 intervention and 15 control schools had beverage and /or snack vending machines , compared with 11 intervention and 11 control schools at the end of the study . At the end of study , all of the intervention schools with beverage vending machines , but only one out of the nine control schools , met the beverage goal . The snack goal was met by all of the intervention schools and only one of the four control schools with snack vending machines . APPLICATIONS TO CHILD NUTRITION PROFESSIONALS The HEALTHY study 's vending machine beverage and snack goals were successfully achieved in intervention schools , reducing access to less healthy food items outside the school meals program . Although the effect of these changes on student diet , energy balance and growth is unknown , these results suggest that healthier options for snacks can successfully be offered in school vending machines OBJECTIVE : To evaluate the 6-month impact of a physical activity ( PA ) multilevel intervention on activity patterns and psychological predictors of PA among adolescents . The intervention was directed at changing knowledge and attitudes and at providing social support and environmental conditions that encourage PA of adolescents inside and outside school . SUBJECTS AND DESIGN : R and omised , controlled ongoing field trial ( ICAPS ) in middle-school 's first-level adolescents from eight schools selected in the department of the Bas-Rhin ( Eastern France ) with a cohort of 954 adolescents ( 92 % of the eligible students ) initially aged 11.7±0.6 y. The 6-month changes in participation in leisure organised PA ( LOPA ) , high sedentary ( SED ) behaviour ( > 3h/day ) , self-efficacy ( SELF ) and intention ( INTENT ) towards PA were analysed after controlling for baseline measures and different covariables ( age , overweight , socioprofessional occupation ) , taking into account the cluster r and omisation design . RESULTS : The proportion of intervention adolescents not engaged in organised PA was reduced by 50 % whereas it was unchanged among control students . After adjustment for baseline covariables , LOPA participation significantly increased among the intervention adolescents ( odds ratio ( 95 % confidence interval ) (OR)=3.38 ( 1.42–8.05 ) in girls ; 1.73 ( 1.12–2.66 ) in boys ) , while high SED was reduced ( OR=0.54 ( 0.38–0.77 ) in girls ; 0.52 ( 0.35–0.76 ) in boys ) . The intervention improved SELF in girls , whatever their baseline LOPA ( P<10−4 ) and INTENT in girls with no baseline LOPA ( P=0.04 ) . SELF tended to improve in boys with no baseline LOPA , without reaching statistical significance . When included in the regression , follow-up LOPA was associated with improvement of SELF in girls ( P=0.02 ) and of INTENT in girls with no baseline PA ( P<0.02 ) . The intervention effect was then attenuated . CONCLUSION : After 6 months of intervention , ICAPS was associated with a significant improvement of activity patterns and psychological predictors , indicating a promising approach for modifying the long-term PA level of adolescents The research community has criticized Drug Abuse Resistance Education ( D.A.R.E. ) because the extant literature indicates a lack of evidence that the elementary school program prevents drug use . Yet D.A.R.E. continues to be the most widely implemented drug use prevention program in the United States and has considerable community support . To date , the junior high D.A.R.E. program has not been evaluated . The Minnesota DARE PLUS Project is a r and omized trial of 24 schools and communities . During 1999 - 2001 , students in eight schools will receive the junior high D.A.R.E. curriculum in 7th grade ; eight schools also will receive the curriculum as well as additional parent involvement , peer leadership , and community components in the 7th and 8th grade s ; and eight schools will serve as controls . This article describes the background and conceptualization , the curriculum and additional intervention components , and the evaluation methods of the DARE PLUS Project This article describes the research design of the Multisite Violence Prevention Project ( MVPP ) , organized and funded by the National Center for Injury Prevention and Control ( NCIPC ) at the Centers for Disease Control and Prevention ( CDC ) . CDC 's objectives , refined in the course of collaboration among investigators , were to evaluate the efficacy of universal and targeted interventions design ed to produce change at the school level . The project 's design was developed collaboratively , and is a 2 x 2 cluster-r and omized true experimental design in which schools within four separate sites were assigned r and omly to four conditions : ( 1 ) no-intervention control group , ( 2 ) universal intervention , ( 3 ) targeted intervention , and ( 4 ) combined universal and targeted interventions . A total of 37 schools are participating in this study with 8 - 12 schools per site . The impact of the interventions on two successive cohorts of sixth- grade students will be assessed based on multiple waves of data from multiple sources of information , including teachers , students , parents , and archival data . The nesting of students within teachers , families , schools and sites created a number of challenges for design ing and implementing the study . The final design represents both resolution and compromise on a number of creative tensions existing in large-scale prevention trials , including tensions between cost and statistical power , and between internal and external validity . Strengths and limitations of the final design are discussed BACKGROUND This study evaluated the effects of a school-based dietary intervention program to increase fruit and vegetable consumption among fourth- grade rs . METHODS Twenty-eight elementary schools were r and omized to an immediate intervention condition or to a delayed intervention control condition . Measures of diet and psychosocial variables were collected at base line and 1 and 2 years post-baseline . The intervention included classroom , parent , and cafeteria components . RESULTS Mean daily consumption of fruit and vegetables was higher for the intervention children compared with controls at Follow-up 1 ( X(t ) = 3.96 , X(c ) = 2.28 ) and at Follow-up 2 ( X(t ) = 3.20 , X(c ) = 2.21 ) . Macro- and micronutrient changes favoring the intervention children were also observed at both Follow-up 1 and Follow-up 2 . Mean daily consumption of fruit and vegetables was higher for intervention parents compared with controls at Follow-up 1 ( X(t ) = 4.23,X(c ) = 3.94 ) but not at Follow-up 2 . CONCLUSIONS Strong effects were found for the High 5 intervention on fruit and vegetable consumption , on macro- and micro-nutrients , and on psychosocial variables . Future work is needed to enhance the intervention effects on parents ' consumption and to test the effectiveness of the intervention when delivered by classroom teachers Background The optimal targets and strategies for effectively reducing sedentary behavior among young people are unknown . Intervention research that explores changes in mediated effects as well as in outcome behaviors is needed to help inform more effective interventions . Therefore , the purpose of this study was to examine the mid-intervention mediating effects on children ’s objective ly assessed classroom and total weekday sedentary time in the Transform-Us ! intervention . Methods The results are based on 293 children , aged 7- to 9-years-old at baseline , from 20 schools in Melbourne , Australia . Each school was r and omly allocated to one of four groups , which targeted reducing sedentary time in the school and family setting s ( SB ; n = 74 ) , increasing or maintaining moderate- to vigorous-intensity physical activity in the school and family setting s ( PA ; n = 75 ) , combined SB and PA ( SB + PA ; n = 80 ) , or the current practice control ( C ; n = 64 ) . Baseline and mid-intervention data ( 5–9 months ) were collected in 2010 and analyzed in 2012 . Classroom and total weekday sedentary time was objective ly assessed using ActiGraph accelerometers . The hypothesized mediators including , child enjoyment , parent and teacher outcome expectancies , and child perceived access to st and ing opportunities in the classroom environment , were assessed by question naire . Results The SB + PA group spent 13.3 min/day less in weekday sedentary time at mid-intervention compared to the control group . At mid-intervention , children in the SB group had higher enjoyment of st and ing in class ( 0.9 units ; 5-unit scale ) and all intervention groups had more positive perceptions of access to st and ing opportunities in the classroom environment ( 0.3 - 0.4 units ; 3-unit scale ) , compared to the control group . However , none of the hypothesized mediator variables had an effect on sedentary time ; thus , no mediating effects were observed . Conclusions While beneficial intervention effects were observed on some hypothesized mediating variables and total weekday sedentary time at mid-intervention , no significant mediating effects were found . Given the dearth of existing information , future intervention research is needed that explores mediated effects . More work is also needed on the development of reliable mediator measures that are sensitive to change overtime . Trial registration ACTRN12609000715279IS RCT This article reports on the outcomes of the Teens Eating for Energy and Nutrition at School ( TEENS ) study , a 2-year intervention study conducted in 16 middle schools with a goal of increasing students ’ intakes of fruits , vegetables , and lower fat foods . Despite positive interim results for students r and omized to intervention schools , the positive effects of the intervention were not seen for the primary outcomes at the end of the 2nd year . Positive effects were seen only for a food choice score ( suggesting that the students usually choose lower versus higher fat foods ) and not for measures of food intake . Future studies may need to take a step back toward more controlled efficacy studies in working with this age-group . In addition , future work may consider the use of peer leaders , more intensive teacher training , ongoing formative assessment , and the testing of more powerful environmental change intervention strategies Background Many Australian children are insufficiently active to accrue health benefits and physical activity ( PA ) levels are consistently lower among youth of low socio-economic position . PA levels decline dramatically during adolescence and evidence suggests that competency in a range of fundamental movement skills ( FMS ) may serve as a protective factor against this trend . Methods / design The Supporting Children ’s Outcomes Using Rewards Exercise and Skills ( SCORES ) intervention is a multi-component PA and FMS intervention for primary schools in low-income communities , which will be evaluated using a group r and omized controlled trial . The socio-ecological model provided a framework for the 12-month intervention , which includes the following components : teacher professional learning , student leadership workshops ( including leadership accreditation and rewards , e.g. , stickers , water bottles ) , PA policy review , PA equipment packs , parental engagement via newsletters , FMS homework and a parent evening , and community partnerships with local sporting organizations . Outcomes will be assessed at baseline , 6- and 12-months . The primary outcomes are PA ( accelerometers ) , FMS ( Test of Gross Motor Development II ) and cardiorespiratory fitness ( multi-stage fitness test ) . Secondary outcomes include body mass index [ using weight (kg)/height ( m2 ) ] , perceived competence , physical self-esteem , and resilience . Individual and environmental mediators of behavior change ( e.g. social support and enjoyment ) will also be assessed . The System for Observing Fitness Instruction Time will be used to assess the impact of the intervention on PA within physical education lessons . Statistical analyses will follow intention-to-treat principles and hypothesized mediators of PA behavior change will be explored . Discussion SCORES is an innovative primary school-based PA and FMS intervention design ed to support students attending schools in low-income communities to be more skilled and active . The findings from the study may be used to guide teacher pre-service education , professional learning and school policy in primary schools . Trial registration Australian New Zeal and Clinical Trials Registry No : Background Childhood obesity is not only associated with adult obesity but also with increased risk of adult onset of type 2 diabetes and subsequent coronary heart disease . The potential effects of school-based health intervention programmes on cardiovascular risk and surrogate markers are unclear , as only few studies have attempted to investigate a complete risk profile including a detailed laboratory analysis or micro- and macrovascular function . In this study a comprehensive school-based r and omized intervention programme will be investigated in 10 - 14-year old children addressing the influence of lifestyle intervention on inactivity , cardiometabolic risk factors and early signs of vascular disease . Methods / Design 15 secondary schools in Southern Germany are r and omly assigned to intervention or control schools . Children in the fifth grade ( 10 - 11 years ) will be observed over four years . The study combines a school-based with a home-based approach , aim ing at children , teachers and parents . The main components are weekly lifestyle-lessons for children , taught by regular classroom teachers to increase physical activity in- and outside of school , to improve eating patterns at school and at home , to reduce media consumption and to amplify well-being . In 4 - 6 annual meetings , teachers receive information about health-related topics with worksheets for children and supporting equipment , accounting for school-specific needs and strategies . Parents ' trainings are provided on a regular basis . All examinations are performed at the beginning and at the end of every school year . Anthropometry includes measurements of BMI , waist and upper arm circumferences , skinfold thickness as well as peripheral blood pressure . Blood sampling includes lipid parameters , insulin , glucose , hsCRP , adiponectin , and IL-6 as well as testosteron and estrogen to determine maturation status . Vascular function is non-invasively assessed by measuring arterial stiffness in large arteries using a sphygmograph and by analysing arteriolar and venular diameters in the retinal microcirculation using a non-mydriatric vessel analyser . A question naire is filled out to determine daily physical activity , motivational factors , dietary habits , quality of life ( KINDL-R ) and socio-economic data . Physical fitness is assessed by a six-item test battery . Discussion Our study aims to provide a feasible long-term intervention strategy to re-establish childhood health and to prevent obesity-related cardiovascular dysfunction in children . Trial Registration Background Whilst schools provide a potentially appropriate setting for preventing substance use among young people , systematic review evidence suggests that past interventions in this setting have demonstrated limited effectiveness in preventing tobacco , alcohol and other drug use . Interventions that adopt a mental wellbeing approach to prevent substance use offer considerable promise and resilience theory provides one method to impact on adolescent mental well-being . The aim of the proposed study is to examine the efficacy of a resilience intervention in decreasing the tobacco , alcohol and illicit drug use of adolescents . Methods A cluster r and omised controlled trial with schools as the unit of r and omisation will be undertaken . Thirty two schools in disadvantaged areas will be allocated to either an intervention or a control group . A comprehensive resilience intervention will be implemented , inclusive of explicit program adoption strategies . Baseline surveys will be conducted with students in Grade 7 in both groups and again three years later when the student cohort is in Grade 10 . The primary outcome measures will include self-reported tobacco , alcohol , marijuana and other illicit drug use . Comparisons will be made post-test between Grade 10 students in intervention and control schools to determine intervention effectiveness across all measures . Discussion To the authors ’ knowledge this is the first r and omised controlled trial to evaluate the effectiveness of a comprehensive school-based resilience intervention , inclusive of explicit adoption strategies , in decreasing tobacco , alcohol and illicit drug use of adolescents attending disadvantaged secondary schools . Trial registration Background : Studies of school-based anti-obesity interventions have yielded inconsistent results . Using growth screening data from a school administrative data base , we re-evaluated an obesity prevention strategy that was previously reported to have a beneficial effect on weight status of a sample of students in grade s 5–7 . Methods : Ten K-8 schools ( five control and five intervention ) participated in a 2-year cluster-r and omized trial of a multi-component nutrition education intervention . We obtained student height and weight data for 6 consecutive school years and imputed missing baseline and follow-up measurements ( 53 % and 55 % , respectively ) and defined the target population based on the intent-to-treat principle . We analyzed changes in body mass index ( BMI ) Z-scores via mixed-effects linear regression and in the prevalence of overweight/obesity via conditional logistic regression . We also assessed incidence and remission of overweight/obesity and long-term effects . Results : We analyzed data for 8186 ( 96 % ) K-8 students in the 10 schools ( 4511 in intervention ; 3675 in control ) . From baseline to the end of the intervention period , mean increases in BMI Z-score were 0.10 and 0.09 in the control and intervention groups , respectively ( P=0.671 ) . The prevalence of overweight/obesity increased by 3 % in both groups ( P=0.926 ) . There was no significant intervention effect on the incidence or remission of overweight/obesity . Among 5469 students who attended study schools during both years of the intervention , there was no significant intervention effect . Furthermore , there was no long-term effect among students with up to 2 years of data beyond the end of the intervention . Conclusion : Using routinely collected data for the entire target population , we failed to confirm earlier findings of an intervention effect observed in a subset of students in grade s 5–7 . Volunteer bias in the prior evaluation and /or measurement error in the routinely collected data are potential reasons for the discrepant findings Project Northl and is a r and omized community trial initially implemented in 24 school districts and communities in northeastern Minnesota , with goals of delaying onset and reducing adolescent alcohol use using community-wide , multiyear , multiple interventions . The study targets the Class of 1998 from the 6th to 12th grade s ( 1991 - 1998 ) . The early adolescent phase of Project Northl and has been completed , and reductions in the prevalence of alcohol use at the end of 8th grade were achieved . Phase II of Project Northl and , targeting 11th- and 12th- grade students , uses five major strategies : ( 1 ) direct action community organizing methods to encourage citizens to reduce underage access to alcohol , ( 2 ) youth development involving high school students in youth action teams , ( 3 ) print media to support community organizing and youth action initiatives and communicate healthy norms about underage drinking ( e.g. , providing alcohol to minors is unacceptable ) , ( 4 ) parent education and involvement , and ( 5 ) a classroom-based curriculum for 11th- grade students . This article describes the background , design , implementation , and process measures of the intervention strategies for Phase II of Project Northl and Background The HEALTHY study was design ed to respond to the alarming trends in increasing rates of overweight , obesity , and type 2 diabetes mellitus in youth . The objective of this analysis was to examine the effects of the HEALTHY study on student self-reported dietary intakes ( energy , macronutrients and grams consumed of selected food groups ) . Methods HEALTHY was a cluster-r and omized study in 42 public middle schools . Students , n = 3908 , self-reported dietary intake using the Block Kids Question naire . General linear mixed models were used to analyze differences in dietary intake at the end of the study between intervention and control schools . Results The reported average daily fruit consumption was 10 % higher at the end of the study in the intervention schools than in the control schools ( 138 g or approximately 2 servings versus 122 g , respectively , p = 0.0016 ) . The reported water intake was approximately 2 fluid ounces higher in the intervention schools than in the control ( 483 g versus 429 g respectively ; p = 0.008 ) . There were no significant differences between intervention and control for mean intakes of energy , macronutrients , fiber , grains , vegetables , legumes , sweets , sweetened beverages , and higher- or lower-fat milk consumption . Conclusion The HEALTHY study , a five-semester middle school-based intervention program that integrated multiple components in nutrition , physical education , behavior change , and social marketing-based communications , result ed in significant changes to student 's reported fruit and water intake . Subsequent interventions need to go beyond the school environment to change diet behaviors that may affect weight status of children . Clinical Trials Registration Background Although school-based interventions to promote physical activity in adolescents have been suggested in several recent review s , questions have been raised regarding the effects of the strategies and the methodology applied and for whom the interventions are effective . The aim of the present study was to investigate effects of a school-based intervention program : the HEalth in Adolescents ( HEIA ) study , on change in physical activity , and furthermore , to explore whether potential effects varied by gender , weight status , initial physical activity level and parental education level . Methods This was a cluster r and omized controlled 20 month intervention study which included 700 11-year-olds . Main outcome -variable was mean count per minute ( cpm ) derived from ActiGraph accelerometers ( Model 7164/GT1 M ) . Weight and height were measured objective ly . Adolescents reported their pubertal status in a question naire and parents reported their education level on the consent form . Linear mixed models were used to test intervention effects and to account for the clustering effect of sampling by school . Results The present study showed an intervention effect on overall physical activity at the level of p = 0.05 with a net effect of 50 cpm increase from baseline to post intervention in favour of the intervention group ( 95 % CI −0.4 , 100 ) . Subgroup analyses showed that the effect appeared to be more profound among girls ( Est 65 cpm , CI 5 , 124 , p = 0.03 ) and among participants in the low-activity group ( Est 92 cpm , CI 41 , 142 , p < 0.001 ) , as compared to boys and participants in the high-activity group , respectively . Furthermore , the intervention affected physical activity among the normal weight group more positively than among the overweight , and participants with parents having 13–16 years of education more positively than participants with parents having either a lower or higher number of years of education . The intervention seemed to succeed in reducing time spent sedentary among girls but not among boys . Conclusions A comprehensive but feasible , multi-component school-based intervention can affect physical activity patterns in adolescents by increasing overall physical activity . This intervention effect seemed to be more profound in girls than boys , low-active adolescents compared to high-active adolescents , participants with normal weight compared to the overweight , and for participants with parents of middle education level as opposed to those with high and low education levels , respectively . An implementation of the HEIA intervention components in the school system may have a beneficial effect on public health by increasing overall physical activity among adolescents and possibly among girls and low-active adolescents in particular BACKGROUND School-based social-emotional and character development ( SECD ) programs can influence not only SECD but also academic-related outcomes . This study evaluated the impact of one SECD program , Positive Action ( PA ) , on educational outcomes among low-income , urban youth . METHODS The longitudinal study used a matched-pair , cluster-r and omized controlled design . Student-reported disaffection with learning and academic grade s , and teacher ratings of academic ability and motivation were assessed for a cohort followed from grade s 3 to 8 . Aggregate school records were used to assess st and ardized test performance ( for entire school , cohort , and demographic subgroups ) and absenteeism ( entire school ) . Multilevel growth-curve analyses tested program effects . RESULTS PA significantly improved growth in academic motivation and mitigated disaffection with learning . There was a positive impact of PA on absenteeism and marginally significant impact on math performance of all students . There were favorable program effects on reading for African American boys and cohort students transitioning between grade s 7 and 8 , and on math for girls and low-income students . CONCLUSIONS A school-based SECD program was found to influence academic outcomes among students living in low-income , urban communities . Future research should examine mechanisms by which changes in SECD influence changes in academic outcomes OBJECTIVE HEALTHY is a 3-year middle school intervention program design ed to reduce risk factors for type 2 diabetes . The prevalence of diabetes risk factors at baseline in a cohort of 6,358 sixth- grade students is reported . RESEARCH DESIGN AND METHODS Forty-two schools at seven U.S. sites were r and omly assigned to intervention or control . Students participated in baseline data collection during fall of 2006 . RESULTS Overall , 49.3 % of children had BMI ≥85th percentile , 16.0 % had fasting blood glucose ≥100 mg/dl ( < 1 % had fasting blood glucose ≥126 mg/dl ) , and 6.8 % had fasting insulin ≥30 μU/ml . Hispanic youth were more likely to have BMI , glucose , and insulin levels above these thresholds than blacks and whites . CONCLUSIONS Sixth- grade students in schools with large minority population s have high levels of risk factors for type 2 diabetes . The HEALTHY intervention was design ed to modify these risk factors to reduce diabetes incidence Few studies have tested schoolwide interventions to reduce sexual risk behavior , and none have demonstrated significant schoolwide effects . This study evaluates the schoolwide effects of Safer Choices , a multicomponent , behavioral theory – based HIV , STD , and pregnancy prevention program , on risk behavior , school climate , and psychosocial variables . Twenty urban high schools were r and omized , and cross-sectional sample s of classes were surveyed at baseline , the end of intervention ( 19 months after baseline ) , and 31 months after baseline . At 19 months , the program had a positive effect on the frequency of sex without a condom . At 31 months , students in Safer Choices schools reported having sexual intercourse without a condom with fewer partners . The program positively affected psychosocial variables and school climate for HIV/STD and pregnancy prevention . The program did not influence the prevalence of recent sexual intercourse . Schoolwide changes in condom use demonstrated that a school-based program can reduce the sexual risk behavior of adolescents This article describes the process evaluation of High 5 , a school-based intervention targeting fruit and vegetable consumption among fourth grade rs and their families . The outcome evaluation involved 28 schools r and omized to intervention or control conditions . The intervention included classroom , family , and cafeteria components . Process evaluation was completed on each of these components by using observations , self-report checklists , surveys , and other measures . Results indicated high implementation rates on the classroom activities . Moderate family involvement was attained , perhaps diminishing intervention effects on parent consumption . Cafeterias provided environmental cues , and fruit and vegetable offerings as directed by the program . A lower dose of the intervention was delivered to schools with larger African American enrollments and lower-income families . This article provides insights into the effective elements of a school-based dietary intervention and provides suggestions for process evaluation in similar studies Peer education has become a popular strategy for health promotion interventions with adolescents , but it has not been used widely in school-based nutrition education . This paper describes and reports on the feasibility of the peer leader component of a school-based nutrition intervention for young adolescents design ed to increase fruit and vegetable intakes and lower fat foods . About 1,000 seventh- grade students in eight schools received the nutrition intervention . Of these , 272 were trained as peer leaders to assist the teacher in implementing the activities . Results from a multicomponent process evaluation based on peer leader and classroom student feedback , direct classroom observation , and teacher ratings and interviews are presented . Results show that peer-led nutrition education approaches in schools are feasible and have high acceptability among peer leaders , classroom students , and teachers This paper describes some statistical considerations for the Child and Adolescent Trial for Cardiovascular Health ( CATCH ) , a large-scale community health trial sponsored by the National Heart , Lung , and Blood Institute . The trial involves r and omization of entire schools rather than individual students to the experimental arms . The paper discussed the implication s of this form of r and omization for the design and analysis of the trial . The power calculations and analysis plan for the trial are presented in detail . The h and ling of outmigrating and immigrating students is also discussed Intensive h and washing promotion can reduce diarrheal and respiratory disease incidence . To determine whether less intensive , more scalable interventions can improve health , we evaluated a school-based h and washing program . We r and omized 87 Chinese schools to usual practice s : st and ard intervention ( h and washing program ) or exp and ed intervention ( h and washing program , soap for school sinks , and peer hygiene monitors ) . We compared student absence rates , adjusting for cluster design . In control schools , children experienced a median 2.0 episodes ( median 2.6 days ) of absence per 100 student-weeks . In st and ard intervention schools , there were a median 1.2 episodes ( P = 0.08 ) and 1.9 days ( P = 0.14 ) of absence per 100 student-weeks . Children in exp and ed intervention schools experienced a median 1.2 episodes ( P = 0.03 ) and 1.2 days ( P = 0.03 ) of absence per 100 student-weeks . Provision of a large-scale h and washing promotion program and soap was associated with significantly reduced absenteeism . Similar programs could improve the health of children worldwide Background Childhood obesity is the result of a long lasting imbalance between energy intake and energy expenditure . A major contributing factor is physical inactivity which is closely linked to bone health , cardiovascular disease risk , fitness and psychological factors . The school seems to provide an excellent setting to enhance levels of physical activity ( PA ) . However , there is insufficient data from previous school-based intervention trials on how to enhance overall PA . It is also unknown whether an intervention aim ed at increasing PA is effective in improving the children 's health . The purpose of this paper is to outline the design of a school-based r and omized , controlled trial ( RCT ) aim ing to increase overall PA and to improve fitness and health in 6- to 13-year-old children . Methods / Design 15 schools were r and omized to the intervention ( n = 9 ) or the control ( n = 6 ) group , stratified by geographic region ( urban vs. rural ) and by age ( 1st and 5th grade ) . Participation was given for all children in the intervention group since in this group the intervention was part of the normal school curriculum . The intervention during one academic year consisted of : 1 . two additional physical education classes per week given by trained physical education teachers adding up to a total of five PA classes per week , 2 . short PA breaks ( 2–5 min each ) during academic lessons , 3 . PA home work , and 4 . adaptation of recreational areas around the school . All children underwent anthropometric measurements , blood pressure assessment , fitness testing , measurement of PA and they filled out question naires . At least 70 % of all children agreed to blood sampling and measurements of body composition and bone mineral measurements by dual energy x-ray absorptiometry . The primary endpoints of the study after one year were an increase in total PA by accelerometry , an increase in aerobic fitness measured by the 20 m shuttle run , a decrease in percent body fat derived from skinfold measurements and an increase in quality of life as assessed by the child health question naire in the intervention group compared to the control group . Secondary outcomes were overall fitness , differences in body composition including body fat distribution , cardiovascular risk factors , psychosocial health , bone mineral content and density of femur , lumbar spine and total body and food intake . Discussion Our preliminary data suggest that the children were representative of Swiss children with respect to sex , socio-demographic status , and body mass index . Short-term results can be expected by the beginning of 2007 . We hypothesized that our intervention will lead to an increase in PA , fitness and overall health . Based on our data , we aim to provide important information regarding the influence of such an intervention on these outcome measures in school-aged children and to provide nationwide guidelines to improve PA in children This study evaluated the impact of two targeted family sessions focused on driving issues delivered within the context of the Raising Healthy Children project . The Raising Healthy Children project began in the fall of 1993 , drawing students in the 1st or 2nd grade s from 10 schools . Schools were assigned to an intervention or control condition , and the school-wide , family- and student-focused preventive intervention to address developmentally salient risk and protective factors was delivered during elementary and middle school . The family driving sessions were administered to families in the intervention condition prior to and after teenagers received their driver 's license . The first session consisted of a home visit with families design ed to help parents and their children improve decision-making skills concerning driving and to develop clear st and ards and expectations regarding driving-related behavior . A second session , at the time of licensure , was design ed to help parents and teens develop a written contract that stated family expectations , a plan for monitoring compliance with these expectations , and consequences for compliance or non-compliance . Consistent with the study 's group-r and omized design , intervention effects were assessed with multi-level logistic regression models in which students were grouped by their original school assignment . These models assessed specific effects of the driving sessions by adjusting for control variables measured when students were in 8th grade , prior to the driving sessions . Results indicated that students in the intervention group were more likely than students in the control group to report that they had a written driving contract ( p = .003 , OR = 4.98 ) , and had participated in making the driving rules in the family ( p = .025 , OR = 1.70 ) . Further , students in the intervention group reported significantly fewer risky behaviors including driving under the influence of alcohol ( p = .021 , OR = .45 ) and driving with someone who had been drinking ( p = .038 , OR = .56 ) This study tested the efficacy of two school-based programs for prevention of body weight/fat gain in comparison to a control group , in all participants and in overweight children . The Louisiana ( LA ) Health study utilized a longitudinal , cluster r and omized 3-arm controlled design , with 28 months of follow-up . Children ( N=2060 ; M age = 10.5 years , SD = 1.2 ) from rural communities in Grade s 4 to 6 participated in the study . 17 school clusters ( M = 123 children/cluster ) were r and omly assigned to one of three prevention arms : 1 ) Primary Prevention ( PP ) , an environmental modification program , 2 ) Primary + Secondary Prevention ( PP+SP ) , the environmental program with an added classroom and internet education component , or 3 ) Control ( C ) . Primary outcomes were changes in percent body fat and body mass index z scores . Secondary outcomes were changes in behaviors related to energy balance . Comparisons of PP , PP+SP , and C on changes in body fat and BMI z scores found no differences . PP and PP+SP study arms were combined to create an environmental modification arm ( EM ) . Relative to C , EM decreased body fat for boys ( −1.7 % ± 0.38 % versus −0.14 % ± 0.69 % ) and attenuated fat gain for girls ( 2.9 % ± 0.22 % versus 3.93 % ± 0.37 % ) , but st and ardized effect sizes were relatively small ( < 0.30 ) . In conclusion , this school-based environmental modification programs had modest beneficial effects on changes in percent body fat . Addition of a classroom/internet program to the environmental program did not enhance weight/fat gain prevention , but did impact physical activity and social support in overweight children BACKGROUND The prevalence of adolescent smoking has been increasing rapidly in China . Theory-based smoking prevention programmes in schools may be an effective approach in preventing smoking among Chinese adolescents . METHODS A school-level cluster r and omized controlled trial was conducted among 7th and 8th grade students ( N = 2343 ) in four junior high schools in southern China during 2004 - 06 . The theory-based , multi-level intervention was compared with the st and ard health curriculum . Outcome measures comprised changes in students ' smoking-related knowledge , attitudes and behaviour . RESULTS The mean knowledge scores from baseline to the 1- and 2-year follow-ups increased more in the intervention group than in the control group , whereas there was little change in attitude scores . At the 1-year follow-up ( the total sample ) , the interventions reduced the probability of baseline experimental smokers ' escalating to regular smoker [ 7.9 vs 18.3 % ; adjusted odds ratio ( OR ) 0.34 , 95 % confidence interval ( CI ) 0.12 - 0.97 , P = 0.043 ] , but did not reduce the probability of baseline non-smokers ' initiating smoking ( 7.9 vs 10.6 % ; adjusted OR 0.86 , 95 % CI 0.54 - 1.38 , P = 0.538 ) . At the 2-year follow-up ( only 7th grade students ) , similar proportions of baseline non-smokers initiated smoking in the intervention group and the control group ( 13.5 vs 13.1 % ) , while a possibly lower proportion of baseline experimental smokers escalated to regular smoking in the intervention group than the control group ( 22.6 vs 40.0 % ; adjusted OR 0.43 , 95 % CI 0.12 - 1.57 , P = 0.199 ) . CONCLUSIONS This multi-level intervention programme had a moderate effect on inhibiting the escalation from experimental to regular smoking among Chinese adolescents , but had little effect on the initiation of smoking . The programme improved adolescents ' smoking-related knowledge , but did not change their attitudes towards smoking OBJECTIVE To test the efficacy of 2 programs design ed to reduce high-risk behaviors among inner-city African American youth . DESIGN Cluster r and omized trial . SETTING Twelve metropolitan Chicago , Ill , schools and the communities they serve , 1994 through 1998 . PARTICIPANTS Students in grade s 5 through 8 and their parents and teachers . INTERVENTIONS The social development curriculum ( SDC ) consisted of 16 to 21 lessons per year focusing on social competence skills necessary to manage situations in which high-risk behaviors occur . The school/community intervention ( SCI ) consisted of SDC and school-wide climate and parent and community components . The control group received an attention-placebo health enhancement curriculum ( HEC ) of equal intensity to the SDC focusing on nutrition , physical activity , and general health care . MAIN OUTCOME MEASURES Student self-reports of violence , provocative behavior , school delinquency , substance use , and sexual behaviors ( intercourse and condom use ) . RESULTS For boys , the SDC and SCI significantly reduced the rate of increase in violent behavior ( by 35 % and 47 % compared with HEC , respectively ) , provoking behavior ( 41 % and 59 % ) , school delinquency ( 31 % and 66 % ) , drug use ( 32 % and 34 % ) , and recent sexual intercourse ( 44 % and 65 % ) , and improved the rate of increase in condom use ( 95 % and 165 % ) . The SCI was significantly more effective than the SDC for a combined behavioral measure ( 79 % improvement vs 51 % ) . There were no significant effects for girls . CONCLUSIONS Theoretically derived social-emotional programs that are culturally sensitive , developmentally appropriate , and offered in multiple grade s can reduce multiple risk behaviors for inner-city African American boys in grade s 5 through 8 . The lack of effects for girls deserves further research AIMS To determine the impact of a school-based harm minimization smoking intervention compared to traditional abstinence-based approaches . DESIGN , SETTING AND PARTICIPANTS A school-based cluster r and omized trial was conducted in Perth , Western Australia in 30 government high schools from 1999 to 2000 . Over 4000 students were recruited to participate and schools were assigned r and omly to either the harm minimization intervention or a st and ard abstinence-based programme . INTERVENTION The harm minimization intervention comprised eight 1-hour lessons over 2 years , quitting support from school nurses and enactment of policies to support programme components . Comparison schools implemented st and ard abstinence-based programmes and policies . MEASURES Cigarette smoking was categorized at two levels : regular smoking , defined as smoking on 4 or more days in the previous week ; and 30-day smoking as any smoking within the previous month . FINDINGS At immediate post-test ( 20 months post-baseline ) , after accounting for baseline differences , school-level clustering effects , socio-economic status , gender and family smoking , intervention students were less likely to smoke regularly [ OR = 0.51 , 95 % confidence interval ( CI ) = 0.36 , 0.71 ] or to have smoked within the previous 30 days ( OR = 0.69 , 95 % CI = 0.53 , 0.91 ) . CONCLUSION The school-based adolescent harm minimization intervention appears to have been more effective than the abstinence-based social influences programme at reducing regular smoking The HEALTHY primary prevention trial was design ed and implemented in response to the growing numbers of children and adolescents being diagnosed with type 2 diabetes . The objective was to moderate risk factors for type 2 diabetes . Modifiable risk factors measured were indicators of adiposity and glycemic dysregulation : body mass index ⩾85th percentile , fasting glucose ⩾5.55 mmol l−1 ( 100 mg per 100 ml ) and fasting insulin ⩾180 pmol l−1 ( 30 μU ml−1 ) . A series of pilot studies established the feasibility of performing data collection procedures and tested the development of an intervention consisting of four integrated components : ( 1 ) changes in the quantity and nutritional quality of food and beverage offerings throughout the total school food environment ; ( 2 ) physical education class lesson plans and accompanying equipment to increase both participation and number of minutes spent in moderate-to-vigorous physical activity ; ( 3 ) brief classroom activities and family outreach vehicles to increase knowledge , enhance decision-making skills and support and reinforce youth in accomplishing goals ; and ( 4 ) communications and social marketing strategies to enhance and promote changes through messages , images , events and activities . Expert study staff provided training , assistance , material s and guidance for school faculty and staff to implement the intervention components . A cohort of students were enrolled in sixth grade and followed to end of eighth grade . They attended a health screening data collection at baseline and end of study that involved measurement of height , weight , blood pressure , waist circumference and a fasting blood draw . Height and weight were also collected at the end of the seventh grade . The study was conducted in 42 middle schools , six at each of seven locations across the country , with 21 schools r and omized to receive the intervention and 21 to act as controls ( data collection activities only ) . Middle school was the unit of sample size and power computation , r and omization , intervention and primary analysis BACKGROUND Asthma is a serious problem for low-income preteens living in disadvantaged communities . Among the chronic diseases of childhood and adolescence , asthma has the highest prevalence and related health care use . School-based asthma interventions have proven successful for older and younger students , but results have not been demonstrated for those in middle school . METHODS This r and omized controlled study screened students 10 - 13 years of age in 19 middle schools in low-income communities in Detroit , Michigan . Of the 6,872 students who were screened , 1,292 students were identified with asthma . Schools were matched and r and omly assigned to Program 1 or 2 or control . Baseline , 12 , and 24 months data were collected by telephone ( parents ) , at school ( students ) and from school system records . Measures were the students ' asthma symptoms , quality of life , academic performance , self-regulation , and asthma management practice s. Data were analyzed using multiple imputation with sequential regression analysis . Mixed models and Poisson regressions were used to develop final models . RESULTS Neither program produced significant change in asthma symptoms or quality of life . One produced improved school grade s ( p = .02 ) . The other enhanced self-regulation ( p = .01 ) at 24 months . Both slowed the decline in self-regulation in undiagnosed preteens at 12 months and increased self-regulation at 24 months ( p = .04 ; p = .003 ) . CONCLUSION Programs had effects on academic performance and self-regulation capacities of students . More developmentally focused interventions may be needed for students at this transitional stage . Disruptive factors in the schools may have reduced both program impact and the potential for outcome assessment This study evaluated the effect of Students for Peace , a multi-component violence-prevention intervention , on reducing aggressive behaviors among students of eight middle schools r and omly assigned into intervention or control conditions . The intervention , based on Social Cognitive Theory , included the formation of a School Health Promotion Council , training of peer mediators and peer helpers , training of teachers in conflict resolution , a violence-prevention curriculum , and newsletters for parents . All students were evaluated in the spring of 1994 , 1995 and 1996 ( approximately 9000 students per evaluation ) . Sixth grade rs in 1994 were followed through seventh grade in 1995 or eighth grade in 1996 or both ( n = 2246 ) . Cohort and cross-sectional evaluations indicated little to no intervention effect in reducing aggressive behaviors , fights at school , injuries due to fighting , missing classes because of feeling unsafe at school or being threatened to be hurt . For all variables , the strongest predictors of violence in eighth grade were violence in sixth grade and low academic performance . Although ideal and frequently recommended , the holistic approach to prevention in schools in which teachers , administrators and staff model peaceful conflict resolution is difficult to implement , and , in this case , proved ineffective . The Students for Peace experience suggests that interventions begin prior to middle school , explore social environmental intervention strategies , and involve parents and community members First through fourth grade rs from 22 suburban elementary schools were screened for cross- setting disruptive behavior as eligibility criteria for participation in a longitudinal secondary prevention study aim ed at reducing the risk for serious externalizing behavioral disorders . Three hundred nine subjects participated in either a multicomponent competence enhancement intervention ( MCEI ) or an information/attention control ( IAC ) condition over a 2-year period . Following baseline measurements , initial intervention effects were assessed at the end of intervention Year 1 , at the beginning of intervention Year 2 ( fall of the next school year ) , and at the end of intervention Year 2 . Multi source assessment s were not supportive of the efficacy of the MCEI over the IAC condition . Children in both groups rated themselves as improved over time in terms of increased adaptive skills and decreased school problems and internalizing symptoms . Teacher and parent ratings of externalizing behavior did not yield evidence of positive change , but teachers noted improved problem solving and observers noted a decrease in behavioral interference in both groups over time , possibly as a result of maturation OBJECTIVES A r and omized school based trial sought to increase fruit and vegetable consumption among children using a multicomponent approach . METHODS The intervention , conducted in 20 elementary schools in St. Paul , targeted a multiethnic group of children who were in the fourth grade in spring 1995 and the fifth grade in fall 1995 . The intervention consisted of behavioral curricula in classrooms , parental involvement , school food service changes , and industry support and involvement . Lunchroom observations and 24-hour food recalls measured food consumption . Parent telephone surveys and a health behavior question naire measured psychosocial factors . RESULTS The intervention increased lunchtime fruit consumption and combined fruit and vegetable consumption , lunchtime vegetable consumption among girls , and daily fruit consumption as well as the proportion of total daily calories attributable to fruits and vegetables . CONCLUSIONS Multicomponent school-based programs can increase fruit and vegetable consumption among children . Greater involvement of parents and more attention to increasing vegetable consumption , especially among boys , remain challenges in future intervention research Background Effective interventions to prevent overweight and obesity in children are urgently needed especially in inner-city neighbourhoods where prevalence of overweight and inactivity among primary school children is high . A school based intervention was developed aim ing at the reduction of overweight and inactivity in these children by addressing both behavioural and environmental determinants . Methods / design The main components of the intervention ( Lekker Fit ! ) are the re-establishment of a professional physical education teacher ; three ( instead of two ) PE classes per week ; additional sport and play activities outside school hours ; fitness testing ; classroom education on healthy nutrition , active living and healthy lifestyle choices ; and the involvement of parents . The effectiveness of the intervention is evaluated through a cluster r and omized controlled trial in 20 primary schools among grade s 3 through 8 ( 6–12 year olds ) . Primary outcome measures are BMI , waist circumference and fitness . Secondary outcome measures are assessed in a subgroup of grade 6–8 pupils ( 9–12 year olds ) through classroom question naires and constitute of nutrition and physical activity behaviours and behavioural determinants . Multilevel regression analyses are used to study differences in outcomes between children in the intervention schools and in control schools , taking clustering of children within schools into account . Discussion Hypotheses are that the intervention results in a lower prevalence of children being overweight and an improved mean fitness score , in comparison with a control group where the intervention is not implemented . The results of our study will contribute to the discussion on the role of physical education and physical activity in the school curriculum . Trial registration [ IS RCT N84383524 OBJECTIVE To study the effects of a school-based injury prevention program on physical activity injury incidence and severity . DESIGN Cluster r and omized controlled trial performed from January 1 , 2006 , through July 31 , 2007 . SETTING Forty Dutch primary schools . PARTICIPANTS A total of 2210 children ( aged 10 - 12 years ) . INTERVENTION Schools were r and omized to receive either the regular curriculum or an intervention program that targeted physical activity injuries . OUTCOME MEASURES Incidence and severity of physical activity injuries per 1000 hours of physical activity participation . RESULTS A total of 100 injuries in the intervention group and 104 injuries in the control group were registered . Nonresponse at baseline or follow-up was minimal ( 8.7 % ) . The Cox regression analyses adjusted for clustering showed a small nonsignificant intervention effect on total ( HR , 0.81 ; 95 % confidence interval [ CI ] , 0.41 - 1.59 ) , sports club ( 0.69 ; 0.28 - 1.68 ) , and leisure time injuries ( 0.75 ; 0.36 - 1.55 ) . However , physical activity appeared to be an effect modifier . In those who were less physically active , the intervention had a larger effect . The intervention reduced the total and leisure time injury incidence ( HR , 0.47 ; 95 % CI , 0.21 - 1.06 ; and 0.43 ; 0.16 - 1.14 ; respectively ) . Sports club injury incidence was significantly reduced ( HR , 0.23 ; 95 % CI , 0.07 - 0.75 ) . CONCLUSION We found a substantial and relevant reduction in physical activity injuries , especially in children in the low active group , because of the intervention . This school-based injury prevention program is promising , but future large-scale research is needed This study reports the effect of a school-r and omized fruit and vegetable intervention consisting of a subscription to the Norwegian School Fruit Programme at no parental cost , and the Fruit and Vegetables Make the Marks ( FVMM ) educational programme , both delivered in the school year of 2001 - 02 . Nine r and omly chosen schools received the intervention and 10 schools served as control schools . Participating pupils completed question naires at baseline ( September 2001 ) , at Follow-up 1 ( May-June 2002 ) and at Follow-up 2 ( May 2003 ) . A total of 517 pupils ( 84 % ; mean age , 11.3 years at baseline ) participated in all three surveys . At both Follow-up 1 and Follow-up 2 , strong intervention effects were observed for all-day fruit and vegetable intake ( effect sizes were 0.6 and 0.5 portions , respectively ) . The sustained effect at Follow-up 2 , 1 year after the end of the intervention , can partly be explained by greater participation rates in the School Fruit Programme ( st and ard paid subscription ) . We conclude that the effects observed are most likely due to the no-cost subscription and not due to the FVMM educational programme , and that providing pupils with a piece of fruit or a vegetable at school at no cost for the parents is an effective strategy to increase school children 's intake of fruit and vegetables . The effect is also sustained 1 year after the end of the no-cost subscription , providing increased health benefits OBJECTIVES ICAPS ( Intervention Centred on Adolescents ' Physical activity and Sedentary behaviour ) is aim ed at preventing excessive weight gain and cardiovascular risk in adolescents by promoting physical activity ( PA ) with an emphasis on recreational and daily-life PA , with a lifelong perspective . DESIGN R and omized study design ed to last for four years . Study cohort constituted of 954 first-level students ( 91 % of eligible pupils ) , aged 11.7 + /- 0.6 y ( mean + /- SD ) from four pairs of schools r and omly selected in eastern France , after sociogeographical stratification . In each pair , intervention status was r and omised at school-level . The program , not limited to school setting s , involves multiple partners with three objectives : 1 ) changing attitudes through debates and access to attractive activities during breaks and after-school hours , 2 ) encouraging social support , 3 ) providing environmental conditions that enable PA . Adapted times and places , open participation , emphasis on fun , meeting with others and absence of competitive aspects are used to reduce usual barriers to PA . Accessibility and safety are permanent concerns . RESULTS Prevalence of overweight was 23.7 % . High participation rates were attained ( 50 % participated in at least one weekly activity ) . At six-month , the proportion of intervention adolescents not performing supervised PA out of academic PA was reduced by half ( 36 % to 17 % vs 42 % to 42 % in controls P < 10 - 4 ) ; the proportion of those spending > 3 h/day in sedentary occupations decreased ( 34 % to 28 % vs 27 % to 36 % ; P < 10 - 4 ) . CONCLUSION These data demonstrate the feasibility of implementing a multilevel PA intervention program in adolescents . Six-month results document increased PA and decreased sedentary behaviour Background Physical activity ( PA ) is associated with positive cardio-metabolic health and emerging evidence suggests sedentary behavior ( SB ) may be detrimental to children 's health independent of PA . The primary aim of the Transform-Us ! study is to determine whether an 18-month , behavioral and environmental intervention in the school and family setting s results in higher levels of PA and lower rates of SB among 8 - 9 year old children compared with usual practice ( post-intervention and 12-months follow-up ) . The secondary aims are to determine the independent and combined effects of PA and SB on children 's cardio-metabolic health risk factors ; identify the factors that mediate the success of the intervention ; and determine whether the intervention is cost-effective . Methods / design A four-arm cluster-r and omized controlled trial ( RCT ) with a 2 × 2 factorial design , with schools as the unit of r and omization . Twenty schools will be allocated to one of four intervention groups , sedentary behavior ( SB-I ) , physical activity ( PA-I ) , combined SB and PA ( SB+PA-I ) or current practice control ( C ) , which will be evaluated among approximately 600 children aged 8 - 9 years in school year 3 living in Melbourne , Australia . All children in year 3 at intervention schools in 2010 ( 8 - 9 years ) will receive the intervention over an 18-month period with a maintenance ' booster ' delivered in 2012 and children at all schools will be invited to participate in the evaluation assessment s. To maximize the sample and to capture new students arriving at intervention and control schools , recruitment will be on-going up to the post-intervention time point . Primary outcomes are time spent sitting and in PA assessed via accelerometers and inclinometers and survey . Discussion To our knowledge , Transform-Us ! is the first RCT to examine the effectiveness of intervention strategies for reducing children 's overall sedentary time , promoting PA and optimizing health outcomes . The integration of consistent strategies and messages to children from teachers and parents in both school and family setting s is a critical component of this study , and if shown to be effective , may have a significant impact on educational policies as well as on pedagogical and parenting practice s . Trial registration ACTRN12609000715279 ; Current Controlled Trials IS RCT This report describes the proposed intervention and outcome measurement procedures for the Pathways study . Pathways is a multicenter school-based study aim ed at reducing the alanning increase in the prevalence of obesity in American Indian children . It is design ed as a r and omized clinical trial , involving approximately 2,00 third grade children in 40 schools in seven diferent American Indian communities . During a 3-year feasibility phase , which was just completed , the major components of the intervention ( school food service , classroom curriculum , physical education program , and family involvement ) were developed and pilot-tested . The measurement instruments for body composition ; physical activity ; dietary intake ; and knowledge , attitudes , and behavior were also developed and vali date d. Comprehensive process evaluation procedures also were defined . As of this writing , thefull-scale intervention program is being initiated and is scheduled to be completed in the spring of 200 . The primary aim of the Pathways intervention is to reduce average percent body fat in intervention-school children by at least 3 % compared with control-school children by the end of the 3-year intervention . This goal is to be achieved primarily by an increase in physical activity and a reduction in the perceni of dietary fat intake . The program does not seek to reduce dietary energy intake . Rather , it is based on the assumption that a healthier ; lower-fat diet , combined with an increase in energy expenditure by increased physical activity , will result in fewer excess calories deposited as body fat Students for Peace is a three-year project ( October 1993- September 1996 ) design ed to evaluate a comprehensive , school-based intervention that seeks to prevent violence among sixth- , seventh- , and eighth- grade students in a large urban school district in Texas . This study examines the hypothesis that students exposed to a two-year multiple-component intervention will reduce aggressive behavior compared to students who receive the district 's " usual care " of violence prevention activities . Students for Peace is based largely on Social Learning . Theory ( SLT ) , which addresses both the psychosocial dynamics underlying health behavior and the methods of promoting behavior change , while emphasizing cognitive processes and their effect on behavior . SLT explains human behavior in terms of a model in which three factors-behavior , social-environmental influences , and personal factors ( such as personality , perceptions and expectations , and affect)-all interact . Theoretically , an individual 's behavior is uniquely determined by a combination of these factors ; thus , these factors become the elements for intervention strategies . The intervention program includes four main components : ( 1 ) modification of the school environment , ( 2 ) a violence-prevention curriculum , ( 3 ) peer leadership , and ( 4 ) parent education . Students for Peace is using a nested cross-sectional and cohort design in which school is the unit of design , allocation , and analysis . Eight schools , four intervention and four control , are participating . In May 1994 , a question naire was administered to all students in school the day of the survey . A posttest evaluation was taken in the spring of 1995 and will be followed by a final posttest in spring 1996 . A total of 8,865 students responded to the baseline survey . Nearly all variables indicated comparability between treatment and control conditions . As a population , Students for Peace participants are largely Hispanic ( 65 % ) or African American ( 19 % ) . Violence-related variables indicated 30-day fighting prevalence , 23 % ; 12-month prevalence of injuries due to fighting , 14 % ; 30-day h and -gun carrying prevalence , 11 % ; 30-day prevalence of taunts and threats at school , 27 % , and threats going to and from school , 26 % . Overall , the data from Year 1 activities indicate a population in need of violence-prevention intervention . The challenge is to mold existing district re sources into a theoretically sound program of interventions . If that program is found effective , the district will already have the necessary documentation , personnel , and skills for broader dissemination Objective : To describe the effects of URMEL-ICE , a German school-based intervention for overweight prevention , on children ’s BMI and other measures of fat mass . Methods : A cluster-r and omised controlled design was used . The intervention which focused on physical activity , TV time and soft drink consumption was integrated into a second- grade curriculum and was implemented by classroom teachers themselves . It comprised 29 teaching lessons , 2 short exercise blocks per day and 6 family homework lessons . BMI was assessed as primary outcome measure , waist circumference and skinfold thickness as secondary outcomes . Data of 945 children were analysed . Results : Multivariate analyses adjusted for baseline values showed no statistically significant effect of the intervention on BMI , but on waist circumference ( –0.85 ; 95 % confidence interval ( 95 % CI ) –1.59 to –0.12 ) and subscapular skinfold thickness ( –0.64 ; 95 % CI –1.25 to –0.02 ) . After additional adjustment for individual time lag between baseline and follow-up , these effects were reduced to –0.60 ( 95 % CI –1.25 to 0.05 ) and –0.61 ( 95 % CI –1.26 to 0.04 ) and lost their statistical significance . Conclusion : This study contributes to the field of r and omised school-based studies on overweight prevention and shows that within a 1-year , integrated intervention no effect on BMI , but a tendency towards effects on fat mass can be achieved BACKGROUND Physical activity is important for weight control and good health ; however , activity levels decline in the adolescent years , particularly in girls . DESIGN Group r and omized controlled trial . SETTING / PARTICIPANTS Middle school girls with English-speaking skills and no conditions to prevent participation in physical activity in 36 schools in six geographically diverse areas of the United States . R and om , cross-sectional sample s were drawn within schools : 6th grade rs in 2003 ( n=1721 ) and 8th grade rs in 2005 ( n=3504 ) and 2006 ( n=3502 ) . INTERVENTION A 2-year study -directed intervention ( fall 2003 to spring 2005 ) targeted schools , community agencies , and girls to increase opportunities , support , and incentives for increased physical activity . Components included programs linking schools and community agencies , physical education , health education , and social marketing . A third-year intervention used school and community personnel to direct intervention activities . MAIN OUTCOME MEASURES The primary outcome , daily MET-weighted minutes of moderate-to-vigorous physical activity ( MET-weighted MVPA ) , was assessed using accelerometry . Percent body fat was assessed using anthropometry . RESULTS After the staff-directed intervention ( pre-stated primary outcome ) , there were no differences ( mean= -0.4 , 95 % CI= -8.2 to 7.4 ) in adjusted MET-weighted MVPA between 8th- grade girls in schools assigned to intervention or control . Following the Program Champion-directed intervention , girls in intervention schools were more physically active than girls in control schools ( mean difference 10.9 MET-weighted minutes of MVPA , 95 % CI=0.52 - 21.2 ) . This difference is about 1.6 minutes of daily MVPA or 80 kcal per week . There were no differences in fitness or percent body fat at either 8th- grade timepoint . CONCLUSION A school-based , community-linked intervention modestly improved physical activity in girls Project Northl and was a r and omized community trial to prevent or delay alcohol use among adolescents . Students in the intervention communities were exposed to a multi-component prevention program in early adolescence and high school . This paper examines the impact of Project Northl and on the trajectories of four scales of the adolescent form of the Minnesota Multiphasic Personality Inventory ( MMPI-A ) . Students in the intervention communities demonstrated lower rates of growth of family problems and alcohol/drug use proneness than students in the delayed-program control communities . The results were more robust for baseline non-drinkers . Editors ’ Strategic Implication s : This experimental study extends the scope of the impact of Project Northl and , already recognized as a model substance abuse prevention program by the Substance Abuse and Mental Health Services Administration . The results suggest that focused prevention programs have the potential to impact young adolescents ’ lives more broadly . Replication and further examination of the mechanisms by which risk factors and outcomes are modified is necessary , but school administrators and public health officials could learn from this promising program and evaluation Background / Objectives : Previous research in the United Kingdom , where there is a school canteen system , has shown that the Food Dudes intervention substantially increases children 's fruit and vegetable consumption . The current study evaluated its effectiveness in Irel and where school meals are not provided and children bring food to school in lunchboxes . Subjects/ Methods : Participants were 4- to 11-year-old children attending two primary schools ; the schools were r and omly assigned to experimental or control conditions ( n=228 and 207 , respectively ) . During the 16-day intervention in the experimental school , children watched video adventures featuring the heroic Food Dudes , and received small rewards for eating fruit and vegetables provided . In both schools , parental provision and children 's consumption of fruit and vegetables in the lunchboxes were assessed at baseline and 12-month follow-up ( Lunchbox measures ) . Fruit and vegetables were provided in both schools over an 8-day baseline phase and the 16-day intervention , and children 's consumption was measured ( school-provided food measures ) . Results : Relative to baseline , consumption of the school-provided foods increased during the intervention in the experimental school ( P<0.001 ) , whereas in the control school it showed a significant decline . At 12-month follow-up , parents in the experimental school provided and their children consumed significantly more lunchbox fruit , vegetables and juice relative to baseline and to the control school ( P<0.001 in all instances ) . Conclusions : The Food Dudes intervention was effective in changing parental provision and children 's consumption of lunchbox fruit and vegetables in Irel and Background and purpose : The lack of effective school-based interventions for preventing obesity in children has caused a call for longer duration of interventions and better reporting on design and evaluation methodology . The purpose of this paper is to present the development of the intervention , the design of the effectiveness study , and the test-retest reliability of the main outcome measures in the HEalth In Adolescents ( HEIA ) study . Methods / design : The HEIA intervention programme was developed based on literature review s , a social ecological framework , and focus groups . The intervention aim ed to increase total physical activity ( PA ) and consumption of fruit and vegetables and to decrease screen time and consumption of sugar-sweetened beverages . The intervention programme consisted of a classroom component , including dietary behaviour lessons , computer tailoring , fruit/vegetable and PA breaks , and posters , and an environmental component including active transport campaigns , equipment , suggestions for easy improvements of schoolyards , inspirational courses for teachers ( all with regards to PA ) , and fact sheets to parents . The effect of the intervention programme is evaluated in a cluster r and omised controlled trial design ( intervention = 12 schools , control = 25 schools ) including process evaluation . Main outcomes include anthropometry , PA , screen time , and consumption of fruit , vegetables , and sugar-sweetened beverages . A 2-week test— retest study was conducted among 114 pupils . Determinants of the behaviours were assessed . Similar data were collected from parents . Children ’s PA was measured objective ly by accelerometers . Conclusions : The HEIA study represents a theoretically informed r and omised trial comprising a comprehensive set of multilevel intervention components with a thorough evaluation using reliable outcome measures . The study will contribute to a better underst and ing of determinants of healthy weight development among young people and how such determinants can be modified Background Declining levels of physical fitness in children are linked to an increased risk of developing poor physical and mental health . Physical activity programs for children that involve regular high intensity physical activity , along with muscle and bone strengthening activities , have been identified by the World Health Organisation as a key strategy to reduce the escalating burden of ill health caused by non-communicable diseases . This paper reports the rationale and methods for a school-based intervention design ed to improve physical fitness and physical activity levels of Grade s 5 and 6 primary school children . Methods / Design Fit-4-Fun is an 8-week multi-component school-based health-related fitness education intervention and will be evaluated using a group r and omized controlled trial . Primary schools from the Hunter Region in NSW , Australia , will be invited to participate in the program in 2011 with a target sample size of 128 primary schools children ( age 10 - 13 ) . The Fit-4-Fun program is theoretically grounded and will be implemented applying the Health Promoting Schools framework . Students will participate in weekly curriculum-based health and physical education lessons , daily break-time physical activities during recess and lunch , and will complete an 8-week ( 3 × per week ) home activity program with their parents and /or family members . A battery of six health-related fitness assessment s , four days of pedometery-assessed physical activity and a question naire , will be administered at baseline , immediate post-intervention ( 2-months ) and at 6-months ( from baseline ) to determine intervention effects . Details of the method ological aspects of recruitment , inclusion criteria , r and omization , intervention program , assessment s , process evaluation and statistical analyses are described . Discussion The Fit-4-Fun program is an innovative school-based intervention targeting fitness improvements in primary school children . The program will involve a range of evidence -based behaviour change strategies to promote and support physical activity of adequate intensity , duration and type , needed to improve health-related fitness . Trial Registration NoAustralia and New Zeal and Clinical Trials Register ( ANZCTR ) : Background The prevalence of childhood obesity among adolescents has been rapidly rising in Mainl and China in recent decades , especially in urban and rich areas . There is an urgent need to develop effective interventions to prevent childhood obesity . Limited data regarding adolescent overweight prevention in China are available . Thus , we developed a school-based intervention with the aim of reducing excess body weight in children . This report described the study design . Methods / design We design ed a cluster r and omized controlled trial in 8 r and omly selected urban primary schools between May 2010 and December 2013 . Each school was r and omly assigned to either the intervention or control group ( four schools in each group ) . Participants were the 4th grade rs in each participating school . The multi-component program was implemented within the intervention group , while students in the control group followed their usual health and physical education curriculum with no additional intervention program . The intervention consisted of four components : a ) classroom curriculum , ( including physical education and healthy diet education ) , b ) school environment support , c ) family involvement , and d ) fun programs/events . The primary study outcome was body composition , and secondary outcomes were behaviour and behavioural determinants . Discussion The intervention was design ed with due consideration of Chinese cultural and familial tradition , social convention , and current primary education and exam system in Mainl and China . We did our best to gain good support from educational authorities , school administrators , teachers and parents , and to integrate intervention components into schools ’ regular academic programs . The results of and lesson learned from this study will help guide future school-based childhood obesity prevention programs in Mainl and China . Trial registration Registration number : PURPOSE The study evaluated whether targeted changes in factors influencing enjoyment of physical education ( PE ) , physical activity enjoyment , and self-efficacy beliefs about participating in physical activity mediated the effect of the Lifestyle Education for Activity Program ( LEAP ) intervention on participation in physical activity . METHODS High schools ( N=24 ) paired on enrollment size , racial composition , urban or rural location , and class structure were r and omized into control ( N=12 ) or experimental ( N=12 ) groups . Of the 4044 girls enrolled and eligible , 2087 ( 51.6 % ) participated in the measurement component of the study . There were 1038 girls in the control group and 1049 girls in the experimental group . INTERVENTION LEAP was a comprehensive school-based intervention emphasizing changes in instruction and school environment design ed to increase physical activity among black and white adolescent girls . It was organized according to the Coordinated School Health Program and included a PE component with core objectives of promoting enjoyment of PE , physical activity enjoyment , and self-efficacy . RESULTS Latent variable structural equation modeling indicated that : 1 ) the intervention had direct , positive effects on physical activity and factors influencing enjoyment of PE , which subsequently explained the effects of increased physical activity enjoyment and self-efficacy on increased physical activity ; and 2 ) an additional , indirect effect of physical activity enjoyment on physical activity operated by an influence on self-efficacy . CONCLUSIONS Increases in enjoyment partially mediated the positive effect of the LEAP intervention . To our knowledge , we have provided the first experimental evidence from a r and omized controlled trial linking increased enjoyment with increased physical activity among black and white adolescent girls Steps to Respect : A Bullying Prevention Program ( STR ) relies on a social – ecological model of prevention to increase school staff awareness and responsiveness , foster socially responsible beliefs among students , and teach social – emotional skills to students to reduce bullying behavior . As part of a school-r and omized controlled trial of STR , we examined predictors and outcomes associated with classroom curriculum implementation in intervention schools . Data on classroom implementation ( adherence and engagement ) were collected from a sample of teachers using a weekly on-line Teacher Implementation Checklist system . Pre-post data related to school bullying-related outcomes were collected from 1,424 students and archival school demographic data were obtained from the National Center for Education Statistics . Results of multilevel analyses indicated that higher levels of program engagement were influenced by school-level percentage of students receiving free/reduced lunch , as well as classroom-level climate indicators . Results also suggest that higher levels of program engagement were related to lower levels of school bullying problems , enhanced school climate and attitudes less supportive of bullying . Predictors and outcomes related to program fidelity ( i.e. , adherence ) were largely nonsignificant . Results suggest that student engagement is a key element of program impact , though implementation is influenced by both school-level demographics and classroom context BACKGROUND Our objective was to evaluate the effects of environmental , policy , and social marketing interventions on physical activity and fat intake of middle school students on campus . DESIGN Twenty-four middle schools were r and omly assigned to intervention or control conditions . Baseline measures were collected in spring 1997 , and interventions were conducted during the 1997 - 1998 and 1998 - 1999 school years SETTING /PARTICIPATION : The schools had mean enrollments of 1109 , with 44.5 % nonwhite students . Over 2 years , physical activity interventions were design ed to increase physical activity in physical education classes and throughout the school day . Nutrition interventions were design ed to provide and market low-fat foods at all school food sources , including cafeteria breakfasts and lunches , a la carte sources , school stores , and bag lunches . School staff and students were engaged in policy change efforts , but there was no classroom health education . MAIN OUTCOMES MEASURES Primary outcomes were measured by direct observation and existing records . RESULTS R and omized regression models ( N = 24 schools ) revealed a significant intervention effect for physical activity for the total group ( p < 0.009 ) and boys ( p < 0.001 ) , but not girls ( p < 0.40 ) . The intervention was not effective for total fat ( p < 0.91 ) or saturated fat ( p < 0.79 ) . Survey data indicated that the interventions reduced reported body mass index for boys ( p < 0.05 ) . CONCLUSIONS Environmental and policy interventions were effective in increasing physical activity at school among boys but not girls . The interventions were not effective in reducing fat intake at school . School environmental and policy interventions have the potential to improve health behavior of the student population , but barriers to full implementation need to be better understood and overcome OBJECTIVE To evaluate the impact of a school-based diabetes mellitus prevention program on low-income fourth- grade Mexican American children . DESIGN A r and omized controlled trial with 13 intervention and 14 control schools . SETTING Elementary schools in inner-city neighborhoods in San Antonio , Tex . PARTICIPANTS Eighty percent of participants were Mexican American and 94 % were from economically disadvantaged households . Baseline and follow-up measures were collected from 1419 ( 713 intervention and 706 control ) and 1221 ( 619 intervention and 602 control ) fourth- grade children , respectively . INTERVENTION The Bienestar Health Program consists of a health class and physical education curriculum , a family program , a school cafeteria program , and an after-school health club . The objectives are to decrease dietary saturated fat intake , increase dietary fiber intake , and increase physical activity . MAIN OUTCOME MEASURES The primary end point was fasting capillary glucose level , and the secondary end points were percentage of body fat , physical fitness level , dietary fiber intake , and dietary saturated fat intake . Fasting capillary glucose level , bioelectric impedance , modified Harvard step test , three 24-hour dietary recalls , weight , and height were collected at baseline and 8 months later . RESULTS Children in the intervention arm attended an average of 32 Bienestar sessions . Mean fasting capillary glucose levels decreased in intervention schools and increased in control schools after adjusting for covariates ( -2.24 mg/dL [ 0.12 mmol/L ] ; 95 % confidence interval , -6.53 to 2.05 [ -0.36 to 0.11 mmol/L ] ; P = .03 ) . Fitness scores ( P = .04 ) and dietary fiber intake ( P = .009 ) significantly increased in intervention children and decreased in control children . Percentage of body fat ( P = .56 ) and dietary saturated fat intake ( P = .52 ) did not differ significantly between intervention and control children . CONCLUSION This intervention showed some positive results , but additional research is needed to examine long-term benefits , translation , and cost-effectiveness OBJECTIVE To determine whether an interactive curriculum that integrates dating violence prevention with lessons on healthy relationships , sexual health , and substance use reduces physical dating violence ( PDV ) . DESIGN Cluster r and omized trial with 2.5-year follow-up ; prespecified subgroup analyses by sex . SETTING Grade 9 health classes . PARTICIPANTS A total of 1722 students aged 14 - 15 from 20 public schools ( 52.8 % girls ) . Intervention A 21-lesson curriculum delivered during 28 hours by teachers with additional training in the dynamics of dating violence and healthy relationships . Dating violence prevention was integrated with core lessons about healthy relationships , sexual health , and substance use prevention using interactive exercises . Relationship skills to promote safer decision making with peers and dating partners were emphasized . Control schools targeted similar objectives without training or material s. MAIN OUTCOME MEASURES The primary outcome at 2.5 years was self-reported PDV during the previous year . Secondary outcomes were physical peer violence , substance use , and condom use . Analysis was by intention-to-treat . RESULTS The PDV was greater in control vs intervention students ( 9.8 % vs 7.4 % ; adjusted odds ratio , 2.42 ; 95 % confidence interval , 1.00 - 6.02 ; P = .05 ) . A significant group x sex interaction effect indicated that the intervention effect was greater in boys ( PDV : 7.1 % in controls vs 2.7 % in intervention students ) than in girls ( 12.1 % vs 11.9 % ) . Main effects for secondary outcomes were not statistically significant ; however , sex x group analyses showed a significant difference in condom use in sexually active boys who received the intervention ( 114 of 168 ; 67.9 % ) vs controls ( 65 of 111 [ 58.6 % ] ) ( P < .01 ) . The cost of training and material s averaged CA$16 per student . CONCLUSION The teaching of youths about healthy relationships as part of their required health curriculum reduced PDV and increased condom use 2.5 years later at a low per-student cost The aim of this study was to evaluate the impact of an intervention program on the patterns of physical activity in 8- to 10-year-old Mexican children from lower socioeconomic status . This study performed a r and omized controlled field trial in 498 children aged 8 - 10 years from 10 public schools of low socioeconomic status in Mexico City . Schools were r and omly assigned to intervention ( n = 5 ) or control ( n = 5 ) groups and followed up during 12 months . Physical and sedentary activities were assessed at the beginning of the program and after 6 and 12 months . At the end of follow-up , there was a significant increase in the performance of moderate physical activity ( MPA ) among children in intervention group who had not performed MPA at baseline any day of the week ( 40 % , P = 0.04 ) but not in the control group ( 8 % , P = not significant ) . The intervention group also showed a significant reduction in the proportion of children who spent more than 3 hours a day playing video games ( from 23 to 13 % , P = 0.01 ) , while control group did not show significant changes . Given these findings , we conclude that intervention was able to modify positively physical activity and reduce time spent on such sedentary activities as video games among those at highest risk studied children Background There is a shortage of information about the factors that mediate physical activity intervention effects which involve youth . The purpose of this study was to examine whether personal , social and physical-environmental factors mediated the intervention effect on physical activity and whether gender and weight status moderated mediated effects in the Health In Adolescents Study – a school-based intervention to promote healthy weight development among young adolescents . Methods Participating schools were r and omized to Control ( n = 25 ) and Intervention ( n = 12 ) . The intervention components to enhance physical activity targeted change through theoretically informed mediators embedded in a social-ecological framework . Accelerometer assessed physical activity ( mean count per minute ) and self-efficacy , enjoyment , perceived social support from parents , teachers and friends and perceived environmental opportunities were measured by question naires at baseline and post-intervention after 20 months among 700 11–13 year-old adolescents ( Intervention = 485 ; Control = 215 ) . The product-of-coefficient test was used to examine mediation . Results No mediating effect of any of the hypothesized mediators was identified and gender and weight status did not moderate any mediated effects with the exception of weight status that moderated the mediated effect of enjoyment . Few intervention effects were seen on the mediators , except for a positive change in social support from teachers among girls and the normal weight , and a negative effect on enjoyment and self-efficacy among the overweight . However , change in enjoyment , self-efficacy , perceived social support from friends and environmental opportunities were associated with change in mean count per minute with some variation across the investigated subgroups , and thus show evidence of being potential mediators of physical activity change in adolescents . Conclusions While no mediation effects were observed , change in both personal and social-environmental factors predicted change in physical activity behavior . Hence , a social- ecological approach targeting a wide range of determinants to promote change in physical activity holds promise . Overweight and normal weight adolescents may not respond in the same way to school-based physical activity interventions . Therefore , strategies to better reach the overweight seem needed . Future studies should continue to identify mediating and moderation mechanisms in physical activity change in adolescents Background The Healthy Options for Nutrition Environments in Schools ( Healthy ONES ) study was an evidence -based public health ( EBPH ) r and omized group trial that adapted the Institute for Healthcare Improvement ’s ( IHI ) rapid improvement process model to implement school nutrition policy and environmental change . Methods A low-income school district volunteered for participation in the study . All schools in the district agreed to participate ( elementary = 6 , middle school = 2 ) and were r and omly assigned within school type to intervention ( n = 4 ) and control ( n = 4 ) conditions following a baseline environmental audit year . Intervention goals were to 1 ) eliminate unhealthy foods and beverages on campus , 2 ) develop nutrition services as the main source on campus for healthful eating ( HE ) , and 3 ) promote school staff modeling of HE . Schools were followed across a baseline year and two intervention years . Longitudinal assessment of height and weight was conducted with second , third , and sixth grade children . Behavioral observation of the nutrition environment was used to index the amount of outside foods and beverages on campuses . Observations were made monthly in each targeted school environment and findings were presented as items per child per week . Results From an eligible 827 second , third , and sixth grade students , baseline height and weight were collected for 444 second and third grade and 135 sixth grade students ( 51 % reach ) . Data were available for 73 % of these enrolled students at the end of three years . Intervention school outside food and beverage items per child per week decreased over time and control school outside food and beverage items increased over time . The effects were especially pronounced for unhealthy foods and beverage items . Changes in rates of obesity for intervention school ( 28 % baseline , 27 % year 1 , 30 % year 2 ) were similar to those seen for control school ( 22 % baseline , 22 % year 1 , 25 % year 2 ) children . Conclusions Healthy ONES adaptation of IHI ’s rapid improvement process provided a promising model for implementing nutrition policy and environmental changes that can be used in a variety of school setting s. This approach may be especially effective in assisting schools to implement the current federally-m and ated wellness policies Background Several school-based fruit and vegetable interventions include activities to involve parents , but not much is know about the effectiveness of such a family component on child and parent intake levels . The current study evaluated the effects of the multi-component school-based intervention , ' the Pro Children Study ' , on mothers ' intake levels . Furthermore , associations between level of involvement in the project and improvement in the mothers ' intake levels were assessed . Methods Effect was evaluated in a cluster r and omized controlled trial in Spain , Norway and the Netherl and s among mothers of 11-year-olds . Of the 1253 mothers with complete data at baseline , 754 and 476 had complete data at first and second follow-up respectively . Fruit and vegetable intake , level of involvement and demographic variables were assessed by a parental question naire . Data was analyzed using multilevel regression analyses . Results Results showed no effect of the intervention on mothers ' fruit and vegetable intake after one year and two year follow-up . Participation rate for the different activities varied by activity and by country , e.g. 3.7–9.4 % visited the website , while 26.4–72.6 % of the mothers participated in the home work assignments . Results further showed that higher involvement levels were associated with higher intake at follow-up . Conclusion The Pro Children Intervention could not increase the fruit and vegetable consumption of the mothers of participating pupils , which might be explained by the low involvement in the project . More research is needed to increase mothers ' involvement in school-based interventions Six schools were r and omly assigned to a multilevel bullying intervention or a control condition . Children in Grade s 3 - 6 ( N=1,023 ) completed pre- and posttest surveys of behaviors and beliefs and were rated by teachers . Observers coded playground behavior of a r and om sub sample ( n=544 ) . Hierarchical analyses of changes in playground behavior revealed declines in bullying and argumentative behavior among intervention-group children relative to control-group children , increases in agreeable interactions , and a trend toward reduced destructive byst and er behavior . Those in the intervention group reported enhanced byst and er responsibility , greater perceived adult responsiveness , and less acceptance of bullying/aggression than those in the control group . Self-reported aggression did not differ between the groups . Implication s for future research on the development and prevention of bullying are discussed This study examined the effects of the Positive Action ( PA ) programme in Chicago Public Schools on problem behaviours among a cohort of elementary school students from grade three through grade five . Using a matched-pair , r and omised control design with 14 elementary schools , approximately 510 fifth- grade rs self-reported lifetime substance use , serious violence-related behaviour , and current bullying and disruptive behaviours . Three-level ( i.e. students nested within schools within school pairs ) overdispersed Poisson models were used to examine programme effects on the number of items endorsed for each of the four outcomes . Findings indicated that students in the intervention endorsed 31 % fewer substance use behaviours ( incidence rate ratio [ IRR ] = 0.69 ) , 37 % fewer violence-related behaviours ( IRR = 0.63 ) and 41 % fewer bullying behaviours ( IRR = 0.59 ) , respectively , compared to students in the control schools . Reduction in reported disruptive behaviours was of a similar magnitude ( 27 % , IRR = 0.73 ) , but was not statistically significant . These results replicate findings of an earlier r and omised trial of the PA programme and extend evidence of its effectiveness to youth attending large urban school systems Objectives : Obesity prevention among children and adolescents is a public health priority ; however , limited school-based intervention trials targeting obesity have been conducted . This article provides an overview of the study design and baseline preliminary findings of our ongoing school-based intervention study . Design : R and omized intervention trial to test a school-based , environmental obesity prevention program in urban low socioeconomic status ( SES ) African-American adolescents . The intervention program was developed based on several behavioral theories and was guided by preliminary findings based on focus group discussion and baseline data . Setting : Four Chicago public schools in the US.Subjects : Over 450 5–7th grade rs and their families and schools were involved . Results : Our baseline data indicate a high prevalence of overweight ( 43 % in boys and 41 % in girls ) and a number of problems in these children 's physical activity and eating patterns . Only 26 % reported spending ⩾20 min engaged in vigorous-moderate exercise in ⩾5 days over the past 7 days ; 29 % reported spending ⩾5 h each day watching TV , playing video games , or using computer . They also consumed too many fried foods and soft drinks . On average , 55 % consumed fried foods ⩾2 times/day over the past 7 days ; regarding soft drinks , 70 % reported consuming ⩾2 times/day . Conclusion : School-based obesity prevention programs are urgently needed in the target US urban , low SES , minority communities . These data can be used to inform intervention activities Background As concern about youth obesity continues to mount , there is increasing consideration of widespread policy changes to support improved nutritional and enhanced physical activity offerings in schools . A critical element in the success of such programs may be to involve students as spokespeople for the program . Making such a public commitment to healthy lifestyle program targets ( improved nutrition and enhanced physical activity ) may potentiate healthy behavior changes among such students and provide a model for their peers . This paper examines whether student 's " public commitment "-- voluntary participation as a peer communicator or in student-generated media opportunities -- in a school-based intervention to prevent diabetes and reduce obesity predicted improved study outcomes including reduced obesity and improved health behaviors . Methods Secondary analysis of data from a 3-year r and omized controlled trial conducted in 42 middle schools examining the impact of a multi-component school-based program on body mass index ( BMI ) and student health behaviors . A total of 4603 students were assessed at the beginning of sixth grade and the end of eighth grade . Process evaluation data were collected throughout the course of the intervention . All analyses were adjusted for students ' baseline values . For this paper , the students in the schools r and omized to receive the intervention were further divided into two groups : those who participated in public commitment activities and those who did not . Students from comparable schools r and omized to the assessment condition constituted the control group . Results We found a lower percentage of obesity ( greater than or equal to the 95th percentile for BMI ) at the end of the study among the group participating in public commitment activities compared to the control group ( 21.5 % vs. 26.6 % , p = 0.02 ) . The difference in obesity rates at the end of the study was even greater among the subgroup of students who were overweight or obese at baseline ; 44.6 % for the " public commitment " group , versus 53.2 % for the control group ( p = 0.01 ) . There was no difference in obesity rates between the group not participating in public commitment activities and the control group ( 26.4 % vs. 26.6 % ) . Conclusions Participating in public commitment activities during the HEALTHY study may have potentiated the changes promoted by the behavioral , nutrition , and physical activity intervention components . Trial Registration Clinical Trials.gov number , Project Northl and was a r and omized trial to reduce alcohol use among adolescents in 24 school districts in northeastern Minnesota . Phase 1 ( 1991 - 1994 ) , when the targeted cohort was in grade s 6 - 8 , included school curricula , parent involvement , peer leadership and community task forces . The Interim Phase ( 1994 - 1996 ) involved minimal intervention . Phase 2 ( 1996 - 1998 ) , when the cohort was in grade s 11 and 12 , included a classroom curriculum , parent education , print media , youth development and community organizing . Outcomes of these interventions were assessed by annual student surveys from 1991 to 1998 , alcohol purchase attempts by young-looking buyers in 1991 , 1994 and 1998 , and parent telephone surveys in 1996 and 1998 . Growth curve analysis was used to examine the student survey data over time . Project Northl and was most successful when the students were young adolescents . The lack of intervention in the Interim Phase when the students were in grade s 9 and 10 had a significant and negative impact on alcohol use . The intervention used with the high school students as those in grade s 11 and 12 made a positive impact on their tendency to use alcohol use , binge drinking and ability to obtain alcohol . There was no impact in Phase 2 on other student-level behavioral and psychosocial factors . Developmentally appropriate , multi-component , community-wide programs throughout adolescence appear to be needed to reduce alcohol use Objective : To assess the impact of an active school model on children ’s physical activity ( PA ) . Design : 16-month cluster r and omised controlled trial . Setting : 10 elementary schools in Greater Vancouver , BC . Participants : 515 children aged 9–11 years . Intervention : Action Schools ! BC ( AS ! BC ) is an active school model that provided schools with training and re sources to increase children ’s PA . Schools implemented AS ! BC with support from either external liaisons ( liaison schools , LS ; four schools ) or internal champions ( champion schools , CS ; three schools ) . Outcomes were compared with usual practice ( UP ) schools ( three schools ) . Main outcome measurements : PA was measured four times during the study using pedometers ( step count , steps/day ) . Results : Boys in the LS group took 1175 more steps per day , on average , than boys in the UP group ( 95 % CI : 97 to 2253 ) . Boys in the CS group also tended to have a higher step count than boys in the UP group ( + 804 steps/day ; 95 % CI : −341 to 1949 ) . There was no difference in girls ’ step counts across groups . Conclusions : The positive effect of the AS ! BC model on boys ’ PA is important in light of the current global trend of decreased PA Background Over the last three decades there has been a substantial increase in the proportion of children who are overweight or obese . The Healthy Lifestyles Programme ( HeLP ) is a novel school-based intervention , using highly interactive and creative delivery methods to prevent obesity in children . Methods / Design We describe a cluster r and omised controlled trial to evaluate the effectiveness and cost effectiveness of HeLP . The intervention has been developed using intervention mapping ( involving extensive stakeholder involvement ) and has been guided by the Information , Motivation , Behavioural Skills model . HeLP includes creating a receptive environment , drama activities , goal setting and reinforcement activities and runs over three school terms . Piloting showed that 9 to 10 year olds were the most receptive and participative . This study aims to recruit 1,300 children from 32 schools ( over half of which will have ≥19 % of pupils eligible for free school meals ) from the southwest of Engl and . Participating schools will be r and omised to intervention or control groups with baseline measures taken prior to r and omisation . The primary outcome is change in body mass index st and ard deviation score ( BMI SDS ) at 24 months post baseline . Secondary outcomes include , waist circumference and percent body fat SDS and proportion of children classified as overweight or obese at 18 and 24 months and objective ly measured physical activity and food intake at 18 months . Between-group comparisons will be made using r and om effects regression analysis taking into account the hierarchical nature of the study design . An economic evaluation will estimate the incremental cost-effectiveness of HeLP , compared to control , from the perspective of the National Health Service (NHS)/third party payer . An in-depth process evaluation will provide insight into how HeLP works , and whether there is any differential uptake or engagement with the programme . Discussion The results of the trial will provide evidence on the effectiveness and cost effectiveness of the Healthy Lifestyles Programme in affecting the weight status of children . Trial registration IS RCT OBJECTIVES To evaluate the effects of a middle-school healthy eating promotion intervention combining environmental changes and computer-tailored feedback , with and without an explicit parent involvement component . DESIGN Clustered r and omised controlled trial . SETTING Fifteen West-Flemish ( Belgian ) middle schools . SUBJECTS A r and om sample of 15 schools with 2991 pupils in 7th and 8th grade s was r and omly assigned to an intervention group with parental support ( n = 5 ) , an intervention group without parental support ( n = 5 ) and a control group ( n = 5 ) . In these 15 schools an intervention combining environmental changes with computer-tailored feedback was implemented . Fat and fruit intake , water and soft drinks consumption were measured with food-frequency question naires in the total sample of children . RESULTS In girls , fat intake and percentage of energy from fat decreased significantly more in the intervention group with parental support , compared with the intervention alone group ( all F>3.9 , P < 0.05 ) and the control group ( all F>16.7 , P < 0.001 ) . In boys , there were no significant decreases in fat intake ( F = 1.4 , not significant ( NS ) ) or percentage of energy from fat ( F = 0.7 , NS ) as a result of the intervention . No intervention effects were found in boys or in girls for fruit ( F = 0.5 , NS ) , soft drinks ( F = 2.6 , NS ) and water consumption ( F = 0.3 , NS ) . CONCLUSIONS Combining physical and social environmental changes with computer-tailored feedback in girls and their parents can induce lower fat intake in middle-school girls . However , to have an impact on the consumption of soft drinks and water , governmental laws that restrict the at-school availability of low-nutritive products may be necessary R and omized trials of complex public health interventions generally aim to identify what works , accrediting specific intervention ' products ' as effective . This approach often fails to give sufficient consideration to how intervention components interact with each other and with local context . ' Realists ' argue that trials misunderst and the scientific method , offer only a ' successionist ' approach to causation , which brackets out the complexity of social causation , and fail to ask which interventions work , for whom and under what circumstances . We counter-argue that trials are useful in evaluating social interventions because r and omized control groups actually take proper account of rather than bracket out the complexity of social causation . Nonetheless , realists are right to stress underst and ing of ' what works , for whom and under what circumstances ' and to argue for the importance of theorizing and empirically examining underlying mechanisms . We propose that these aims can be ( and sometimes already are ) examined within r and omized trials . Such ' realist ' trials should aim to : examine the effects of intervention components separately and in combination , for example using multi-arm studies and factorial trials ; explore mechanisms of change , for example analysing how pathway variables mediate intervention effects ; use multiple trials across context s to test how intervention effects vary with context ; draw on complementary qualitative and quantitative data ; and be oriented towards building and validating ' mid-level ' program theories which would set out how interventions interact with context to produce outcomes . This last suggestion resonates with recent suggestions that , in delivering truly ' complex ' interventions , fidelity is important not so much in terms of precise activities but , rather , key intervention ' processes ' and ' functions ' . Realist trials would additionally determine the validity of program theory rather than only examining ' what works ' to better inform policy and practice in the long-term The purpose was to investigate the degree of implementation and appreciation of a comprehensive school-r and omized fruit and vegetable intervention program and to what extent these factors were associated with changes in reported fruit and vegetable intake . The study was conducted among 10- to 13-year old children exposed to the intervention during the school year 2003 - 04 in Norway , Spain and the Netherl and s. Children , parents and teachers completed question naires regarding ( i ) the implementation of the school curriculum , ( ii ) parental involvement , ( iii ) distribution of fruit and vegetables at school , ( iv ) children 's appreciation of the project and ( v ) children 's intake levels . Univariate analyses of covariance and multilevel multivariate regression analyses indicated that teacher-reported level of implementation of the school curriculum and schoolchildren 's appreciation of the project were important determinants of changes in intake . The results point to the importance of optimal implementation of an attractive school curriculum Study objective : The aim of this study was to determine the effect of a multilevel school based intervention on adolescents ’ emotional wellbeing and health risk behaviours . Design : School based cluster r and omised controlled trial . Students were surveyed using laptop computers , twice in the first year of intervention and annually thereafter for a further two years . Setting : Secondary schools . Participants : 2678 year 8 students ( 74 % ) participated in the first wave of data collection . Attrition across the waves was less than 3 % , 8 % , and 10 % respectively with no differential response rate between intervention and control groups at the subsequent waves ( 98 % v 96 % ; 92 % v 92 % , and 90 % v 89 % respectively ) . Main results : A comparatively consistent 3 % to 5 % risk difference was found between intervention and control students for any drinking , any and regular smoking , and friends ’ alcohol and tobacco use across the three waves of follow up . The largest effect was a reduction in the reporting of regular smoking by those in the intervention group ( OR 0.57 , 0.62 , and 0.72 at waves 2 , 3 , and 4 respectively ) . There was no significant effect of the intervention on depressive symptoms , and social and school relationships . Conclusions : While further research is required to determine fully the processes of change , this study shows that a focus on general cognitive skills and positive changes to the social environment of the school can have a substantial impact on important health risk behaviours Background There is limited knowledge as to whether obesity prevention interventions are able to produce change in the determinants hypothesized to precede change in energy balance-related behaviors in young people . The aim of this study was to evaluate the effect of a multi-component intervention on a wide range of theoretically informed determinants of physical activity ( PA ) and sedentary behavior ( SB ) . Moderation effects of gender , weight status and parental education level and whether the perceived intervention dose received influenced the effects were also explored . Methods The HEIA study was a 20-month school-based , r and omized controlled trial to promote healthy weight development . In total , 1418 11-year-olds participated at baseline and post-intervention assessment . Enjoyment , self-efficacy , perceived social support from parents , teachers and friends related to PA , perceived parental regulation of TV-viewing and computer/game-use and perceived social inclusion at schools were examined by covariance analyses to assess overall effects and moderation by gender , weight status and parental education , mid-way and post-intervention . Covariance analyses were also used to examine the role of intervention dose received on change in the determinants . Results At mid-way enjoyment ( p = .03 ) , perceived social support from teachers ( p = .003 ) and self-efficacy ( p = .05 ) were higher in the intervention group . Weight status moderated the effect on self-efficacy , with a positive effect observed among the normal weight only . At post-intervention results were sustained for social support from teachers ( p = .001 ) , while a negative effect was found for self-efficacy ( p = .02 ) . Weight status moderated the effect on enjoyment , with reduced enjoyment observed among the overweight . Moderation effects for parental education level were detected for perceived social support from parents and teachers . Finally , positive effects on several determinants were observed among those receiving a high as opposed to a low intervention dose . Conclusion The intervention affected both psychological and social-environmental determinants . Results indicate that social support from teachers might be a potential mediator of PA change , and that overweight adolescents might be in need of specially targeted interventions to avoid reducing their enjoyment of PA . Further studies should continue to assess how intervention effectiveness is influenced by the participants ’ self-reported dose of intervention received Objective To assess the effectiveness of a school based physical activity programme during one school year on physical and psychological health in young schoolchildren . Design Cluster r and omised controlled trial . Setting 28 classes from 15 elementary schools in Switzerl and r and omly selected and assigned in a 4:3 ratio to an intervention ( n=16 ) or control arm ( n=12 ) after stratification for grade ( first and fifth grade ) , from August 2005 to June 2006 . Participants 540 children , of whom 502 consented and presented at baseline . Intervention Children in the intervention arm ( n=297 ) received a multi-component physical activity programme that included structuring the three existing physical education lessons each week and adding two additional lessons a week , daily short activity breaks , and physical activity homework . Children ( n=205 ) and parents in the control group were not informed of an intervention group . For most outcome measures , the assessors were blinded . Main outcome measures Primary outcome measures included body fat ( sum of four skinfolds ) , aerobic fitness ( shuttle run test ) , physical activity ( accelerometry ) , and quality of life ( question naires ) . Secondary outcome measures included body mass index and cardiovascular risk score ( average z score of waist circumference , mean blood pressure , blood glucose , inverted high density lipoprotein cholesterol , and triglycerides ) . Results 498 children completed the baseline and follow-up assessment s ( mean age 6.9 ( SD 0.3 ) years for first grade , 11.1 ( 0.5 ) years for fifth grade ) . After adjustment for grade , sex , baseline values , and clustering within classes , children in the intervention arm compared with controls showed more negative changes in the z score of the sum of four skinfolds ( −0.12 , 95 % confidence interval −0.21 to −0.03 ; P=0.009 ) . Likewise , their z scores for aerobic fitness increased more favourably ( 0.17 , 0.01 to 0.32 ; P=0.04 ) , as did those for moderate-vigorous physical activity in school ( 1.19 , 0.78 to 1.60 ; P<0.001 ) , all day moderate-vigorous physical activity ( 0.44 , 0.05 to 0.82 ; P=0.03 ) , and total physical activity in school ( 0.92 , 0.35 to 1.50 ; P=0.003 ) . Z scores for overall daily physical activity ( 0.21 , −0.21 to 0.63 ) and physical quality of life ( 0.42 , −1.23 to 2.06 ) as well as psychological quality of life ( 0.59 , −0.85 to 2.03 ) did not change significantly . Conclusions A school based multi-component physical activity intervention including compulsory elements improved physical activity and fitness and reduced adiposity in children . Trial registration Current Controlled Trials IS RCT N15360785 BACKGROUND . The prevalence and seriousness of childhood obesity has prompted calls for broad public health solutions that reach beyond clinic setting s. Schools are ideal setting s for population -based interventions to address obesity . OBJECTIVE . The purpose of this work was to examine the effects of a multicomponent , School Nutrition Policy Initiative on the prevention of overweight ( 85.0th to 94.9th percentile ) and obesity ( > 95.0th percentile ) among children in grade s 4 through 6 over a 2-year period . METHODS . Participants were 1349 students in grade s 4 through 6 from 10 schools in a US city in the Mid-Atlantic region with ≥50 % of students eligible for free or reduced-price meals . Schools were matched on school size and type of food service and r and omly assigned to intervention or control . Students were assessed at baseline and again after 2 years . The School Nutrition Policy Initiative included the following components : school self- assessment , nutrition education , nutrition policy , social marketing , and parent outreach . RESULTS . The incidences of overweight and obesity after 2 years were primary outcomes . The prevalence and remission of overweight and obesity , BMI z score , total energy and fat intake , fruit and vegetable consumption , body dissatisfaction , and hours of activity and inactivity were secondary outcomes . The intervention result ed in a 50 % reduction in the incidence of overweight . Significantly fewer children in the intervention schools ( 7.5 % ) than in the control schools ( 14.9 % ) became overweight after 2 years . The prevalence of overweight was lower in the intervention schools . No differences were observed in the incidence or prevalence of obesity or in the remission of overweight or obesity at 2 years . CONCLUSION . A multicomponent school-based intervention can be effective in preventing the development of overweight among children in grade s 4 through 6 in urban public schools with a high proportion of children eligible for free and reduced-priced school meals OBJECTIVE The present study aim ed to determine whether a multi-component school-based intervention can maintain children 's fruit and vegetable intake post eligibility for free school fruit and vegetables . DESIGN A r and om sample of fifty-four English primary schools was r and omised to receive the 10-month intervention Project Tomato , a multi-component theory-based intervention , or the control . Each group consisted of twenty-seven schools . SETTING Children 's intake of fruit and vegetables is below recommendations . The English School Fruit and Vegetable Scheme has a short-term impact on intake while children are eligible for the scheme . SUBJECTS Dietary measurements were collected from 658 Year 2 pupils aged 7 - 8 years at baseline and at follow-up 20 months later . RESULTS Following an intention to treat analysis , the intervention as delivered compared with the control had no impact on the intake of fruit and vegetables ( 2 g/d , 95 % CI -23 , 26 g/d ) or on the number of portions of fruit ( 0.0 portions , 95 % CI - 0.3 , 0.3 ) or vegetables ( 0.0 portions , 95 % CI - 0.2 , 0.3 ) consumed daily by children . Intake of fruit and vegetables at school and home dropped by ≈ 100 g/d and 50 g/d , respectively , between baseline and follow-up in both the intervention and control groups . CONCLUSIONS Implementation of the intervention was low , with associated lack of impact on fruit and vegetable consumption in children . Alternatives to the delivery of an intervention by teachers and parents are needed to improve the dietary intake of primary -school children The aim of this study was to assess the effects of a 2-year cluster-r and omized physical activity and dietary intervention program among 7-year-old ( at baseline ) elementary school participants on body composition and objective ly measured cardiorespiratory fitness . Three pairs of schools were selected and matched , then r and omly selected as either an intervention ( n = 151 ) or control school ( n = 170 ) . None of the effect sizes of body composition were statistically significant . Children in the intervention group increased their fitness by an average of 0.37 z score units more than the controls ( 95 % CI:-0.27 to 1.01 , P = 0.18 ) , representing an improvement of 0.286 W/kg . Boys had higher fitness ( mean(diff ) = 0.35 z scores , 95 % CI : 0.13 - 0.58 , P = 0.001 ) than girls , independent of study group , fitness z score at baseline and body mass index . Post hoc analysis showed that the intervention school with the highest fitness z score change was significantly different from two of the lowest control schools ( mean(diff ) = 0.83 z scores , 95 % CI : 0.44 - 1.21 , P < 0.0001 and mean(diff ) = 0.70 z scores , 95 % CI : 0.29 - 1.10 , P = 0.01 ) , but it was also significantly different from the lowest intervention school ( mean(diff ) = 0.59 z scores , 95 % CI : 0.19 - 0.99 , P = 0.05 ) . The results of this intervention are inconclusive as regards to the effects on fitness , but the intervention did not have any statistically significant effect on body composition BACKGROUND Elementary schools represent both a source of childhood sun exposure and a setting for educational interventions . METHODS Sun Protection of Florida 's Children was a cluster r and omized trial promoting hat use at ( primary outcome ) and outside of schools among fourth- grade students during August 8 , 2006 , through May 22 , 2007 . Twenty-two schools were r and omly assigned to the intervention ( 1115 students ) or control group ( 1376 students ) . Intervention schools received classroom sessions targeting sun protection attitudes and social norms . Each student attending an intervention school received two free wide-brimmed hats . Hat use at school was measured by direct observation and hat use outside of school was measured by self-report . A subgroup of 378 students ( 178 in the intervention group and 200 in the control group ) underwent serial measurements of skin pigmentation to explore potential physiological effects of the intervention . Generalized linear mixed models were used to evaluate the intervention effect by accounting for the cluster r and omized trial design . All P values were two-sided and were cl aim ed as statistically significant at a level of .05 . RESULTS The percentage of students observed wearing hats at control schools remained essentially unchanged during the school year ( baseline = 2 % , fall = 0 % , and spring = 1 % ) but increased statistically significantly at intervention schools ( baseline = 2 % , fall = 30 % , and spring = 41 % ) ( P < .001 for intervention effect comparing the change in rate of hat use over time at intervention vs control schools ) . Self-reported use of hats outside of school did not change statistically significantly during the study ( control : baseline = 14 % , fall = 14 % , and spring = 11 % ; intervention : baseline = 24 % , fall = 24 % , and spring = 23 % ) nor did measures of skin pigmentation . CONCLUSIONS The intervention increased use of hats among fourth- grade students at school but had no effect on self-reported wide-brimmed hat use outside of school or on measures of skin pigmentation We report the design , rationale , and statistical procedures used in Pathways , a r and omized , school-based intervention for the primary prevention of obesity in American Indian children . The intervention , which is now being implemented in 7 American Indian communities around the country , includes a health-promotion curriculum , a physical education program , a school meal program , and a family involvement component . Forty-one schools serving American Indian children were r and omly assigned to be either intervention or control groups . The intervention will begin in the third grade and continue through the end of the fifth grade . Efficacy of intervention will be assessed by differences in mean percentage body fat , calculated by a prediction equation , between intervention and control schools at the end of the fifth grade . Power computations indicate that the study has power to detect a mean difference of 2.8 % in body fat . Data analysis will use intention-to-treat concepts and the mixed linear model . The study will be completed in 2000 The Project Northl and peer participation program tested the feasibility of involving students in the planning and promotion of alcohol-free social activities for their peers and to determine whether such participation was associated with reduced alcohol use . The peer program was offered in 20 northeastern Minnesota schools when the study cohort was in seventh grade ; students completed a survey in the beginning of sixth grade and at the end of sixth grade and seventh grade . Nearly 50 % of the study cohort participated in the program . At the end of seventh grade , after controlling for confounders , an association was observed between student involvement with planning activities and a lower rate of alcohol use . This association was strongest among students who had reported alcohol use at the beginning of sixth grade . This cohort study suggests adolescent involvement in planning their own alcohol-free activities may be an efficacious strategy to prevent or reduce the prevalence of alcohol use among youth . Future studies are warranted to evaluate this association using experimental research design Fast Track is a multisite , multicomponent preventive intervention for young children at high risk for long-term antisocial behavior . Based on a comprehensive developmental model , intervention included a universal-level classroom program plus social skills training , academic tutoring , parent training , and home visiting to improve competencies and reduce problems in a high-risk group of children selected in kindergarten . At the end of Grade 1 , there were moderate positive effects on children 's social , emotional , and academic skills ; peer interactions and social status ; and conduct problems and special-education use . Parents reported less physical discipline and greater parenting satisfaction/ease of parenting and engaged in more appropriate/consistent discipline , warmth/positive involvement , and involvement with the school . Evidence of differential intervention effects across child gender , race , site , and cohort was minimal BACKGROUND We examined the effects of a multicomponent , school-based program addressing risk factors for diabetes among children whose race or ethnic group and socioeconomic status placed them at high risk for obesity and type 2 diabetes . METHODS Using a cluster design , we r and omly assigned 42 schools to either a multicomponent school-based intervention ( 21 schools ) or assessment only ( control , 21 schools ) . A total of 4603 students participated ( mean [ + /- SD ] age , 11.3 [ + /- 0.6 years ; 54.2 % Hispanic and 18.0 % black ; 52.7 % girls ) . At the beginning of 6th grade and the end of 8th grade , students underwent measurements of body-mass index ( BMI ) , waist circumference , and fasting glucose and insulin levels . RESULTS There was a decrease in the primary outcome --the combined prevalence of overweight and obesity -- in both the intervention and control schools , with no significant difference between the school groups . The intervention schools had greater reductions in the secondary outcomes of BMI z score , percentage of students with waist circumference at or above the 90th percentile , fasting insulin levels ( P=0.04 for all comparisons ) , and prevalence of obesity ( P=0.05 ) . Similar findings were observed among students who were at or above the 85th percentile for BMI at baseline . Less than 3 % of the students who were screened had an adverse event ; the proportions were nearly equivalent in the intervention and control schools . CONCLUSIONS Our comprehensive school-based program did not result in greater decreases in the combined prevalence of overweight and obesity than those that occurred in control schools . However , the intervention did result in significantly greater reductions in various indexes of adiposity . These changes may reduce the risk of childhood-onset type 2 diabetes . ( Funded by the National Institutes of Health and the American Diabetes Association ; Clinical Trials.gov number , NCT00458029 . BACKGROUND Inadequate opportunities for physical activity at school and overall low levels of activity contribute to the high prevalence of overweight and obesity in American-Indian children . METHODS A school-based physical activity intervention was implemented which emphasized increasing the frequency and quality of physical education ( PE ) classes and activity breaks . Changes in physical activity were assessed using the TriTrac-R3D accelerometer in a sub sample of 580 of the students ( 34 % ) r and omly selected from the Pathways study cohort . Baseline measures were completed with children in second grade . Follow-up measurements were obtained in the spring of the fifth grade . RESULTS Intervention schools were more active ( + 6.3 to + 27.2 % ) than control schools at three of the four sites , although the overall difference between intervention and control schools ( approximately 10 % ) was not significant ( P>0.05 ) . Boys were more active than girls by 17 to 21 % ( P < or = .01 ) at both baseline and follow-up . CONCLUSIONS Despite the trend for greater physical activity at three of four study sites , and an overall difference of approximately 10 % between intervention and control schools , high variability in accelerometer AVM and the opportunity to measure physical activity on only 1 day result ed in a the failure to detect the difference as significant This article presents the results of a mediation analysis of Project MYTRI ( Mobilizing Youth for Tobacco Related Initiatives in India ) , a r and omized , controlled trial of a multiple-component , school-based tobacco prevention program for sixth- to ninth- grade rs ( n = 14,085 ) in Delhi and Chennai , India . A mediation analysis identifies how an intervention achieves its effects . In MYTRI , changes in students ’ ( a ) knowledge about the negative health effects of tobacco , ( b ) beliefs about its social consequences , ( c ) reasons to use tobacco , ( d ) reasons not to use tobacco , ( e ) advocacy skills self-efficacy , and ( f ) normative beliefs about tobacco use were significantly associated with reductions in students ’ intentions to use tobacco and tobacco use behaviors . In contrast , changes in students ’ perceptions of the prevalence of smoking and chewing tobacco were significantly related to increases in students ’ intentions to use and use of tobacco . Implication s for intervention design are considered Elementary schools and child care setting s in rural New Hampshire participated in a sun protection program that reached more than 4,200 children . The program was part of a successful multifaceted community intervention targeting children ages 2 - 9 . Program components included curricular material s , training and support for school/child care staff , and parent outreach . Evaluation showed good uptake of the curriculum by teachers and child care providers , improvements in sun protection policy in participating schools and child care setting s , and significant knowledge and attitude improvements in fourth grade children tested , as well as actual behavior change . The study highlighted the importance of flexible , developmentally appropriate curricular material s and active engagement of principals and directors in policy review . In addition , for parent outreach programs to be successful , children needed to participate Summary The effects of physical activity on bone strength acquisition during growth are not well understood . In our cluster r and omized trial , we found that participation in a novel school-based physical activity program enhanced bone strength acquisition and bone mass accrual by 2–5 % at the femoral neck in girls ; however , these benefits depended on teacher compliance with intervention delivery . Our intervention also enhanced bone mass accrual by 2–4 % at the lumbar spine and total body in boys . Introduction We investigated the effects of a novel school-based physical activity program on femoral neck ( FN ) bone strength and mass in children aged 9–11 yrs . Methods We used hip structure analysis to compare 16-month changes in FN bone strength , geometry and bone mineral content ( BMC ) between 293 children who participated in Action Schools ! BC ( AS ! BC ) and 117 controls . We assessed proximal femur ( PF ) , lumbar spine ( LS ) and total body ( TB ) BMC using DXA . We compared change in bone outcomes between groups using linear regression accounting for the r and om school effect and select covariates . Results Change in FN strength ( section modulus , Z ) , cross-sectional area ( CSA ) , subperiosteal width and BMC was similar between control and intervention boys , but intervention boys had greater gains in BMC at the LS ( + 2.7 % , p = 0.05 ) and TB ( + 1.7 % , p = 0.03 ) than controls . For girls , change in FN-Z tended to be greater ( + 3.5 % , p = 0.1 ) for intervention girls than controls . The difference in change increased to 5.4 % ( p = 0.05 ) in a per- protocol analysis that included girls whose teachers reported 80 % compliance . Conclusion AS ! BC benefits bone strength and mass in school-aged children ; however , our findings highlight the importance of accounting for teacher compliance in classroom-based physical activity interventions OBJECTIVE To evaluate the process of smoking prevention and control among Chinese adolescent with a model on health promotion in junior high school . METHODS A cluster-r and omized , controlled and schooled-based trial on smoking prevention was conducted among 2343 students at four secondary schools in Huangpu District of Guangzhou . Students ' reports and investigators ' daily records were used to evaluate the intervention measures . RESULTS During the one-year period of intervention ( Dec. 2004 through Dec. 2005 ) , eighteen activities had been implemented among students , teachers , parents and cigarette retailers . Ranked by the rate of awareness , the top six activities were shown as follows : " the nicotine toxicity experiment " ( 90.7 % ) , " agreement of building families free of smoking"(77.7 % ) , " a letter to parents " ( 77.1 % ) , " no-smoking signs " ( 76.5 % ) , " Blackboard information about health and smoking " ( 75.0 % ) , and " signature on the 18th World Day of No Smoking " ( 70.2 % ) . Among all the activities , " the nicotine toxicity experiment " had the highest rate of participation ( 88.5 % ) , followed by " a letter to parents " ( 73.6 % ) , " agreement of building families free of smoking " ( 69.8 % ) , " health education through experiments"(68.6 % ) , " health education through multimedia " ( 65.7 % ) and " signature on the 18th World Day of No Smoking " ( 65.6 % ) . The top seven activities in which students showed greatest interests were " the nicotine toxicity experiment " ( 64.5 % ) , " signature on the 18th World Day of No Smoking " ( 33.0 % ) , " health education through experiments " ( 31.2 % ) , " health education through multimedia " ( 29.8 % ) , " class meetings with a thesis of smoking " ( 26.8 % ) , " health pamphlets " ( 26.6 % ) , " specific textbooks " ( 25.9 % ) . The extent of students ' general satisfaction to the work of tobacco control in school during the last year was 52.4 % . The biggest perceived shortcoming for the intervention plan was the low participation of students . CONCLUSION Some intervention measures had not been fully carried out among the students and only covered part of them . It is necessary to adjust the previous intervention measures through keeping the nicotine toxicity experiment , health education through multimedia and other measures with extensive participation of students and at the same time , to avoid literal material s , exhibition boards and traditional single-way health education program This paper describes a preventive intervention trial called EARLY ALLIANCE which is aim ed at reducing risk for three adverse outcomes in childhood and adolescence : conduct problems , substance abuse , and school failure . The structure of the prevention trial is unique because two linked design s are being implemented concurrently . The primary design focuses on children at elevated risk for adverse outcomes , and compares a targeted , multi context ual preventive intervention with family , classroom , peer relational , and academic components to a universal , schoolwide preventive intervention that emphasizes peaceful conflict management and serves as a " usual care " control condition . The secondary design focuses on children at lower risk for adverse outcomes and compares a universally administered classroom program to the control condition . The paper describes the theoretical foundation for EARLY ALLIANCE , the goals of the prevention trial , the rationale for design choices , and the methods employed BACKGROUND Substantial differences exist in how and where physical education ( PE ) is conducted in elementary schools throughout the United States . Few effectiveness studies of large-scale interventions to improve PE have been reported . DESIGN Multicenter r and omized trial . SETTING / PARTICIPANTS The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) was implemented in PE classes in 96 schools ( 56 intervention , 40 control ) in four study centers : California , Louisiana , Minnesota , and Texas . INTERVENTION The 2.5-year PE intervention consisted of professional development sessions , curricula , and follow-up consultations . MAIN OUTCOME MEASURES Intervention effects on student physical activity and lesson context in PE were examined by teacher type ( PE specialists and classroom teachers ) and lesson location ( indoors and outdoors ) . RESULTS Differential effects by teacher type and lesson location were evidence d for both physical activity and lesson context . Observations of 2016 lessons showed that intervention schools provided more moderate-to-vigorous physical activity ( p=0.002 ) and vigorous physical activity ( p=0.02 ) than controls . Classroom teachers improved physical activity relatively more than PE specialists , but PE specialists still provided longer lessons and more physical activity . Classroom teachers increased lesson length ( p=0.02 ) and time for physical fitness ( p=0.03 ) . CONCLUSIONS The intervention improved PE of both specialists ' and classroom teachers ' lessons . States and districts should ensure that the most qualified staff teaches PE . Interventions need to be tailored to meet local needs and conditions , including teacher type and location of lessons OBJECTIVES We assessed the effectiveness of a 2-year multicomponent , school-based intervention design ed to reduce tobacco use rates among adolescents in an urban area of India . METHODS Students from 32 schools in Delhi and Chennai , India , were recruited and r and omly assigned to an intervention or control group . Baseline , intermediate , and outcome data were collected from 2 cohorts of 6th- and 8th- grade students in 2004 ; 14,063 students took part in the study and completed a survey in 2004 , 2005 , or 2006 . The intervention consisted of behavioral classroom curricula , school posters , a parental involvement component , and peer-led activism . The main outcome measures were self-reported use of cigarettes , bidis ( small h and -rolled , often flavored , cigarettes ) , and chewing tobacco and future intentions to smoke or use chewing tobacco . RESULTS Findings showed that students in the intervention group were significantly less likely than were students in the control group to exhibit increases in cigarette smoking or bidi smoking over the 2-year study period . They were also less likely to intend to smoke or chew tobacco in the future . CONCLUSIONS School-based programs similar to the intervention examined here should be considered as part of a multi strategy approach to reducing tobacco use among young people in India INTRODUCTION AND AIMS Declines in adolescent smoking prevalence have slowed recently , result ing in increased interest and literature in tobacco harm minimisation . To date , harm reduction strategies have focused largely on modifying the product and alternative ( safer ) mechanisms of nicotine delivery . There has been little exploration of primary harm minimisation to prevent the onset of regular smoking among young people . A major concern expressed about harm reduction interventions and young people is that they may increase experimentation among non-users . DESIGN AND METHODS The Smoking Cessation for Youth Project was a 2-year school-based cluster r and omised controlled trial conducted in 30 Western Australian schools . Results on the primary outcome showed a significant reduction in regular smoking among 4636 13 - 15-year-olds receiving a harm minimisaton versus st and ard intervention . This paper addresses the intervention effects on 2078 students who had not smoked at baseline . RESULTS At 20-month follow-up , smoking initiation was slightly lower among intervention students than comparison students ( who received a largely abstinence-based intervention ) , although this difference did not attain statistical significance ( OR=0.86 ; 95 % confidence interval : 0.68 , 1.09 ) . DISCUSSION AND CONCLUSIONS This study provided limited evidence to suggest that harm minimisation is a superior approach to abstinence-based interventions for non-smokers . However , this intervention did not contribute to increased experimentation among non-smokers . Although more trials are required , these results indicate that fears of potential negative iatrogenic effects from school-based harm minimisation interventions may be unwarranted The HEALTHY primary prevention trial was design ed to reduce risk factors for type 2 diabetes in middle school students . Middle schools at seven centers across the United States participated in the 3-year study . Half of them were r and omized to receive a multi-component intervention . The intervention integrated nutrition , physical education ( PE ) and behavior changes with a communications strategy of promotional and educational material s and activities . The PE intervention component was developed over a series of pilot studies to maximize student participation and the time ( in minutes ) spent in moderate-to-vigorous physical activity ( MVPA ) , while meeting state-m and ated PE guidelines . The goal of the PE intervention component was to achieve ⩾150 min of MVPA in PE classes every 10 school days with the expectation that it would provide a direct effect on adiposity and insulin resistance , subsequently reducing the risk of type 2 diabetes in youth . The PE intervention component curriculum used st and ard lesson plans to provide a comprehensive approach to middle school PE . Equipment and PE teacher assistants were provided for each school . An expert in PE at each center trained the PE teachers and assistants , monitored delivery of the intervention and provided ongoing feedback and guidance OBJECTIVE To evaluate the effects of a 2-year middle school physical activity and healthy food intervention , including an environmental and computer-tailored component on BMI and BMI z-score in boys and girls . RESEARCH METHODS AND PROCEDURES A r and om sample of 15 schools with seventh and eighth grade rs was r and omly assigned to three conditions : an intervention with parental support group , an intervention-alone group , and a control group . Weight and height were measured at the beginning and end of each school year to assess BMI and BMI z-score . A physical activity and healthy food program was implemented over 2 school years . RESULTS In girls , BMI and BMI z-score increased significantly less in the intervention with parental support group compared with the control group ( p < 0.05 ) or the intervention-alone group ( p = 0.05 ) . In boys , no significant positive intervention effects were found . DISCUSSION This was the first study evaluating the effectiveness of an intervention combining environmental changes with personal computer-tailored feedback on BMI and BMI z-score in middle school children . After 2 school years , BMI and BMI z-score changed in a more positive direction in girls as a result of the intervention with parental support OBJECTIVE Project Northl and is an ongoing prevention trial with the objective of reducing underage drinking and related problems . Phase I focused on early adolescence and this study describes the multiple interventions , highlighting its parent components . METHOD A cohort design was used with sixth grade rs from 24 school districts ( N = 2,35 1 : 97 % of the eligible population : 51.3 % boys ) , r and omly assigned to intervention or reference condition . Phase I ended in eighth grade ( N = 1,901 : 81 % retention rate ) . Both dem and and supply reduction guided the interventions . This study examined Project Northl and 's impact using MMPI-A scales assessing clinical problems related to adolescents ' alcohol and other drug use ( Alcohol/Drug Problems Proneness scale ; Alcohol/Drug Problems Acknowledgement scale ) , as well as MMPI-A scales related to school functioning ( Adolescent-School Problems Content scale : Adolescent-Low Aspirations Content scale ) and family functioning ( Adolescent-Family Problems Content scale ) . RESULTS Results showed significant reductions on the MMPI-A Proneness scale for those exposed to the interventions . The greatest program effects were among baseline nonusers of alcohol . CONCLUSIONS Results suggest that the impact of Project Northl and is not only on specifically targeted alcohol and drug use behaviors and their predictive factors , but also on intra-individual and familial factors generally considered precursors of more extensive problem behaviors and more resistant to change . Furthermore , the engaging home-based sixth- grade intervention , the Slick Tracy Home Team Program , is a promising population -based prevention approach that may generalize to other serious problems within a young person 's family Objectives : To determine the impact of a peer-led education program , developed in Australia , on health-related outcomes in high school students with asthma in Jordan . Methods : In this cluster-r and omized controlled trial , 4 high schools in Irbid , Jordan , were r and omly assigned to receive the Adolescent Asthma Action program or st and ard practice . Bilingual health workers trained 24 peer leaders from Year 11 to deliver asthma education to younger peers from Year 10 ( n = 92 ) , who in turn presented brief asthma skits to students in Years 8 and 9 ( n = 148 ) and to other members of the school community in the intervention schools . Students with asthma ( N = 261 ) in Years 8 , 9 , and 10 completed baseline surveys in December 2006 and 3 months after the intervention . Results : Students from the intervention group reported clinical ly significant improvements in health-related quality of life ( mean difference : 1.35 [ 95 % confidence interval : 1.04–1.76 ] ) , self-efficacy to resist smoking ( mean difference : 4.63 [ 95 % confidence interval : 2.93–6.35 ] ) , and knowledge of asthma self- management ( mean difference : 1.62 [ 95 % confidence interval : 1.15–2.19 ] ) compared with the control group . Conclusions : This trial demonstrated that the Adolescent Asthma Action program can be readily adapted to suit different cultures and context s. Adolescents in Jordan were successful in teaching their peers about asthma self-management and motivating them to avoid smoking . The findings revealed that peer education can be a useful strategy for health promotion programs in Jordanian schools when students are given the opportunity and training OBJECTIVE To evaluate the cost-effectiveness and cost benefit of Safer Choices , a school-based human immunodeficiency virus , other sexually transmitted diseases , and unintended pregnancy prevention intervention for high school students . METHODS The baseline cost-effectiveness and cost benefit were derived in 4 steps : ( 1 ) estimation of intervention costs ; ( 2 ) adaptation of the Bernoulli model to translate increases in condom use into cases of human immunodeficiency virus and other sexually transmitted diseases averted , and development of a model to translate increases in contraceptive use into cases of pregnancy averted ; ( 3 ) translation of cases averted into medical costs and social costs averted ; and ( 4 ) calculation of the net benefit of the program . Multivariable sensitivity analysis was performed to determine the robustness of the base-case results . RESULTS Under base-case assumptions , at an intervention cost of $ 105,243 , Safer Choices achieved a 15 % increase in condom use and an 11 % increase in contraceptive use within 1 year among 345 sexually active students . An estimated 0.12 cases of human immunodeficiency virus , 24.37 cases of chlamydia , 2.77 cases of gonorrhea , 5.86 cases of pelvic inflammatory disease , and 18.5 pregnancies were prevented . For every dollar invested in the program , $ 2.65 in total medical and social costs were saved . Results of most of the scenarios remained cost saving under a wide range of model variable estimates . CONCLUSIONS The Safer Choices program is cost-effective and cost saving in most scenarios considered . School-based prevention programs of this type warrant careful consideration by policy makers and program planners . Program cost data should be routinely collected in evaluations of adolescent prevention programs We investigated whether barriers to onsite parental involvement in the Bienestar Health Program Parent Component could be identified and whether participation rates could be increased by addressing these barriers . All nonparticipating parents of fourth- grade students of San Antonio Independent School District from 4 schools , which were selected r and omly from 20 intervention schools in Bienestar , were invited to take part in this study . A total of 47 of 223 ( 21 % ) parents engaged in one of four focus groups offered . Parents identified barriers to their involvement in Bienestar that fit into five descriptive categories : ( a ) low value , ( b ) high cost , ( c ) competing family dem and s , ( d ) concerns about the program design , and ( e ) social role norms . The Bienestar Parent Component was then modified according to the focus group findings , which result ed in a marked increase in parental involvement from 17 % to 37 % overall . These findings suggest that even when parents are involved in the initial design of parent-friendly and culturally sensitive programs , as was the case for Bienestar , maximizing parental involvement may require additional assessment , identification , and remediation of barriers The effects of a school-based social-emotional and character development program , Positive Action , on the developmental trajectory of social-emotional and character-related behaviors was evaluated using data from three school-based r and omized trials in elementary schools . Results come from 1 ) 4 years of data from students in 20 Hawai’i schools , 2 ) 3 years of data from students in 14 schools in Chicago and 3 ) 3 years of data from students in 8 schools in a southeastern state . R and om intercept , multilevel , growth-curve analyses showed that students in both control and Positive Action schools exhibited a general decline in the number of positive behaviors associated with social-emotional and character development that were endorsed . However , the Positive Action intervention significantly reduced these declines in all three trials . Taken together , these analyses 1 ) give insight into the normative trajectory of behaviors associated with social-emotional and character development and 2 ) provide evidence for the effectiveness of Positive Action in helping children maintain a relatively beneficial developmental trajectory Abstract This article reports the effects of a comprehensive elementary school-based social-emotional and character education program on school-level achievement , absenteeism , and disciplinary outcomes utilizing a matched-pair , cluster-r and omized , controlled design . The Positive Action Hawai'i trial included 20 racially/ethnically diverse schools ( M enrollment = 544 ) and was conducted from the 2002–03 through the 2005–06 academic years . Using school-level archival data , analyses comparing change from baseline ( 2002 ) to 1-year posttrial ( 2007 ) revealed that intervention schools scored 9.8 % better on the TerraNova ( 2nd ed . ) test for reading and 8.8 % on math , that 20.7 % better in Hawai'i Content and Performance St and ards scores for reading and 51.4 % better in math , and that intervention schools reported 15.2 % lower absenteeism and fewer suspensions ( 72.6 % ) and retentions ( 72.7 % ) . Overall , effect sizes were moderate to large ( range = 0.5–1.1 ) for all of the examined outcomes . Sensitivity analyses using permutation models and r and om-intercept growth curve models substantiated results . The results provide evidence that a comprehensive school-based program , specifically developed to target student behavior and character , can positively influence school-level achievement , attendance , and disciplinary outcomes concurrently This article discusses the findings of Focus Group Discussion s ( FGDs ) that were conducted as a formative assessment for Project MYTRI ( Mobilizing Youth for Tobacco Related Initiatives in India ) , a r and omized , multicomponent , school-based trial to prevent and control tobacco use among youth in India . Forty-eight FGDs were conducted with students ( N = 435 ) in sixth and eighth grade s in six schools in Delhi , India . Key findings include : ( a ) students in government schools reported as “ consumers ” of tobacco , whereas students in private schools reported as “ commentators ” ; ( b ) parents and peers have a strong influence on youth tobacco use ; ( c ) chewing gutkha is considered less harmful and more accessible than smoking cigarettes ; ( d ) schools are not promoting tobacco control activities ; and ( e ) students were enthusiastic about the role government should play in tobacco control . These findings are being used to develop a comprehensive intervention program to prevent and control tobacco use among Indian youth OBJECTIVES To assess the outcome of oral health promotion in schoolchildren over a 3-year period in Yichang City , Hubei , China . METHODS In a cluster r and omized controlled trial , the concept of the World Health Organization Health Promoting Schools Project was applied to primary schoolchildren . Seven intervention schools and eight control schools were r and omly selected from one district by stratified cluster sampling . The study was conducted as a 3-year follow-up study . After 3 years , 661 children remained in the intervention group and 697 children in the control group . Data on dental caries , plaque accumulation , and sulcus bleeding were collected by clinical examination , while behavioural data were gathered by self-administered question naires . RESULTS The 3-year net mean DMFS increment score was 0.22 in the intervention schools and 0.35 in the control schools ( P < 0.013 ) . A statistically significant difference in mean plaque ( P < 0.013 ) and sulcus bleeding ( P < 0.005 ) increment scores after 3 years was found between the two groups . Statistically significant higher scores were observed in restorations received and sealants placed , and a lower score in untreated dental caries , in children from the intervention group than the control group after 3 years ( P < 0.01 ) . In addition , more children in the intervention schools adopted regular oral health behavioural practice s such as brushing their teeth at least twice a day , visiting the dentist within the past calendar year , and using fluoride toothpaste . CONCLUSION The study suggests that the school-based oral health promotion was an effective way to reduce new caries incidence , improve oral hygiene and establish positive oral health behavioural practice s in the targeted schoolchildren PURPOSE The objective of this study was to evaluate the impact of a school-based intervention ( Program X ) incorporating pedometers and e-mail support on physical activity , sedentary behavior , and healthy eating in adolescents . METHODS A r and omized control trial was used to evaluate the impact of the Program X intervention . Six schools ( N = 124 participants ; mean age 14.1 + /- .8 years ) were r and omized to intervention or control conditions for the 6-month study period . Objective ly recorded physical activity ( mean steps/day ) , self-reported sedentary behavior , and dietary habits were measured at baseline and at 6-month follow-up and intervention effects were assessed using repeated- measures analysis of variance and chi(2 ) tests . RESULTS Participants in the intervention group increased their step counts by 956 + /- 4107 steps/day ( boys ) and 999 + /- 1999 ( girls ) . Repeated- measures analysis of variance revealed significant group-by-time interactions for boys ( F = 7.4 , p = .01 , d = .80 ) and girls ( F = 29.6 , p < .001 , d = 1.27 ) for mean steps/day . The intervention significantly decreased the number of energy-dense/low-nutrient snacks consumed by boys ( chi(2 ) = 4.0 , p = .043 ) and increased the number of fruit serves among girls ( chi(2 ) = 4.8 , p = .028 ) . The intervention did not have a statistically significant effect on sedentary behavior . CONCLUSION A school-based intervention incorporating physical activity monitoring using pedometers and e-mail support was successful in promoting physical activity and selected healthy eating behaviors in adolescent boys and girls The aim of this study was to examine modifiable biological , psychological , behavioral and social-environmental correlates of physical activity among 1129 Norwegian 11-year-old children within a cross-sectional sample from the HEalth In Adolescents study . Physical activity was assessed by accelerometer , and weight and height were measured objective ly . Age- and gender-specific cut-off points proposed by the International Obesity Task Force were used to define body mass index . Social-environmental variables were self-reported by question naire . Hierarchical regression ( linear mixed models ) revealed that normal weight children scored higher on percentage daily moderate-to-vigorous physical activity [ % daily moderate to vigorous physical activity ( MVPA ) ] than overweight/obese children ( P<0.001 ) . Self-efficacy ( P<0.01 ) and perceived social support from friends ( P<0.01 ) were positively associated with children 's % daily MVPA , and a negative association was found for computer/game-use on weekends ( P<0.01 ) . A moderator effect of weight category ( normal vs overweight/obese ) in the relationship between computer/game-use on weekends and % daily MVPA was detected ( P<0.05 ) , reflecting that higher computer/game-use on weekends was associated with lower % MVPA among the overweight/obese , but not among the normal weight . Modifiable correlates from multiple domains accounted for 14 % of the variance in % daily MVPA . Prospect i ve and intervention studies are needed to examine whether these factors act as mediators for physical activity change in pre-adolescent children BACKGROUND School safety and quality affect student learning and success . This study examined the effects of a comprehensive elementary school-wide social-emotional and character education program , Positive Action , on teacher , parent , and student perceptions of school safety and quality utilizing a matched-pair , cluster-r and omized , controlled design . The Positive Action Hawai'i trial included 20 racially/ethnically diverse schools and was conducted from 2002 - 2003 through 2005 - 2006 . METHODS School-level archival data , collected by the Hawai'i Department of Education , were used to examine program effects at 1-year post-trial . Teacher , parent , and student data were analyzed to examine indicators of school quality such as student safety and well-being , involvement , and satisfaction , as well as overall school quality . Matched-paired t-tests were used for the primary analysis , and sensitivity analyses included permutation tests and r and om-intercept growth curve models . RESULTS Analyses comparing change from baseline to 1-year post-trial revealed that intervention schools demonstrated significantly improved school quality compared to control schools , with 21 % , 13 % , and 16 % better overall school quality scores as reported by teachers , parents , and students , respectively . Teacher , parent , and student reports on individual school- quality indicators showed improvement in student safety and well-being , involvement , satisfaction , quality student support , focused and sustained action , st and ards-based learning , professionalism and system capacity , and coordinated team work . Teacher reports also showed an improvement in the responsiveness of the system . CONCLUSIONS School quality was substantially improved , providing evidence that a school-wide social-emotional and character education program can enhance school quality and facilitate whole-school change Through-school nutrition and physical activity interventions are design ed to help reduce excess weight gain and risk of chronic disease . From 2004 to 2006 , Project Energize was delivered in the Waikato Region of New Zeal and as a longitudinal r and omised controlled study of 124 schools ( year 1 - 6 ) , stratified by rurality and social deprivation , and r and omly assigned to intervention or control . Children ( 686 boys and 662 girls ) aged 5 ( 1926 ) and 10 ( 1426 ) years ( 692 interventions and 660 controls ) had height , weight , body fat ( by bioimpedance ) and resting blood pressure ( BP ) measured at baseline and 2 years later . Each intervention school was assigned an ' Energizer ' ; a trained physical activity and nutrition change agent , who worked with the school to achieve goals based on healthier eating and quality physical activity . After adjustment for baseline measures , rurality and social deprivation , the intervention was associated with a reduced accumulation of body fat in younger children and a reduced rate of rise in systolic BP in older children . There was some evidence that the pattern of change within an age group varied with rurality , ethnicity and sex . We conclude that the introduction of an ' Energizer led ' through-school programme may be associated with health benefits over 2 years , but the trajectory of this change needs to be measured over a longer period . Attention should also be paid to the differing response by ethnicity , sex , age group and the effect of rurality and social deprivation Health benefits of physical activity in children are well known . However , a drawback is the risk of physical activity-related injuries . Children are at particular risk for these injuries , because of a high level of exposure . Because of the high prevalence of physical activity injuries and the negative short- and long-term consequences , prevention of these injuries in children is important . This article describes how we systematic ally developed a school-based physical activity injury prevention programme using the intervention mapping ( IM ) protocol .IM describes a process for developing theory- and evidence -based health promotion programmes . The development can be described in six steps : ( i ) perform a needs assessment ; ( ii ) identify programme and performance objectives ; ( iii ) select methods and strategies ; ( iv ) develop programme ; ( v ) adopt and implement ; and ( vi ) evaluate . First , the results of the needs assessment showed the injury problem in children and the different risk factors for physical activity injuries . Based on the results of the needs assessment the main focus of the injury prevention programme was described . Second , the overall programme objective of the injury prevention programme was defined as reducing the incidence of lower extremity physical activity injuries . Third , theoretical methods and practical strategies were selected to accomplish a decrease in injury incidence . The theoretical methods used were active learning , providing cues and scenariobased risk information , and active processing of information . The practical strategy of the injury prevention programme was an 8-month course about injury prevention to be used in physical education classes in primary schools . Fourth , programme material s that were used in the injury prevention programme were developed , including newsletters for children and parents , posters , exercises to improve motor fitness , and an information website . Fifth , an implementation plan was design ed in order to ensure that the prevention programme would be implemented , adopted and sustained over time . Finally , an evaluation plan was design ed . The injury prevention programme is being evaluated in a cluster r and omized controlled trial with more than 2200 children from 40 primary schools throughout the Netherl and s . The IM process is a useful process for developing an injury prevention programme . Based on the steps of the IM we developed an 8-month injury prevention programme to be used in physical education classes of primary schools Objective : To investigate why urban Indian 6th grade rs may be using more tobacco than urban Indian 8th grade rs . Design : Cross-sectional survey of students conducted in the summer of 2004 , as the baseline evaluation tool for a group-r and omised tobacco prevention intervention trial ( Project MYTRI ) . Mixed-effects regression models were used to ( 1 ) examine the relationship between 15 psychosocial risk factors and current use of any tobacco , by grade ; and ( 2 ) examine differences in psychosocial risk factors , by grade . Setting : Thirty-two private ( high socioeconomic status ( SES ) ) and government ( low-mid SES ) schools in two large cities in India ( Delhi and Chennai ) . Subjects : Students in the 6th and 8th grade in these schools ( n = 11642 ) . Among these , 50.6 % resided in Delhi ( v Chennai ) , 61.4 % attended a government school ( v a private school ) , 52.9 % were enrolled in 6th grade ( v 8th ) , and 54.9 % were male ( v female ) . Main outcome measure : Current ( past 30 day ) use of any tobacco , including chewing tobacco ( for example , gutkha ) , bidis , or cigarettes . Result : Almost all psychosocial factors were significantly related to tobacco use , for students in both grade s. Some of the strongest correlates included social susceptibility to and social norms about use . Exposure to tobacco advertising was a strong correlate of tobacco use for 6th grade rs , but not for 8th grade rs . Sixth grade rs scored lower than 8th grade rs on almost all factors , indicating higher risk . Conclusions : The “ risk profile ” of 6th grade rs suggests they would be vulnerable to use and to begin using tobacco , as well as to outside influences that may encourage use Project Northl and is design ed to prevent alcohol use among young adolescents . The project is ongoing in 24 school districts , r and omly assigned to intervention or reference conditions . Multiple interventions begin with sixth grade rs and continue through eighth grade . The reference districts offer their st and ard health curricula . Evaluation consists of school surveys with the cohort ( N = 2201 ) and telephone surveys of half their parents . This article describes the sixth- grade home-based intervention , the Slick Tracy Home Team . Findings of broad-based participation across sex , race , and risk status were documented , as well as some increases in knowledge and family communication about alcohol use This article compares four mixed-model analyses valid for group-r and omized trials ( GRTs ) involving a nested cohort design with a single pretest and posttest . This study makes estimates of intraclass correlations ( ICCs ) available to investigators planning GRTs addressing dietary outcomes . It also provides formulae demonstrating the potential benefits to the st and ard error of the intervention effect ( σΔ ) from adjustments for both fixed and time-varying covariates and correlations over time . These estimates will allow other research ers using these variables to plan their studies by estimating a priori detectable differences and sample size requirements for any of the four analytic options . These methods are demonstrated using data from the Teens Eating for Energy and Nutrition at School study . Mixed-model analyses of covariance proved to be the most powerful analysis in that data set . The formulae may be applied to any dependent variable in any GRT given corresponding information for those variables on the parameters that define the formulae This study evaluated the impact of a universal school-based violence prevention program on social-cognitive factors associated with aggression and nonviolent behavior in early adolescence . The effects of the universal intervention were evaluated within the context of a design in which two cohorts of students at 37 schools from four sites ( N = 5,581 ) were r and omized to four conditions : ( a ) a universal intervention that involved implementing a student curriculum and teacher training with sixth grade students and teachers ; ( b ) a selective intervention in which a family intervention was implemented with a subset of sixth grade students exhibiting high levels of aggression and social influence ; ( c ) a combined intervention condition ; and ( d ) a no-intervention control condition . Short-term and long-term ( i.e. , 2-year post-intervention ) universal intervention effects on social-cognitive factors targeted by the intervention varied as a function of students ’ pre-intervention level of risk . High-risk students benefited from the intervention in terms of decreases in beliefs and attitudes supporting aggression , and increases in self-efficacy , beliefs and attitudes supporting nonviolent behavior . Effects on low-risk students were in the opposite direction . The differential pattern of intervention effects for low- and high-risk students may account for the absence of main effects in many previous evaluations of universal interventions for middle school youth . These findings have important research and policy implication s for efforts to develop effective violence prevention programs This study examined the impact of a school-based preventive intervention on cannabis use in adolescence , using a cluster-r and omized trial of a multilevel intervention aim ed at improving social relationships within schools by promoting change in school environment . Four waves of data were collected at baseline ( 1997 , Year 8 : mean age 13 years ) and six , 18 , and 30 months later ( 1999 , Year 10 : mean age 16 years ) . Self-reported substance use , school engagement , and sociodemographic data were collected using computer-administered question naires . Some 2.678(74 % ) Year 8 students participated ( wave 1 ) with minimal attrition ( 10 % by wave 4 ) . Adjusting for baseline use , weak evidence existed for an intervention effect on the prevalence of any use at Year 10 ( OR 0.75 , 95 % CI 0.54 , 1.05 ) and incident weekly use ( OR 0.72 , 95 % CI 0.39 , 1.33 ) . These effects were reduced after adjusting for confounders . Moderate evidence suggested an interaction effect between intervention group and tobacco use ( p = 0.04 ) , suggesting the intervention was more effective for non-smokers at baseline ( Adj . OR 0.50 , 95 % CI 0.26 , 0.98 ) . This study indicates that a multi-level school-based program may provide an innovative direction for sustainable school interventions with the potential to reduce substance use STUDY OBJECTIVE This study assessed the impact of a comprehensive school-based asthma program on symptoms , grade s , and school absences in children , and parents ' asthma management practice s. DESIGN R and omized controlled trial . SETTING Fourteen elementary schools in low-income neighborhoods in Detroit , MI . PARTICIPANTS Eight hundred thirty-five children with asthma in grade s 2 through 5 and their parents . INTERVENTION The intervention entailed six components for children , their parents , classmates , and school personnel to encourage and enable disease management . MEASUREMENTS AND RESULTS Parents completed telephone interviews and the schools provided data at baseline and 24 months after intervention . At follow-up , treatment children with persistent disease had significant declines in both daytime ( 14 % fewer , p < 0.0001 ) and nighttime ( 14 % fewer , p < 0.0001 ) symptoms . Among children with both mild intermittent and persistent disease , those in the treatment group had 17 % fewer daytime symptoms ( p < 0.0001 ) but 40 % more nighttime symptoms . Treatment children had higher grade s for science ( p < 0.02 ) but not reading , mathematics , or physical education . No differences in school absences for all causes between groups were noted in school records . However , parents of treatment group children reported fewer absences attributable to asthma in the previous 3 months ( 34 % fewer , p < 0.0001 ) and 12 months ( 8 % fewer , p < 0.05 ) . Parents of treatment children had higher scores ( 2.19 greater , p = 0.02 ) on an asthma management index . The program may have stimulated attention to symptoms at night by parents of children with mild intermittent disease . Overall , the intervention provided significant benefits , particularly for children with persistent asthma UNLABELLED This 16-month r and omized , controlled school-based study compared change in tibial bone strength between 281 boys and girls participating in a daily program of physical activity ( Action Schools ! BC ) and 129 same-sex controls . The simple , pragmatic intervention increased distal tibia bone strength in prepubertal boys ; it had no effect in early pubertal boys or pre or early pubertal girls . INTRODUCTION Numerous school-based exercise interventions have proven effective for enhancing BMC , but none have used pQCT to evaluate the effects of increased loading on bone strength during growth . Thus , our aim was to determine whether a daily program of physical activity , Action Schools ! BC ( AS ! BC ) would improve tibial bone strength in boys and girls who were pre- ( Tanner stage 1 ) or early pubertal ( Tanner stage 2 or 3 ) at baseline . MATERIAL S AND METHODS Ten schools were r and omized to intervention ( INT , 7 schools ) or control ( CON , 3 schools ) . The bone-loading component of AS ! BC included a daily jumping program ( Bounce at the Bell ) plus 15 minutes/day of classroom physical activity in addition to regular physical education . We used pQCT to compare 16-month change in bone strength index ( BSI , mg2/mm4 ) at the distal tibia ( 8 % site ) and polar strength strain index ( SSIp , mm3 ) at the tibial midshaft ( 50 % site ) in 281 boys and girls participating in AS ! BC and 129 same-sex controls . We used a linear mixed effects model to analyze our data . RESULTS Children were 10.2+/-0.6 years at baseline . Intervention boys tended to have a greater increase in BSI ( + 774.6 mg2/mm4 ; 95 % CI : 672.7 , 876.4 ) than CON boys ( + 650.9 mg2/mm4 ; 95 % CI : 496.4 , 805.4 ) , but the difference was only significant in prepubertal boys ( p=0.03 for group x maturity interaction ) . Intervention boys also tended to have a greater increase in SSIp ( + 198.6 mm3 ; 95 % CI : 182.9 , 214.3 ) than CON boys ( + 177.1 mm3 ; 95 % CI : 153.5 , 200.7 ) . Change in BSI and SSIp was similar between CON and INT girls . CONCLUSIONS Our findings suggest that a simple , pragmatic program of daily activity enhances bone strength at the distal tibia in prepubertal boys . The precise exercise prescription needed to elicit a similar response in more mature boys or in girls might be best addressed in a dose-response trial BACKGROUND Physical inactivity is a risk behavior for cardiovascular and other diseases . Schools can promote public health objectives by increasing physical activity among youth . METHODS The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) was a multicenter , r and omized trial to test the effectiveness of a cardiovascular health promotion program in 96 public schools in four states . A major component of CATCH was an innovative , health-related physical education ( P+ ) program . For 2.5 years , r and omly assigned schools received a st and ardized PE intervention , including curriculum , staff development , and follow-up . RESULTS Systematic analysis of 2,096 PE lessons indicated students engaged in more moderate-to-vigorous physical activity ( MVPA ) in intervention than in control schools ( P = 0.002 ) . MVPA during lessons in intervention schools increased from 37.4 % at baseline to 51.9 % , thereby meeting the established Year 2000 objective of 50 % . Intervention children reported 12 more min of daily vigorous physical activity ( P = 0.003 ) and ran 18.6 yards more than control children on a 9-min run test of fitness ( P = 0.21 ) . CONCLUSIONS The implementation of a st and ardized curriculum and staff development program increased children 's MVPA in existing school PE classes in four geographic and ethnically diverse communities . CATCH PE provides a tested model for improving physical education in American schools BACKGROUND Pathways was the first multicenter American-Indian school-based study to test the effectiveness of an obesity prevention program promoting healthy eating and physical activity . METHODS Pathways employed a nested cohort design in which 41 schools were r and omized to intervention or control conditions and students within these schools were followed as a cohort ( 1,704 third grade rs at baseline ) . The study 's primary endpoint was percent body fat . Secondary endpoints were levels of fat in school lunches ; time spent in physical activity ; and knowledge , attitudes , and behaviors regarding diet and exercise . Quality control ( QC ) included design of data management systems which provided st and ardization and quality assurance of data collection and processing . Data QC procedures at study centers included manuals of operation , training and certification , and monitoring of performance . Process evaluation was conducted to monitor dose and fidelity of the interventions . Registration and tracking systems were used for students and schools . RESULTS No difference in mean percent body fat at fifth grade was found between the intervention and control schools . Percent of calories from fat and saturated fat in school lunches was significantly reduced in the intervention schools as was total energy intake from 24-hour recalls . Significant increases in self-reported physical activity levels and knowledge of healthy behaviors were found for the intervention school students . CONCLUSIONS The Pathways study results provide evidence demonstrating the role schools can play in public health promotion . Its study design and QC systems and procedures provide useful models for other similar school based multi- or single-site studies OBJECTIVE This article examines the impact of a universal social-emotional learning program , the Fast Track PATHS ( Promoting Alternative Thinking Strategies ) curriculum and teacher consultation , embedded within the Fast Track selective prevention model . METHOD The longitudinal analysis involved 2,937 children of multiple ethnicities who remained in the same intervention or control schools for Grade s 1 , 2 , and 3 . The study involved a clustered r and omized controlled trial involving sets of schools r and omized within 3 U.S. locations . Measures assessed teacher and peer reports of aggression , hyperactive-disruptive behaviors , and social competence . Beginning in first grade and through 3 successive years , teachers received training and support and implemented the PATHS curriculum in their classrooms . RESULTS The study examined the main effects of intervention as well as how outcomes were affected by characteristics of the child ( baseline level of problem behavior , gender ) and by the school environment ( student poverty ) . Modest positive effects of sustained program exposure included reduced aggression and increased prosocial behavior ( according to both teacher and peer report ) and improved academic engagement ( according to teacher report ) . Peer report effects were moderated by gender , with significant effects only for boys . Most intervention effects were moderated by school environment , with effects stronger in less disadvantaged schools , and effects on aggression were larger in students who showed higher baseline levels of aggression . CONCLUSIONS A major implication of the findings is that well-implemented multiyear social-emotional learning programs can have significant and meaningful preventive effects on the population -level rates of aggression , social competence , and academic engagement in the elementary school years This r and omized controlled trial evaluated the effectiveness of a multicomponent Health Promoting Schools ( HPS ) intervention program in improving self-reported smoking outcomes among a cohort of adolescents in 22 public secondary schools in the Hunter Region of New South Wales , Australia . Pre-test surveys were completed by students in the first 2 years of secondary school , with a 2-year post-test survey . Multivariate analyses examined intervention effect for the main outcome , post-test smoking behavior , controlling for pre-test smoking status , school and other confounders . The sample comprised the cohort of 1852 students who completed both surveys . The results demonstrated that the HPS program failed to improve smoking behavior over the 2 years ( equal increase of 10 % in both groups ) . The program was successful in improving smoking knowledge , but not attitudes , in intervention versus control group ( P < 0.001 ) . Independent predictors of post-test smoking included : pre-test smoking [ odds ratio ( OR ) = 5.44 ; 95 % confidence interval ( CI ) = 3.20 - 9.28 ] , being female ( OR = 0.55 ; CI = 0.35 - 0.87 ) , having more close friends who smoked ( OR = 1.42 ; CI = 1.33 - 1.52 ) , peer group having no clear opinion about smoking ( OR = 3.23 ; CI = 1.27 - 8.27 ) , having more positive and less negative attitudes towards smoking , and being less involved in school activities . We discuss method ological issues in multicomponent community-based interventions , and highlight the strengths and limitations of this study A smoking prevention project in six European countries ( European Smoking prevention Framework Approach ) was developed , featuring activities for adolescents , schools and parents , including out-of-school activities . Consensus meetings result ed in agreement between the countries on goals , objectives and theoretical methods . Countries ' specific objectives were also included . National diversities required country-specific methods to realize the goals and objectives . The community intervention trial was used as the research design . Since interventions took place at the community level , communities or regions were allocated at r and om to the experimental or control conditions . Complete r and omization was achieved in four countries . At baseline , smoking prevalence among 23 125 adolescents at the start of the project was 5.6 % for regular smoking and 4.0 % for daily smoking . Smoking prevalence rates were higher among girls than boys in all countries as far as weekly smoking was concerned . Process evaluations revealed that the project 's ambitions were high , but were limited by various constraints including time and delays in receiving funds . Future smoking prevention projects should aim to identify the effective components within the social influence approach as well as within broader approaches and on reaching sustained effects Objectives . Bicycle-related injury remains a major cause of death and injury hospitalization among Australian children . The study aim ed to assess the effectiveness of a whole-school intervention to increase the correct wearing of bicycle helmets by primary school children . Methods . A r and omized intervention trial was conducted in 27 Western Australian primary schools . A major component of the intervention was a peer-led classroom curriculum for 10–12 year old children . Helmet use by cyclists was observed as children were leaving school at baseline ( May 2000 ) and after the first year and second year of the intervention . A cohort of 10–11 year old children in study schools completed a self-administered question naire at the same three data collection points . Results . Over the 2 years of the study , observed helmet wearing rates declined by 13 % in the control group ( from 93 % at baseline to 80 % at post-test 2 ) and by 5 % in the intervention group ( from 89 % to 84 % ) ( F = 1.745 , p = 0.185 ) . Among the Grade 5/6 cohort students who were regular riders , the likelihood of reporting always wearing a helmet was 1.9 times higher at post-test 1 ( z = 2.51 , p = 0.012 ) and 1.7 times higher at post-test 2 ( z = 2.13 , p = 0.033 ) for the intervention group than the control group students who did not always wear a helmet at baseline . Conclusions . The data suggest that school-based activities can arrest the rate of decline in helmet use by children . Using peer teachers is a useful strategy to engage students in normative-based protective behaviours . The logistical challenges this strategy presents appear to be worth the outcomes Abstract Objectives : To implement a school based health promotion programme aim ed at reducing risk factors for obesity and to evaluate the implementation process and its effect on the school . Design : Data from 10 schools participating in a group r and omised controlled crossover trial were pooled and analysed . Setting : 10 primary schools in Leeds . Participants : 634 children ( 350 boys and 284 girls ) aged 7 - 11 years . Main outcome measures : Response rates to question naires , teachers ' evaluation of training and input , success of school action plans , content of school meals , and children 's knowledge of healthy living and self reported behaviour . Results : All 10 schools participated throughout the study . 76 ( 89 % ) of the action points determined by schools in their school action plans were achieved , along with positive changes in school meals . A high level of support for nutrition education and promotion of physical activity was expressed by both teachers and parents . 410 ( 64 % ) parents responded to the question naire concerning changes they would like to see implemented in school . 19 out of 20 teachers attended the training , and all reported satisfaction with the training , re sources , and support . Intervention children showed a higher score for knowledge , attitudes , and self reported behaviour for healthy eating and physical activity . Conclusion : This programme was successfully implemented and produced changes at school level that tackled risk factors for obesity . What is already known on this topic Prevention of obesity is an increasingly important aspect of health promotion Few trials have investigated school based primary prevention programmes directed at obesity What this study adds The programme was successful in producing school level changes to tackle risk factors for obesity High levels of participation indicated support from schools , staff , parents , and pupils Positive changes were seen in school meals , tuck shops , and playground BACKGROUND A growing awareness of health promotion and positive lifestyle change , coupled with the knowledge that cardiovascular risk has its origins in childhood , has led to the development of health promotion programs in the elementary school . While most school-based programs target specific behaviors or enlist singular intervention modalities , the Heart Smart cardiovascular school health promotion targeted the total school environment with a multidisciplinary approach to prompt the school 's varied institutions to implement changes in curriculum , school lunch , and physical education . METHODS Components of the Heart Smart environmental intervention included : ( a ) a school lunch program providing cardiovascular healthful food choices , reduced in fat by 30 % and in sodium and sugar by 50 % ; ( b ) a physical education program promoting personal fitness and aerobic conditioning ; and ( c ) cardiovascular risk factor screening , measuring fasting lipids and lipoproteins , anthropometrics , and blood pressure . Changes in cardiovascular risk factor status , school lunch selection s , and exercise performance were compared . RESULTS Screening participants showed greater improvement in health knowledge than non participants . School lunch choices were successfully altered , and children whose lunch choices were cardiovascular healthful evidence d the greatest cholesterol reduction . Improvements in run/walk performance were related in predicted directions to the overall cardiovascular risk profile . Increases in high-density lipoprotein cholesterol were observed at intervention schools . CONCLUSION Observations indicate a relationship between behavior change and physiologic changes achieved in a total school health promotion to reduce cardiovascular risk BACKGROUND This study evaluated the effects of the Lifestyle Education for Activity Program ( LEAP ) , a comprehensive school-based intervention emphasizing changes in instruction and school environment , on variables derived from social-cognitive theory ( SCT ) as mediators of change in physical activity among black and white adolescent girls . METHODS Twenty-four high schools paired on enrollment size , racial composition , urban , suburban , or rural location , and class structure were r and omized into control ( n = 12 ) or experimental ( n = 12 ) groups . There were 1038 girls in the control group and 1049 girls in the experimental group . The multicomponent intervention emphasized the enhancement of self-efficacy and development of behavioral skills by using curricular activities within physical education classes and health education instruction . The primary outcomes were self-efficacy , outcome -expectancy value , goal setting , satisfaction , and physical activity . RESULTS Latent variable structural equation modeling indicated that : ( 1 ) self-efficacy and satisfaction exhibited synchronous , cross-sectional relationships with physical activity ; ( 2 ) the intervention had direct effects on self-efficacy , goal setting , and physical activity ; and ( 3 ) self-efficacy partially mediated the effect of intervention on physical activity . CONCLUSIONS To our knowledge , this study provides the first evidence from a r and omized controlled trial that manipulation of self-efficacy results in increased physical activity among black and white adolescent girls . The results encourage the use of self-efficacy as a targeted , mediator variable in interventions design ed to increase physical activity among girls AIMS The goal of this group-r and omized trial was to test the effectiveness of an adapted alcohol use preventive intervention for urban , low-income and multi-ethnic setting s. DESIGN AND SETTING Sixty-one public schools in Chicago were recruited to participate , were grouped into neighborhood study units and assigned r and omly to intervention or ' delayed program ' control condition . PARTICIPANTS The study sample ( n = 5812 students ) was primarily African American , Hispanic and low-income . INTERVENTION Students , beginning in sixth grade ( age 12 years ) , received 3 years of intervention strategies ( curricula , family interventions , youth-led community service projects , community organizing ) . MEASUREMENTS Students participated in yearly classroom-based surveys to measure their alcohol use and related risk and protective factors . Additional evaluation components included a parent survey , a community leader survey and alcohol purchase attempts . FINDINGS Overall , the intervention , compared with a control condition receiving ' prevention as usual ' , was not effective in reducing alcohol use , drug use or any hypothesized mediating variables ( i.e. related risk and protective factors ) . There was a non-significant trend ( P = 0.066 ) that suggested the ability to purchase alcohol by young-appearing buyers was reduced in the intervention communities compared to the control communities , but this could be due to chance . Secondary outcome analyses to assess the effects of each intervention component indicated that the home-based programs were associated with reduced alcohol , marijuana and tobacco use combined ( P = 0.01 ) , with alcohol use alone approaching statistical significance ( P = 0.06 ) . CONCLUSIONS Study results indicate the importance of conducting evaluations of previously vali date d programs in context s that differ from the original study sample . Also , the findings highlight the need for further research with urban , low-income adolescents from different ethnic background s to identify effective methods to prevent and reduce alcohol use INTRODUCTION . Do child obesity prevention research and intervention measures have the potential to generate adverse concerns about body image by focussing on food , physical activity and body weight ? Research findings now demonstrate the emergence of body image concerns in children as young as 5 years . In the context of a large school-community-based child health promotion and obesity prevention study , we aim ed to address the potential negative effects of height and weight measures on child wellbeing by developing and implementing an evidence -informed protocol to protect and prevent body image concerns . fun ' n healthy in Morel and ! is a cluster r and omised controlled trial of a child health promotion and obesity prevention intervention in 23 primary schools in an inner urban area of Melbourne , Australia . Body image considerations were incorporated into the study philosophies , aims , methods , staff training , language , data collection and reporting procedures of this study . This was informed by the published literature , professional body image expertise , pilot testing and implementation in the conduct of baseline data collection and the intervention . This study is the first record of a body image protection protocol being an integral part of the research processes of a child obesity prevention study . Whilst we are yet to measure its impact and outcome , we have developed and tested a protocol based on the evidence and with support from stakeholders in order to minimise the adverse impact of study processes on child body image concerns This paper describes an intervention to increase high school students ' fruit and vegetable consumption . Twelve schools were r and omized to intervention or control conditions . The cohort ( 2,213 students ; 56 % females , 84 % Caucasian ) were followed from 9th to 12th grade s. Interventions comprised a media campaign , classroom workshops , school meal modification , and parental support . Usual daily servings of fruit/vegetables increased 14 % in the intervention compared to the control group ( p > 0.001 ) the first three years . At follow-up , consumption within the control group also increased , result ing in no significant difference between groups . Intervention group knowledge scores and awareness indicators were significantly higher than those of the control group ( p < 0.0001 ) . Gimme 5 provided a first model to show that dietary habits of high school students can be influenced by positive media messages relative to that age group , increased exposure to a variety of tasty products , and minimal classroom activity HEALTHY was a multi-center primary prevention trial design ed to reduce risk factors for type 2 diabetes in adolescents . Seven centers each recruited six middle schools that were r and omized to either intervention or control . The HEALTHY intervention integrated multiple components in nutrition , physical education , behavior change and communications and promotion . The conceptual rationale as well as the design and development of the behavior intervention component are described . Pilot study data informed the development of the behavior intervention component . Principles of social learning and health-related behavior change were incorporated . One element of the behavior intervention component was a sequence of peer-led , teacher-facilitated learning activities known as FLASH ( Fun Learning Activities for Student Health ) . Five FLASH modules were implemented over five semesters of the HEALTHY study , with the first module delivered in the second semester of the sixth grade and the last module in the second semester of the eighth grade . Each module contained sessions that were design ed to be delivered on a weekly basis to foster self-awareness , knowledge , decision-making skills and peer involvement for health behavior change . FLASH behavioral practice incorporated individual and group self-monitoring challenges for eating and activity . Another element of the behavior intervention component was the family outreach strategy for extending changes in physical activity and healthy eating beyond the school day and for supporting the student 's lifestyle change choices . Family outreach strategies included the delivery of newsletters and supplemental packages with material s to promote healthy behavior in the home environment during school summer and winter holiday breaks . In conclusion , the HEALTHY behavior intervention component , when integrated with total school food and physical education environmental changes enhanced by communications and promotional campaigns , is a feasible and acceptable mechanism for delivering age-appropriate social learning for healthy eating and physical activity among an ethnically diverse group of middle school students across the United States Background / Aims : The Pro Children Project was design ed to assess fruit and vegetable consumption in European schoolchildren and their parents , as well as determinants of the children ’s consumption patterns . A second objective was to develop and test strategies , applicable across Europe , for promoting consumption of fruits and vegetables among schoolchildren and their parents . In this paper , the rationale , theoretical background , overall design and implementation of the project is presented . Methods : Surveys of national , representative sample s of 11-year-old schoolchildren and their parents were conducted in 9 countries , i.e. in Austria , Belgium , Denmark , Icel and , the Netherl and s , Norway , Portugal , Spain and Sweden . Comprehensive school-based educational programmes have been developed and tested in three setting s , i.e. in Spain , the Netherl and s and in Norway . A precoded 24-hour recall form combined with a set of food frequency questions assessing regular intake were used to assess fruit and vegetable consumption . Determinants were assessed employing a comprehensive theoretical framework including personal , social and environmental factors related to fruit and vegetable consumption . The intervention programmes have been tested employing a group-r and omized trial design where schools have been r and omly allocated to an intervention arm and a delayed intervention arm . Surveys among all participating children and their parents were conducted prior to the initiation of the intervention , immediately after the end of the intervention and at the end of the subsequent school year . Conclusion : The project is expected to provide new information of great importance for improving our underst and ing of consumption patterns of fruits and vegetables and for guiding future efforts to promote increased consumption patterns across Europe The purpose of this article is to present the intermediate results for Project MYTRI , a school-based , multiple component intervention design ed to prevent and reduce many forms of tobacco use ( chewing tobacco , cigarettes , and bidis ) among youth in India . The intervention is based on effective models in the United States “ translated ” for use in this context . The intervention targets two cohorts of students who were in the 6th and 8th grade when the study started . Thirty-two schools in Delhi ( north India ) and Chennai ( south India ) were r and omized to receive the intervention ( n = 16 ) or serve as a delayed intervention control ( n = 16 ) . Students in these schools were surveyed before the intervention began and at an intermediate point , 1 year into this 2-year intervention ( n = 8,369 ) . A test of the changes in risk factors for tobacco use between the baseline and intermediate surveys revealed that , compared with the control , students in the intervention condition ( a ) had better knowledge about the health effects of tobacco ( P < 0.01 ) ; ( b ) believed that there were more negative social consequences to using tobacco ( P = 0.04 ) ; ( c ) had fewer reasons to use tobacco ( P < 0.01 ) ; ( d ) had more reasons not to use tobacco ( P = 0.03 ) ; ( e ) were less socially susceptible to chewing ( P = 0.04 ) and smoking ( P = 0.03 ) tobacco ; ( f ) perceived fewer peers and adults around them smoked ( P < 0.01 ) or chewed ( P < 0.01 ) tobacco ; ( g ) felt that tobacco use was not acceptable , especially among their peers ( P < 0.01 ) ; ( h ) were more confident in their ability to advocate for tobacco control ( P = 0.03 ) ; ( i ) were more knowledgeable about tobacco control policies ( P < 0.01 ) ; and ( j ) supported these policies , too ( P = 0.04 ) . Fewer students in the intervention condition reported having intentions to smoke tobacco in the next year ( P = 0.02 ) or chew tobacco when they reached college ( P < 0.01 ) . No changes in actual tobacco use were observed at this stage of the study . ( Cancer Epidemiol Biomarkers Prev 2007;16(6):1050–6 OBJECTIVE To evaluate the effects of an antibullying school intervention in elementary schools . DESIGN Two-year follow-up r and omized intervention group-control group . SETTING Forty-seven elementary schools in the Netherl and s. PARTICIPANTS Three thous and eight hundred sixteen children aged 9 to 12 years . INTERVENTION During the first study year , an antibullying school program was implemented in the schools in the intervention group . MAIN OUTCOME MEASURES A question naire measuring bullying behavior , depression , psychosomatic complaints , delinquent behavior , and satisfaction with school life and peer relationships was filled out by the students at 3 times to obtain the following data : a baseline measurement , a first-effect measurement at the end of the first year , and a second-effect measurement at the end of the second year . RESULTS The number of bullied children decreased by 25 % in the intervention group compared with the control group ( relative risk , 0.75 ; 95 % confidence interval , 0.57 - 0.98 ) . The intervention group also showed a decline in the scale scores of victimization ( -1.06 vs 0.28 ; P < .01 ) and active bullying behaviors ( -0.47 vs 0.12 , P < .05 ) . Self-reported peer relationships also improved in the intervention schools ( 0.48 vs 0.11 ; P < .05 ) , and there was a trend for a decrease in reported depression in the intervention schools ( -0.33 vs -0.10 ; P < .10 ) . At follow-up , there were no differences between the intervention and control groups for the outcome measures . Schools had also lowered their antibullying activities during the second study year . CONCLUSIONS An antibullying school policy can reduce bullying behavior . To keep bullying at a consistently low level , schools must continue antibullying measures every year . Continued counseling may help schools in their efforts to establish a lasting antibullying policy BACKGROUND Childhood obesity has become a health problem in urban areas in China . Intervention to reduce childhood obesity should be of high priority . School-based intervention programmes are needed to deal with the growing prevalence of childhood obesity in China . METHODS Five primary schools were selected r and omly for this study in the Beijing urban area in China ; two were allocated to the intervention group and three to the control group . A total of 2425 children ( 1029 children in intervention schools and 1396 children in control schools ) took part in the study for 3 years . In the intervention group , children and their parents were involved in a programme of nutrition education and physical activity . Control school students followed their usual health and physical education curriculum with no extra intervention . RESULTS After the 3-year intervention , the prevalence of overweight and obesity were significantly lower in the intervention schools than in the control schools ( overweight : 9.8 % vs. 14.4 % , P < 0.01 ; obesity : 7.9 % vs. 13.3 % , P < 0.01 ) . The prevalence of overweight and obesity decreased by 26.3 % and 32.5 % in intervention schools respectively after intervention . The prevalence of overweight and obesity increased in control schools . There was also significant difference in body mass index between intervention and control schools ( 18.2 + /- 2.6 vs. 20.3 + /- 3.4 , P < 0.01 ) after intervention . More non-obese children became obese in the control schools ( 7.0 % ) than in the intervention schools ( 2.4 % ) at end line ( P < 0.01 ) . Among the children who were obese at baseline , 49.2 % remained obese at end line in intervention schools while 61.9 % remained obese in control schools ( P < 0.01 ) . CONCLUSIONS Our study showed that an intervention programme could be feasible in schools in Beijing , China . The prevalence of overweight and obesity was reduced in schoolchildren in Beijing through an intervention focused on nutrition education and physical activity . Overweight and obesity children as well as normal weight children and their parents should be involved in such an intervention programme To evaluate the effectiveness of an intensive h and hygiene campaign on reducing absenteeism caused by influenza-like illness ( ILI ) , diarrhea , conjunctivitis , and laboratory-confirmed influenza , we conducted a r and omized control trial in 60 elementary schools in Cairo , Egypt . Children in the intervention schools were required to wash h and s twice each day , and health messages were provided through entertainment activities . Data were collected on student absenteeism and reasons for illness . School nurses collected nasal swabs from students with ILI , which were tested by using a qualitative diagnostic test for influenza A and B. Compared with results for the control group , in the intervention group , overall absences caused by ILI , diarrhea , conjunctivitis , and laboratory-confirmed influenza were reduced by 40 % , 30 % , 67 % , and 50 % , respectively ( p<0.0001 for each illness ) . An intensive h and hygiene campaign was effective in reducing absenteeism caused by these illnesses Project Northl and is a r and omized trial design ed to create , implement and evaluate multilevel , community-wide strategies to prevent alcohol use among adolescents . This paper will focus on the mediating outcomes of the early adolescent phase of Project Northl and when the students in the study cohort were in Grade s 6 - 8 . The project was conducted in 24 school districts and adjacent communities in northeastern Minnesota . The intervention consisted of social-behavioral curricula in schools , peer leadership activities , parental involvement and education , and community-wide activities . At the end of 3 years of intervention , significantly fewer students in the intervention school districts reported alcohol use than students in the reference districts . Mediation analyses were conducted to investigate if the intervention 's effects on mediating variables could explain the reduction in alcohol use . Important mediators of Project Northl and 's effect on alcohol use were : ( 1 ) peer influence to use , including normative estimates , ( 2 ) functional meanings of alcohol use , ( 3 ) attitudes and behaviors associated with alcohol and drug problems like stimulus seeking , rule violations and bad judgement , and ( 4 ) parent-child alcohol-related communication around alcohol use . In addition , among those who did not use alcohol at baseline , self-efficacy to refuse offers of alcohol was a significant mediator BACKGROUND Professional sports organizations in the United States have notable celebrity status , and several teams have used this " star power " to collaborate with local schools toward the goal of affecting childhood obesity ( e.g. , NFL Play 60 ) . Program effectiveness is unknown owing to the absence of comprehensive evaluations for any of these initiatives . In 2006 , the Memphis Grizzlies , the city 's National Basketball Association ( NBA ) franchise , launched " Get Fit with the Grizzlies , " a 6-week , curricular addition focusing on nutrition and physical activity for the 4th and 5th grade s in Memphis City Schools . The health-infused mini-unit was delivered by the physical education teachers during their classes . National and local sponsors whose business objectives matched the " Get Fit " objectives were solicited to fund the program . Here we highlight the program evaluation results from the first year of " Get Fit " and the Journal of School Health article . However , the " Get Fit " program has now taken place in Memphis area schools for 5 years . During the 2010 - 11 school-year , " Get Fit " evolved into a new program called " Healthy Home Court " with Kellogg 's as the primary sponsor . " Healthy Home Court " included the original fitness part of the program and added a breakfast component at high schools where data indicated great need . Kellogg 's sponsored special " carts " with healthy breakfast options ( i.e. , fruit , protein bars ) for students to grab and eat . This program matched their existing program " Food Away from Home . " Research supports the objectives of these programs and has shown that breakfast consumption can have a positive impact on academic achievement , behavior in school , and overall health status . METHOD Survey research employed over the first 4 years measured health knowledge acquisition and health behavior change using a matched pre/post test design ( n=2210 ) in r and omly chosen schools ( n=18 ) from all elementary schools in the Memphis area . McNemar 's test for significance ( < 05 ) was applied to measure correct answers pre and post . Also , breakfast attendance numbers were observed for intervention high schools and compared with breakfast attendance numbers from control high schools . RESULTS Analyses confirmed that , from the first year through this past one ( 2010 - 11 ) , there was significant health knowledge acquisition and health behavior improvement at post-intervention . Breakfast numbers matched these findings . Also , exit polling that took place at one intervention high school indicated the students attending the breakfast assembly gained knowledge and positively changed attitudes regarding the academic and health benefits of eating a healthy breakfast . CONCLUSIONS This community-school-home initiative using a professional team 's celebrity platform is largely overlooked by school districts and should be considered as an effective way to confront childhood obesity BACKGROUND Pathways , a r and omized trial , evaluated the effectiveness of a school-based multicomponent intervention to reduce fatness in American-Indian schoolchildren . The goal of the Pathways food service intervention component was to reduce the fat in school lunches to no more than 30 % of energy from fat while maintaining recommended levels of calories and key nutrients . METHODS The intervention was implemented by school food service staff in intervention schools over a 3-year period . Five consecutive days of school lunch menu items were collected from 20 control and 21 intervention schools at four time periods , and nutrient content was analyzed . RESULTS There was a significantly greater mean reduction in percent energy from fat and saturated fat in the intervention schools compared to the control schools . Mean percentages of energy from fat decreased from 33.1 % at baseline to 28.3 % at the end of the study in intervention schools compared to 33.2 % at baseline and 32.2 % at follow-up in the control schools ( P<0.003 ) . There were no statistically significant differences for calories or nutrients between intervention and control schools . CONCLUSIONS The Pathways school food lunch intervention documented the feasibility of successfully lowering the percent of energy from fat , as part of a coordinated obesity prevention program for American-Indian children PURPOSE To evaluate the effects of a middle school physical activity intervention , new in combining an environmental and computer tailored component ; and to evaluate the effects of parental involvement . METHODS A clustered r and omized controlled design was used . A r and om sample of 15 schools with 7th and 8th grade rs was r and omly assigned to one of three conditions : ( a ) intervention with parental support , ( b ) intervention alone , and ( c ) control group . The intervention was new in combining environmental strategies with computer-tailored feedback to increase levels of moderate to vigorous physical activity . The intervention was implemented by the school staff . Physical activity was measured through a question naire in the total sample and with accelerometers in a sub sample of adolescents . RESULTS The intervention with parental support led to an increase in self-reported school-related physical activity of , on average , 6.4 minutes per day ( p < or = .05 , d = .40 ) . Physical activity of light intensity measured with accelerometers decreased with , on average , 36 minutes per day as a result of the intervention with parental support ( p < or = .05 , d = .54 ) . Physical activity of moderate to vigorous intensity measured with accelerometers significantly increased with on average 4 minutes per day in the intervention group with parental support , while it decreased with almost 7 minutes per day in the control group ( p < or = .05 , d = .46 ) . CONCLUSIONS The physical activity intervention , implemented by the school staff , result ed in enhanced physical activity behaviors in both middle school boys and girls . The combination of environmental approaches with computer-tailored interventions seemed promising BACKGROUND School readiness , conceptualized as three components including emotional self-regulation , social competence , and family/school involvement , as well as absence of conduct problems play a key role in young children 's future interpersonal adjustment and academic success . Unfortunately , exposure to multiple poverty-related risks increases the odds that children will demonstrate increased emotional dysregulation , fewer social skills , less teacher/parent involvement and more conduct problems . Consequently intervention offered to socio-economically disadvantaged population s that includes a social and emotional school curriculum and trains teachers in effective classroom management skills and in promotion of parent-school involvement would seem to be a strategic strategy for improving young children 's school readiness , leading to later academic success and prevention of the development of conduct disorders . METHODS This r and omized trial evaluated the Incredible Years ( IY ) Teacher Classroom Management and Child Social and Emotion curriculum ( Dinosaur School ) as a universal prevention program for children enrolled in Head Start , kindergarten , or first grade classrooms in schools selected because of high rates of poverty . Trained teachers offered the Dinosaur School curriculum to all their students in bi-weekly lessons throughout the year . They sent home weekly dinosaur homework to encourage parents ' involvement . Part of the curriculum involved promotion of lesson objectives through the teachers ' continual use of positive classroom management skills focused on building social competence and emotional self-regulation skills as well as decreasing conduct problems . Matched pairs of schools were r and omly assigned to intervention or control conditions . RESULTS Results from multi-level models on a total of 153 teachers and 1,768 students are presented . Children and teachers were observed in the classrooms by blinded observers at the beginning and the end of the school year . Results indicated that intervention teachers used more positive classroom management strategies and their students showed more social competence and emotional self-regulation and fewer conduct problems than control teachers and students . Intervention teachers reported more involvement with parents than control teachers . Satisfaction with the program was very high regardless of grade levels . CONCLUSIONS These findings provide support for the efficacy of this universal preventive curriculum for enhancing school protective factors and reducing child and classroom risk factors faced by socio-economically disadvantaged children To test the effectiveness of the Child and Adolescent Trial for Cardiovascular Health ( CATCH ) program , a r and omized trial was conducted in 96 elementary schools in four regions of the United States . Results from the original trial indicated a significant positive effect on the delivery of physical education ( PE ) . All 56 former intervention schools ( FI ) , 20 r and omly selected former control schools ( FC ) , and 12 newly selected unexposed control schools ( UC ) were assessed 5 years postintervention . Results indicate a strong secular trend of increasing moderate to vigorous physical activity ( MVPA ) in PE classes among both FC and UC schools . The FI schools surpassed the Healthy People 2010 goal for MVPA during PE lesson time ( i.e. , 50 % ) , whereas the FC and UC schools came close to it . Barriers to implementing CATCH PE included insufficient training and lower importance of PE compared to other academic areas and indicate the need for in-service training OBJECTIVES We sought to test the efficacy of an intervention that was design ed to promote social inclusion and commitment to education , in reducing among students health risk behaviors and improving emotional well-being . METHODS The design was a cluster-r and omized trial in 25 secondary schools in Victoria , Australia . The subjects were 8th- grade students ( aged 13 to 14 y ) in 1997 ( n=2545 ) and subsequent 8th- grade students in 1999 ( n=2586 ) and 2001 ( n=2463 ) . The main outcomes were recent substance use , antisocial behavior , initiation of sexual intercourse , and depressive symptoms . RESULTS At 4-year follow-up , the prevalence of marked health risk behaviors was approximately 20 % in schools in the comparison group and 15 % in schools in the intervention group , an overall reduction of 25 % . In ordinal logistic regression models a protective effect of intervention was found for a composite measure of health risk behaviors in unadjusted models ( odds ratio [OR]= 0.69 ; 95 % confidence interval [CI]= 0.50 , 0.95 ) and adjusted models ( OR= 0.71 ; CI = 0.52 , 0.97 ) for potential confounders . There was no evidence of a reduction in depressive symptoms . CONCLUSION The study provides support for prevention strategies in schools that move beyond health education to promoting positive social environments The purpose of this paper is to describe the process evaluation model for the classroom curricula of the Child and Adolescent Trial for Cardiovascular Health ( CATCH ) Project . The process evaluation plan specifically targets how much each curriculum was implemented , to what degree it was implemented as design ed , and the barriers to implementation . Additionally , the rationale for each of the process evaluation measures and the instrument development process are presented . Data result ing from these measures will be essential in order to answer questions regarding the internal validity of the main outcomes of the project . Specific examples and sample results are provided from the CATCH third- grade classroom curriculum , which was implemented the first year of CATCH . A discussion also is presented of how the findings from a sample of these measures were used to gain additional insight on the salient features of the curriculum , and how those features may be related to student outcomes Objective : The impact of a multicomponent intervention programme on the sexual health of adolescents was assessed in rural Tanzania . Design : A community-r and omized trial . Methods : Twenty communities were r and omly allocated to receive either a specially design ed programme of interventions ( intervention group ) or st and ard activities ( comparison group ) . The intervention had four components : community activities ; teacher-led , peer-assisted sexual health education in years 5–7 of primary school ; training and supervision of health workers to provide ‘ youth-friendly ’ sexual health services ; and peer condom social marketing . Impacts on HIV incidence , herpes simplex virus 2 ( HSV2 ) and other sexual health outcomes were evaluated over approximately 3 years in 9645 adolescents recruited in late 1998 before entering years 5 , 6 or 7 of primary school . Results : The intervention had a significant impact on knowledge and reported attitudes , reported sexually transmitted infection symptoms , and several behavioural outcomes . Only five HIV seroconversions occurred in boys , whereas in girls the adjusted rate ratio ( intervention versus comparison ) was 0.75 [ 95 % confidence interval ( CI ) 0.34 , 1.66 ] . Overall HSV2 prevalences at follow-up were 11.9 % in male and 21.1 % in female participants , with adjusted prevalence ratios of 0.92 ( CI 0.69 , 1.22 ) and 1.05 ( CI 0.83 , 1.32 ) , respectively . There was no consistent beneficial or adverse impact on other biological outcomes . The beneficial impact on knowledge and reported attitudes was confirmed by results of a school examination in a separate group of students in mid-2002 . Conclusion : The intervention substantially improved knowledge , reported attitudes and some reported sexual behaviours , especially in boys , but had no consistent impact on biological outcomes within the 3-year trial period This study evaluated the effects of a school-based intervention on growth trajectories of smoking , drinking , and antisocial behavior among early adolescents . Seven middle schools were r and omized to intervention or comparison conditions and students in two successive cohorts ( n = 1484 ) provided five waves of data from sixth to ninth grade . The Going Places Program , included classroom curricula , parent education , and school environment components . Latent growth curve analyses demonstrated significant treatment group effects , including reducing increases in friends who smoke , outcome expectations for smoking , and smoking progression , but had non-significant effects on drinking or antisocial behavior . The Going Places Program was effective in preventing increases in smoking progression , but its efficacy as a more cross-cutting problem behavior preventive intervention was not confirmed Substance use outcomes were examined for 351 youth participating in a r and omized controlled trial design ed to assess the efficacy of a school-based multimodal universal preventive intervention , Linking the Interests of Families and Teachers ( LIFT ) . Frequency of any use of tobacco , alcohol , and other drugs was assessed via self-report from grade s 5 through 12 . Latent variable growth models specified average level , linear growth and accelerated growth . The LIFT intervention had a significant effect on reducing the rate of growth in use of tobacco and illicit drugs , particularly for girls , and had an overall impact on average levels of use of tobacco , alcohol , and illicit drugs . Average tobacco use reductions were mediated by increases in family problem solving . The intervention had significant indirect effects on growth in substance use through intervention effects on reduced playground aggression and increased family problem solving . The intervention was also associated with roughly a 10 % reduced risk in initiating tobacco and alcohol use . Implication s for future studies of multimodal preventive interventions are discussed BACKGROUND Food service directors have a concern that federal reimbursement is not meeting the dem and s of increasing costs of healthier meals . The purpose of this article is to report the food option changes and the annual revenues and expenses of the school food service environment . METHODS The HEALTHY study was a 3-year ( 2006 to 2009 ) r and omized , cluster- design ed trial conducted in 42 middle schools at 7 field centers . The schools selected had at least 50 % of students who were eligible for free or reduced-price lunch or who belonged to a minority group . A r and omly assigned half of the HEALTHY schools received a school health intervention program consisting of 4 integrated components : nutrition , physical activity , behavioral knowledge and skills , and social marketing . The nutrition component consisted of changing the meal plans to meet 5 nutrition goals . Revenue and expense data were collected from income statements , federal meal records , à la carte sale sheets , school store sale sheets , donated money/food records , and vending machines . RESULTS Although more intervention schools reached the nutritional goals than control schools , revenues and expenses were not significantly different between groups . CONCLUSION The HEALTHY study showed no adverse effect of school food policies on food service finances Raising Healthy Children is a cluster-r and omized study of a school-based intervention aim ed at preventing problem behaviors among children recruited into the project in the first or second grade of elementary school . Multilevel analysis was used to compare students in intervention and control schools with respect to whether they transferred out of their original schools . Students in intervention schools were less likely to transfer within the first 5 years of the project . A multilevel discrete-time survival model that included both time-varying and context ual variables revealed that the difference in hazard of transfer was greatest in the earlier years of the project The School Nutrition Dietary Assessment Study provides current data on the nutritional quality and adequacy of the National School Lunch Program ( NSLP ) and the School Breakfast Program ( SBP ) as well as on the dietary intakes of students participating in these programs . The study demonstrates that the NSLP and SBP meals and children 's total diets do not conform to the recommendations of the US Department of Agriculture and the National Research Council and confirms the need to improve the nutritional quality of the nation 's school meal program and student 's overall dietary intakes . In this regard , the Child and Adolescent Trial for Cardiovascular Health ( CATCH ) is the first collaborative , school-based field trial that tests the effectiveness of a multi-level intervention design ed to reduce the fat , saturated fat , and sodium content of school meals and student 's diets . This commentary highlights the findings and questions raised by the School Nutrition Dietary Assessment Study and presents an overview of CATCH , including the implication s and significant questions that can be addressed by this intervention study PURPOSE To measure the relative impact of a school-based human immunodeficiency virus (HIV)- , sexually transmitted disease (STD)- , and pregnancy-prevention intervention on sexual risk-taking behaviors of different subgroups of students . METHODS Twenty schools were r and omly assigned to receive Safer Choices or a st and ard knowledge-based HIV-education program . Safer Choices was design ed to reduce unprotected sex by delaying initiation of sex , reducing its frequency , or increasing condom use . Its five components included : school organization , an intensive curriculum with staff development , peer re sources and school environment , parent education , and school-community linkages . A total of 3869 9th- grade students were tracked for 31 months . Results are presented for initiation of sex , frequency of unprotected sex , number of unprotected sexual partners , condom use , and contraceptive use . These results are presented separately by gender , race/ethnicity , prior sexual experience , and prior sexual risk-taking . Statistical analyses included multilevel , repeated measures logistic and Poisson regression models . RESULTS Safer Choices had one or more positive behavioral effects on all subgroups . On four outcomes that could be affected by condom use , it had a greater impact on males than on females . It had greater effects on Hispanics , including a delay in sexual activity , than on other racial/ethnic groups . Its greatest overall effect was an increase in condom use among students who had engaged in unprotected sex before the intervention . CONCLUSIONS Safer Choices reduced one or more measures of sexual risk taking over 31 months among all groups of youth , and was especially effective with males , Hispanics , and youth who engaged in unprotected sex and thus were at higher risk for HIV , other STD infections and pregnancy The KiVa antibullying program has been widely implemented in Finnish comprehensive schools since 2009 . The program is predicated on the idea that a positive change in the behaviors of classmates can reduce the rewards gained by the perpetrators of bullying and consequently their motivation to bully in the first place . KiVa involves both universal and bullying specific actions to prevent the emergence of new cases of bullying , stop ongoing bullying , and reduce the negative consequences of victimization . The program has been evaluated in a r and omized controlled trial involving 234 Finnish schools and during broad dissemination across Finnish schools ( the evaluation involving almost one thous and schools ) with positive findings . The program content and the implementation model are presented in this article , and the findings from the evaluation studies are summarized BACKGROUND The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) was the first multicenter school-based research study to employ the fundamentals of clinical trials including the st and ardized protocol and Manuals of Operation , a steering committee for study governance , a distributed data system , an extensive quality control system , and a Data and Safety Monitoring Board . METHOD CATCH tested the effectiveness of changes in school lunches , physical education , smoking policy , curricula , and family activities . Ninety-six elementary schools in four states were r and omized to intervention or control conditions . The baseline cohort comprised 5 , 106 ethnically diverse third grade rs followed through fifth grade . RESULTS The percentages of calories from fat and saturated fat were reduced significantly more in the intervention school lunches than among the controls . Significant increases in moderate to vigorous activity levels in existing physical education classes were made as well . Changes in self-reported dietary , physical activity , and psychosocial measures were significant . There were no significant differences in the physiological measures . Measurement error was generally low for all physiologic measures except skinfolds , indicating a high level of reliability . Across all sites , the coefficients of variation for lipids , height , and weight were less than 3 % , whereas for skinfolds , they were considerably higher , ranging from 6 to 8 % . Intraclass correlations for lipid studies were also uniformly high at 0.99 . Interobserver agreement scores for SOFIT were greater than 90 % for 9 of the 11 activities observed . Data entry error rates were low with less than five errors per 1,000 fields for all forms . CONCLUSIONS The CATCH results provided more scientific evidence on the importance of schools in the population approach to health promotion . Many of the strategies used in this complex multicenter trial in the areas of design and analysis , measurement , training , data management , and quality control protocol s might be appropriate for adoption in other studies Project Energize is a through-school nutrition and activity programme that is being evaluated in a 2-year , cluster-r and omised , longitudinal study . The present paper describes the background of the programme and study , the programme development and delivery , the study methodology including r and omisation , measurement and analysis tools and techniques , and the mix of the study population . The programme is being delivered to sixty-two primary schools with sixty-two control schools , each limb containing about 11,000 students . The children in the evaluation cohort are 5 or 10 years old at enrolment ; the r and omisation protocol has achieved post-consent enrolment of 3,000 evaluation participants , who are comparable by age , sex and school decile . End-point measures include body composition and associated physical characteristics , fitness , home and school environment and practice OBJECTIVES The purpose of this study was to evaluate the effect of a school-based intervention program to reduce overweight and improve fitness in primary school children . METHODS A cluster r and omized controlled design was used over one school year with schools as unit of r and omization . In total 20 schools and 2,622 children aged 6 - 12 years ( grade s 3 - 8 ) from multi-ethnic , low income inner-city neighbourhoods in Rotterdam , Netherl and s , participated . The intervention , named Lekker Fit ! ( Enjoy being fit ! ) was a multi-component intervention based on behavioural and ecological models . Main components of the intervention are the implementation of three physical education ( PE ) sessions a week by a professional PE teacher , additional sport and play activities outside school hours and an educational program . Main primary outcome measures were weight status , body mass index ( BMI ) , waist circumference and fitness ( 20 m shuttle run ) . RESULTS Significant positive intervention effects were found for percentage overweight children ( OR 0.53 ; 95 % CI 0.36 - 0.78 ) , waist circumference ( -1.29 cm ; 95 % CI -2.16 to -0.42 cm ) and 20 m shuttle run ( 0.57 laps ; 95 % CI 0.13 - 1.01 laps ) among pupils of grade s 3 - 5 ( 6 - 9-year olds ) . The prevalence of overweight in grade s 3 - 5 increased by 4.3 % in the control group and by 1.3 % in the intervention group . No significant effects were found for BMI or for grade s 6 - 8 ( 9 - 12-year olds ) . CONCLUSIONS Our results provide evidence for the effectiveness of the multi-component intervention Lekker Fit ! among pupils of grade s 3 - 5 and adds to the growing body of evidence that school-based programs with a focus on PA are most effective in reducing childhood obesity . [ IS RCT N84383524 ] BACKGROUND The positive of the Norwegian anti-bullying programme ( Olweus , 1992 ) stimulated other countries to tackle bully/victim problems . However , outcome studies found rather low levels of effect or even inconsistent results . AIMS The purpose of the present study was to evaluate behavioural effectiveness of a school-based anti-bullying approach within Flemish schools . In addition , specific attention was given to the relationship between outcome findings and external support . SAMPLE A total of 18 schools , comprising 1104 primary and secondary school children were recruited for this study . Students ranged in age from 10 to 16 years . METHOD For this study , an experimental pre-test/post-test design was used which included a control group . Three groups were established . The first group , Treatment with Support , involved students from schools that implemented a school-based anti-bullying intervention with additional support from the research group . The second group , Treatment without Support , also involved students from schools that implemented a school-based anti-bullying programme . However , in contrast with those falling under the first condition , this group of schools could not appeal to the research group for additional help . The last group involved students from schools that did not implement the anti-bullying programme and served as a Control condition . Repeated measures analyses of variance were carried out . RESULTS The findings regarding the effects of the school-based anti-bullying intervention programme on the extent of bullying and victimisation showed a mixed pattern of positive changes in primary schools and zero outcomes in secondary schools . The findings regarding the effects of external support revealed limited outcomes . CONCLUSIONS The outcomes of the evaluation study confirm that a school-based anti-bullying intervention strategy can be effective in reducing problems with bullying , especially within primary schools . It was argued that the developmental characteristics of secondary school students interfered with the programme outcomes . In addition , the findings revealed no extra effects of specific training sessions Project Northl and is a community-wide research program funded by the National Institute on Alcoholism and Alcohol Abuse , for a 5-year period ( 1990 - 95 ) . The aim of the study is to prevent or delay onset of alcohol use among young adolescents , as well as to reduce use among those who are already drinkers . Twenty communities were recruited in northeastern Minnesota , an area referred to as the Northl and , Arrowhead or Iron Range region , and then were r and omly assigned to either Education or Delayed Program conditions . The 10 Education school districts have agreed to participate in 3 years of intervention programs in schools , with parents and in the community-at-large . One group of young adolescents , the Class of 1998 ( sixth grade students in the 1991 - 92 school year ) , form the study cohort . Surveys ( 1991 - 94 ) of the Class of 1998 , their parents , community leaders and alcohol merchants are the primary components of the program 's evaluation . Many conceptual and method ological questions emerged during the development of the research protocol s for Project Northl and over the past 2 years . These questions are the impetus for this article . Specifically , the focus on young adolescents and alcohol use was selected , as contrasted with older adolescents or with multiple problem behaviors . The project was design ed using a community-wide model that addresses both supply and dem and issues , rather than limited to a school-based model . Intervention strategies and evaluation methods were chosen that could address community-level as well as individual-level behavior change , which required the development and application of new technologies . The rationale for these decisions may be useful to others considering community-wide health promotion efforts OBJECTIVE The objective of this study was to examine the effects of an integrated , multi-component , school-based intervention programme on cardiovascular disease ( CVD ) risk factors among a multi-ethnic cohort of middle school students . METHODS HEALTHY was a cluster r and omized , controlled , primary prevention trial . Middle school was the unit of r and omization and intervention . Half of the schools were assigned to an intervention programme consisting of changes in the total school food environment and physical education classes , enhanced by educational outreach and behaviour change activities and promoted by a social marketing campaign consisting of reinforcing messages and images . Outcome data reported ( anthropometrics , blood pressure and fasting lipid levels ) were collected on a cohort of students enrolled at the start of 6th grade ( ∼11 - 12 years old ) and followed to end of 8th grade ( ∼13 - 14 years old ) . RESULTS Forty-two middle schools were enrolled at seven field centres ; 4363 students provided both informed consent and CVD data at baseline and end of study . The sample was 52.7 % female , 54.5 % Hispanic , 17.6 % non-Hispanic Black , 19.4 % non-Hispanic White and 8.5 % other racial/ethnic combinations , and 49.6 % were categorized as overweight or obese ( body mass index ≥ 85th percentile ) at baseline . A significant intervention effect was detected in the prevalence of hypertension in non-Hispanic Black and White males . The intervention produced no significant changes in lipid levels . CONCLUSIONS The prevalence of some CVD risk factors is high in minority middle school youth , particularly males . A multi-component , school-based programme achieved only modest reductions in these risk factors ; however , promising findings occurred in non-Hispanic Black and White males with hypertension BACKGROUND Depressive disorders are experienced by 3 - 5 % of the adolescent population at any point of time . They adversely affect adolescent development in a range of areas and greatly increase risk for suicide . The present study investigated the effectiveness of a universal intervention design ed to reduce depressive symptoms among students commencing high school . METHODS Twenty-five pairs of secondary schools matched on socio-economic status were r and omly assigned to either an intervention or a comparison group ( n = 5,634 Year 8 students ) . The intervention extended over a 3-year period and utilised a comprehensive classroom curriculum programme , enhancements to the school climate , improvements in care pathways , and community forums . A range of measures completed by students , average age at baseline = 13.1 years ( SD = .5 ) , and teachers was used to assess changes in depressive symptoms , risk and protective factors relevant to depression , and the quality of the school environment . RESULTS Changes in the level of depressive symptoms and in the levels of risk and protective factors experienced by students in the two groups did not differ significantly over the 3 years of the study . Furthermore , statistically significant differences in the ratings of school climate across this time period were found only for staff-rated assessment s. CONCLUSIONS Despite using an extensive , structured programme , based on best evidence to increase protective factors and reduce risk factors at the individual and school levels , the intervention did not reduce levels of depressive symptoms among participating adolescents . The results draw attention to the difficulties faced when implementing large-scale , school-based , universal preventive interventions . These include the need to develop methods to effectively train teachers across large geographical regions to deliver new interventions with fidelity , the difficulty of engaging young adolescents with prevention programmes , and the long period of time required to implement policy and practice changes at ' whole-school ' levels The HEALTHY study was a r and omized , controlled , multicenter , middle school-based , multifaceted intervention design ed to reduce risk factors for the development of type 2 diabetes . The study r and omized 42 middle schools to intervention or control , and followed students from the sixth to the eighth grade s. Participants were a racially , ethnically and geographically diverse cohort from across the United States . Here , we describe the conceptual underpinnings and design of the social marketing-based communications component of the HEALTHY study intervention that combined changes in the school nutrition and physical education ( PE ) environment with behavior change initiatives . The communications intervention component coordinated multiple elements to deliver campaigns that served to integrate and support all aspects of the HEALTHY intervention . The campaigns unfolded across five semesters of middle school , each targeting a specific theme related to the HEALTHY objectives . Communications campaigns comprised ( 1 ) core elements such as br and ing , posters , banners and visual and verbal messaging , ( 2 ) student events supporting the nutrition , PE and behavior intervention components through the application of social marketing and communications strategies , including the incorporation of student-generated media and ( 3 ) distribution of premiums and theme enhancers to extend the visibility of the study beyond the intervention environment . Formative research conducted with students , parents and school administrators was used to refine the communications strategy . Student peer communicators selected from the student body were involved to influence the normative student environment . Marketing and creative design experts developed a br and , logo , activities and material s. In the latter half of the study , student-generated messages and media were used to reflect local interests and culture and enhance peer influence . The HEALTHY intervention delivery and impact were strengthened by the communications strategies . The HEALTHY experience provides practical considerations for systematic ally incorporating a social marketing-based communications approach within future school-based health behavior interventions OBJECTIVES Project Northl and is an efficacy trial with the goal of preventing or reducing alcohol use among young adolescents by using a multilevel , communitywide approach . METHODS Conducted in 24 school districts and adjacent communities in northeastern Minnesota since 1991 , the intervention targets the class of 1998 ( sixth- grade students in 1991 ) and has been implemented for 3 school years ( 1991 to 1994 ) . The intervention consists of social-behavioral curricula in schools , peer leadership , parental involvement/education , and communitywide task force activities . Annual surveys of the class of 1998 measure alcohol use , tobacco use , and psychosocial factors . RESULTS At the end of 3 years , students in the intervention school districts report less onset and prevalence of alcohol use than students in the reference districts . The differences were particularly notable among those who were nonusers at baseline . CONCLUSIONS The results of Project Northl and suggest that multilevel , targeted prevention programs for young adolescents are effective in reducing alcohol use The objectives of this study were to examine outcomes of the Minnesota D.A.R.E. Plus Project on violence-related behaviors among middle school students and mediation analyses that test how the intervention was effective in reducing physical and verbal violence . Twenty-four schools were r and omly assigned to the D.A.R.E. middle school curriculum , the D.A.R.E. Plus multicomponent intervention , or control . The study cohort completed a self-report question naire at baseline and two follow-ups . The results showed that boys had higher rates of violence and victimization than girls . The D.A.R.E. Plus program was more effective in preventing violence among boys than among girls . It appears that the small behavioral effect that D.A.R.E. Plus did demonstrate on physical and verbal violence among boys was entirely mediated by a decrease of norms that support violence , an increase in outcome expectancies about being violence-free , and an increase in parental consequences for fighting PURPOSE To describe the Gatehouse Project which addresses the social context of high school with an aim of changing students ' sense of school connection and in turn , health risk behavior and well-being . METHODS Distinguishing features of the project were its conceptual framework , implementation process , and evaluation design . The conceptual framework derived from attachment theory and focused on three aspects of the school social context : security , communication , and participation . Implementation was st and ardized around a survey of the school social environment , creation of a school-based action team , and the implementation of strategies matched to a school 's profile of need . In addition , an early high school curriculum addressed the skills relevant to social functioning and emotional adjustment . The evaluation design was based on a cluster r and omized trial involving 26 schools . It used follow-up of an individual cohort and repeat cross-sectional surveys to capture outcomes at an individual student and whole-school level . RESULTS AND CONCLUSIONS The Gatehouse Project drew on both health and education research to develop and coordinate a broad-based school health promotion intervention . It represents a promising new direction for school-based preventive work OBJECTIVE The present analysis evaluates the overall appreciation and implementation of an intervention , Project Tomato , design ed to maintain fruit and vegetable intake in children aged 8 - 9 years . DESIGN A r and om sample of fifty-four English primary schools ( 658 children ) were r and omised to either the intervention group or the control . The intervention group received a multi-component programme delivered in school by teachers and items sent home for parents/children . Dietary measurements were collected at baseline and follow-up . The intervention participants completed question naires on the intervention material s , to identify implementation and appreciation of the intervention , and other environmental mechanisms . SETTING Fifty-four primary schools were r and omly selected , with twenty-seven schools allocated to the intervention group . SUBJECTS A total of 311 children received the intervention . RESULTS Implementation of the intervention was low , 21·3 % of school items and 56·0 % of home items were implemented . The intervention material s were well received by teachers , parents and children . Other mechanisms that may affect fruit and vegetable intake were explored . Children who ate their main meal with their parents 3 - 7 nights/week on average consumed 37·6 ( 95 % CI 9·8 , 65·4 ) g more fruit and vegetables than children who ate with their parents 0 - 2 times/week . CONCLUSIONS Implementation of the trial components was poor . However , the results identified the importance of parental environment and mealtime structure on children 's fruit and vegetable intake OBJECTIVE To evaluate the impact of a multi-component school-based physical activity intervention ( Fit-4-Fun ) on health-related fitness and objective ly measured physical activity in primary school children . METHODS Four Hunter primary schools were recruited in April , 2011 and r and omized by school into treatment or control conditions . Participants included 213 children ( mean age = 10.72 years ± 0.6 ; 52.2 % female ) with the treatment group ( n = 118 ) completing the 8-week Fit-4-Fun Program . Participants were assessed at baseline and 6-month follow-up , with a 91 % retention rate . Cardio-respiratory fitness ( CRF ) ( 20 m shuttle run ) was the primary outcome , and secondary outcomes included body composition ( BMI , BMI ( Z ) ) , muscular fitness ( 7-stage sit-up test , push-up test , basketball throw test , St and ing Jump ) , flexibility ( sit and reach ) and physical activity ( 7 days pedometry ) . RESULTS After 6-months , significant treatment effects were found for CRF ( adjusted mean difference , 1.14 levels , p < 0.001 ) , body composition ( BMI mean , -0.96 kg/m(2 ) , p < 0.001 and BMI z-score mean -0.47 z-scores , p < 0.001 ) , flexibility ( sit and reach mean , 1.52 cm , p = 0.0013 ) , muscular fitness ( sit-ups ) ( mean 0.62 stages , p = 0.003 ) and physical activity ( mean , 3253 steps/day , p < 0.001 ) . There were no group by time effects for the other muscular fitness measures . CONCLUSIONS A primary school-based intervention focusing on fitness education significantly improved health-related fitness and physical activity levels in children The objective of the present study was to evaluate the effects of the Pro Children intervention on schoolchildren 's fruit and vegetable ( FV ) intake after 1 and 2 years of follow-up . The intervention combined a FV curriculum with efforts to improve FV availability at schools and at home . Effects were examined in a group-r and omised trial among 1,472 10 - 11-year-old children from sixty-two schools in Norway , the Netherl and s and Spain . FV intake was assessed by means of vali date d self-administered question naires completed before the intervention ( September 2003 ) , immediately after the first year of the intervention ( May 2004 ) and 1 year later ( May 2005 ) . Data were analysed using multilevel linear regression analyses with age and sex as covariates . Significant intervention effects for FV intake were found at first follow-up in the total sample . The adjusted FV intake reported by the children from intervention schools was 20 % higher than FV intake reported by children from control schools . At 1 year later , a significant impact was only observed in Norway . Positive intervention effects on FV intake occurred both at school and outside school . We conclude that the Pro Children intervention is a promising means to promote European schoolchildren 's FV intakes , but mainly fruit intake , in the short term . As shown in Norway , where the intervention was best implemented , the intervention might also result in longer-term effects . Further strategies need to be developed that can improve implementation , have an impact on vegetable intake and can secure sustained effects This study examines peer resistance skills following a 21-lesson classroom-based intervention to build healthy relationships and decrease abusive and health-risk behaviors among adolescents . The Fourth R instructs students in positive relationship skills , such as negotiation and delay , for navigating challenging peer and dating scenarios . Observational data from 196 grade 9 students participating in a larger cluster r and omized controlled trial were used to evaluate post-intervention acquisition of peer resistance skills . Pairs of students engaged in a role play paradigm with older student actors , where they were subjected to increasing pressure to comply with peer requests related to drugs and alcohol , bullying , and sexual behavior . Specific and global measures of change in peer resistance responses were obtained from two independent sets of observers , blinded to condition . Specific peer resistance responses ( negotiation , delay , yielding to pressure , refusal , and compliance ) were coded by research assistants ; global peer resistance responses were rated by teachers from other schools ( thinking / inquiry , application , communication , and perceived efficacy ) . Students who received the intervention were more likely to demonstrate negotiation skills and less likely to yield to negative pressure relative to controls . Intervention students were also more likely to use delay than controls ; control girls were more likely to use refusal responses ; the number of times students complied with peer requests did not differ . Teacher ratings demonstrated significant main effects favoring intervention youth on all measures . Program and research implication s are highlighted PURPOSE To assess the impact of an adolescent sexual health intervention on the use of health services by young people in Tanzania . METHODS Twenty communities , including 39 health facilities , were r and omly allocated to the intervention or comparison arm . Health workers from the intervention arm were trained in the provision of youth-friendly health services , as part of a package of interventions . Independent process evaluations were conducted in health facilities , and simulated patients visited clinics using sexual and reproductive health problem scenarios . The impact on health facility attendances were assessed in 1998 ( baseline ) and 1999 - 2001 . Reported sexually transmitted infection ( STI ) symptoms and use of health services were evaluated in young people in the trial cohort . RESULTS The mean monthly attendance for STI symptoms per health facility , per month was .5 for young males and 1.0 for young females at baseline . Attendance by young males was greater in the intervention communities in 1999 - 2000 after adjustment for baseline differences ( p = .005 ) , and this difference increased over time ( p-trend = .022 ) . The mean difference in attendance was however relatively modest , at 1.1 per month in 2001 after adjustment for baseline ( 95 % CI : .5 , 1.7 ) . There was weaker evidence of an intervention effect on attendance by young women ( p = .087 ) . Few condoms were distributed , although a greater number were distributed in intervention facilities ( p = .008 ) . Generally , intervention health workers tended to be less judgmental and provided more comprehensive information . CONCLUSIONS Training staff to provide more youth-friendly health services can increase the utilization of health services for suspected STIs by young people , especially among young men Objectives . This study evaluated the long-term effectiveness of Safer Choices , a theory-based , multi-component educational program design ed to reduce sexual risk behaviors and increase protective behaviors in preventing HIV , other STDs , and pregnancy among high school students . Methods . The study used a r and omized controlled trial involving 20 high schools in California and Texas . A cohort of 3869 ninth- grade students was tracked for 31 months from fall semester 1993 ( baseline ) to spring semester 1996 ( 31-month follow-up ) . Data were collected using self-report surveys administered by trained data collectors . Response rate at 31-month follow-up was 79 % . Results . Safer Choices had its greatest effect on measures involving condom use . The program reduced the frequency of intercourse without a condom during the three months prior to the survey , reduced the number of sexual partners with whom students had intercourse without a condom , and increased use of condoms and other protection against pregnancy at last intercourse . Safer Choices also improved 7 of 13 psychosocial variables , many related to condom use , but did not have a significant effect upon rates of sexual initiation . Conclusions . The Safer Choices program was effective in reducing important risk behaviors for HIV , other STDs , and pregnancy and in enhancing most psychosocial determinants of such behavior BACKGROUND School-based study recruitment efforts are both time consuming and challenging . This paper highlights the recruitment strategies employed by the national , multisite Trial of Activity for Adolescent Girls ( TAAG ) , a study design ed to measure the effectiveness of an intervention to reduce the decline of physical activity levels among middle school-aged girls . TAAG provided a unique opportunity to recruit large cohorts of r and omly sample d girls within 36 diverse middle schools across the United States . METHODS Key elements of the formative planning , coordination , and design of TAAG 's recruitment efforts included flexibility , tailoring , and the use of incentives . Various barriers , including a natural disaster , political tension , and district regulations , were encountered throughout the recruitment process , but coordinated strategies and frequent communication between the 6 TAAG sites were helpful in tailoring the recruitment process at the 36 intervention and control schools . RESULTS Progressively refined recruitment strategies and specific attention to the target audience of middle school girls result ed in overall study recruitment rates of 80 % , 85 % , and 89 % , for the baseline , posttest , and follow-up period , respectively . DISCUSSION The steady increase in recruitment rates over time is attributed to an emphasis on successful strategies and a willingness to modify less successful methods . Open and consistent communication , an increasingly coordinated recruitment strategy , interactive recruitment presentations , and participant incentives result ed in an effective recruitment campaign OBJECTIVE To test psychosocial mediators of the effects of an intervention in reducing the rate of growth of violence among adolescents . METHOD Five hundred and seventy-one African American adolescent males participated in this r and omized trial . Multilevel modeling techniques were used to ascertain both intervention and mediated effects . RESULTS Intervention significantly reduced rate of growth of violence and 5 social and psychological factors in the treatment group relative to the control group . Four of these social and psychological factors were found to be complete mediators between the intervention and its preventive effects . CONCLUSION Changing psychological mediating variables is central to reducing youth violence Latino children spend more time in sedentary activities than other American children , and only ~1 in 5 Latino children in public elementary and middle schools meet all 6 fitness st and ards in statewide fitness testing . Schools that facilitate physical activity ( PA ) by maintaining playgrounds and providing physical education classes have children who are more active and less overweight . The aims of the present study were to examine the extent to which several social and physical environmental changes in school setting s result ed in observed changes in area characteristics and children 's activity levels during recess . Thirteen elementary schools serving predominantly Mexican American children were r and omized into control or activity and nutrition environmental intervention conditions . Playgrounds and activities were restructured in 6 intervention schools to promote more PA . After 1 y , there were no overall statistical differences between treatment groups in PA or sedentary behavior in these setting s and results did not differ by gender . Changing the social and physical environments to promote children 's moderate-to-vigorous PA is important to the design of active and healthy recess environments . The present results are not conclusive as to the link between these interventions and actual behavior , but show sufficient promise for further population and setting specific research A theory-based multicomponent intervention ( Gimme 5 ) was design ed and implemented to impact fourth- and fifth- grade children ’s fruit , juice , and vegetable ( FJV ) consumption and related psychosocial variables . Gimme 5 was a r and omized controlled intervention trial with school ( n = 16 elementary ) as unit of r and om assignment and analysis . Participants included the cohort of students who were in the third grade in the winter of 1994 and students who joined them in the fourth and fifth grade s. The intervention included a curriculum , newsletters , videotapes , and point-of-purchase education . Evaluation included 7-day food records and psychosocial measures from students , telephone interviews with parents , and observational assessment s. Favorable results were observed for consumption of FJV combined , FJV consumed at weekday lunch , eating FJV self-efficacy , social norms , asking behaviors , and knowledge . A theory-based school nutrition education program can help change children ’s FJV consumption and impact factors at home that predispose to FJV consumption , but changes were small , and their persistence is unknown UNLABELLED BACKGROUND . There are strong theoretical reasons for including a family component with a school-based intervention aim ed at eating , activity , and smoking behaviors , but the empirical findings to date are limited and show mixed results . The overall CATCH family intervention added only knowledge and attitudinal effects , but no additional behavioral outcomes . This study provides a dose analysis of the family component of the CATCH study by assessing the effect of the level of adult participation . METHOD This secondary analysis included students who attended a CATCH family intervention school during all 3 years of the study . The extent of the adult-child interaction , the key aspect of the CATCH family intervention , was measured by the number of activity packets that an adult household member completed with the child . Multiple regression analysis was used to assess the association of adult participation with the child 's knowledge , attitudes , and behaviors related to diet and physical activity . RESULTS Statistically significant results suggested that dose effects were found for knowledge and attitudes related to diet and physical activity . These effects were more pronounced for minority and male students . CONCLUSIONS These results suggest that dose response of a family intervention has been shown in the acquisition of positive knowledge and attitudes toward health habit changes . The methodology of dose response can be applied to other health promotion projects R and omized trials of school-based health promotion programs present unique design and analytical issues not widely discussed in the research literature . This article describes the Safer Choices study --a school-based program for prevention of HIV , other sexually transmitted diseases , and pregnancy -- to illustrate critical method ological issues involved in large-scale , school-based intervention trials , particularly those evaluating interventions with a school-wide focus . The issues presented are : 1 ) comparability of the intervention and control groups even when few units are r and omized ; 2 ) factors that affect the decision to use a cohort or cross-sectional design ; and 3 ) appropriate analysis strategy when the unit of r and omization and intervention is at the school level , but observations are at the student level The ' active school ' model offers promise for promoting school-based physical activity ( PA ) ; however , few intervention trials have evaluated its effectiveness . Thus , our purpose was to : ( 1 ) describe Action Schools ! BC ( AS ! BC ) and its implementation ( fidelity and feasibility ) and ( 2 ) evaluate the impact of AS ! BC on school provision of PA . Ten elementary schools were r and omly assigned to one of the three conditions : Usual Practice ( UP , three schools ) , Liaison ( LS , four schools ) or Champion ( CS , three schools ) . Teachers in LS and CS schools received AS ! BC training and re sources but differed on the level of facilitation provided . UP schools continued with regular PA . Delivery of PA during the 11-month intervention was assessed with weekly Activity Logs and intervention fidelity and feasibility were assessed using Action Plans , workshop evaluations , teacher surveys and focus groups with administrators , teachers , parents and students . Physical activity delivered was significantly greater in LS ( + 67.4 min/week ; 95 % CI : 18.7 - 116.1 ) and CS ( + 55.2 min/week ; 95 % CI : 26.4 - 83.9 ) schools than UP schools . Analysis of Action Plans and Activity Logs showed fidelity to the model and moderate levels of compliance ( 75 % ) . Teachers were highly satisfied with training and support . Benefits of AS ! BC included positive changes in the children and school climate , including provision of re sources , improved communication and program flexibility . These results support the use of the ' active school ' model to positively alter the school environment . The AS ! BC model was effective , providing more opportunities for " more children to be more active more often " and as such has the potential to provide health benefits to elementary school children The Gatehouse Project is an innovative , comprehensive approach to mental health promotion in secondary schools . It sets out to promote student engagement and school connectedness as the way to improve emotional well-being and learning outcomes . The key elements of the whole-school intervention are the establishment and support of a school-based adolescent health team ; the identification of risk and protective factors in each school ’s social and leaning environment from student surveys ; and , through the use of these data , the identification and implementation of effective strategies to address these issues . The project evaluation used a cluster-r and omized controlled trial design involving 26 schools with initial results demonstrating considerable success in reducing smoking rates among Year 8 children . This article describes and accounts for how system-level changes have been made in schools through a process of capacity building . This encourages teachers , parents , and students to view the core business of education differently OBJECTIVE To reduce tobacco use among adolescents . METHODS Thirty schools in New Delhi , India , were r and omly assigned to 3 conditions : school-based and family-based intervention , school-based intervention only , or control group . Students were in the seventh grade at pretest ( N = 4,776 ) . The smoking intervention included posters , booklets , classroom activities , debates , and a signature campaign . The family intervention involved home activities . The survey measured tobacco knowledge , attitudes , offers , use , and intentions . RESULTS Intervention students were significantly less likely than controls to have been offered , received , experimented with , or have intentions to use tobacco . CONCLUSION The project had a significant impact on tobacco use BACKGROUND The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) tested the effectiveness of a multilevel intervention aim ed at promoting a healthful school environment and positive eating and physical activity behaviors in children . The CATCH Eat Smart Program targeted the school food service staff and aim ed to lower the total fat , saturated fat , and sodium content of school meals . METHODS The Eat Smart intervention was conducted in 56 intervention schools over a 2(1/2)-year period.+Five consecutive days of school menu , recipe , and vendor product information were collected from intervention and control schools at three intervals , Fall 1991 , Spring 1993 , and Spring 1994 , to assess the nutrient content of school menus as offered . RESULTS There was a significantly greater mean reduction in the percentage of calories from total fat ( adjusted mean difference -4.1 % ; P < 0.0001 ) and saturated fat ( adjusted mean difference -1.3 % ; P = 0.003 ) in intervention compared with control schools from baseline to follow-up . Although the sodium content of school lunches increased in both conditions , the mean increase was significantly lower in intervention schools ( adjusted mean difference -89 mg ; P = 0.034 ) . There were no statistically significant differences for total amounts of cholesterol , carbohydrate , protein , dietary fiber , total sugars , calcium , iron , vitamin A value , and vitamin C. Average total calories decreased significantly ; however , the mean total calories ( 683 kcal ) for intervention schools remained above one-third of the Recommended Dietary Allowances for this age group . CONCLUSIONS The CATCH Eat Smart intervention successfully lowered the total fat and saturated fat content of school lunches as offered , while maintaining recommended amounts of calories and essential nutrients BACKGROUND The purpose of this study was to examine the impact of fat reduction on vitamin and mineral density in the diets of groups of children who participated in the CATCH school-based intervention study for 2 1/2 years . METHODS Twenty-four-hour dietary recalls were collected on 1,182 children residing in four states and with diverse ethnic background s , at baseline when they were in third grade and again at follow-up when they were in fifth grade . RESULTS With a 2.4 % reduction in total fat intake from baseline levels in the intervention group , mean changes in vitamin and mineral intakes per 1,000 kcal of this group were small yet significant compared with the control group . As mean fat intake decreased , the nutrient density of most vitamins and minerals increased ; the sole exceptions were vitamin E and sodium . Mean intake of all vitamins and minerals studied exceeded 2/3 of the RDA at both baseline and follow- up for both the intervention and the control groups . No significant differences were noted between treatment groups for the percentages of children meeting 2/3 or more of the RDA at both baseline and follow-up periods . CONCLUSIONS CATCH was successful in maintaining mean vitamin and mineral intakes of intervention group children when total dietary fat was reduced OBJECTIVE To compare fruit and vegetable servings calculated from 24-hour dietary recall data using 3 methods : a counting scheme developed for the 5 A Day for Better Health study , a method developed by the University of Minnesota Cancer Prevention Research Unit to quantify total consumption of fruits and vegetables , and a counting scheme based on the US Food and Drug Administration 's Reference Amounts . The counting methods differ by food items counted and by serving sizes for those items . SUBJECTS/ SETTING Record-assisted 24-hour dietary recalls were collected from 617 r and omly selected fourth- grade students ( 317 girls , 300 boys ) from 23 schools in St Paul , Minn , participating in the Minnesota 5 A Day Power Plus Program . DESIGN The dietary recalls were analyzed using the Minnesota Nutrition Data System ( version 2.6/8a/23 ) . Total servings of fruits and vegetables , servings of vegetables , servings of fruits plus juices , servings of fruit juice , and servings of fruit excluding juice were tallied using each counting method . STATISTICAL ANALYSES A mixed-model Poisson regression analysis was conducted to compare numbers of servings calculated using the 3 methods . RESULTS Counts of daily total fruits and vegetables averaged 3.9 servings with the 5 A Day method , 4.1 servings using US Food and Drug Administration Reference Amounts , and 5.1 servings with the Minnesota Cancer Prevention Research Unit method ( P < .0001 ) . APPLICATIONS Because the different counting methods yield different tallies of fruit and vegetable intake , it is important for research ers and practitioners interested in fruit and vegetable consumption to be clear about their uses of the data before choosing a counting scheme BACKGROUND Cardiovascular risk factors and related behaviors begin during youth . METHODS As part of the Child and Adolescent Trial for Cardiovascular Health , 4,019 children from four states and representing multiple ethnic groups were measured for selected risk factors both at baseline and after 2(1/2 ) years of intervention . Common protocol s were used for both examinations at the four sites . RESULTS Overall , changes in obesity , blood pressure , and serum lipids in the intervention group , compared with the control group , were not statistically significant . Total cholesterol , the primary physiologic outcome measure , decreased by 1.3 mg/dl over time in the intervention group and by 0.9 mg/dl ( P > 0.05 ) in the control group . Different risk factor patterns for boys and girls and among three ethnic groups were noted . CONCLUSIONS Although the school-based program effected significant institutional changes in food service and physical education class and although the children made significant changes in eating and physical activity behaviors , these did not translate to significant changes in risk factors at these ages . These behavioral changes , however , if sustained into adulthood , have the potential to influence cardiovascular risk reduction The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) is a multicenter trial design ed to test the effectiveness of school and family-based cardiovascular health promotion for preadolescents . CATCH interventions target multiple cardiovascular health behaviors such as dietary intake of fat and sodium , physical activity , and tobacco use . Evaluation includes physiological , psychosocial , behavioral , and process measures . An important aspect of the process evaluation is the assessment of environmental factors and " secular events " in both intervention and control schools that may affect outcomes independently of the CATCH interventions . With such information , CATCH investigators are able to isolate the impact of the CATCH intervention from competing ( non-CATCH ) factors as well as " track " proximal ( i.e. , immediate and short term ) changes related to the intervention that may in turn lead to " distal " ( long-term ) behavior change . The School Health Question naire , the major process evaluation tool for monitoring secular and environmental changes in the schools , is described in detail , and data describing tobacco-related environmental factors and secular events are presented The purpose of the study was to evaluate the impact of the Going Places Program and mediation of treatment effects . Seven middle schools were r and omized to intervention or comparison conditions and students ( n = 1,320 ) in two successive cohorts provided five waves of data from sixth through eighth grade . The Going Places Program included classroom curriculum , parent education , and school environment components . Latent growth curve analyses demonstrated significant treatment group effects on outcome expectancies , friends who smoke , and smoking . Friends who smoke mediated the program effect on adolescents ’ smoking progression . The protective effect of the Going Places Program on smoking progression was due in part to the prevention of increases in friends who smoke This study evaluated the effectiveness of the first year of Safer Choices , a theoretically based , multicomponent HIV , STD , and pregnancy prevention program for high school youth . The study featured a r and omized trial involving 20 schools in California and Texas , with a cohort of 3,869 ninth- grade students . Students who completed both the baseline and the first follow-up survey approximately seven months later were included in the analysis ( n = 3,677 ) . Safer Choices enhanced 9 of 13 psychosocial variables including knowledge , self efficacy for condom use , normative beliefs and attitudes regarding condom use , perceived barriers to condom use , risk perceptions , and parent-child communication . Safer Choices also reduced selected risk behaviors . Specifically , Safer Choices reduced the frequency of intercourse without a condom in the three months prior to the survey , increased use of condoms at last intercourse , and increased use of selected contraceptives at last intercourse Gimme 5 : A Fresh Nutrition Concept for Students ( Gimme 5 ) was a 4-year intervention targeting increased fruit and vegetable consumption by high school students . Twelve schools were r and omized to intervention or control conditions . The cohort ( 2,213 students ; 56 % female , 84 % Euro-American ) were followed from 9th to 12th grade . Interventions were composed of a school-based media campaign , classroom workshops , school meal modification , and parental involvement . For each of the four Gimme 5 intervention components , process evaluation measures were developed to assess program dose , penetration , and utilization , as well as external competing factors . Process evaluation results are presented to illustrate the various functions of process evaluation data . These include , but are not limited to , describing program implementation , quality control and monitoring , and explaining study outcomes . The implementation of process evaluation systems to complement the outcome measures in a high school – based intervention provides useful strategies for a more comprehensive approach to program evaluation Sustaining effective school-based prevention programs is critical to improving youth and population -based health . This article reports on results from the Aban Aya Sustainability Project , an effort to sustain a school-based prevention program that was tested via a r and omized trial and targeted violence , drug use , and risky sex-related behaviors among a cohort of 5th- grade African American children followed through 10th grade . Sustainability project health educators trained parent educators to deliver the Aban Aya prevention curriculum in five schools , and project research ers studied the result ant curricular implementation and relations between the research and school-based teams . Study results showed uneven implementation across the five schools that we largely attributed to parent educator preparation and parent educator-health educator relations . These and related results are discussed to answer the study 's primary research question : How viable was the sustainability project 's parent-centered approach to sustaining a school-based prevention program BACKGROUND This study tests the feasibility of an innovative school-based program for obesity prevention among adolescent girls . New Moves was implemented as a multicomponent , girls-only , high-school physical education class . METHODS Six schools were equally r and omized into intervention and control conditions . Data were collected at baseline , postintervention , and 8-month follow-up to assess program impact on physical activity , eating patterns , self-perceptions , and body mass index ( BMI ) among 89 girls in the intervention and 112 girls in the control conditions . Program evaluation also included interviews with school staff , parent surveys , and participant interviews and process evaluation surveys . RESULTS The feasibility of implementing New Moves was high , as indicated by strong satisfaction among participants , parents , and school staff , and by program sustainability . Participants perceived a positive program impact on their physical activity , eating patterns , and self-image . Girls in the intervention significantly progressed in their stage of behavioral change for physical activity from baseline to follow-up . However , for the majority of outcome variables , differences between intervention and control schools at postintervention and follow-up were not statistically significant . CONCLUSIONS New Moves was well received and fills a needed niche within school physical education programs . An exp and ed intervention and evaluation is needed to enhance and assess long-term program effectiveness There is a worldwide epidemic of obesity with far-reaching consequences for the health of our nation . Prevention of obesity , especially in children , has been deemed by public health policy makers to be one of the most important objectives for our country . This prevention project , called Louisiana ( LA ) Health , will test whether modification of environmental and behavioral factors can prevent inappropriate weight gain in children from rural parishes of Louisiana who are enrolled in the fourth to sixth grade s during Year 1 . The primary aim of the LA Health project is to test the efficacy of two school-based approaches for obesity prevention : primary prevention alone and a combination of primary and secondary prevention which will be compared to a no-intervention control group using a cluster r and omization research design , with 17 school clusters r and omly assigned to the three treatment arms . The study will span 3 years and will provide critical tests of strategies that : 1 ) modify the child 's environment as a primary prevention strategy and 2 ) provide health behavior modification via classroom instruction and internet counseling as a secondary prevention strategy . The study will also recruit a similar sample of students to measure changes in body weight relative to height , gender , and age over the same three-year period BACKGROUND This study evaluates the effects of a 3-year smoking prevention programme in secondary schools in Helsinki . The study is part of the European Smoking prevention Framework Approach ( ESFA ) , in which Denmark , Finl and , the Netherl and s , Portugal , Spain and the UK participated . METHODS A total of 27 secondary schools in Finl and participated in the programme ( n = 1821 ) . Schools were r and omised into experimental ( 13 ) and control groups ( 14 ) . The programme included 14 information lessons about smoking and refusal skills training . The 3-year smoking prevention programme was also integrated into the st and ard curriculum . The community-element of the programme included parents , parish confirmation camps and dentists . The schools in the experimental group received the prevention programme and the schools in the control group received the st and ard health education curriculum . RESULTS Among baseline never smokers ( 60.8 % ) , the programme had a significant effect on the onset of weekly smoking in the experimental group [ OR = 0.63 ( 0.45 - 0.90 ) P = 0.009 ] when compared with the control group . Being female , doing poorly at school , having parents and best friends who smoke and more pocket money to spend compared with others were associated with an increased likelihood of daily and weekly smoking onset . These predictors did not have an interaction effect with the experimental condition . CONCLUSION This study shows that a school- and community-based smoking prevention programme can prevent smoking onset among adolescents BACKGROUND The Pathways study was a r and omized , 3-year trial of obesity prevention in American Indian Children . An important goal of the Pathways intervention was to significantly decrease the percentage of calories eaten as fat by the intervention children , relative to controls . This paper reports the effects of the Pathways intervention on dietary intake . METHODS Two types of dietary data were analyzed from r and om sample s of children in 41 schools : direct observation of school lunch intake at baseline ( 2nd grade ) and follow-up ( 5th grade ) ( n=470 ) , and 24-hour dietary recalls at follow-up only ( n=620 ) . Nutrient contents of school meals and recalls were calculated by NDS and NDS-R software ( University of Minnesota ) , using vendor products and recipes from each school . RESULTS Based on lunch observations , the intervention was associated with significant decreases in mean percentage of calories from total fat ( 3.6 % ) and saturated fat ( 2.1 % ) relative to controls , and a significant increase in the percentage of calories from total carbohydrate ( 3.7 % ) . Compared with the control children , intervention children reported significantly smaller 24-hour intakes of energy ( 263 kcal ) , protein ( 9.5 g ) , total fat ( 15.1 g ) , saturated fat ( 6.0 g ) , and polyunsaturated fat ( 2.3 g ) ; and as a percent of calories , total fat ( 2.5 % ) and saturated fat ( 1.1 % ) . Mean intake of carbohydrates as a percentage of calories was significantly greater in intervention children by 2.5 % , compared with controls . CONCLUSIONS The Pathways intervention successfully reduced the intake of percent calories from fat and saturated fat , at school lunch and over the whole day The present study investigated the effects of the KiVa antibullying program on students ’ anxiety , depression , and perception of peers in Grade s 4–6 . Furthermore , it was investigated whether reductions in peer-reported victimization predicted changes in these outcome variables . The study participants included 7,741 students from 78 schools who were r and omly assigned to either intervention or control condition , and the program effects were tested with structural equation modeling . A cross-lagged panel model suggested that the KiVa program is effective for reducing students ’ internalizing problems and improving their peer-group perceptions . Finally , changes in anxiety , depression , and positive peer perceptions were found to be predicted by reductions in victimization . Implication s of the findings and future directions for research are discussed BACKGROUND Effective interventions to reduce the incidence of HIV , other sexually transmitted infections ( STIs ) and unwanted pregnancy among adolescents in sub-Saharan Africa are urgently needed . This paper describes the rationale and design of a r and omised trial of the impact of an innovative sexual health intervention among adolescents in rural Mwanza Region , Tanzania . METHODS The MEMA kwa Vijana intervention comprises a teacher-led , peer-assisted sexual health education programme for students in the last 3 years of primary school , training and supervision of health workers in the provision of youth-friendly health services , peer condom promotion and distribution , and wider community activities . Detailed process evaluation was conducted and the impact of the intervention was evaluated through a community-r and omised trial in which a cohort of 9645 adolescents was followed up for 3 years . Both process and impact evaluation used multiple assessment methods . Impact measures included incidence and prevalence of HIV and other STIs , pregnancy rates , knowledge and reported attitudes and sexual behaviour , as well as qualitative assessment s. RESULTS Results of the baseline survey of the cohort have been presented previously . The outcome of the trial will be reported separately . CONCLUSIONS Behaviour change interventions among adolescents have been widely advocated , but there have been few rigorously design ed trials of their effectiveness , particularly in developing countries , and measurement of sexual behaviour is particularly problematic in this age group . The MEMA kwa Vijana trial was undertaken to address these problems and to collect rigorous evidence on the effectiveness of an innovative intervention , design ed to be implemented on a very large scale BACKGROUND Reducing sun exposure during childhood may prevent skin cancer later in life . Sun protection increased immediately following implementation of the SunSafe multicomponent , community-based intervention delivered in 1996 through schools , day care centers , primary care offices , and beach recreation areas . Whether sun protection levels would remain higher than preintervention levels the following summer was unknown . METHODS A r and omized controlled trial based in 10 New Hampshire towns addressed children 's use of protective clothing , shade , and sunscreen at freshwater beach areas . The intervention was provided initially between March and May 1996 . A brief project follow-up contact was provided to schools , day care centers , beaches , and primary care offices between March and May 1997 to restock intervention material s and to answer questions . Observations of 1490 children during June through August of 1997 were compared with observations made prior to any intervention between June and August of 1995 . RESULTS In intervention towns , the proportion of children using at least some sun protection increased by 0.15 from 0.58 in 1995 to 0.73 in 1997 while the proportion in control towns increased by 0.03 ( P = 0.033 ) . This increase was due to more use of sunscreen , but not more use of protective clothing or shade . In 1997 , care-givers of children in intervention towns reported receiving more sun protection information from school and health care sources than control town caregivers ( 62 % versus 33 % , P < 0.006 ) . CONCLUSIONS In intervention communities , a higher proportion of children used sun protection in 1997 than at baseline . Increases from 1995 to 1997 were similar in magnitude to short-term increases between 1995 and 1996 that we have been previously reported BACKGROUND This study evaluated a school-based obesity intervention for elementary school children ( N = 835 ) where health professionals assisted teachers with the integration of healthy messages into the school curriculum . METHODS Schools were r and omized into a professional-facilitated intervention ( PFI ; N = 4 ) or a self-help ( SH ; N = 3 ) condition . Changes in weight-based outcomes were assessed in students enrolled in the second grade from all 7 schools ( overall : N = 835 students ; PFI : N = 509 students , SH : N = 326 students ) . Students were between ages 7 and 9 and from diverse ethnic background s ( Asian = 25.3 % , Black = 23.3 % , Hispanic = 23.1 % , White = 28.3 % ) . The sample included 321 overweight/obese ( BMI ≥ 85th percentile ) , 477 normal-weight ( BMI ≥ 5th percentile and < 85th percentile ) , and 37 underweight ( BMI < 5th percentile ) students . RESULTS After 2 years , children who were overweight/obese in the PFI condition significantly reduced their st and ardized BMI ( z BMI ) compared to children in the SH condition ( Wald χ(2 ) = 28.7 , p < .001 ) . End-of-year grade s decreased for overweight/obese students in both conditions ; however , students in the PFI exhibited a smaller decrease in grade s compared to the SH condition ( Wald χ(2 ) = 80.3 , p < .001 ) . CONCLUSION The results indicate that an obesity prevention program where health professionals assist teachers by integrating healthy messages into existing curriculum was effective in reducing z BMI compared to the SH condition Progress has been made in underst and ing the outcome effects of preventive interventions and treatments design ed to reduce children 's conduct problems . However , limited research has explored the factors that may affect the degree to which an intervention is likely to benefit particular individuals . This study examines selected child , family , and community baseline characteristics that may predict proximal outcomes from the Fast Track intervention . The primary goal of this study was to examine predictors of outcomes after 3 years of intervention participation , at the end of 3rd grade . Three types of proximal outcomes were examined : parent-rated aggression , teacher-rated oppositional – aggressive behavior , and special education involvement . The relation between 11 risk factors and these 3 outcomes was examined , with separate regression analyses for the intervention and control groups . Moderate evidence of prediction of outcome effects was found , although none of the baseline variables were found to predict all 3 outcomes , and different patterns of prediction emerged for home versus school outcomes Social influences on smoking uptake were examined in latent growth curve analyses of data from 1,320 youths assessed 5 times during 6th to 9th grade . Initial smoking stage predicted increases in number of friends who smoked , indicating selection ; however , initial number of friends who smoked did not predict smoking stage progression , indicating no significant effect of socialization . Associations over time among smoking stage progression , affiliation with friends who smoke , and parenting behaviors were significant , suggesting dynamic , reciprocal relationships . Parental involvement , monitoring , and expectations provided direct protective effects against smoking progression as well as indirect effects , by limiting increases in number of friends who smoke . These results are consistent with the peer selection hypothesis , confirm the powerful association over time of social influences with smoking , and provide the first evidence that parenting behavior may protect against smoking progression by limiting increases in number of friends who smoke Multicomponent interventions are recommended for health behavior change among adolescents . However , it is difficult to disentangle the effects of multiple intervention components . This article reports outcomes associated with varying levels of exposure to a school-based nutrition intervention . Teens Eating for Energy and Nutrition at School ( TEENS ) . Four incremental exposures were possible : ( 1 ) control group , ( 2 ) school environment interventions only , ( 3 ) classroom plus environment interventions , and ( 4 ) peer leaders plus classroom plus environment interventions . Pattems suggesting dose response were observed , with peer leaders reporting the largest increases in fruit , vegetable , and lower fat food consumption . Students exposed to classroom plus environment interventions also improved , whereas students exposed only to school environment interventions showed trends toward choosing lower fat foods and declining fruit intake and no change in vegetable intake . Control students ' choices remained stable . Future studies may investigate mechanisms for peer leaders ' changes , maximizing curriculum effectiveness , and improving environmental interventions BACKGROUND This paper describes the methods used in " High 5 , " a school-based study to increase fruit and vegetable consumption for cancer risk reduction . METHODS Twenty-eight elementary schools were matched and r and omized to intervention or control conditions . All students were assessed based on diet and psychosocial variables at baseline and one and two years post-baseline . The intervention included classroom , parent , and environmental components . RESULTS The study recruited 1,698 families and retained 85 % . The two conditions were equivalent at baseline ; 50 % female students , 81 % to 84 % European-American students , and 2.9 servings of fruit and vegetables per day . Good completion was achieved across the intervention components ( e.g. , 90 % of lessons taught , 72 % of parent material s read , 3.6 servings of fruit and vegetables offered in cafeterias ) . CONCLUSIONS The use of school-based programs , with strong evaluation design s , will enhance knowledge about the modification of nutrition behavior and cancer risk in children . Lessons learned from the study are reported OBJECTIVES Many adolescent girls fail to meet national guidelines for physical activity , and the prevalence of obesity is increasing among this group . Our study examined the effects of a comprehensive school-based intervention on physical activity among high-school girls . METHODS A group-r and omized controlled field trial was conducted at 24 high schools . A school-based sample of 2744 girls ( 48.7 % African American , 46.7 % White ) participated in a measurement protocol when they were in eighth and then ninth grade . A comprehensive physical activity intervention was design ed to change the instructional program and the school environment to increase support for physical activity among girls . RESULTS At follow-up , 45 % of girls in the intervention schools and 36 % of girls in the control schools reported vigorous physical activity during an average of 1 or more 30-minute time blocks per day over a 3-day period . CONCLUSIONS A comprehensive school-based intervention can increase regular participation in vigorous physical activity among high-school girls Mobilising Youth for Tobacco-Related Initiatives in India ( Project MYTRI ) is a r and omized community trial to prevent tobacco use among students in Grade s 6 through 9 in 32 private and government schools in Delhi and Chennai , India ( N = 12,484 ) . The project is a partnership between research ers and practitioners in the United States and India . This article describes the steps that were carried out to ensure that prior effective programs are appropriate and applicable to India . These steps involve ( a ) developing a conceptual behavioral intervention model , ( b ) ensuring the appropriateness of the model for urban India , ( c ) developing intervention strategies that modify factors in the model , ( d ) implementing the MYTRI program with more than 5,000 students , and ( e ) evaluating the process and outcomes of the intervention . Data to date suggest that this process has been successful , including high participation rates , teacher perceptions of appropriateness , and agreements for further implementation Fast Track is a conduct-problem prevention trial that derives its intervention from longitudinal research on how serious and chronic adolescent problem behaviors develop . Over 9,000 kindergarten children at 4 sites in 3 cohorts were screened , and 891 were identified as high risk and then r and omly assigned to intervention or control groups . Beginning in Grade 1 , high-risk children and their parents were asked to participate in a combination of social skills and anger-control training , academic tutoring , parent training , and home visiting . A multiyear universal classroom program was delivered to the core schools attended by these high-risk children . By the end of third grade , 37 % of the intervention group was determined to be free of serious conduct-problem dysfunction , in contrast with 27 % of the control group . Teacher ratings of conduct problems and official records of use of special education re sources gave modest effect-size evidence that the intervention was preventing conduct problem behavior at school . Parent ratings provided additional support for prevention of conduct problems at home . Parenting behavior and children 's social cognitive skills that had previously emerged as proximal outcomes at the end of the 1st year of intervention continued to show positive effects of the intervention at the end of third grade Complex interventions are more than the sum of their parts , and interventions need to be better theorised to reflect this Many people think that st and ardisation and r and omised controlled trials go h and in h and . Having an intervention look the same as possible in different places is thought to be paramount . But this may be why some community interventions have had weak effects . We propose a radical departure from the way large scale interventions are typically conceptualised . This could liberate interventions to be responsive to local context and potentially more effective while still allowing meaningful evaluation in controlled design s. The key lies in looking past the simple elements of a system to embrace complex system functions and processes . The suitability of cluster r and omised trials for evaluating interventions directed at whole communities or organisations remains vexed.1 It need not be.2 Some health promotion advocates ( including the WHO European working group on health promotion evaluation ) believe r and omised controlled trials are inappropriate because of the perceived requirement for interventions in different sites to be st and ardised or look the same.1 3 4 They have ab and oned r and omised trials because they think context level adaptation , which is essential for interventions to work , is precluded by trial design s. An example of context level adaptation might be adjusting educational material s to suit various local learning styles and literacy levels . Lead thinkers in complex interventions , such as the UK 's Medical Research Council , also think that trials of complex interventions must “ consistently provide as close to the same intervention as possible ” by “ st and ardising the content and delivery of the intervention.”5 By contrast , however , they do not see this as a reason to reject r and omised controlled trials . These divergent views have led to problems on two fronts . Firstly , the field of health promotion is being turned away from r and omised OBJECTIVES We assessed the effectiveness of a 5-year trial of a comprehensive school-based program design ed to prevent substance use , violent behaviors , and sexual activity among elementary-school students . METHODS We used a matched-pair , cluster-r and omized , controlled design , with 10 intervention schools and 10 control schools . Fifth- grade rs ( N = 1714 ) self-reported on lifetime substance use , violence , and voluntary sexual activity . Teachers of participant students reported on student ( N = 1225 ) substance use and violence . RESULTS Two-level r and om-effects count models ( with students nested within schools ) indicated that student-reported substance use ( rate ratio [ RR ] = 0.41 ; 90 % confidence interval [ CI ] = 0.25 , 0.66 ) and violence ( RR = 0.42 ; 90 % CI = 0.24 , 0.73 ) were significantly lower for students attending intervention schools . A 2-level r and om-effects binary model indicated that sexual activity was lower ( odds ratio = 0.24 ; 90 % CI = 0.08 , 0.66 ) for intervention students . Teacher reports substantiated the effects seen for student-reported data . Dose-response analyses indicated that students exposed to the program for at least 3 years had significantly lower rates of all negative behaviors . CONCLUSIONS Risk-related behaviors were substantially reduced for students who participated in the program , providing evidence that a comprehensive school-based program can have a strong beneficial effect on student behavior OBJECTIVE To examine the effects of a multi-component , theory-based , 2.5-year intervention on children 's fruit and vegetable consumption , preferences , knowledge and body mass index . METHODS Four inner city elementary schools in the Northeastern United States were r and omized to an intervention ( n=149 ) or control group ( n=148 ) in 2005 . Fruit and vegetable consumption during school lunch ( measured by plate waste ) , preferences , and knowledge , as well as body mass index , were assessed five times across 3.5 years ( pre-intervention , spring 2006 , 2007 , 2008 and 2009 ) . Hierarchical linear modeling was used to analyze program outcomes . RESULTS At the first post-test assessment , children in the experimental group ate 0.28 more servings/lunch of fruit and vegetable relative to children in the control group and changes in fruit and vegetable consumption were found in each year throughout the program . However , this effect declined steadily across time so that by the delayed one-year follow-up period there was no difference between the groups in fruit and vegetable consumption . There were persistent intervention effects on children 's knowledge . There were no effects on fruit and vegetable preferences and body mass index throughout the study . CONCLUSION Although there was initial fruit and vegetable behavior change , annual measurements indicated a gradual decay of behavioral effects . These data have implication s for the design of school-based fruit and vegetable interventions OBJECTIVE To develop a scoring algorithm and evaluate the reliability and validity of scores from the Child and Adolescent Trial for Cardiovascular Health ( CATCH ) Food Checklist ( CFC ) as measures of total fat , saturated fat , and sodium intake in middle school students . DESIGN R and omized , controlled trial in which participants were assigned to 1 of 3 study protocol s that varied the order of CFC and 24-hour dietary recall administration . Criterion outcomes were percent energy from total fat , percent energy from saturated fat , and sodium intake in milligrams . SUBJECTS/ SETTING A multiethnic sample ( 33 % ethnic and racial minorities ) of 365 seventh- grade students from 8 schools in 4 states . STATISTICAL ANALYSES Multivariable regression models were used to calibrate the effects of individual food checklist items ; bootstrap estimates were used for cross-validation ; and kappa statistics , Pearson correlations , t tests , and effect sizes were employed to assess reliability and validity . RESULTS The median same-day test-retest reliability kappa for the 40 individual CFC food items was 0.85 . With respect to item validity , the median kappa statistic comparing student choices to those identified by staff dietitians was 0.54 . Test-retest reliability coefficients ranged from 0.84 to 0.89 for CFC total nutrient scores . Correlations between CFC scores and 24-hour recall values were 0.36 for total fat , 0.36 for saturated fat , and 0.34 for sodium ; CFC scores were consistent with hypothesized gender differences in nutrient intake . APPLICATIONS/ CONCLUSIONS The CFC is a reliable and valid tool for measuring fat , saturated fat , and sodium intake in middle school students . Its brevity and ease of administration make the CFC a cost-effective way to measure middle school students ' previous day 's intake of selected nutrients in school surveys and intervention studies This paper describes development , over a five-year period , of the Hunter Region Health Promoting Schools Project in New South Wales ( NSW ) , Australia . The project implemented the principles and philosophy of the Health Promoting Schools concept and evaluated its effectiveness using a r and omized controlled trial involving 22 public secondary schools . An overview of the preliminary intervention model based on the health promoting schools philosophy and trialed in a pilot study is provided . The authors also outline barriers to , and difficulties in , implementing the philosophically based intervention model in the secondary school setting . The current intervention approach , which evolved over five years , is described in relation to the roles played by project team members and school communities . In addition , the authors outline guiding principles arising from the new approach which facilitated adoption of health promotion strategies in secondary school setting OBJECTIVE Summarizes the research and intervention design of a new trial to evaluate an adaptation of Project Northl and , a multicomponent , community-wide alcohol prevention program for culturally diverse youth living in a large city . The original Project Northl and was successful in reducing alcohol use among a sample of mostly White , rural adolescents . METHODS We highlight the steps taken to adapt the intervention strategies for culturally diverse inner-city youth , families , and neighborhoods . The research design is a r and omized controlled trial to evaluate the effectiveness of the adapted Project Northl and for reducing the early onset and prevalence of alcohol use among young urban adolescents . CONCLUSION The information gained from this trial , including the process of adaptation of prevention strategies , will be beneficial for alcohol-use prevention efforts within diverse urban communities across the country The aim of the present study was to evaluate the effects of a middle school physical activity and healthy eating intervention , including an environmental and computer-tailored component , and to investigate the effects of parental involvement . A r and om sample of 15 schools with seventh and eight grade rs was r and omly assigned to one of three conditions : ( i ) intervention with parental involvement , ( ii ) intervention alone and ( iii ) control group . In 10 schools , an intervention , combining environmental changes with computer-tailored feedback , was implemented over 2 school years . In five intervention schools , increased parental support was added . Physical activity was measured with question naires in the total sample and with accelerometers in a sub- sample of children . Fat intake , fruit , water and soft drink consumption were measured using food-frequency question naires . Results showed significant positive intervention effects on physical activity in both genders and on fat intake in girls . Parental involvement did not increase intervention effects . It can be concluded that physical activity and eating behaviours of middle school children can be improved by school-based strategies combining environmental and personal interventions . The use of personalized computer-tailored interventions seems to be a promising tool for targeting adolescents but needs to be further explored Purpose . To describe a 4-year intervention targeting fruit/vegetable consumption by high school students . Design . This is a cohort study involving six pairs of schools ( n = 12 ) matched on gender , race , enrollment , and location with schools r and omly assigned within pairs to intervention or control conditions . Setting . Twelve Archdiocese of New Orleans high schools . Subjects . Cohort was defined as students ( n = 2339 ) who were ninth- grade rs in the 1993–94 school year who provided baseline data . Intervention . Four components of the intervention are : ( 1 ) school-wide media-marketing campaign , ( 2 ) school-wide meal and snack modification , ( 3 ) classroom workshops and supplementary subject matter activities , and ( 4 ) parental involvement . Measures . Focus groups were conducted for target population input and program development . Process evaluation included student feedback on media-marketing intervention material s and activities reported here . Process measures also included school meal participation , student characteristics , and verification of intervention activities . Results . Focus groups indentified barriers to increased consumption of fruit and vegetables as lack of availability , variety , and inconsistency in taste . Student attitudes were favorable regarding a school program to improve diet and parental involvement . Low consumption of fruits/vegetables was reported . After a 2-month school-wide program introduction utilizing various media-marketing material s and activities , 93 % of students were aware of the program and 96 % could identify the healthy eating message . Conclusions . Program development can be guided and enriched by student input via focus groups . Media-marketing activities effectively delivered health messages and attracted students ' attention . Material s and activities used were acceptable channels for increasing awareness , positive attitudes , and knowledge about fruits/vegetables HEALTHY was a 3-year middle school-based primary prevention trial to reduce modifiable risk factors for type 2 diabetes in youth . The study was conducted at seven centers across the country . This paper describes the recruitment and retention activities employed in the study . Schools and students were the focus of recruitment and retention . Each center was responsible for the recruitment of six schools ; eligibility was based on ability to enroll a sufficient number of predominately minority and lower socioeconomic status students . Study staff met with district superintendents and school principals to verify the eligibility of schools , and to ascertain how appropriate the school would be for conducting the trial . Sixth grade students were recruited employing a variety of techniques ; students and their parents did not know whether their school was r and omized to the intervention or control arm . This cohort was followed through sixth , seventh and eighth grade s. In the eighth grade , an additional sample of students who were not originally enrolled in the study was recruited in a similar manner to participate in data collection to allow for cross-sectional and dose-response secondary analyses . Parents signed informed consent forms and children signed informed assent forms , as per the needs of the local Institutional Review Board . Parents received a letter describing the results of the health screening for their children after data collection in sixth and eighth grade s. Retention of schools and students was critical for the success of the study and was encouraged through the use of financial incentives and other strategies . To a large extent , student withdrawal due to out-migration ( transfer and geographical relocation ) was beyond the ability of the study to control . A multi-level approach that proactively addressed school and parent concerns was crucial for the success of recruitment and retention in the HEALTHY study PURPOSE To investigate the effectiveness of a universal intervention design ed to reduce depressive symptoms experienced by adolescents at high school . The results from annual assessment s during the 3-year intervention and a 2-year follow-up are reported . METHODS Twenty-five pairs of secondary schools matched on socio-economic status were r and omly assigned to either an intervention or a comparison group ( n = 5,633 year 8 students , mean age = 13.1 years , SD = .5 ) . The intervention used a comprehensive classroom curriculum program , enhancements to school climate , improvements in care pathways , and community forums . A range of measures completed by students and teachers was used to assess changes in depressive symptoms , risk and protective factors relevant to depression , and the quality of the school environment . RESULTS Changes in the levels of depressive symptoms and in the levels of risk and protective factors experienced by students in the two groups did not differ significantly over the 5 years of the study . Statistically significant differences in the ratings of school climate across this time were found only for teacher-rated assessment s. CONCLUSIONS There was little evidence that a multicomponent universal intervention delivered over a 3-year period reduced levels of depressive symptoms among participating students . Implementing universal interventions to improve student mental health is difficult in school setting s that commonly have a crowded agenda of educational and health-related programs . Successful implementation will require programs which are perceived by teachers and students as relevant to educational and learning goals , and which can be effectively delivered in conjunction with other school programs OBJECTIVE Our primary objective was to determine whether a novel ' active school ' model -- Action Schools ! BC -- improved the cardiovascular disease ( CVD ) risk profile in elementary-school children . Our secondary objective was to determine the percentage of children with elevated CVD risk factors . METHODS We undertook a cluster-r and omized controlled school-based trial with 8 elementary schools across 1 school year , in British Columbia , Canada , beginning in 2003 . Boys and girls ( n=268 , age 9 - 11 years ) were r and omly assigned ( by school ) to usual practice ( UP , 2 schools ) or intervention ( INT , 6 schools ) groups . We assessed change between groups in cardiovascular fitness ( 20-m Shuttle Run ) , blood pressure ( BP ) , and body mass index ( BMI , wt/ht(2 ) ) . We evaluated total cholesterol ( TC ) , total : high-density cholesterol ( TC : HDL-C ) , low-density lipoprotein , apolipoprotein B , C-reactive protein and fibrinogen on a subset of volunteers ( n=77 ) . RESULTS INT children had a 20 % greater increase in fitness and a 5.7 % smaller increase in BP compared with children attending UP schools ( P<0.05 ) . Forty five percent of children had at least one elevated risk factor ( fitness , BP or BMI ) at baseline . There were no significant differences between groups for change in BMI or in any of the blood variables . CONCLUSION Action Schools ! BC was an effective school-based physical activity model for improving the CVD risk profile of elementary-school children . Our multi-component intervention exposed children to fitness enhancing physical activity . It may be important for education stakeholders to adequately re source the delivery of the active school models if cardiovascular health benefits are to be achieved on a population basis Background Community-based interventions are needed to reduce the burden of childhood obesity . Purpose To evaluate the impact of a multi-level promotora-based ( Community Health Advisor ) intervention to promote healthy eating and physical activity and prevent excess weight gain among Latino children . Methods Thirteen elementary schools were r and omized to one of four intervention conditions : individual/family level ( Family-only ) , school/community level ( Community-only ) , combined ( Family + Community ) , or a measurement-only condition . Participants were 808 Latino parents and their children enrolled in kindergarten through 2nd grade . Measures included parent and child body mass index ( BMI ) and a self-administered parent survey that assessed several parent and child behaviors . Results There were no significant intervention effects on children ’s BMI z-score . The family intervention changed several obesity-related child behaviors ( e.g. , fruit/vegetable consumption ) and these were mediated by changes in parenting variables ( e.g. , parent monitoring ) . Conclusion A promotora-based behavioral intervention was efficacious at changing parental factors and child obesity-related health behaviors The present study tested the impact of a parent behavior-management intervention on child depressive and internalizing symptoms . One hundred eighty-one children were r and omly assigned to receive a videotape modeling parenting intervention , the Incredible Years , or to a wait-list control group . Children who received the intervention were more likely to have lower mother-rated mood and internalizing symptoms at post-treatment , compared with children in a wait-list control group . The effect sizes observed in the present intervention fell in the small-to-medium range for the sample as a whole , and some evidence supported the authors ' hypothesis that effects would be strongest for children with baseline internalizing symptoms in the clinical range . Subsequent analyses also revealed that perceived changes in parenting effectiveness mediated the effect of treatment on children 's post-treatment internalizing symptoms . The finding was consistent with study hypotheses and social learning explanations of child internalizing symptoms that guided selection of putative mechanisms . Implication s for counseling psychologists and for design ing interventions and prevention strategies for children with internalizing symptoms are discussed . ( PsycINFO Data base Record ( c ) 2010 APA , all rights reserved ) Background Substance use is highly prevalent among Dutch adolescents . The Healthy School and Drugs program is a nationally implemented school-based prevention program aim ed at reducing early and excessive substance use among adolescents . Although the program 's effectiveness was tested in a quasi-experimental design before , many program changes were made afterwards . The present study , therefore , aims to test the effects of this widely used , renewed universal prevention program . Methods / Design A r and omized clustered trial will be conducted among 3,784 adolescents of 23 secondary schools in The Netherl and s. The trial has three conditions ; two intervention conditions ( i.e. , e-learning and integral ) and a control condition . The e-learning condition consists of three digital learning modules ( i.e. , about alcohol , tobacco , and marijuana ) that are sequentially offered over the course of three school years ( i.e. , grade 1 , grade 2 , and grade 3 ) . The integral condition consists of parental participation in a parental meeting on substance use , regulation of substance use , and monitoring and counseling of students ' substance use at school , over and above the three digital modules . The control condition is characterized as business as usual . Participating schools were r and omly assigned to either an intervention or control condition . Participants filled out a digital question naire at baseline and will fill out the same question naire three more times at follow-up measurements ( 8 , 20 , and 32 months after baseline ) . Outcome variables included in the question naire are the percentage of binge drinking ( more than five drinks per occasion ) , the average weekly number of drinks , and the percentage of adolescents who ever drunk a glass of alcohol and the percentage of adolescents who ever smoked a cigarette or a joint respectively for tobacco and marijuana . Discussion This study protocol describes the design of a r and omized clustered trial that evaluates the effectiveness of a school-based prevention program . We expect that significantly fewer adolescents will engage in early or excessive substance use behaviors in the intervention conditions compared to the control condition as a direct result of the intervention . We expect that the integral condition will yield most positive results , compared with the e-learning condition and control condition . Trial registration The protocol for this study is registered with the Nederl and s Trial Register |
13,214 | 29,693,726 | Two combination regimens had the poorest rankings for side-effects .
Carbetocin had similar risk for side-effects compared with oxytocin although the quality evidence was very low for vomiting and for fever , and was low for hypertension .
Ergometrine plus oxytocin combination , carbetocin , and misoprostol plus oxytocin combination were more effective for preventing PPH ≥ 500 mL than the current st and ard oxytocin .
Ergometrine plus oxytocin combination was more effective for preventing PPH ≥ 1000 mL than oxytocin .
Misoprostol plus oxytocin combination evidence is less consistent and may relate to different routes and doses of misoprostol used in the studies . | BACKGROUND Postpartum haemorrhage ( PPH ) is the leading cause of maternal mortality worldwide .
Prophylactic uterotonic drugs can prevent PPH , and are routinely recommended .
There are several uterotonic drugs for preventing PPH but it is still debatable which drug is best .
OBJECTIVES To identify the most effective uterotonic drug(s ) to prevent PPH , and generate a ranking according to their effectiveness and side-effect profile . | Abstract Objective To evaluate whether routine administration of sublingual misoprostol 600 μg after delivery reduces postpartum haemorrhage . Design R and omised double blind placebo controlled trial . Setting Primary health centre in Bissau , Guinea-Bissau , West Africa . Participants 661 women undergoing vaginal delivery . Intervention Misoprostol 600 μg or placebo administered sublingually immediately after delivery . Main outcome measures Postpartum haemorrhage , defined as a loss of ≥ 500 ml and decrease in haemoglobin concentration after delivery . Results The incidence of postpartum haemorrhage was not significantly different between the two groups , the relative risk being 0.89 ( 95 % confidence interval 0.76 to 1.04 ) in the misoprostol group compared with the placebo group . Mean blood loss was 10.5 % ( −0.5 % to 20.4 % ) lower in the misoprostol group than in the control group . Severe postpartum haemorrhage of ≥ 1000 ml or ≥1500 ml occurred in 17 % ( 56 ) and 8 % ( 25 ) in the placebo group and 11 % ( 37 ) and 2 % ( 7 ) in the misoprostol group . Significantly fewer women in the misoprostol group experienced a loss of ≥1000 ml ( 0.66 , 0.45 to 0.98 ) or ≥ 1500 ml ( 0.28 , 0.12 to 0.64 ) . The decrease in haemoglobin concentration tended to be less in the misoprostol group , the mean difference between the two groups being 0.16 mmol/l ( −0.01 mmol/l to 0.32 mmol/l ) . Conclusion Sublingual misoprostol reduces the frequency of severe postpartum haemorrhage Purpose In India , two third of maternal deaths occur in rural areas where there is lack of transportation facilities , lack of refrigeration to store the injectable uterotonic drug such as oxytocin , lack of skilled personnel to administer them and lack of sterile syringes and needles . Hence , this study was conceived to evaluate misoprostol as a safe , effective , easily administered non-parenteral drug in the prevention of postpartum hemorrhage . Methods This study was conducted during the period from August 2012 to July 2014 . Low risk women with singleton pregnancy at term admitted for vaginal delivery were eligible for the study . A total of 500 women were r and omized to two groups , 250 in each group , either to receive 400 mcg misoprostol sublingually or 10 units oxytocin intramuscularly at the delivery of anterior shoulder . Patient factors , labor parameters , blood loss and side effects were noted . Results The women in both the groups were well matched with respect to age , parity , gestational age and labor parameters . There was statistical significance in the blood loss ( p = 0.04 ) between the two groups . The average blood loss was 70 ml in misoprostol group and 75 ml in oxytocin group . Shivering was the statistically significant side effect ( p = 0.004 ) in the misoprostol group and nausea was the statistically significant side effect ( p = 0.003 ) in the oxytocin group . Conclusions Sublingual misoprostol is as effective as intramuscular oxytocin as a prophylactic oxytocic in the active management of third stage of labor for prevention of postpartum hemorrhage OBJECTIVE In the poor underdeveloped countries , anaemia is very common in pregnant women . Maternal mortality is four times higher in severely anaemic women than non-anaemic ones and postpartum haemorrhage ( PPH ) is the most common cause of death . Its main cause is uterine atony , which accounts for more than 70 % . The objective of this study is to evaluate the use of sublingual misoprostol in different doses of 600 , 800 and 1000μg in management of the third stage of labor , with regards to blood loss and incidence of atonic postpartum haemorrhag ( APPH ) . STUDY DESIGN Double blind r and omized controlled study METHODS One thous and and two hundred parturient were studied in a control and three study groups , each composed of 300 women . Methylergometrine 0.2 mg IM injection and sublingual misoprostol 600 , 800 and 1000 μg tablets were given to women in control and the three study groups respectively , immediately after delivery . OUTCOME MEASURES Duration of the third stage of labour , Blood loss in the third stage of labour , Outcomes in anaemic compared to non-anaemic women , Incidance of atonic postpartum haemorrhage in different groups , Haemoglobin deficit after 24 hrs of delivery , Changes in the women 's blood pressure during the study , Side effects of the drug , and , Women 's acceptability of sublingual misoprostol administration . RESULTS Only significant reduction in blood loss and haemoglobin deficits were seen in the third stage of labour and after delivery in women used misoprostol doses of 800 μg and 1000 μg . The incidences of PPH in studied women and controls were almost similar , ranging between 2 and 3 % . Similar results were seen in anaemic and non-anaemic women with a higher incidence of APPH in the non-misoprostol user anaemic women . Side effects of the drug were dose related . CONCLUSION Misoprostol in high dose may be used for managing third stage of labour to reduce maternal morbidity and mortality due to APPH particularly , in the poor underdeveloped countries where , facilities to deliver in health centers , purchase and store the oxytocic ampoules or medically trained persons are not readily available in all places . Benefits of large dose misoprostol outweigh its side effects The haemodynamic effects of oxytocin receive scant attention in pharmacology texts , but may be clinical ly significant in vulnerable patients . Despite prescriber information recommending a dose of 5 international units by slow i.v . injection , it is the authors ' experience that it is very common practice in the UK to give 10 units as a rapid injection . We therefore conducted a r and omised , double-blind study of the haemodynamic changes induced by rapid bolus of 5 or 10 units of oxytocin in 34 healthy term parturients at caesarean section under spinal anaesthesia . There was a small but statistically significant ( P < 0.05 ) reduction in mean arterial pressure from baseline 30 s after a 10-unit bolus . However , large , statistically significant increases in heart rate and cardiac output occurred 1 min after 5 units and 2 min after 10 units . These changes peaked 1 min after oxytocin administration and were greater in the 10-unit group ( P < 0.05 ) . The importance of these findings is that some women with hypovolaemia or cardiac disease may be unable to mount these compensatory responses and are therefore at risk of haemodynamic collapse after oxytocin boluses . This has been illustrated by a maternal death reported to the Confidential Enquiries into Maternal Deaths in the United Kingdom . The need to adhere to a dose regimen of 5 units by slow injection needs re-emphasis , but no evidence exists to cl aim that even this will be haemodynamically inert . We therefore recommend that oxytocin boluses be avoided in women with hypovolaemia or cardiac disease INTRODUCTION Although the third stage of labour is usually uneventful , several significant complications may be encountered that may lead to maternal morbidity and mortality , especially primary postpartum haemorrhage . The objective of this study was to compare 400 ug oral misoprostol with 10 IU intramuscular oxytocin in the active management of the third stage of labour . METHODS This was a prospect i ve r and omised controlled clinical trial in which 200 parturients at term who had vaginal delivery were r and omly assigned into two groups : oral misoprostol and intramuscular oxytocin , after the delivery of the baby and the clamping of the umbilical cord . The primary outcome was the incidence of primary postpartum haemorrhage . Secondary outcomes included a drop in haemoglobin concentration 48 hours after delivery , the need for extra oxytocics , duration of the third stage of labour and side effects of the oxytocics . These results were subjected to statistical analysis using chi-square test or student 's t-test . RESULTS No occurrence of primary postpartum haemorrhage or significant difference in the drop in haemoglobin concentration levels was reported after delivery ( p-value is 0.49 ) , and no significant differences were observed in other secondary outcome measures with the exception of nausea , which occurred solely in the misoprostol group ( 4 percent , p-value is 0.04 ) . CONCLUSION Oral misoprostol appeared to be as effective and as safe as intramuscular oxytocin in the active management of the third stage of labour OBJECTIVE To compare the effects of oral misoprostol 800 mug with intramuscular oxytocin 10 IU in routine management of the third stage of labour . METHODS This r and omized controlled trial was performed in a rural district hospital in Ghana , West Africa , and enrolled women in labour with anticipated vaginal delivery and no known medical contraindication to prostagl and in administration . Women were r and omized to receive oral misoprostol 800 mug or intramuscular oxytocin 10 IU . Blood sample s were taken to determine hemoglobin concentration before delivery and at 12 hours post partum . Treatment was administered at delivery of the anterior shoulder . The primary outcome was the change in hemoglobin concentration from before to after delivery . Secondary outcomes included other measures of blood loss and presumed medication side effects . RESULTS In total , 450 women were enrolled in the study . Their baseline characteristics were similar . There was no significant difference between the groups in the change in hemoglobin concentration ( misoprostol 1.07 g/dL and oxytocin 1.00 g/dL ) . The only significant secondary outcomes were shivering ( 80.7 % with misoprostol vs. 3.6 % with oxytocin ) and pyrexia ( 11.4 % with misoprostol , none with oxytocin ) . CONCLUSION Routine use of oral misoprostol 800 microg appears to be as effective as 10 IU parenteral oxytocin in minimizing blood loss during the third stage of labour , as determined by change in hemoglobin concentration . Misoprostol appears to be a safe , inexpensive , and effective uterotonic for use in rural and remote areas , where intravenous oxytocin may be unavailable Summary In this study , 100 singleton pregnant women underwent a caesarean delivery under general anaesthesia and were studied in terms of postpartum bleeding using oxytocin or misoprostol . Patients were r and omly divided into two equal groups . One group received two tabs of misoprostol 200 μg sublingually and the second group took intravenous infusion of 20 units of oxytocin at the rate of 10 cc/min immediately after delivery until full contraction of the uterine . The amount of blood loss was lower in misoprostol group comparing with oxytocin group ( 608.91 ml vs 673.9 ml ) ( p = 0.048 ) and this difference was statistically significant . The need to give additional oxytocin therapy in oxytocin group ( 36 % ) was significantly higher than misoprostol group ( 14 % ) ( p = 0.032 ) . It seems that the efficacy of sublingual misoprostol is equivalent to that of low dose intravenous oxytocin in reducing postpartum haemorrhage at caesarean section . Misoprostol has some other advantages like long shelf -life , stability at room temperature and oral use International research partnerships bring together some of the best and the brightest in an effort to tackle global health problems . Such collaborations also pose complex challenges , such as maintaining ethical principles in the conduct of research in developing nations . In implementing a r and omized clinical trial to reduce postpartum hemorrhage ( PPH ) during childbirth in rural India , U.S. and Indian collaborators addressed three such issues : the appropriateness of an ethical r and omized controlled trial in the developing world , the inclusion of a placebo arm , and the relevance of informed consent in a semiliterate rural population Background The two most commonly used uterotonic drugs in caesarean section are oxytocin and carbetocin , a synthetic oxytocin analogue . Carbetocin has a longer half-life when compared to oxytocin , result ing in a reduced use of additional uterotonics . Oxytocin is known to cause fewer cardiovascular side effects when administered as a short-infusion compared to as an intravenous bolus . Based on these findings , we aim at comparing carbetocin 100 mcg given as a slow intravenous bolus with carbetocin 100 mcg applied as a short-infusion in 100 ml 0.9 % sodium chloride in women undergoing a planned or unplanned caesarean delivery . We hypothesise uterine contraction not to be inferior to a bolus application ( primary efficacy endpoint ) and greater haemodynamic stability to be achieved after a short-infusion than after a bolus administration , as measured by heart rate and mean arterial blood pressure ( primary safety endpoint ) . Methods / Design This is a prospect i ve , double-blind , r and omised controlled , investigator-initiated , non-inferiority trial taking place at the University Hospital Basel , Switzerl and .Uterine tone is quantified by manual palpation by the obstetrician using a linear analogue scale from 0 to 100 at 2 , 3 , 5 and 10 minutes after cord clamping . We will evaluate whether the lower limit of the confidence interval for the difference of the maximal uterine tone within the first 5 minutes after cord clamping between both groups does not include the pre-specified non-inferiority limit of −10 . Both haemodynamic secondary endpoints will be analysed using a linear regression model , adjusting for the baseline value and the dosage of vasoactive drug given between cord clamping and 1 minute thereafter , in order to investigate superiority of a short-infusion as compared to a bolus application . We will follow the extension of CONSORT guidelines for reporting the results of non-inferiority trials . Discussion Haemodynamic stability and adequate uterine tone are important outcomes in caesarean sections . The results of this trial may be used to optimise these factors and thereby increase patient safety due to a reduction in cardiovascular side effects . Trial registration Clinical trials.gov NCT02221531 on 19 August 2014 and www.kofam.ch SNCTP000001197 on 15 November 2014 OBJECTIVE To assess the effectiveness of 800 microg of rectal misoprostol compared with an intravenous infusion of 5 IU of oxytocin as prophylaxis against postpartum hemorrhage ( PPH ) . METHODS A total of 514 women in labor were r and omized into two groups ( 257 women in each ) . Within 1 minute of delivery of the anterior shoulder participants in group 1 received 800 microg of rectal misoprostol and 1 ampoule of normal saline in 5 mL lactated Ringer solution intravenously ; group 2 received a rectal placebo tablet and 5 IU of oxytocin in 5 mL lactated Ringer solution intravenously . RESULTS Both groups were comparable regarding the need for uterotonics , blood transfusion , and hematocrit drop of 10 % or greater , 24 hours post partum ( P=0.54 , P=0.25 , and P=0.85 , respectively ) . Fever was significantly higher among misoprostol patients ( 18.7 % vs 0.8 % , P<0.001 ) . CONCLUSIONS Routine use of 800 microg of rectal misoprostol was effective in reducing blood loss after delivery . We recommend the regimen for low-re source , busy obstetric setting Objective To evaluate the side effects of 600 μg misoprostol orally during the first 24 hours after administration in the third stage of labour Purpose In order to prevent postpartum hemorrhage in caesarean section under spinal anesthesia , patients routinely receive oxytocin . In this study we compared the efficacy of Methylergonovine and Oxytocin on hemodynamic stability and bleeding amount in caesarean section . Material s and methods In this r and omised controlled trial study , 80 patients c and i date for elective caesarean section under spinal anesthesia divided to two groups : 40 patients in control group received oxytocin and 40 ones in case group received methylergonovine . Results There was no differences between groups in Mean age , baseline hemodynamic values , after spinal anesthesia and recovery ( except diastolic blood pressure min 20 ) , time of uterine atony , dizziness ; nausea and vomiting . After drug administration ( oxytocin and methylergonovine ) , systolic blood pressure in minutes 1 , 10 , 15 and diastolic blood pressure in minutes 1 , 3 , 20 increased in case group statistically more than control group . In control group , heart rate in minutes 1 , 5 increased significantly more than the other group . Mean arterial blood pressure in minutes 1 , 3 , 5 , 10 , 15 reduced significantly more than in control group . Need to vasoconstrictor drug statistically was less in case group ( p < 0.0001 ) . Conclusion Methylergonovine induced significantly more hemodynamic stability . Adverse effects were similar between two groups . We recommend the use of methylergonovine in patients with caesarean section under spinal anesthesia because of its hemodynamic stability and low need to vasoconstrictor drugs It is perhaps surprising that as yet no consensus exists among clinicians concerning the best way to prevent postpartum hemorrhage . The present study was conducted as an attempt to evaluate the scope of 125 µg ( note the dosage ) of carboprost tromethamine given intramuscularly in comparison with intravenous methyl ergometrine . Two hundred and fifteen parturients were r and omly assigned to use either drug at the time of delivery of anterior shoulder of the baby . The outcome measures were duration of third stage the measured blood loss after placental delivery and the incidence of side effects . Amount of blood loss was quantified by noting the increment in weight of st and ardised tampons which were placed high up in the vagina immediately after placental delivery . Weight of blood in grams was considered equal to volume in ml . ( excerpt OBJECTIVE To estimate the effects of adding intravenous tranexamic acid ( TA ) to the st and ard active management of third-stage labor to reduce vaginal blood loss during the third and fourth stages of labor . STUDY DESIGN A prospect i ve , double-blind , equivalence r and omized , controlled study was performed . Women were r and omly allocated to receive an intravenous infusion of TA ( experimental group , n = 228 ) or 5 % glucose ( placebo group , n = 226 ) at delivery of the anterior shoulder . Active management of the third stage of labor , which includes prophylactic injection of 10 IU of oxytocin within 2 minutes of birth , early clamping of the umbilical cord , and controlled cord traction following delivery , was used in both groups . The primary outcome was mean blood loss during the third and fourth stages of labor . RESULTS Mean estimated blood loss at the third and fourth stages of labor was significantly lower in the experimental group than that in the placebo group ( 261.5 ± 146.8 mL versus 349.98 ± 188.85 mL , respectively ; p < 0.001 ) . The frequency of postpartum hemorrhage > 500 mL was also lower in the experimental group ( 4 , 1.8 % ) compared with that in the placebo controls ( 15 , [ 6.8 % ] ; relative risk , 3.76 ; 95 % confidence interval , 1.27 to 11.15 ; p = 0.01 ) . No episode of thrombosis occurred in the women who received TA . CONCLUSIONS The use of TA with st and ard active management of the third stage of labor reduced postpartum blood loss , and no increase in the incidence of thromboembolic events was observed Purpose Prevention of postpartum haemorrhage ( PPH ) is essential in the pursuit of improved health care for women . Oxytocin , the most commonly used uterotonic agent to prevent PPH , has no established the route of administration . In this study we aim ed to compare whether the mode of oxytocin administration , i.e. , intravenous and intramuscular administration , has an effect on the potential benefits and side effects . Material s and methods A total of 256 women were r and omised into two groups : intramuscular group ( 128 ) or intravenous group ( 128 ) . Results Estimated blood loss during the third stage of labour was similar between the two groups ( p = 0.572 ) . Further there were no statistically significant difference was noted between the two groups in terms of the mean duration of labor , duration of the third stage of labor , manual removal of the placenta , need for instrumental delivery , need for blood transfusion , PPH ≥500 mL , PPH ≥1000 mL , or length of hospital stay . Conclusion Using oxytocin by intravenous and intramuscular route has a similar efficacy and adverse effects OBJECTIVE To evaluate the effect of preoperative administration of rectal misoprostol on blood loss during and after elective cesarean delivery . METHODS A r and omized controlled trial was conducted among 400 women scheduled for elective cesarean delivery . The study group ( n=200 ) received 400 μg of misoprostol . The control group ( n=200 ) received placebo . Study medications were administered rectally after catheter insertion and shortly before skin incision . The main outcome measures were intra-operative blood loss , postpartum blood loss at 24 hours , and difference between preoperative and postoperative hematocrit values . RESULTS The mean intra-operative and postpartum blood loss was significantly lower in the study group than the control group : 429 ± 234 mL and 185 ± 95 mL versus 620 ± 375 mL and 324 ± 167 mL , respectively ( P=0.001 for both comparisons ) . The difference between the preoperative and postoperative hematocrit values was also significantly lower in the study group than the control group ( 4.62 ± 2.45 versus 8.15 ± 3.84 ; P=0.02 ) . Admissions to the neonatal intensive care unit and Apgar scores at 1 and 5 minutes were comparable between the 2 groups . CONCLUSION Preoperative treatment with 400 μg rectal misoprostol significantly reduced blood loss related to elective cesarean delivery The use of umbilical vein injection of oxytocin was compared with traditional management of the third stage of labor . Pregnant women were r and omized to receive intravenous oxytocin after the delivery of the placenta ( n = 25 ) or oxytocin via the umbilical vein immediately after cord clamping ( n = 25 ) . Those who received umbilical vein oxytocin had a shorter third stage of labor ( 4.1 versus 9.4 minutes ) , less measured blood loss ( 135 versus 373 ml ) , and a lower drop in hematocrit ( 3.9 % versus 6.2 % ) . Intraumbilical vein oxytocin appears to be a useful alternative to traditional management of the third stage of labor Objective To compare oral misoprostol 400 μg with intramuscular oxytocin 10 IU in the routine management of the third stage OBJECTIVES a ) To compare the clinical effect of rectal misoprostol with intramuscular syntometrine in reducing blood loss in the third stage of labour b ) to determine the severity and incidence of side effects of both drugs and c ) to measure blood loss , patient tolerance and acceptance of rectal misoprostol . METHODS One hundred and forty parturients were r and omly allocated to receive intramuscular syntometrine ( syntocinon 10 IU + ergometrine 0.5 mg ) or rectal misoprostol 400 microg within five minutes of the delivery of the anterior shoulder Blood loss was measured by the use of a plastic collection drape . Additional oxytocic therapy was instituted for uterine atony or if blood loss was in excess of one litre . RESULTS There was no significant difference in patient demographics of each treatment group ( Table 1 ) . There was no difference in mean duration of the third stage of labour ( 8.4 + /- 14 min vs 7.8 + /- 6.6 min ) . The mean blood loss from those parturients receiving misoprostol ( 180.1 + /- 120 mls ) was not significantly different ( p = 0.5 ) from those receiving syntometrine ( 197 + /- 176.97 mls ) for the active management of the third stage of labour Treatment with syntometrine was associated with a significant elevation of post-partum systolic blood pressure compared with misoprostol treatment ( mean increase 0.57 + /- 18.79 mmHg vs -1.43 + /- 14.17 mmHg , ( mean + /- SD ) , p < 0.04 ) . Rectal misoprostol was well tolerated in 88.5 % of participants , 11.4 % reported that insertion was uncomfortable , of which 2.8 % reported that they would have preferred parenteral drug administration . CONCLUSION The clinical effect of rectal misoprostol and intramuscular syntometrine were not different at the doses used in the active management of the third stage of labour in this study . Rectal misoprostol was well tolerated by the patients and had a low side effect profile . Blood loss assessment using the blood collection drape is of invaluable benefit in re source -poor setting OBJECTIVE : To estimate the minimum effective intravenous dose of oxytocin required for adequate uterine contraction after cesarean delivery for labor arrest . METHODS : A r and omized single-blinded study was undertaken in 30 parturients undergoing cesarean deliveries under epidural anesthesia for labor arrest despite intravenous oxytocin augmentation . Oxytocin was administered as a slow intravenous bolus immediately after delivery of the infant , according to a biased coin up-down sequential allocation scheme . After assisted spontaneous delivery of the placenta , the obstetrician , blinded to the oxytocin dose , assessed uterine contraction as either satisfactory or unsatisfactory . Additional boluses of oxytocin were administered as required , followed by a maintenance infusion . Data were interpreted and analyzed by a logistic regression model at 95 % confidence intervals . RESULTS : All patients received oxytocin infusions at a mean ± st and ard deviation of 9.8 ± 6.3 hours before cesarean delivery ( maximum infusion dose 10.3 ± 8.2 mU/min ) . The minimum effective dose of oxytocin required to produce adequate uterine response in 90 % of women ( ED90 ) was estimated to be 2.99 IU ( 95 % confidence interval 2.32–3.67 ) . The estimated blood loss was 1,178 ± 716 mL. CONCLUSION : Women requiring cesarean delivery for labor arrest after oxytocin augmentation require approximately 3 IU rapid intravenous infusion of oxytocin to achieve effective uterine contraction after delivery . This dose is 9 times more than previously reported after elective cesarean delivery in nonlaboring women at term , suggesting oxytocin receptor desensitization from exogenous oxytocin administration during labor . Therefore , alternative uterotonic agents , rather than additional oxytocin , may achieve superior uterine contraction and control of blood loss during cesarean delivery for labor arrest . LEVEL OF EVIDENCE : BACKGROUND Postpartum haemorrhage is one of the most important causes of maternal death . OBJECTIVES To evaluate the effect of active management of the third stage of labour on the amount of blood loss in the third and fourth stages of labour , and the duration of the third stage of labour . METHODS A r and omised controlled trial was completed on 200 women who gave birth at a maternity unit in Iran . In the intervention group ( n=100 ) , 10IU of oxytocin was injected intramuscularly into the mother following birth of the anterior shoulder of the baby . After clamping and cutting the umbilical cord , the uterus was pushed upwards and posterior , while the cord was pulled down with constant and intermittent traction until the placenta was delivered . In the control group ( n=100 ) , on observing signs of placental separation , the placenta was expulsed by maternal force . In both groups of women , blood loss was measured at birth using collecting devices , and drapes and sheets were weighed to estimate blood loss . FINDINGS Mean blood loss during the third stage of labour was 216.93+/-165.16 ml and 232.12+/-150.35 ml in the intervention and control groups , respectively ; the difference was not significant ( p=0.49 ) . In contrast , mean blood loss during the fourth stage of labour differed significantly ( 422.62+/-324.7 ml and 327.27+/-255.99 ml in the intervention and control groups , respectively ; p=0.02 ) . The mean duration of the third stage of labour was less in the intervention group than in the control group ( 4.69+/-5.51 mins and 6.34+/-5.03 mins ; p=0.028 ) . CONCLUSIONS Active management did not decrease blood loss during the third stage of labour , but did decrease the duration of this stage . Active management was associated with increased blood loss during the fourth stage of labour . Due to conflicting results between studies , further research should be undertaken to determine the optimal method by which to manage the third stage of labour Objectives To determine the effects of adding an oxytocin infusion to bolus oxytocin on blood loss at elective caesarean section . Design Double blind , placebo controlled , r and omised trial , conducted from February 2008 to June 2010 . Setting Five maternity hospitals in the Republic of Irel and . Participants 2069 women booked for elective caesarean section at term with a singleton pregnancy . We excluded women with placenta praevia , thrombocytopenia , coagulopathies , previous major obstetric haemorrhage ( > 1000 mL ) , or known fibroids ; women receiving anticoagulant treatment ; those who did not underst and English ; and those who were younger than 18 years . Intervention Intervention group : intravenous slow 5 IU oxytocin bolus over 1 minute and additional 40 IU oxytocin infusion in 500 mL of 0.9 % saline solution over 4 hours ( bolus and infusion ) . Placebo group : 5 IU oxytocin bolus over 1 minute and 500 mL of 0.9 % saline solution over 4 hours ( placebo infusion ) ( bolus only ) . Main outcomes Major obstetric haemorrhage ( blood loss > 1000 mL ) and need for an additional uterotonic agent . Results We found no difference in the occurrence of major obstetric haemorrhage between the groups ( bolus and infusion 15.7 % ( 158/1007 ) v bolus only 16.0 % ( 159/994 ) , adjusted odds ratio 0.98 , 95 % confidence intervals 0.77 to 1.25 , P=0.86 ) . The need for an additional uterotonic agent in the bolus and infusion group was lower than that in the bolus only group ( 12.2 % ( 126/1033 ) v 18.4 % ( 189/1025 ) , 0.61 , 0.48 to 0.78 , P<0.001 ) . Women were less likely to have a major obstetric haemorrhage in the bolus and infusion group than in the bolus only group if the obstetrician was junior rather than senior ( 0.57 , 0.35 to 0.92 , P=0.02 ) . Conclusion The addition of an oxytocin infusion after caesarean delivery reduces the need for additional uterotonic agents but does not affect the overall occurrence of major obstetric haemorrhage . Trial Registration Current Controlled Trials IS RCT N17813715 AIM To assess the effectiveness of oral misoprostol compared with methylergometrine in the prevention of primary post-partum hemorrhage during the third stage of labor . METHODS This was a r and omized controlled trial of 864 singleton low-risk pregnant women . The outcomes were total blood loss , duration of the third stage of labor and peripartal change in hematocrit . Comparisons were by the chi2-test and Student t-test . Relative risks were calculated for side-effects profile . A P-value of less than 0.05 was statistically significant . RESULTS The bio data of all the participants were similar . The mean blood loss for the misoprostol and methylergometrine groups was 191.6 + /- 134.5 mL and 246.0 + /- 175.5 mL , respectively ( 95 % CI : -79.3 to -39.5 mL ) . The mean duration of the third stage of labor was 19.6 + /- 2.4 min and 9.4 + /- 3.3 min in the misoprostol and methylergometrine groups , respectively ( 95 % CI : 9.82 - 10.58 min ) . More subjects had blood loss > 500 mL , 42 ( 9.7 % ) versus 6 ( 1.4 % ) , and peripartal hematocrit change greater than 10 % , 38 ( 8.8 % ) versus 5 ( 1.2 % ) , in the methylergometrine group than in the misoprostol group , respectively . Also , more subjects received additional oxytocic in the methylergometrine group , compared to the misoprostol group ( 80 [ 18.5 % ] versus 33 [ 7.6 % ] patients , respectively ) . CONCLUSIONS Orally administered misoprostol was more effective in reducing blood loss during the third stage of labor than intramuscular methylergometrine . However , there were more subjects in the misoprostol group in whom duration of the third stage of labor was greater than 15 min and who also had manual placental removal than in the methylergometrine group Background Oral misoprostol , administered by trained health-workers is effective and safe for preventing postpartum haemorrhage ( PPH ) . There is interest in exp and ing administration of misoprostol by non-health workers , including task-shifting to pregnant women themselves . However , the use of misoprostol for preventing PPH in home-births remains controversial , due to the limited evidence to support self-administration or leaving it in the h and s of non-health workers . This study aim ed to determine if antenatally distributing misoprostol to pregnant women to self-administer at home birth reduces PPH . Methods Between February 2013 and March 2014 , we conducted a stepped-wedge cluster-r and omized trial in six health facilities in Central Ug and a. Women at 28 + weeks of gestation attending antenatal care were eligible . Women in the control-arm received the st and ard-of-care ; while the intervention-arm were offered 600mcg of misoprostol to swallow immediately after birth of baby , when oxytocin was not available . The primary outcome ( PPH ) was a drop in postpartum maternal haemoglobin ( Hb ) by ≥ 2g/dl , lower than the prenatal Hb . Analysis was by intention-to-treat at the cluster level and we used a paired t-tests to assess whether the mean difference between the control and intervention groups was statistically significant . Results 97 % ( 2466/2545 ) of eligible women consented to participate ; 1430 and 1036 in the control and intervention arms respectively . Two thous and fifty-seven of the participants were successfully followed up and 271 ( 13.2 % ) delivered outside a health facility . There was no significant difference between the study group in number of women who received a uterotonic at birth ( control 80.4 % vs intervention 91.4 % , mean difference = -11.0 % , 95 % confidence interval [ CI ] -25.7 % to 3.6 % , p = 0.11 ) . No woman took misoprostol before their baby ’s birth . Shivering and fever were 14.9 % in the control arm compared to 22.2 % in the intervention arm ( mean difference = -7.2 % , 95 % CI -11.1 % to -3.7 % ) , p = 0.005 ) . There was a slight , but non-significant , reduction in the percentage of women with Hb drop ≥ 2g/dl from 18.5 % in the control arm to 11.4 % in the intervention arm ( mean difference = 7.1 % , 95 % CI -3.1 % to 17.3 % , p = 0.14 ) . Similarly , there was no significant difference between the groups in the primary outcome in the women who delivered at home ( control 9.6 % vs intervention 14.5 % , mean difference -4.9 ; 95 % CI -12.7 to 2.9 ) , p = 0.17 ) . Conclusion This study was unable to detect a significant reduction in PPH following the antenatal distribution of misoprostol . The study was registered with Pan-African Clinical Trials Network ( PACTR201303000459148 , on 19/11/2012 ) AIM Obstetricians sometimes administer intramyometrial oxytocin to stimulate uterine contraction during cesarean section , but its effects have not been well investigated . We performed a r and omized , double-blind study to test the hypothesis that a small dose of intramyometrial oxytocin would induce acceptable uterine contractility more quickly and with fewer hemodynamic side-effects than the same dose administered intravenously . METHODS Forty women with a single fetus at ≥36 weeks of gestational age scheduled for elective cesarean section under spinal anesthesia were r and omized to the intravenous and intramyometrial groups to receive oxytocin at 0.07 IU/kg . The drug was administered immediately after umbilical cord clamping . Systolic blood pressure , heart rate , intraoperative blood loss , uterine tone , total amount of intraoperative oxytocin , and additional uterotonic drugs administered in the first 24 h were compared . RESULTS Maximum uterine contractility was achieved after 2 and 10 min for the intravenous and intramyometrial groups , respectively . The mean hemodynamic parameters of the intramyometrial group were stable . In contrast , the intravenous group showed a reduction in systolic blood pressure after 2 - 4 min and increased heart rate after 1 - 2 min . Intraoperative blood loss , total oxytocin dose , and frequency of additional uterotonic drugs were comparable between the two groups . CONCLUSION Although intraoperative blood loss was comparable , a small dose of intramyometrial oxytocin was inappropriate to obtain a prompt and acceptable uterine contraction during cesarean section Oxytocin has been the oxytocic of choice for Active Management of Third Stage of Labor ( AMTSL ) [ 1 ] . Misoprostol would be a suitable alternative in low re source setting s where drug delivery is hampered by storage and problems of parenteral administration . In patients who are vomiting , unable to take medications or under anesthesia , rectal administration may be associated with fewer side effects and ease of administration [2].The use of additional uterotonics is significantly higher with rectal 400 mcg misoprostol than with oxytocin [ 3 ] . It is possible that a higher dose of rectal misoprostol may be more effective in reducing blood loss . A prospect i ve , double-blind , r and omized pilot study was undertaken in the Post Graduate Institute of Medical Education and Research ( PGIMER ) , Ch and igarh , India to determine the effectiveness and safety of rectal administration of 600 mcg misoprostol compared to oxytocin as part of the AMTSL in women at low risk for PPH . The study was approved by the ethical committee of the Institute . Two hundred women in spontaneous labor were recruited , and a written informed consent was Postpartum hemorrhage is the leading cause of maternal mortality in India , accounting for 25 - --30 % of all maternal deaths [ 1 ] . A large number of deliveries still occur at home , especially in rural areas . Injectable uterotonics are not necessarily applicable to these setting s , as their effective use requires safe administration and special storage to maintain stability . In this prospect i ve double blind r and omized study conducted in 2005 - 06 at the Postgraduate Institute of Medical Education and Research ( PGIMER ) , Ch and igarh , India , 200 women at low risk of PPH were r and omized to receive either two tablets of misoprostol ( 400 mcg ) sublingually or 1ml of methylergometrine ( 200 mcg ) intramuscularly at the delivery of anterior shoulder of baby . Identical looking placebo tablets and injections were used . Primary and secondary outcomes measured are shown in Table 1 . The duration of third stage , mean blood loss and need for additional oxytocics was similar in Background Postpartum hemorrhage is a significant cause of maternal mortality and morbidity , worldwide . Objectives The aim of this study was to compare the efficacy between carbetocin and syntometrine in prevention of postpartum hemorrhage . Material s and Methods This study was a double blind r and omized clinical trial that carried out on 200 pregnant women referred to Shabiehkhani maternity center of Kashan , during 2011 . The first group received intramuscular syntometrine and the second group received intramuscular carbetocin after placental delivery . All of the participants were followed for 24 hours and blood pressure , pulse rate , uterine tone , hemoglobin concentration at first and 24 hours after delivery , and the need for additional uterotonic drugs and drug side effects were evaluated . Finally all data were analyzed using t-test , chi square tests and logistic regression . Results The mean fall in hemoglobin level in the carbetocin group was significantly lower than the syntometrine group ( P < 0.001 ) . Also there were significant differences between the two groups , regarding additional uterotonic drug requirements ( P = 0.002 ) . Moreover systolic blood pressure and uterine tone immediately and 30 minutes after drug administration were significantly different ( P < 0.001 ) . Incidence rate of tachycardia in the carbetocin group was 13 % , in contrast to 5 % in the syntometrine group ( P = 0.04 ) . Conclusions This study revealed that carbetocin is more effective than syntometrine in prevention of postpartum hemorrhages . Thus it can be used as a good alternative of syntometrine for low-risk women Objective . The main objective of this study was to identify factors associated with variation in the rate of acute postpartum hemorrhage ( PPH ) , defined as blood loss ≥ 500 mL within 2 hours of delivery , observed in a r and omized clinical trial of misoprostol for the prevention of PPH , conducted in rural India . Although the women in the misoprostol group had a significantly lower probability of having a PPH , we also noted a reduction in the rate of PPH in the placebo group over the course of the study . We hypothesized that this was due to the changing skills of the auxiliary nurse midwives ( ANMs ) over the course of the study . Methods . We conducted a post-hoc analysis examining variation in PPH rates over the duration of the trial among the women r and omized to the placebo arm ( n = 808 ) . Descriptive , correlation analysis and generalized estimating equations ( GEE ) were used to predict PPH rates . With no direct measure of ANM skills , we used proxy measures , including : ( 1 ) the ANM 's point of entry into the study ( original ANMs at the initiation of the trial were less skilled than replacement ANMs ) ; ( 2 ) the study duration , representing exposure of the ANM to ongoing training and monitoring ; and ( 3 ) duration of the second stage of labor as a measure of improved delivery practice s. Results . As the study duration increased , the duration of the second stage of labor decreased ( −0.12 , p = 0.001 ) and as the duration of the second stage of labor decreased , the rate of PPH decreased ( 0.0282 ; 95 % CI 0.0201–0.0363 ) . For each 10-minute increase in the duration of second stage labor increased PPH odds by 7.1 % and each 30-day duration of the trial decreased PPH odds by 3.4 % . Additionally , a patient delivered by an original ANM was 3.14 times more likely to have a PPH compared to a patient delivered by a replacement ANM . Conclusions . Declining PPH rates were associated with improved skills and delivery practice s that decreased duration of the second stage of labor . These improvements appeared to be consistent with the introduction of the more skilled replacement ANMs as well as ongoing training and monitoring for all ANMs over the duration of the trial Background . We conducted a double‐blind r and omized controlled trial to compare a conventional regimen of oxytocin and ergometrine with administration of the prostagl and in E2 analogue , sulprostone , for prophylaxis of postpartum hemorrhage in high‐risk women Abstract The aim of the study was to compare the efficacy of sublingual misoprostol in addition to intravenous oxytocin , with oxytocin alone , in reducing blood loss during and following caesarean section . A total of 120 women undergoing caesarean delivery at the University College Hospital , Ibadan , were r and omised into two equal groups . In Group A , 20 IU of intravenous oxytocin was given after umbilical cord clamping , while in Group B , the women received 400 μg misoprostol sublingually and 20 IU oxytocin intravenously . The outcome measures were blood loss , additional uterotonics , change in packed cell volume and side-effect profile . Associations between variables were determined by the χ2 and Student 's t-test . Relative risks were calculated for side-effects ; the level of significance was p < 0.05 . Intraoperative and postoperative blood loss were significantly lower in Group B ( 451.3 ml vs 551.2 ml , p = 0.007 ; 22.7 vs 42.2 ml , p < 0.001 , respectively ) . In Group B , women were 7.4 ( p < 0.001 ) and 9.0 ( p = 0.008 ) times more likely to experience shivering and fever , respectively . The need for additional uterotonics was greater in the oxytocin group ( 66.7 % vs 27.6 % , p < 0.001 ) . The addition of sublingual misoprostol to intravenous oxytocin reduces postpartum blood loss and the need for additional uterotonics . There is however , an increased risk of shivering and fever with this combination The injection of varying volumes of normal saline solution , alone or with oxytocin , into the umbilical vein immediately after delivery was studied in 125 normal women delivered at term . Thirty seconds after cord clamping , either 20 ml ( group 1 , n = 25 women ) , 30 ml ( group 2 , n = 25 ) or 40 ml ( group 3 , n = 25 ) of normal saline solution alone , or oxytocin 10 units in 20 ml saline solution ( group 4 , n = 25 ) or ozytoxin 10 units in 40 ml saline solution ( group 5 , n = 25 ) were injected into the umbilical vein 1 cm from the introitus just proximal to the umbilical clamp . The mean ( ± SD ) duration of placental expulsion was similar in the five study groups . We conclude that neither the volume of the solution nor the oxytocin injected intra‐mumbilically has any effect on the duration of the third stage of normal labor OBJECTIVE --To compare intramuscular oxytocin alone and intramuscular oxytocin with ergometrine ( Syntometrine ) for their effect in reducing the risk of postpartum haemorrhage when both are used as part of the active management of the third stage of labour . DESIGN --Double blind , r and omised controlled trial . SETTING --Two metropolitan teaching hospitals in Perth , Western Australia . SUBJECTS -- All women who expected a vaginal birth during the period of the trial . Informed consent was obtained . MAIN OUTCOME MEASURES --Postpartum haemorrhage , nausea , vomiting , and increased blood pressure . RESULTS --3497 women were r and omly allocated to receive oxytocin-ergometrine ( n = 1730 ) or oxytocin ( n = 1753 ) . Rates of postpartum haemorrhage ( > or = 500 ml or > or = 1000 ml ) were similar in both arms ( odds ratio 0.90 ( 0.82 ) ; 95 % confidence interval 0.75 to 1.07 ( 0.59 to 1.14 ) at 500 ml ( 1000 ml ) threshold ) . The use of oxytocin-ergometrine was associated with nausea , vomiting , and increased blood pressure . CONCLUSIONS --There are few advantages but several disadvantages for the routine use of oxytoxinergometrine when prophylactic active management of the third stage of labour is practised . Further investigation of dose-response for oxytocin may be warranted A r and omised , controlled trial of 1429 women was carried out to compare ' active ' management of the third stage of labour , using i.v . Ergometrine 0.5 mg , with a method of ' physiological ' management , in women at ' low risk ' to haemorrhage . In the " active " management group a higher incidence of the following complications was found:- manual removal of placenta ( p less than 0.0005 ) , problems such as nausea ( p less than 0.0005 ) , vomiting ( p less than 0.0005 ) , and severe after-birth pains ( p less than 0.02 ) , hypertension ( p less than 0.0001 ) and secondary postpartum haemorrhage ( p less than 0.02 ) . The incidence of postpartum haemorrhage ( blood loss greater than 500 ml ) and postnatal haemoglobins less than 10 gm/100 were higher in the ' physiological ' group ( p less than 0.0005 , p less than 0.002 ) . No difference was found in the need for blood transfusion in either group . The routine use of i.v . Ergometrine 0.5 mg during the third stage of labour in women at ' low risk ' to haemorrhage does not appear to be necessary and has many adverse effects . Further studies comparing different methods of ' physiological ' management are recommended in order to reduce to a minimum the incidence of postpartum haemorrhage and anaemia OBJECTIVE To characterize the pharmacokinetics and adverse-effect profile of rectally administered misoprostol . METHODS To assess absorption of rectally administered misoprostol , 20 women were r and omized to receive misoprostol 600 μg by either oral or rectal administration after delivery . Blood sample s were obtained at 0 , 7.5 , 15 , 30 , 45 , 60 , 90 , 120 , and 240 minutes and analyzed for serum concentrations of misoprostol free acid by enzyme-linked immunosorbent assay . Additionally , 275 women were r and omized to receive rectal 400 μg , rectal 600 μg , or oral 600 μg misoprostol after delivery . Self- assessment question naires were used to ascertain the adverse-effect profiles . RESULTS Misoprostol tablets are absorbed rectally even though they are formulated for oral use . The area under the curve ( integral of concentration and time graph ) for rectal misoprostol was higher by 121 pg.h/mL ( 95 % confidence interval [ CI ] 34.2 , 246.2 ) than for oral misoprostol . The rectal route group had a mean maximum serum concentration 144 pg/mL lower than that for the oral route ( 95 % CI 63 , 225 ) . This maximum was achieved on average 23 minutes later than in the oral group ( 95 % CI 10 , 35 ) . Shivering was reported by 76 % of the patients in the oral 600-μg arm , 56 % of the patients in the rectal 400-μg arm , and 54 % of the patients in the rectal 600-μg arm . The relative risk of shivering in the combined rectal groups is 73 % that of the oral group ( 95 % CI 61 % , 86 % ) . Severe shivering reported by patients was significantly reduced , by 72 % , in rectal groups compared with the oral group ( 95 % CI 60 % , 81 % ) . CONCLUSION Misoprostol administered rectally is associated with lower peak levels and a reduction in adverse effects compared with the oral route . Increasing rectal doses may achieve higher efficacy without reducing the acceptability of the treatment Oxytocin was administered in a r and omized fashion via either the umbilical or maternal intravenous route . Women who received intraumbilical oxytocin had significantly greater calculated blood loss compared with those who received peripheral administration ( P = .01 ) . This greater blood loss was confirmed by a decrease in hematocrit and hemoglobin concentrations after delivery . There was no difference between the groups in the length of the third stage of labor . The incidence of fetomaternal transfusion was higher in the intraumbilical group ( P = .07 ) . We conclude that intraumbilical oxytocin is no more beneficial than peripheral administration Objective To compare intravenous oxytocin administration ( Partocon ® 10 IU ) with saline solution in the management of postpartum haemorrhage in the third stage of labour Abstract Background Post-partum hemorrhage ( PPH ) is the most common direct cause of maternal mortality and timely intervention can save many lives . Objective To compare the effectiveness of sublingual misoprostol to intravenous oxytocin in preventing post-partum hemorrhage in low risk vaginal birth . Methods One hundred patients with no risk factor for PPH were r and omly allocated to receive 600 μg misoprostol administered sublingually or 10 IU of intravenous oxytocin immediately after the delivery of baby . Main outcome measures were post-partum blood loss , drop in hemoglobin in 24 h , duration of third stage of labor , and drug-related adverse effects . Results Mean age , parity and gestational age were similar in both groups . Mean blood loss was significantly lower in oxytocin group ( 114.28 ± 26.75 versus 149.50 ± 30.78 ml ; p = 0.00 ) . Drop in hemoglobin was 0.31 ± 0.16 versus 0.49 ± 0.21 g% ( p = 0.01 ) in oxytocin and misoprostol group , respectively . Duration of third stage labor was shorter in oxytocin group ( median 5 min , IQR : 4.5–5.5 versus 5.5 min , IQR : 5–6 min , p < 0.01 ) . Although fever and shivering were common adverse effects with misoprostol but were not clinical ly significant . Conclusion Intravenous oxytocin is more efficacious than sublingual misoprostol in preventing PPH in institutional deliveries Background : The administration of uterotonic agents during cesarean delivery is highly variable . The authors hypothesized a “ rule of threes ” algorithm , featuring oxytocin 3 IU , timed uterine tone evaluations , and a systematic approach to alternative uterotonic agents , would reduce the oxytocin dose required to obtain adequate uterine tone . Methods : Sixty women undergoing elective cesarean delivery were r and omized to receive a low-dose bolus or continuous infusion of oxytocin . To blind participants , the rule group simultaneously received intravenous oxytocin ( 3 IU/3 ml ) and a “ wide-open ” infusion of 0.9 % normal saline ( 500 ml ) ; the st and ard care group received intravenous 0.9 % normal saline ( 3 ml ) and a “ wide-open ” infusion of oxytocin ( 30 IU in 0.9 % normal saline/500 ml ) . Uterine tone was assessed at 3 , 6 , 9 , and 12 min , and if inadequate , additional uterotonic agents were administered . Uterine tone , total dose and timing of uterotonic agent use , maternal hemodynamics , side effects , and blood loss were recorded . Results : Adequate uterine tone was achieved with lower oxytocin doses in the rule versus st and ard care group ( mean , 4.0 vs. 8.4 IU ; point estimate of the difference , 4.4 ± 1.0 IU ; 95 % CI , 2.60 to 6.15 ; P < 0.0001 ) . No additional oxytocin or alternative uterotonic agents were needed in either group after 6 min . No differences in the uterine tone , maternal hemodynamics , side effects , or blood loss were observed . Conclusion : A “ rule of threes ” algorithm using oxytocin 3 IU results in lower oxytocin doses when compared with continuous-infusion oxytocin in women undergoing elective cesarean delivery The effects of intravenous oxytocin on thoracic epidural pressure during cesarean section were studied in 90 parturients ( American Society of Anesthesiologists physical atatus class I or II ) after obtaining informed consent . The subjects were r and omized to either a control ( control group ; n=30 ) , bolus ( bolus group ; n=30 ) or drip treatment group ( drip group ; n=30 ) . The subjects were anesthetized with 11 approximately 12 mg of intrathecal isobaric bupivacaine ( 0.5 % ) . An epidural catheter placed at Th 11/12 was connected to a pressure transducer to continuously monitor thoracic epidural pressure . Ten units of oxytocin were administered over 30 seconds in the bolus group and over 5 minutes in the drip group after fetus delivery . We analyzed epidural pressure , mean blood pressure , and heart rate , until 5 minutes after fetus delivery . Epidural pressures in both bolus and drip groups increased after fetus delivery compared with control group ( P<0.0001 ) . Epidural pressure immediately after placental delivery in the bolus group was higher than in the control group ( p<0.0001 ) and epidural pressure at 5 minutes after fetus delivery in the drip group was higher than in the control group ( p=0.0452 ) . There were no significant differences in changes in blood pressure and heart rate among the three groups . We concluded that the increase in epidural pressure with intravenous administration of oxytocin 10 units over 5 minutes was lower than with intravenous administration of oxytocin 10 units over 30 seconds after fetus delivery Summary : This is a multicentre , blocked , r and omized trial to compare the efficacy of oral misoprostol 400μg with current injectable uterotonic agents ( oxytocin/Syntometrine ) used prophylactically in the third stage of labour . Main outcome measures were blood loss , use of a second uterotonic agent and difference in haemoglobin level from antepartum to postpartum . Data analysis from 863 women showed a statistically significant increase in both the mean blood loss ( p < 0.001 ) and the rate of postpartum haemorrhage > 500mL , ( RR 2.72 : 95 % Cl 1.73–4.27 ) in the misoprostol group compared to the oxytocin/Syntometrine group . The use of a second uterotonic agent was higher in the misoprostol group ( RR 2.89 : 95 % Cl 2.00–4.18 ) as well as a greater decrease in postpartum haemoglobin ( p = 0.015 ) . Oral misoprostol 400μg is significantly less effective than the traditional intramuscular uterotonic agents currently used and therefore can not be considered as a viable option to these agents in the management of the third stage of labour The effect of an intraumbilical prostagl and in ( PG ) F2 alpha injection on the third stage of normal labor was studied in 54 normal , laboring women at term . Either 1 mg of PGF2 alpha diluted to 20 mL in normal saline ( 27 women ) or 20 mL of normal saline alone ( 27 women ) was injected into the umbilical vein immediately after delivery using a r and omized , double-blind protocol . The mean ( + /- SD ) duration of the third stage was 7.31 + /- 6.37 minutes in the PGF2 alpha patients and 8.94 + /- 7.10 in the normal saline patients . Intraumbilical PGF2 alpha did not influence the third stage of normal labor OBJECTIVE To assess the effectiveness and safety of the administration of misoprostol , an orally active prostagl and in , in addition to routine uterotonic therapy as part of the active management of the third stage of labor . METHODS The present study was a hospital-based , de central ized , multi-center , r and omized , placebo-controlled , double-blind trial . We enrolled 1103 women ( out of a target sample size of 1180 ) at 4 hospitals in South Africa , Ug and a , and Nigeria . Participants received a sublingual dose of 400 μg of misoprostol or a placebo , in addition to st and ard active management of the third stage of labor , after vaginal birth . RESULTS The baseline characteristics of the participants were comparable . The difference in the primary outcome of blood loss of 500 mL or more within 1 hour of r and omization was not significant between the 2 groups ( misoprostol 22/546 [ 4.0 % ] versus placebo 35/553 [ 6.3 % ] ; relative risk , 0.64 ; 95 % confidence interval , 0.38 - 1.07 ) . Shivering and pyrexia occurred more frequently in the misoprostol group . No maternal deaths occurred . CONCLUSION The present study did not confirm a beneficial effect of administering 400 μg of misoprostol , in addition to routine uterotonic therapy , during the third stage of labor , but was consistent with other trials showing a cumulative modest benefit . Where routine uterotonics are available for prophylactic use , any potential benefit of misoprostol might not outweigh the likelihood of adverse effects The objective of the study was to find out the efficacy and safety of tranexamic acid in reducing blood loss during and after the lower segment caesarean section based on pre- and postoperative haemoglobin level . A prospect i ve r and omised , case-control , study was conducted on 100 women undergoing lower segment caesarean section . Fifty of them were given tranexamic acid immediately before the surgery and compared with 50 others to whom tranexamic acid was not given . Blood loss was measured up to two days . Haemoglobin level was estimated before caesarean section and two days after . Urine analysis , liver and renal functions were tested in both the groups . In this study , it was found that tranexamic acid reduced the quantity of blood loss from placental delivery to 2 days postpartum : 990 ml in the study group versus 1004 ml in the control group . The fall of haemoglobin was significantly less in the study group ( 1.214 g/dl ) in comparision to control ( 1.7256 g/dl ) ( p < 0.0001 ) . No complications or side-effects were reported in either group . No adverse neonatal outcome was also noted . Therefore tranexamic acid significantly reduced the amount of blood loss during and after the lower segment caesarean section and its use was not associated with any side-effects or complications . Tranexamic acid can be used safely and effectively in women undergoing lower segment caesarean section The objective of this study was to determine whether intraumbilical injection of oxytocin shortens the third stage of labor . A r and omized , double-blind , placebo-controlled trial was used to assess the effectiveness of an intraumbilical injection of oxytocin on the duration of the third stage . Following r and omization , each of 79 women received 30 mL of saline ( N = 40 ) or 20 U of oxytocin in 30 mL of saline ( N = 39 ) . The primary outcome of interest was the effect on the duration of the third stage . Secondary outcomes examined were change in hemoglobin and percentage of undelivered placenta after 15 minutes . There was no difference in the duration of the third stage between the two groups ( 7.8 + /- 6.1 min in the saline-only group versus 5.9 + /- 2.6 min in the oxytocin group ) . The change in hemoglobin was significantly lower in the oxytocin group ( 1.3 + /- 0.9 g/dL in the oxytocin group versus 1.8 + /- 0.9 g/dL in the saline-only group ) . The percentage of undelivered placentas beyond 15 minutes was significantly lower in the oxytocin group ( 0 % in the oxytocin group versus 12.5 % in the saline-only group ) . The study concluded that intraumbilical vein injection of oxytocin reduced the rate of placentas remaining undelivered beyond 15 minutes and subsequent blood loss A r and omised , controlled trial of 1429 women was carried out to compare ' active ' management of the third stage of labour , using i.v . Ergometrine 0.5 mgs , with a method of ' physiological ' management , in women at ' low risk ' to haemorrhage . A separate sub- study , with 168 women in each of the two groups , examined the possible effects of Ergometrine on serum prolactin levels and the duration of breast feeding . No difference was found in peak ( post-suckling ) serum prolactin levels taken from 126 women between 48 and 72 hours postnatal . Further studies with larger sample sizes would give a more dependable result . Women who did not receive the drug Ergometrine were more likely to continue breast feeding for longer than four weeks than those who did ( p less than 0.05 ) . It is recommended that this drug should not be given routinely to women intending to breast feed BACKGROUND Postpartum haemorrhage is a leading cause of maternal morbidity and mortality . Active management of the third stage of labour , including use of a uterotonic agent , has been shown to reduce blood loss . Misoprostol ( a prostagl and in E1 analogue ) has been suggested for this purpose because it has strong uterotonic effects , can be given orally , is inexpensive , and does not need refrigeration for storage . We did a multicentre , double-blind , r and omised controlled trial to determine whether oral misoprostol is as effective as oxytocin during the third stage of labour . METHODS In hospitals in Argentina , China , Egypt , Irel and , Nigeria , South Africa , Switzerl and , Thail and , and Vietnam , we r and omly assigned women about to deliver vaginally to receive 600 microg misoprostol orally or 10 IU oxytocin intravenously or intramuscularly , according to routine practice , plus corresponding identical placebos . The medications were administered immediately after delivery as part of the active management of the third stage of labour . The primary outcomes were measured postpartum blood loss of 1000 mL or more , and the use of additional uterotonics without an unacceptable level of side-effects . We chose an upper limit of a 35 % increase in the risk of blood loss of 1000 mL or more as the margin of clinical equivalence , which was assessed by the confidence interval of the relative risk . Analysis was by intention to treat . FINDINGS 9264 women were assigned misoprostol and 9266 oxytocin . 37 women in the misoprostol group and 34 in the oxytocin group had emergency caesarean sections and were excluded . 366 ( 4 % ) of women on misoprostol had a measured blood loss of 1000 mL or more , compared with 263 ( 3 % ) of those on oxytocin ( relative risk 1.39 [ 95 % CI 1.19 - 1.63 ] , p<0.0001 ) . 1398 ( 15 % ) women in the misoprostol group and 1002 ( 11 % ) in the oxytocin group required additional uterotonics ( 1.40 [ 1.29 - 1.51 ] , p<0.0001 ) . Misoprostol use was also associated with a significantly higher incidence of shivering ( 3.48 [ 3.15 - 3.84 ] ) and raised body temperature ( 7.17 [ 5.67 - 9.07 ] ) in the first hour after delivery . INTERPRETATION 10 IU oxytocin ( intravenous or intramuscular ) is preferable to 600 microg oral misoprostol in the active management of the third stage of labour in hospital setting s where active management is the norm OBJECTIVE To compare rectal misoprostol with oxytocin for routine management of the third stage of labour . STUDY DESIGN A total of 240 parturient women were r and omized , at three University of Toronto teaching hospitals , to receive either rectal misoprostol ( 400 microg ) after delivery of the infant or parenteral oxytocin ( 5 units i.v . or 10 units i.m . ) with the delivery of the anterior shoulder , when possible , or 5 units i.v . or i.m after the delivery of the placenta . The primary outcome measure was change in hemoglobin ( Delta[Hgb ] ) from admission in early labour to day one postpartum . SETTING The labour ward of three University of Toronto teaching hospitals : St. Michael 's , Toronto General , and Mount Sinai . POPULATION Labouring women either nulliparous or multiparous with no known risk for excessive third stage blood loss ; vertex presentation ; no previous Caesarean delivery ; induced , spontaneous , or augmented labour . RESULTS No difference in Delta[Hgb ] was observed between the two groups ; the Delta[Hgb ] in the oxytocin and misoprostol groups were 1.43 g/L ( 95 % confidence interval [ CI ] , 1.2 - 1.6 g/L ) and 1.59 g/L ( 95 % CI , 1.4 - 1.8 g/L ) respectively ( p = 0.35 ) . Secondary outcome measures ( excessive third stage bleeding , duration of third stage of labour , need for manual removal of the placenta or the need for additional oxytocics ) did not differ between the two groups . CONCLUSION Rectal misoprostol is of equivalent efficacy to parenteral oxytocin for the prevention of primary postpartum hemorrhage . Rectal misoprostol is an appropriate uterotonic agent for routine management of the third stage of labour Background 600 mcg of oral misoprostol reduces the incidence of postpartum haemorrhage ( PPH ) , but in previous research this medication has been administered by health workers . It is unclear whether it is also safe and effective when self-administered by women . Methods This placebo-controlled , double-blind r and omised trial enrolled consenting women of at least 34 weeks gestation , recruited over a 2-month period in Mbale District , Eastern Ug and a. Participants had their haemoglobin measured antenatally and were given either 600mcg misoprostol or placebo to take home and use immediately after birth in the event of delivery at home . The primary clinical outcome was the incidence of fall in haemoglobin of over 20 % in home births followed-up within 5 days . Results 748 women were r and omised to either misoprostol ( 374 ) or placebo ( 374 ) . Of those enrolled , 57 % delivered at a health facility and 43 % delivered at home . 82 % of all medicine packs were retrieved at postnatal follow-up and 97 % of women delivering at home reported self-administration of the medicine . Two women in the misoprostol group took the study medication antenatally without adverse effects . There was no significant difference between the study groups in the drop of maternal haemoglobin by > 20 % ( misoprostol 9.4 % vs placebo 7.5 % , risk ratio 1.11 , 95 % confidence interval 0.717 to 1.719 ) . There was significantly more fever and shivering in the misoprostol group , but women found the medication highly acceptable . Conclusions This study has shown that antenatally distributed , self-administered misoprostol can be appropriately taken by study participants . The rarity of the primary outcome means that a very large sample size would be required to demonstrate clinical effectiveness . Trial registration This study was registered with the IS RCT N Register ( IS RCT N70408620 ) AIM With the increasing rate of cesarean delivery ( CD ) worldwide , there is a need for a revision of practice s to prevent post-partum hemorrhage ( PPH ) after CD . In search of a safe , cheap and effective alternative to oxytocin for prevention of PPH during the postoperative period of CD , the present study aim ed to compare rectally administrated misoprostol with i.v . oxytocin infusion . METHODS A r and omized , placebo-controlled , double-blind prospect i ve trial was undertaken on 192 women who did not have risk factors for PPH and who had an uneventful emergency CD under spinal anesthesia . They were r and omly allocated to receive either 800 mg of rectal misoprostol or an i.v . infusion of oxytocin at the end of operation . Primary outcome measures were the amount of postoperative ( 24 h ) blood loss and incidence of PPH during the postoperative period . The secondary outcome measures were the postoperative drop in hemoglobin concentration after 24 h , need for additional uterotonic and blood transfusion , and side-effects/complications during the 24-h observation period . RESULTS There was a significant reduction of blood loss in the misoprostol group compared with the oxytocin group ( 144.5 ± 100.1 vs 191.7 ± 117.1 , P < 0.0001 ) . The two groups were similar in terms of the secondary outcome parameters . CONCLUSION Rectally administrated 800-mg misoprostol may be an effective alternative to oxytocin infusion to prevent PPH after CD BACKGROUND Misoprostol , an inexpensive , stable , orally active prostagl and in analogue , has been suggested for use in the prevention of postpartum haemorrhage . Potential side-effects , however , need to be quantified . OBJECTIVE To compare the rate of postpartum shivering and pyrexia following oral misoprostol 600 micrograms and placebo . DESIGN A double-blind placebo-controlled trial . Women in labour were r and omly allocated to receive either misoprostol 600 micrograms orally or placebo after delivery . Conventional oxytocics were given immediately if blood loss was thought to be more than usual . Side-effects were recorded . Postpartum blood loss in the first hour was measured by collection in a special flat plastic bedpan . SETTING The labour ward of an academic hospital in Johannesburg , with 7,000 deliveries per annum . MAIN OUTCOME MEASURES Shivering and pyrexia . RESULTS The groups were well matched . Misoprostol use was associated with more shivering ( 44 % versus 11 % , relative risk ( RR ) 4.03 , 95 % confidence interval ( CI ) 2.85 - 5.70 ) , pyrexia > or = 37.8 degrees C ( 38 % v. 6 % , RR 6.23 , CI 3.89 - 9.97 ) , 1-hour systolic blood pressure > or = 140 mmHg ( 33 % v. 25 % , RR 1.32 , CI 1.03 - 1.70 ) , and diastolic blood pressure > or = 90 mmHg ( 10.5 % v. 3.0 % , RR 3.44 , CI 1.67 - 7.11 ) . There were no other significant differences . The study was not design ed to be large enough to assess a difference in blood loss > or = 1,000 ml ( 9 % v. 9.7 % , RR 0.93 , CI 0.56 - 1.53 ) . Possible effects on blood loss may have been obscured by the lesser use of additional oxytocics in the misoprostol group ( 14 % v. 18 % , RR 0.78 , CI 0.54 - 1.13 ) . CONCLUSIONS This study has shown the association of postpartum oral misoprostol 600 micrograms with shivering , pyrexia and hypertension . The increased blood pressure , as for the trend towards increased abdominal pain , may be secondary to the uterotonic effect of misoprostol . Large r and omised trials are needed to assess the effectiveness of misoprostol in the prevention of postpartum haemorrhage , against which the disadvantages demonstrated here can be weighed Please cite this paper as : Mobeen N , Durocher J , Zuberi N , Jahan N , Blum J , Wasim S , Walraven G , Hatcher J. Administration of misoprostol by trained traditional birth attendants to prevent postpartum haemorrhage in homebirths in Pakistan : a r and omised placebo‐controlled trial . BJOG 2011;118:353–361 The aim of this study was to compare carboprost with oxytocin for the prevention of postpartum hemorrhage ( PPH ) in females with a high risk of PPH undergoing cesarean delivery . Patients were r and omly divided into three groups that received different uterotonics ( oxytocin , carboprost and oxytocin plus carboprost ) during cesarean section , following the delivery of the infant . A total of 117 females ( age range , 19–40 years ) at 35–40 weeks gestation who delivered by cesarean between December , 2010 and May , 2012 were included in this study . There were 29 cases of twins , 12 cases of polyhydramnios , 23 cases of placenta previa and 53 cases of fetal macrosomia . There were 37 patients in the oxytocin group , 36 in the carboprost group and 44 in the oxytocin plus carboprost group . No significant differences were identified in maternal age , gravidity/parity , gestational age and reason for cesarean delivery between the three groups . The median blood loss in the oxytocin , carboprost and oxytocin plus carboprost groups was 610 , 438 and 520 ml , respectively . The blood loss in the carboprost group was significantly lower than that in the oxytocin and oxytocin plus carboprost groups ( both P<0.05 ) . Vomiting occurred in eight patients from the carboprost group , two from the oxytocin group and two from the oxytocin plus carboprost group ( P=0.036 ) . Carboprost was more effective than oxytocin in preventing PPH in high-risk patients undergoing cesarean delivery In this study the effect of intraumbilical vein oxytocin on duration and amount of blood loss in third stage of labour was studied . Pregnant women were r and omized into two groups of fifty each . Study group was managed with 10 units of oxytocin diluted with 10 ml of normal saline given through umbilical vein while control group was managed with 10 units of oxytocin in 500 ml of normal saline through intravenous infusion after delivery of the baby . The mean blood loss in the third stage of labour was 143.30 ml for the control group and 151.43 ml for the study group while the duration of the third stage of labour was 6.02 and 5.42 minutes for each group . There was no significant difference in the duration and amount of blood loss between the two groups BACKGROUND This study tested the hypotheses that active management of the third stage of labour lowers the rates of primary postpartum haemorrhage ( PPH ) and longer-term consequences compared with expectant management , in a setting where both managements are commonly practised , and that this effect is not mediated by maternal posture . BACKGROUND 1512 women judged to be at low risk of PPH ( blood loss > 500 mL ) were r and omly assigned active management of the third stage ( prophylactic oxytocic within 2 min of baby 's birth , immediate cutting and clamping of the cord , delivery of placenta by controlled cord traction or maternal effort ) or expectant management ( no prophylactic oxytocic , no cord clamping until pulsation ceased , delivery of placenta by maternal effort ) . Women were also r and omly assigned upright or supine posture . Analyses were by intention to treat . FINDINGS The rate of PPH was significantly lower with active than with expectant management ( 51 [ 6.8 % ] of 748 vs 126 [ 16.5 % ] of 764 ; relative risk 2.42 [ 95 % CI 1.78 - 3.30 ] , p<0.0001 ) . Posture had no effect on this risk ( upright 92 [ 12 % ] of 755 vs supine 85 [ 11 % ] of 757 ) . Objective measures of blood loss confirmed the results . There was more vomiting in the active group but no other important differences were detected . INTERPRETATION Active management of the third stage reduces the risk of PPH , whatever the woman 's posture , even when midwives are familiar with both approaches . We recommend that clinical guidelines in hospital setting s advocate active management ( with oxytocin alone ) . However , decisions about individual care should take into account the weights placed by pregnant women and their caregivers on blood loss compared with an intervention-free third stage OBJECTIVE To study whether paramedical workers from rural primary health centers in India are able to administer oral misoprostol and actively manage the third stage of labor to prevent postpartum hemorrhage ( PPH ) . METHOD Cluster r and omization was used to enroll 1200 women at 30 peripheral health centers from 5 states in India , 600 forming the study 's intervention group ( active management of the third stage of labor with 600 mug of oral misoprostol ) and 600 forming the comparison group ( in which the current government guidelines for the prevention of PPH were followed ) . The primary outcome was blood loss after delivery , which was measured using a calibrated blood collection drape . RESULTS Age , literacy level , occupation , and gravidity were similar in the 2 groups . More than 70 % of women in both groups had moderate anemia ( hemoglobin level < 10 g/dL ) . Paramedical workers followed instructions in almost all deliveries in the intervention group ( 99 % ) . There was a significant reduction in duration of the third stage of labor ( 7.9 + /- 4.2 min vs. 10.9 + /- 4.3 min ; p < .001 ) and median blood loss after delivery ( 100 mL vs. 200 mL ; p < .001 ) in the intervention group . Overall , a low incidence of PPH was observed ( < 1 % ) in both groups . A greater number of women had moderate to severe shivering ( 12.7 % vs. 0.5 % ) and a temperature higher than 38 degrees C ( 9.7 % vs. 4.3 % ) in the intervention group , which was statistically significant . CONCLUSION Simple interventions can be easily implemented in rural health care setting s to reduce the blood loss during labor . This finding has significant implication s for developing countries , in which the prevalence of anemia is high Objective To compare the efficacy and side effects of 0.2 mg methyl-ergometrine IM , 400 μg misoprostol sublingual and 125 μg 15 methyl PGF2α IM in active management of third stage of labor . Method Two hundred low risk pregnant women with induced or spontaneous labor were r and omized to receive either 400 μg misoprostol sublingually or 0.2 mg methyl-ergometrine intramuscularly or 125 μg 15-methyl PGF2α intramuscularly , after the delivery of anterior shoulder of baby . The main outcome measures were : blood loss more than 500 ml , need for additional oxytoxic drug , change in hemoglobin level and side effects due to drugs . Results The median estimated blood loss , blood loss more than 500 ml , need for additional oxytocic drug and change in hemoglobin levels were similar in all three groups . The significant side effects in the misoprostol group were shivering , pyrexia ( temperature > 38 ° C ) and vomiting , which were self-limiting . Diarrhea was significantly more in the 15 methyl PGF2α group . Three women in methyl-ergometrine group underwent manual removal of placenta . One woman in misoprostol group received blood transfusion . ConclusionS ublingual misoprostol appears to be as effective as intramuscular methyl-ergometrine and intramuscular 15-methyl PGF2α in the prevention of postpartum hemorrhage . It can be a good alternative in re source poor setting OBJECTIVE The purpose of our study was to observe the influence of dexmedetomidine on complications caused by hemabate in patients undergoing caesarean section . METHODS A total of 120 females ( age range , 20 - 40 years ) at 35 - 40 weeks gestation who delivered by cesarean between September , 2014 and December , 2014 were enrolled in our study . Patients were r and omly allocated into three groups that received intravenously physiological saline 20 mL ( placebo group ) , lower dose ( 0.5 μg kg(-1 ) ) of dexmedetomidine ( low-dex gruop ) and higher dose ( 1 μg kg(-1 ) ) of dexmedetomidine ( high-dex group ) during cesarean section , following the delivery of the infant and intramuscular hemabate injection . RESULTS Nausea , vomiting , chest congestion and elevated blood pressure were the most common adverse events of placebo group . Compared with placebo group , the above mentioned adverse reactions decreased significantly in both low-dex group and high-dex group ( P<0.05 ) , whereas there were no significant difference between low-dex group and high-dex group ( P>0.05 ) . As to patient satisfaction score , low-dex group and high-dex group were all higher than placebo group ( P<0.05 ) . Furthermore , there were more patients satisfied with high-dex group than low-dex group ( P<0.05 ) . CONCLUSION Dexmedetomidine ( 0.5 μg kg(-1 ) and 1 μg kg(-1 ) ) were all effective in preventing adverse reactions introduced by hemabate and improve parturients ' satisfaction in patients undergoing cesarean delivery . And higher dose ( 1 μg kg(-1 ) ) of dexmedetomidine is superior to lower dose ( 0.5 μg kg(-1 ) ) in patient satisfaction Background : Postpartum hemorrhage ( PPH ) and anemia thereafter can be a life threatening condition in parturients undergoing lower segment cesarean section ( LSCS ) , especially when anemia is present . Aim : The objective of this study was to assess two doses of Tranexamic acid ( TXA ) in reducing intra operative blood loss and incidence of PPH , in terms of both efficacy and safety profiles , when used prophylactically . Methods : A monocenter prospect i ve case control double blind r and omized study was carried out on a consecutive series of 90 anemic patients undergoing LSCS , with hemoglobin between 7 - 10 g percent . Three r and om groups were formed . Group T1 ( n=30 ) received 10mg/kg TXA in 20 ml of 5 % dextrose intravenously , while T2 group ( n=30 ) received 15mg/kg . Group C ( n=30 ) received a placebo . Drug was administered prophylactically 20 min before skin incision . Blood loss was measured from placental delivery up to 24 hours by method of weight and volume . Staistical Analysis : To compare quantitative data between two groups , t-test , and for more than two groups ANOVA was used . To compare the mean for non- parametric data between two groups Mann – Whitney test was used , while in case of more than two groups Kruskal – Wallis test was employed . Probability ( p ) value was considered significant when it was 0.05 or less . Results : TXA significantly reduced blood loss in both the study groups . Mean total blood loss was 527.17±88.666 ml , 376.83±31.961ml and 261.17±56.777 ml in group C , T1 , and T2 respectively . While reduction of blood loss in T1 group compared to control group was 146.34±56.32ml , it was 262±31.51ml in T2 group . Difference between T1 and T2 was 115.66±24.81ml , which was statistically significant ( P<0.05 ) . Postoperative blood loss was insignificant in all three groups . Pre- and post-operative hemoglobin levels differed significantly when compared to control group . Blood transfusion was needed in two patients in the control group , whereas no patient in groups T1 and T2 needed transfusion ( P=0.02 ) . No significant adverse effect was seen in all the three groups . Conclusion : Hence , TXA was found to be effective in reducing blood loss and transfusion in anemic parturients undergoing LSCS . 15mg/kg dose of TXA was more efficacious than the 10mg/kg dose and without any undue increase in adverse events . Postpartum anemia is a public health problem worldwide and TXA could prove to be a very useful drug to prevent blood loss and transfusions in patients undergoing LSCS , especially in the anemic subgroup OBJECTIVE --To compare the effects on fetal and maternal morbidity of routine active management of third stage of labour and expectant ( physiological ) management , in particular to determine whether active management reduced incidence of postpartum haemorrhage . DESIGN --R and omised trial of active versus physiological management . Women entered trial on admission to labour ward with allocation revealed just before vaginal delivery . Five months into trial high rate of postpartum haemorrhage in physiological group ( 16.5 % v 3.8 % ) prompted modification of protocol to exclude more women and allow those allocated to physiological group who needed some active management to be switched to fully active management . Sample size of 3900 was planned , but even after protocol modification a planned interim analysis after first 1500 deliveries showed continuing high postpartum haemorrhage rate in physiological group and study was stopped . SETTING --Maternity hospital . PARTICIPANTS --Of 4709 women delivered from 1 January 1986 to 31 January 1987 , 1695 were admitted to trial and allocated r and omly to physiological ( 849 ) or active ( 846 ) management . Reasons for exclusion were : refusal , antepartum haemorrhage , cardiac disease , breech presentation , multiple pregnancy , intrauterine death , and , after May 1986 , ritodrine given two hours before delivery , anticoagulant treatment , and any condition needing a particular management of third stage . INTERVENTIONS --All but six women allocated to active management actually received it , having prophylactic oxytocic , cord clamping before placental delivery , and cord traction ; whereas just under half those allocated to physiological management achieved it . A fifth of physiological group received prophylactic oxytocic , two fifths underwent cord traction and just over half clamping of the cord before placental delivery . ENDPOINT -- Reduction in incidence of postpartum haemorrhage from 7.5 % under physiological management to 5.0 % under active management . MEASUREMENTS AND MAIN RESULTS --Incidence of postpartum haemorrhage was 5.9 % in active management group and 17.9 % in physiological group ( odds ratio 3.13 ; 95 % confidence interval 2.3 to 4.2 ) , a contrast reflected in other indices of blood loss . In physiological group third stage was longer ( median 15 min v 5 min ) and more women needed therapeutic oxytocics ( 29.7 % v 6.4 % ) . Apgar scores at one and five minutes and incidence of neonatal respiratory problems were not significantly different between groups . Babies in physiological group weighed mean of 85 g more than those in active group . When women allocated to and receiving active management ( 840 ) were compared with those who actually received physiological management ( 403 ) active management still produced lower rate of postpartum haemorrhage ( odds ratio 2.4;95 % CI1.6 to 3.7 ) . CONCLUSIONS --Policy of active management practised in this trial reduces incidence of postpartum haemorrhage , shortens third stage , and results in reduced neonatal packed cell volume OBJECTIVE The purpose of this study was to compare misoprostol 600 microg intrarectally with conventional oxytocics in the treatment of third stage of labor . STUDY DESIGN In a controlled trial , 1606 women were r and omly grouped to receive ( 1 ) oxytocin 10 IU plus rectal misoprostol , ( 2 ) rectal misoprostol , ( 3 ) oxytocin 10 IU , and ( 4 ) oxytocin 10 IU plus methylergometrine . The main outcome measures were the incidence of postpartum hemorrhage and a drop in hemoglobin concentration from before delivery to 24 hours after delivery . RESULTS The incidence of postpartum hemorrhage was 9.8 % in the group that received only rectal misoprostol therapy compared with 3.5 % in the group that received oxytocin and methylergometrine therapy ( P = .001 ) . There were no significant differences among the 4 groups with regard to a drop in hemoglobin concentrations . Significantly more women needed additional oxytocin in the group that received only rectal misoprostol therapy , when compared with the group that received oxytocin and methylergometrine therapy ( 8.3 % vs 2.2 % ; P < .001 ) . The primary outcome measures were similar in the group that received only rectal misoprostol therapy and the group that received only oxytocin therapy . CONCLUSION Rectal misoprostol is significantly less effective than oxytocin plus methylergometrine for the prevention of postpartum hemorrhage BACKGROUND ECG changes , similar to those seen during myocardial ischaemia , together with symptoms of chest pain , are common during Caesarean section ( CS ) . We hypothesized that oxytocin administration has cardiovascular effects leading to these symptoms and ECG changes . METHODS Forty women undergoing elective CS under spinal anaesthesia were given an i.v . bolus of either 10 IU of oxytocin ( Group OXY-CS , n=20 ) or 0.2 mg of methylergometrine ( Group MET-CS , n=20 ) , in a double-blind , r and omized fashion after delivery . Ten healthy , non-pregnant , non-anaesthetized women were used as normal controls ( Group OXY-NC , n=10 ) and were given 10 IU of oxytocin i.v . Twelve-lead ECG , on-line , computerized vectorcardiography ( VCG ) , and invasive arterial pressure were recorded . RESULTS Oxytocin produced a significant increase in heart rate , + 28 ( SD 4 ) and + 52 ( 3 ) beats min(-1 ) [ mean ( SEM ) ; P<0.001 ] , decreases in mean arterial pressure , -33 ( 2 ) and -30 ( 3 ) mm Hg ( P<0.001 ) , and increases in the spatial ST-change vector magnitude ( STC-VM ) , + 77 ( 12 ) and + 114 ( 8) microV ( P<0.001 ) , in CS patients and controls , respectively . Symptoms of chest pain and subjective discomfort were simultaneously present . Methylergometrine produced mild hypertension and no significant ECG changes . CONCLUSIONS Oxytocin administered as an i.v . bolus of 10 IU induces chest pain , transient profound tachycardia , hypotension , and concomitant signs of myocardial ischaemia according to marked ECG and STC-VM changes . The effects are related to oxytocin administration and not to pregnancy , surgical procedure , delivery , or sympathetic block from spinal anaesthesia The authors analysed the effect of the i.v . oxytocin induced third stage of labour in a controlled trial concerning 1000 patients . The appliance of such an policy in a unit that already had a fairly active management of delivery was very encouraging . The incidence of post-partum haemorrhage ( greater than 500 ml ) is significantly ( P less than 0.001 ) less than in the control group ; and the same for severe haemorrhage . The third stage is significantly ( P less than 0.001 ) shorter in the oxytocin-injected group than in the control group . Moreover , there is no significant difference between the two groups for retained placenta . The economy of blood transfusion , which is a major concern nowadays , could be the real interest of this active management of the third stage of labour Objective . To investigate the side effects of 600 μg oral misoprostol given for the mother and the newborn to prevent postpartum hemorrhage ( PPH ) . Methods . One thous and six hundred twenty women delivering at home or subcentres in rural India were r and omised to receive misoprostol or placebo in the third stage of labour . Women were evaluated for shivering , fever , nausea , vomiting and diarrhea at 2 and 24 h postpartum . Newborns were evaluated within 24 h for diarrhea , vomiting and fever . Symptoms were grade d as absent , mild-to-moderate or severe . Results . Women who received misoprostol had a significantly greater incidence of shivering ( 52%vs . 17 % , p < 0.001 ) and fever ( 4.2%vs . 1.1 % , p < 0.001 ) at 2 h postpartum compared with women who received placebo . At 24 h , women in the misoprostol group experienced significantly more shivering ( 4.6%vs . 1.4 % , p < 0.001 ) and fever ( 1.4%vs . 0.4 % , p < 0.03 ) . There were no differences in nausea , vomiting or diarrhea between the two groups . There were no differences in the incidence of vomiting , diarrhea or fever for newborns . Conclusions . Misoprostol is associated with a significant increase in postpartum maternal shivering and fever with no side effects for the newborn . Given its proven efficacy for the prevention of PPH , the benefits of misoprostol are greater than the associated risks Cynthia Stanton and colleagues conducted a cluster-r and omized controlled trial in rural Ghana to assess whether oxytocin given by injection by community health officers at home births was a feasible and safe option in preventing postpartum hemorrhage . Please see later in the article for the Editors ' Background Hemorrhage is the leading direct cause of maternal death globally . While oxytocin is the drug of choice for postpartum hemorrhage prevention , its use has generally been limited to health facilities . This trial assesses the effectiveness , safety , and feasibility of exp and ing the use of prophylactic intramuscular oxytocin to peripheral health care providers at home births in four predominantly rural districts in central Ghana . Methods This study is design ed as a community-based cluster-r and omized trial in which Community Health Officers are r and omized to provide ( or not provide ) an injection of oxytocin 10 IU via the UnijectTM injection system within one minute of delivery of the baby to women who request their presence at home at the onset of labor . The primary aim is to determine if administration of prophylactic oxytocin via Uniject ™ by this cadre will reduce the risk of postpartum hemorrhage by 50 % relative to deliveries which do not receive the prophylactic intervention . Postpartum hemorrhage is examined under three sequential definitions : 1 ) blood loss ≥500 ml ( BL ) ; 2 ) treatment for bleeding ( TX ) and /or BL ; 3 ) hospital referral for bleeding and /or TX and /or BL . Secondary outcomes address safety and feasibility of the intervention and include adverse maternal and fetal outcomes and logistical concerns regarding assistance at home births and the storage and h and ling of oxytocin , respectively . Discussion Results from this trial will build evidence for the effectiveness of exp and ing the delivery of this established prophylactic intervention to peripheral setting s. Complementary data on safety and logistical issues related to this intervention will assist policymakers in low-income countries in selecting both the best uterotonic and service delivery strategy for postpartum hemorrhage prevention . Results of this trial are expected in mid-2013 . The trial is registered at Clinical Trials.gov : NCT01108289 Background Postpartum hemorrhage ( PPH ) is a major cause of maternal mortality , accounting for one quarter of all maternal deaths worldwide . Estimates of its incidence in the literature vary widely , from 3 % to 15 % of deliveries . Uterotonics after birth are the only intervention that has been shown to be effective in preventing PPH . Tranexamic acid ( TXA ) , an antifibrinolytic agent , has been investigated as a potentially useful complement to uterotonics for prevention because it has been proved to reduce blood loss in elective surgery , bleeding in trauma patients , and menstrual blood loss . R and omized controlled trials for PPH prevention after cesarean ( n = 10 ) and vaginal ( n = 2 ) deliveries show that women who received TXA had significantly less postpartum blood loss without any increase in their rate of severe adverse effects . However , the quality of these trials was poor and they were not design ed to test the effect of TXA on the reduction of PPH incidence . Large , adequately powered , multicenter r and omized controlled trials are required before the widespread use of TXA to prevent PPH can be recommended . Methods and design A multicenter , double-blind , r and omized controlled trial will be performed . It will involve 4000 women in labor for a planned vaginal singleton delivery , at a term ≥ 35 weeks . Treatment ( either TXA 1 g or placebo ) will be administered intravenously just after birth . Prophylactic oxytocin will be administered to all women . The primary outcome will be the incidence of PPH , defined by blood loss ≥500 mL , measured with a graduated collector bag . This study will have 80 % power to show a 30 % reduction in the incidence of PPH , from 10.0 % to 7.0 % . Discussion In addition to prophylactic uterotonic administration , a complementary component of the management of third stage of labor acting on the coagulation process may be useful in preventing PPH . TXA is a promising c and i date drug , inexpensive , easy to administer , and simple to add to the routine management of deliveries in hospitals . This large , adequately powered , multicenter , r and omized placebo-controlled trial seeks to determine if the risk-benefit ratio favors the routine use of TXA after delivery to prevent PPH.Trial registration Clinical Trials.gov NCT02302456 ( November 17 , 2014 In a double-blind r and omized controlled trial , Esther Atukunda and colleagues evaluated whether sublingual misoprostol administered to women in labor was non-inferior to intramuscular oxytocin in preventing postpartum hemorrhage and reducing blood loss . Please see later in the article for the Editors ' BACKGROUND The cardiovascular effects of oxytocin in animal models and women undergoing Caesarean section include tachycardia , hypotension and decrease in cardiac output . These can be sufficient to cause significant compromise in high-risk patients . We aim ed to find a simple way to decrease these risks whilst retaining the benefits of oxytocin in decreasing bleeding after delivery . Method . We recruited 30 women undergoing elective Caesarean section . They were r and omly allocated to receive 5 u of oxytocin either as a bolus injection ( bolus group ) or an infusion over 5 min ( infusion group ) . These women had their heart rate and intra-arterial blood pressure recorded every 5 s throughout the procedure . The haemodynamic data , along with the estimated blood loss , were compared between the groups . RESULTS Marked cardiovascular changes occurred in the bolus group ; the heart rate increased by 17 ( 10.7 ) beats min(-1 ) [ mean ( sd ) ] compared with 10 ( 9.7 ) beats min(-1 ) in the infusion group . The mean arterial pressure decreased by 27 ( 7.6 ) mm Hg in the bolus group compared with 8 ( 8.7 ) mm Hg in the infusion group . There were no differences in the estimated blood loss between the two groups . CONCLUSION We recommend that bolus doses should be used with caution , and further studies should ascertain if oxytocin is equally effective in reducing blood loss when given at a slower rate BACKGROUND New indications for misoprostol include medical abortion , cervical softening , induction of labor and treatment of postpartum hemorrhage . Various routes of misoprostol administration under study include oral , vaginal , buccal , sublingual and rectal . MATERIAL S AND METHODS This was an open-label , r and omized , cross-over study of the pharmacokinetic differences of buccal vs. sublingual misoprostol 800 mug in 10 healthy women . RESULTS Of the 10 women enrolled , 2 withdrew after experiencing excessive cramping from the sublingual route of misoprostol . The mean misoprostol plasma concentration-time curves at 4 h [ area under the curve (AUC)0 - 4 ) ] and the maximum concentration ( C(max ) ) showed that levels were significantly higher for sublingual administration than the buccal route . Buccal misoprostol administration result ed in fewer symptoms and was found to be more acceptable . CONCLUSIONS Sublingual administration of misoprostol had a higher AUC and C(max ) compared with buccal administration . The pharmacokinetics may help to determine the best application of misoprostol depending on the indication Background Postpartum haemorrhage remains an important cause of maternal death despite treatment with conventional therapy . Uncontrolled studies and one r and omised comparison with conventional oxytocics have reported dramatic effects with high-dose misoprostol , usually given rectally , for treatment of postpartum haemorrhage , but this has not been evaluated in a placebo-controlled trial . Methods The study was conducted at East London Hospital Complex , Tembisa and Chris Hani Baragwanath Hospitals , South Africa . Routine active management of the third stage of labour was practised . Women with more than usual postpartum bleeding thought to be related to inadequate uterine contraction were invited to participate , and to sign informed consent . All routine treatment was given from a special ' Postpartum Haemorrhage Trolley ' . In addition , participants who consented were enrolled by drawing the next in a series of r and omised treatment packs containing either misoprostol 5 × 200 μg or similar placebo , which were given 1 orally , 2 sublingually and 2 rectally . Results With misoprostol there was a trend to reduced blood loss ≥500 ml in 1 hour after enrolment measured in a flat plastic ' fracture bedpan ' , the primary outcome ( 6/117 vs 11/120 , relative risk 0.56 ; 95 % confidence interval 0.21 to 1.46 ) . There was no difference in mean blood loss or haemoglobin level on day 1 after birth < 6 g/dl or blood transfusion . Side-effects were increased , namely shivering ( 63/116 vs 30/118 ; 2.14 , 1.50 to 3.04 ) and pyrexia > 38.5 ° C ( 11/114 vs 2/118 ; 5.69 , 1.29 to 25 ) . In the misoprostol group 3 women underwent hysterectomy of whom 1 died , and there were 2 further maternal deaths . Conclusions Because of a lower than expected incidence of the primary outcome in the placebo group , the study was underpowered . We could not confirm the dramatic effect of misoprostol reported in several unblinded studies , but the results do not exclude a clinical ly important effect . Larger studies are needed to assess substantive outcomes and risks before misoprostol enters routine use Background Postpartum heammorrhage ( PPH ) , defined as blood loss greater than or equal to 500 ml within 24 hours after birth , is the leading cause of maternal deaths globally and in India . Misoprostol is an important option for PPH management in setting where oxytocin ( the gold st and ard for PPH prevention and treatment ) in not available or not feasible to use . For the substantial number of deliveries which take place at home or at lower level heatlh facilities in India , misoprostol pills can be adminstered to prevent PPH . The st and ard approach using misoprostol is to administer it prophylactically as primary prevention ( 600 mcg ) . An alternative strategy could be to administer misoprostol only to those who are at high risk of having PPH i.e. as secondary prevention . Methods This study reports on the relative cost per person of a strategy involving primary versus secondary prevention of PPH using misoprostol . It is based on a r and omized cluster trial that was conducted in Bijapur district in Karnataka , India between December 2011 and March 2014 among pregnant women to compare two community-level strategies for the prevention of PPH : primary and secondary . The analysis was conducted from the government perspective using an ingredient approach . Results The cluster trial showed that there were no significant differences in clinical outcomes between the two study arms . However , the results of the cost analysis show that there is a difference of INR 6 ( US$ 0.1 ) per birth for implementing the strategies primary versus secondary prevention . In India where 14.9 million births take place at sub-centres and at home , this additional cost of INR 6 per birth translates to an additional cost of INR 94 ( US$ 1.6 ) million to the government to implement the primary prevention compared to the secondary prevention strategy . Conclusion As clinical outcomes did not differ significantly between the two arms in the trial , taking into account the difference in costs and potential issues with sustainability , secondary prevention might be a more strategic option Postpartum hemorrhage is an important cause of maternal morbidity and mortality after delivery . Active management of postpartum hemorrhage by an uterotonic drug decreases the rate of postpartum hemorrhage . The aim of this study is to evaluate the efficacy of rectal misoprostol for prevention of postpartum hemorrhage . This double blind r and omized clinical trial was performed on full term pregnant women c and i date for vaginal delivery , referred to Zahedan Imam Ali Hospital during 2008 - 2009 . They were r and omly divided into two groups of rectal misoprostol and oxytocin . The women in misoprostol group received 400 μg rectal misoprostol after delivery and the women in oxytocin group received 3 IU oxytocin in 1 L ringer serum , intravenously . Rate of bleeding , need to any surgery interventions , rate of transfusion and changes in hemoglobin and hematocrite were compared between two groups . A total of 400 patients ( 200 cases in misoprostol group and 200 in oxytocin group ) entered to the study . Rate of bleeding > 500 cc was significantly higher in oxytocin group than misoprostol group ( 33 % vs. 19 % ) ( p = 0.005 ) . Also , need to excessive oxytocin for management of postpartum hemorrhage was significantly lower in misoprostol group than oxytocin group ( 18 % vs. 30 % ) ( p = 0.003 ) . Decrease in hematocrite was significantly more observed in oxytocin group than misoprostol group ( mean decrease of hematocrite was 1.3 ± 1.6 in misoprostol group and 1.6 ± 2.2 in oxytocin group ) . Two groups were similar in terms of side-effects . Rectal misoprostol as an uterotonic drug can decrease postpartum hemorrhage and also can prevent from decrease of hemoglobin as compared to oxytocin Purpose A r and omized study involving pregnant women was conducted to compare the effectiveness of a single intravenous ( IV ) injection of carbetocin with that of a st and ard 2-h oxytocin IV infusion with respect to intraoperative blood loss in the prevention of uterine atony after cesarean section ( CS ) . The two treatments also were compared for safety and ability to maintain adequate uterine tone and to reduce the incidence and severity of postpartum hemorrhage ( PPH ) in women at risk for this condition . Methods Between 1 September 2007 and 5 January 2008 , we enrolled 104 patients with at least one risk factor for PPH undergoing CS in a r and omized , controlled clinical trial . We compared the effect of a single 100 microg IV dose of carbetocin with that of a st and ard 2-h ten international units ( IU ) IV infusion of oxytocin . The primary outcome was the proportion of patients requiring additional oxytocic intervention for uterine atony . Fiftytwo women received 100 microg carbetocin IV immediately after placental delivery , while 52 women received 10 IU oxytocin IV infusion . Complete blood count was collected at entry and 24 h postpartum . All outcome measures , including the need for additional uterotonic agents or uterine massage , and blood loss , were analyzed using chi-square , Fisher exact , and Student ’s t tests . Results A single 100 microg IV injection of carbetocin was as effective as a continuous 2-h infusion of oxytocin in controlling intraoperative blood loss after placental delivery . Mean blood loss after carbetocin administration was 30 ml less than after oxytocin administration ( P = 0.5 ) . The percentage of patients with blood loss ≤500 ml was greater with carbetocin ( 81 vs. 55 % ; P = 0.05 ) . Carbetocin enhanced early postpartum uterine involution . The fundus was below the umbilicus in more patients who received carbetocin at 0 , 2 , 6 , and 24 h on the ward ( P < 0.05 ) . The main additional uterotonic agent used was a further administration of oxytocin ( 20 IU in physiological solution 500 ml at an infusion rate of 200 ml/h ) . In the carbetocin group , 20 of the 52 women ( 38.4 % ) required at least one uterine massage compared to 30 of the 52 women ( 57.7 % ) in the oxytocin group ( P < 0.01 ) . Overall , uterotonic intervention was clinical ly indicated in two of the women ( 3.8 % ) receiving carbetocin compared to five of the women ( 9.6 % ) given an IV oxytocin infusion ( P < 0.01 ) . The odds ratio of treatment failure requiring oxytocic intervention was 1.83 ( 95 % confidence interval , CI , 0.9–2.6 ) times higher in the oxytocin group compared with the carbetocin group . Conclusions Carbetocin makes possible to obtain , with a single IV injection , results equivalent to those of oxytocin on the maintenance of uterine tonicity and the limitation of blood losses , in the peri- and in the post-operative period , during a delivery by CS . It has in addition a comparable tolerance . Even in our series adverse events are practically of the same type and similar frequency in both study groups . Thus , the effectiveness of carbetocin consists , thanks to its long half-life , on an unique injection , whereas oxytocin requires repeated injections or a perfusion of several hours , with a variability of the administered doses Postpartum hemorrhage ( PPH ) is the commonest cause of maternal death worldwide . Studies suggest that the use of misoprostol may be beneficial in clinical setting s where oxytocin is unavailable . The aim of this study was to compare the safety and efficacy of oxytocin and misoprostol when used in the prevention of PPH . In a double-blind r and omized controlled trial , 400 pregnant women who had a vaginal delivery were assigned into two groups : to receive either 20 IU of oxytocin in 1000 mL Ringer 's solution and two placebo tablets or 400 mcg oral misoprostol ( as two tablets ) and 2 mL normal saline in 1000 mL Ringer 's solution . The quantity of blood loss was higher in the oxytocin group in comparison to the misoprostol group . There was no significant difference in the decrease in hematocrit and hemoglobin between the two groups . Although there was no significant difference in the need for transfusions between the two groups , the patients in the oxytocin group had greater need for additional oxytocin . Results from this study indicate that it may be considered as an alternative for oxytocin in low re source clinical setting s. This study is registered with Clinical Trials.gov NCT01863706 OBJECTIVE : Methergine increases constriction of uterine musculature which may facilitate sloughing of endometrial debris , close uterine vessels , and prevent post-cesarean endometritis . The objective of this study was to evaluate the efficacy of methergine in preventing endometritis in patients undergoing non-elective cesarean section delivery . METHODS : Eighty patients undergoing non-elective cesarean section were enrolled in a prospect i ve r and omized clinical trial of methergine ( 41 ) versus no methergine ( 39 ) administration during the postpartum period . The hospital records were abstract ed after discharge to compare the postpartum course . RESULTS : There were no significant demographic differences between the two groups . The women receiving methergine had a significant reduction in the rate of postoperative endometritis ( 10 % vs. 36 % , P < 0.005 ) . In addition , the mean postoperative hemoglobin was significantly higher in the methergine treated group ( P < 0.001 ) . CONCLUSIONS : The use of methergine postpartum in women undergoing non-elective cesarean sections significantly reduces the incidence of postoperative endometritis and blood loss Summary Background Millennium Development Goal ( MDG ) 5 calls for a reduction of 75 % in the maternal mortality ratio ( MMR ) between 1990 and 2015 . We estimated levels and trends in maternal mortality for 183 countries to assess progress made . Based on MMR estimates for 2015 , we constructed scenario-based projections to highlight the accelerations needed to accomplish the Sustainable Development Goal ( SDG ) global target of less than 70 maternal deaths per 100,000 live births globally by 2030 . Methods We up date d the open access UN Maternal Mortality Estimation Inter-agency Group ( MMEIG ) data base . Based upon nationally-representative data for 171 countries , we generated estimates of maternal mortality and related indicators with uncertainty intervals using a Bayesian model , which extends and refines the previous UN MMEIG estimation approach . The model combines the rate of change implied by a multilevel regression model with a time series model to capture data -driven changes in country-specific MMRs , and includes a data model to adjust for systematic and r and om errors associated with different data sources . Results The global MMR declined from 385 deaths per 100,000 live births ( 80 % uncertainty interval ranges from 359 to 427 ) in 1990 to 216 ( 207 to 249 ) in 2015 , corresponding to a relative decline of 43.9 % ( 34.0 to 48.7 ) during the 25-year period , with 303,000 ( 291,000 to 349,000 ) maternal deaths globally in 2015 . Regional progress in reducing the MMR since 1990 ranged from an annual rate of reduction of 1.8 % ( 0 to 3.1 ) in the Caribbean to 5.0 % ( 4.0 to 6.0 ) for Eastern Asia . Regional MMRs for 2015 range from 12 ( 11 to 14 ) for developed regions to 546 ( 511 to 652 ) for sub-Saharan Africa . Accelerated progress will be needed to achieve the SDG goal ; countries will need to reduce their MMRs at an annual rate of reduction of at least 7.5 % . Interpretation Despite global progress in reducing maternal mortality , immediate action is required to begin making progress towards the ambitious SDG 2030 target , and ultimately eliminating preventable maternal mortality . While the rates of reduction that are required to achieve country-specific SDG targets are ambitious for the great majority of high mortality countries , the experience and rates of change between 2000 and 2010 in selected countries – those with concerted efforts to reduce the MMR- provide inspiration as well as guidance on how to accomplish the acceleration necessary to substantially reduce preventable maternal deaths . Funding Funding from grant R-155 - 000 - 146 - 112 from the National University of Singapore supported the research by LA and SZ . AG is the recipient of a National Institute of Child Health and Human Development , grant # T32-HD007275 . Funding also provided by USAID and HRP ( the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research , Development and Research Training in Human Reproduction ) OBJECTIVE Comparison of 3 regimens for third-stage management after second-trimester intravaginal misoprostol termination . STUDY DESIGN Prospect i ve r and omized trial . Three third-stage management strategies were compared : 10 units of intramuscular oxytocin ( group 1 ) , 600 microg oral misoprostol ( group 2 ) , or no additional medication ( group 3 ) after fetal expulsion . Primary study outcome was the incidence of placental retention . RESULTS Two hundred fifty-one women were r and omly assigned to the groups . There was a significant difference in placental retention rates : group 1 , 8 of 83 ( 10 % ) vs group 2 , 24 of 83 ( 29 % ) vs group 3 , 26 of 85 ( 31 % ) ; P = .002 . Blood loss was significantly lower in group 1 , 100 mL ( interquartile ranges , 50 - 200 ) vs group 2 , 200 mL ( interquartile ranges , 100 - 370 ) vs group 3 , 200 mL ( interquartile ranges , 100 - 375 ) ; P < .001 . Requirement for blood transfusion : group 1 , 1 of 83 ( 1 % ) vs group 2 , 1 of 83 ( 1 % ) vs group 3 , 5 of 85 ( 6 % ) ; P = .103 . CONCLUSION Intramuscular oxytocin administered after fetal delivery after second-trimester medical termination significantly increases placental expulsion rates and decreases short-term postpartum blood loss Background . The single most common direct obstetric disorder accounting for 25 % of all maternal deaths globally is severe hemorrhage , generally occurring postpartum . Nearly all these deaths occur in the developing world . The role of oxytocic drugs in the management of the third stage of labor as a strategy to reduce maternal mortality has been emphasized . However , the adverse effects of these oxytocic agents , in particular ergometrine , have not been properly evaluated in our environment . Objectives . To evaluate the effect of ergometrine and oxytocin on the cardiovascular system when used for active management of the third stage of labor . Study design . A double-blind , r and omized controlled study was carried out at the Federal Medical Centre , Makurdi over 24 months . Five hundred and ten patients were r and omized to treatment with either 0.5 mg of intramuscular ergometrine or 10 IU of intravenous oxytocin , respectively , as single injections . Their effects on the cardiovascular system were observed using blood pressure as a marker . Results . Ergometrine unlike oxytocin was observed to cause a significant rise in blood pressure , and this effect was most marked in the first 24 hours of the puerperium . Conclusions . These results suggest that ergometrine may be safe in normotensive parturients but hazardous in hypertensive parturients in whom oxytocin would be a safer option The incidences of postpartum haemorrhage and retained placenta have decreased with the use of synthetic oxytocin and controlled cord traction . Whether such treatment is valuable is open to question because of the lack of clinical and physiological studies . The physiological effects of synthetic oxytocin on plasma concentrations of oxytocin and events during delivery were assessed . Plasma oxytocin concentration was determined in serial sample s during the late second stage and throughout the third stage of labour in 25 women . Ten women received combined ergotamine and synthetic oxytocin intramuscularly and 15 were not treated . The geometric mean plasma oxytocin concentration significantly increased in the women given oxytocin when measured before and after delivery of the fetal anterior shoulder ( 3.1 ( SD 2.0 ) pmol/l before and 15.9 ( 2.7 ) pmol/l after ) . Six of the women who did not receive treatment showed a significant increase in geometric mean plasma oxytocin concentration before and after delivery of the fetal shoulder ( 3.2 ( 2.0 ) pmol/l before and 6.4 ( 2.0 ) pmol/l after ) and nine did not show an increase ( geometric mean 2.4 ( 3.1 ) pmol/l before and 2.2 ( 2.2 ) pmol/l after ) . Of these nine women , two had an abnormal third stage of delivery ; one woman had a postpartum haemorrhage and one required manual removal of the placenta . As it is impossible to predict which women will show a rise in the plasma concentration of endogenous oxytocin , intramuscular oxytocin should be given routinely Objective : The purpose of this prospect i ve , r and omised , double‐blind , placebo‐controlled study was to assess the effects of a 5‐IU oxytocin bolus and placebo infusion versus a 5‐IU oxytocin bolus and 30 IU infusion on the control of blood loss at elective lower segment caesarean section ( C/S ) Blood loss and the frequency of vomiting were assessed at 88 spontaneous vertex deliveries . An i.v . injection of oxytocin 10 u was as effective as ergometrine 0.5 mg in controlling bleeding from the uterus after delivery . The continuous infusion of a dilute solution of oxytocin in the first stage of labour was not followed by an increased blood loss at delivery . Oxytocin infusions were maintained for 1 h after delivery . Vomiting or retching occurred in 13 % of the mothers who received i.v . ergometrine . None of the women who received oxytocin suffered emetic sequelae Objective To compare the effect of intramuscular Syntometrine and Syntocinon in the management of the third stage of labour The objective of this study was to compare four different doses of oxytocin to determine its minimal effective dose during elective cesarean section . A prospect i ve , double-blind , r and omized study was undertaken in 40 healthy term parturients presenting for elective cesarean section under regional anesthesia . Subjects were assigned to one of four groups . Group I received 5 IU , Group II 10 IU , Group III 15 IU , and Group IV 20 IU of oxytocin after clamping of the umbilical cord . Uterine tone was assessed by palpation on a linear analog scale ( LAS ) of 0 to 10 ( 0 = completely atonic , 10 = fully contracted ) at 5 , 10 , 15 and 20 min after the start of oxytocin infusion . Estimated blood loss ( EBL ) and the difference in pre- and postoperative hematocrit ( Delta Hct ) were also recorded . At alpha = 0.05 , the study design had a power of 95 % to detect a 25 % difference in the LAS between the four groups . There were no differences in the uterine tone in the four groups at any of the four intervals . EBL and Delta Hct were similar in all four groups . There appears to be no benefit in terms of degree of uterine contraction and amount of blood loss to administering more than 5 IU of intravenous oxytocin to term parturients undergoing elective cesarean section with a neuraxial block . ( Anesth Analg 1997;84:753 - 6 BACKGROUND Postpartum hemorrhage ( PPH ) is an important cause of maternal morbidity and mortality especially in the developing countries.,Compared to expectant management , active management decreases the incidence of PPH . OBJECTIVE To compare the effectiveness of rectal misoprostol with intramuscular oxytocin in the prevention of postpartum hemorrhage . METHODS This is a prospect i ve , r and omized and analytical study from 1 st September 2009 to 28th February 2010 at Department of Obstetrics and Gynecology , Dhulkhel Hospital - Kathm and u University Hospital , Dhulikhel , Nepal . A total of 200 women were included to receive either 1000 micrograms rectal misoprostol tablets or 10 units of oxytocin intramuscularly . Primary outcome measures were the incidence of postpartum hemorrhage or a change in hematocrit or hemoglobin from admission to day two post delivery . Secondary outcome measures including severe postpartum hemorrhage and the duration of the third stage of labor were noted . Also the side effects of both misoprostol and oxytocin were recorded . RESULTS The frequency of postpartum hemorrhage was 4 % in the misoprostol subjects and 6 % in the control subjects ( P=0.886 ) There were no significant difference among the groups in the drop of hematocrit ( P>0.05 ) . Secondary outcome measures including severe postpartum hemorrhage and the duration of the third stage of labor were similar in both groups . Similarly , the side effects between the misoprostol and oxytocin group within 6 hours was statistically significant ( p=0.003 ) whereas the side effects within 24 hours was statistically not significant ( p=0.106 ) . CONCLUSION Rectal misoprostol is as effective as intravenous oxytocin in preventing postpartum hemorrhage with the similar incidence of side effects and is worthwhile to be used as a uterotonic agent for the routine management of third stage of labor OBJECTIVE : To assess the effects of oxytocin bolus or infusion on maternal hemodynamics in the third stage of labor . METHODS : In a r and omized , double-blind , double-dummy fashion , 99 women received an intravenous oxytocin bolus ( 10 IU push ) and 102 women received an infusion ( 10 IU in 500 mL saline at 125 mL/h ) at delivery of the anterior shoulder . Mean arterial pressure and heart rate were measured every minute for 10 minutes , then every 5 minutes for the next 20 minutes . These serial measurements were analyzed using a 2-factor analysis of variance for repeated measures . RESULTS : Serial mean arterial pressure measures varied significantly between groups ( interaction effect , P = .002 ) . Mean arterial pressure ( ± st and ard deviation ) nadirs were reached after 10 minutes , 80.9 ( ± 11.0 ) mm Hg in the bolus group compared with 77.0 ( ± 12.1 ) mm Hg in the dilute infusion group . The mean difference ( 95 % confidence interval ) between groups was 4.0 ( 0.7–7.2 ) mm Hg . Serial heart rate measures also varied between groups ( interaction effect , P < .001 ) . Mean heart rate ( ± st and ard deviation ) peaked 1 minute after the oxytocin infusion , 115 ( ± 27 ) beats per minute ( bpm ) in the bolus group compared with 109 ( ± 21 ) bpm in the dilute infusion group . The mean difference ( 95 % confidence interval ) between groups was 6.6 bpm ( −0.1 to 13.3 ) . The dilute oxytocin infusion group experienced a greater mean estimated blood loss ( 423.7 mL compared with 358.1 mL , P = .029 , t test ) , increased use of additional oxytocics ( 35.3 % compared with 22.2 % , P = .044 , Fisher exact test ) and a greater drop in hemoglobin ( admission minus postpartum ) ( 17.4g/L compared with 11.4g/L , P = .002 , t test ) compared with the oxytocin bolus group . CONCLUSION : Bolus oxytocin of 10 IU is not associated with adverse hemodynamic responses and can safely be administered to women with intravenous access in the third stage of labor for postpartum hemorrhage prophylaxis . LEVEL OF EVIDENCE : OBJECTIVES To explore the efficacy and safety of tranexamic acid at caesarian section ( CS ) . STUDY DESIGN Prospect i ve , r and omized , case-controlled clinical trial . POPULATION One hundred and eighty primiparas were r and omized into two groups . The study group , 91 women , received tranexamic acid immediately before CS whereas the control group , 89 women did not . METHOD Blood was collected during two periods . The first period was from placental delivery to the end of CS and the second was from the end of CS to 2 h postpartum . The quantity of blood was measured and compared between the two groups . Complete blood count , urinalysis , liver and renal function , prothrombin time and activity , were tested in the two groups . RESULTS Tranexamic acid significantly reduced the quantity of blood from the end of CS to 2 h postpartum : 42.75 + /- 40.45 ml in the study group versus 73.98 + /- 77.09 ml in the control group ( P=0.001 ) . It also significantly reduced the quantity of total blood from placental delivery to 2 h postpartum : 351.57 + /- 148.20 ml in the study group , 439.36 + /- 191.48 ml in the control group ( P=0.002 ) . No complications or side effects were reported in either group . CONCLUSIONS Tranexamic acid statistically reduces the extent of bleeding from placental delivery to 2 h postpartum and its use was not associated with any side effects or complications . Thus , tranexamic acid can be used safely and effectively to reduce bleeding result ing from CS BACKGROUND Oxytocin , the gold-st and ard treatment for post-partum haemorrhage , needs refrigeration , intravenous infusion , and skilled providers for optimum use . Misoprostol , a potential alternative , is increasingly used ad hoc for treatment of post-partum haemorrhage ; however , evidence is insufficient to lend support to recommendations for its use . This trial established whether sublingual misoprostol is non-inferior to intravenous oxytocin for treatment of post-partum haemorrhage in women receiving prophylactic oxytocin . METHODS In this double-blind , non-inferiority trial , 31 055 women exposed to prophylactic oxytocin had blood loss measured after vaginal delivery at five hospitals in Burkina Faso , Egypt , Turkey , and Vietnam ( two secondary -level and three tertiary-level facilities ) . 809 ( 3 % ) women were diagnosed with post-partum haemorrhage and were r and omly assigned to receive 800 mug misoprostol ( n=407 ) or 40 IU intravenous oxytocin ( n=402 ) . Providers and women were masked to treatment assignment . Primary endpoints were cessation of active bleeding within 20 min and additional blood loss of 300 mL or more after treatment . Clinical equivalence of misoprostol would be accepted if the upper bound of the 97.5 % CI fell below the predefined non-inferiority margin of 6 % . All outcomes were assessed from the time of initial treatment . This study is registered with Clinical Trials.gov , number NCT00116350 . FINDINGS All r and omly assigned participants were analysed . Active bleeding was controlled within 20 min after initial treatment for 363 ( 89 % ) women given misoprostol and 360 ( 90 % ) given oxytocin ( relative risk [ RR ] 0.99 , 95 % CI 0.95 - 1.04 ; crude difference 0.4 % , 95 % CI -3.9 to 4.6 ) . Additional blood loss of 300 mL or greater after treatment occurred for 139 ( 34 % ) women receiving misoprostol and 123 ( 31 % ) receiving oxytocin ( RR 1.12 , 95 % CI 0.92 - 1.37 ) . Shivering ( 152 [ 37 % ] vs 59 [ 15 % ] ; RR 2.54 , 95 % CI 1.95 - 3.32 ) and fever ( 88 [ 22 % ] vs 59 [ 15 % ] ; 1.47 , 1.09 - 1.99 ) were significantly more common with misoprostol than with oxytocin . Six women had hysterectomies and two women died . INTERPRETATION Misoprostol is clinical ly equivalent to oxytocin when used to stop excessive post-partum bleeding suspected to be due to uterine atony in women who have received oxytocin prophylactically during the third stage of labour Abstract Objective : To evaluate the efficacy of tranexamic acid ( TA ) in decreasing blood loss during and after elective caesarean section ( CS ) . Methods : This prospect i ve r and omized trial was conducted among 124 pregnant women subjected to term elective CS . Patients were equally divided into two groups . Study group received 10 mg/kg TA intravenously 5 min before skin incision while the control group did not . In addition , both groups received 10 units oxytocin and 1 ml ergometrine after delivery of the fetus . Blood loss in both groups was measured from placental delivery to end of the surgery and from end of the surgery to 2 h postpartum . Hemoglobin and hematocrit values were determined preoperatively and on the third day postpartum ( before discharge ) for all cases . Maternal and neonatal adverse effects in study groups were recorded . Results : TA group showed lower amount of blood loss ( 391 ml ) when compared to control group ( 597 ml ) . Risk estimation has revealed that treatment with TA result ed in decrease in risk of postpartum blood loss by 30 % . Hemoglobin and hematocrit levels were significantly lower in the control group on the third post-operative day . Conclusion : TA reduces blood loss during and immediately after CS . Its use in caesarean delivery may be considered especially in cases where blood loss is expected to be high or in anemic patients OBJECTIVES Our purpose was to compare the controlled cord traction technique with the minimal intervention technique for delivery of the placenta . The primary outcome was the incidence of postpartum hemorrhage . Secondary outcomes included duration of third stage of labor , frequency of retained placenta , hemorrhagic shock , the need for blood transfusion , and the need for uterotonic agents to control postpartum hemorrhage . STUDY DESIGN A total of 1648 women who were delivered vaginally were r and omly allocated during labor to the controlled cord traction group ( n = 827 ) or the minimal intervention group ( n = 821 ) . In the controlled cord traction group women received oxytocin , 10 units intramuscularly , with delivery of the baby 's anterior shoulder , after which the placenta was delivered actively by controlled cord traction ( Br and t- And rews method ) . In the minimal intervention group the placenta was delivered by maternal pushing . Continuous intravenous oxytocin was given after delivery of the placenta . Odds ratios with 95 % confidence intervals were calculated for each variable . RESULTS The overall incidence of postpartum hemorrhage was significantly lower in the controlled cord traction group ( 5.8 % vs 11 % ; odds ratio 0.50 , 95 % confidence interval 0.34 to 0.73 ) . The incidence of retained placenta ( > or = 30 minutes ) was 1.6 % in the controlled cord traction group and 4.5 % in the minimal intervention group ( odds ratio 0.31 , 95 % confidence interval 0.15 to 0.63 ) . Significantly more patients in the minimal intervention group required additional uterotonic agents to control hemorrhage ( 5.1 % vs 2.3 % ; odds ratio 0.44 , 95 % confidence interval 0.24 to 0.78 ) . CONCLUSION The controlled cord traction technique for delivery of the placenta results in a significantly lower incidence of postpartum hemorrhage and retained placenta , as well as less need for uterotonic agents , compared with the minimal intervention technique OBJECTIVE To compare the effect of prophylactic use of oxytocin and ergometrine in management of the third stage of labor . METHODS A prospect i ve r and omized study of 600 women assigned to receive either oxytocin or ergometrine in the third stage of labor . Outcome measures were the predelivery and 48-hour postdelivery hematocrit , duration of the third stage , specific side effects , and incidence of postpartum hemorrhage . Statistical analyses were done using the t test for continuous variables and chi2 test for categorical variables . The level of significance was set at P<0.05 . RESULTS There were no significant differences between the 2 groups in maternal age , gestational age , duration of third stage , birth weights , risk for retained placenta , manual removal of placenta , or need for additional oxytocics . Patients in the ergometrine group were at significant risk for nausea , vomiting , headaches , and elevated blood pressure ( P=0.0001 ) . CONCLUSION Oxytocin is as effective as ergometrine at reducing the incidence of postpartum hemorrhage , but without the undesirable side effects of nausea , vomiting , and elevated blood pressure associated with ergometrine OBJECTIVE The goal of this study was to compare carbetocin , a long-acting oxytocin analog , with oxytocin in the prevention of uterine atony after cesarean section . STUDY DESIGN We enrolled 694 patients undergoing elective cesarean section in a Canadian multicenter , double-blind , r and omized clinical trial . We compared the effect of a single 100 microg dose of carbetocin with that of a st and ard 8-hour infusion of oxytocin . The primary outcome was the proportion of patients requiring additional oxytocic intervention for uterine atony . A variable sample size , sequential design was used . RESULTS The overall oxytocic intervention rate was 7.4 % . The odds of treatment failure requiring oxytocic intervention was 2.03 ( 95 % confidence interval 1.1 to 2.8 ) times higher in the oxytocin group compared with the carbetocin group , respectively , 32 of 318 ( 10.1 % ) versus 15 of 317 ( 4.7 % ) , P < .05 . CONCLUSIONS Carbetocin , a new drug for the prevention of uterine atony , appears to be more effective than a continuous infusion of oxytocin and has a similar safety profile Postpartum hemorrhage is the leading cause of maternal deaths in the developing world accounting for 30 % of such deaths in areas where maternal mortality is high ; in the developed world it is the cause of maternal deaths in less than 10 % of births . The present study was conducted in Lok Nayak Hospital New Delhi India during a 1-year period from 2002 to 2003 . Two hundred pregnant women fulfilled the inclusion criteria i.e. all primigravidas with singleton pregnancy who underwent normal vaginal delivery . These women were r and omly allocated to either the ( A ) misoprostol ( Misoprost- 200 CIPLA Boisar Road Paighar Thane ) group or ( B ) the control group receiving methylergometrine ( Mem Neon Laboratories Virgonagar Bangalore 560049 ) in a 1:1 ratio by r and om number sequence . Group A received 600 Ag of misoprostol orally immediately after giving birth and after division of the umbilical cord . Group B received 0.2 mg of methylergometrine intravenously at delivery of the anterior shoulder of the infant . ( excerpt Abstract Objective : Cesarean section is associated with more blood loss than vaginal delivery . This could increase the risk of morbidity and mortality especially among anemic women . The objective of the trial is to assess the possible effect of tranexamic acid on blood loss during and after elective cesarean section . Methods : We conducted a r and omized controlled trial at Women 's Health Hospital , Assiut University , Assiut , Egypt . All pregnant women with singleton fetus planned to have elective cesarean section at ≥37 wks gestation were r and omized to receive 1 g tranexamic acid slowly intravenously over 10 min before elective cesarean section group or not . Blood loss was measured during and for two hours after operation . Any side effects , complications , medications , changes in vital signs and duration of hospital stay were recorded . This study is registered , number ACTRN12612000313831 . Results : Seven hundred and forty women were r and omized ( 373 in study group and 367 in control group ) . Mean total blood loss was 241.6 ( SE 6.77 ) ml in the tranexamic acid group versus 510 ( SE 7.72 ) ml in the control group . The mean drop in hematocrit and hemoglobin levels were statistically significantly lower in the tranexamic acid group than in the control group . There were no statistically or clinical ly significant differences in other outcomes . Conclusions : Pre-operative use of tranexamic acid is associated with reduced blood loss during and after elective cesarean section . This could be of benefit for anemic women or those who refuse blood transfusion Background : Little is known about maternal hemodynamics after Cesarean delivery . Uterine contractions may increase cardiac output . Oxytocin is the first-line treatment for uterine atony , although the effects of the long-acting oxytocin analogue carbetocin are comparable with that of oxytocin . The authors analyzed the effects of i.v . oxytocin 5 U , carbetocin 100 µg , and placebo on hemodynamics , uterine tone , adverse events , and blood loss after Cesarean delivery . Methods : This was a r and omized , double-blinded , placebo-controlled , parallel-group comparison of carbetocin and oxytocin after elective Cesarean delivery of singletons under spinal anesthesia ( n = 76 ) . Continuously measured invasive systolic arterial pressure was the primary outcome measure . Results : The mean systolic arterial pressure decrease was 28 mmHg ( 95 % CI , 22–34 ) after oxytocin and 26 mmHg ( 95 % CI , 20–31 ) after carbetocin . The decrease was greatest after 80 ( 95 % CI , 71–89 ) and 63 s ( 95 % CI , 55–72 ) , respectively ( P = 0.006 ) . The differences were nearly undetectable after 2.5 min , although the effect of carbetocin was slightly greater than placebo ( P < 0.001 ) . The group differences in systolic arterial pressure decreased over 5 min and were gone at 1 h. Heart rate and cardiac output increased in all three groups . Stroke volume increased after oxytocin and carbetocin but was unchanged after placebo . Conclusions : The hemodynamic side effects of oxytocin 5 U and carbetocin 100 µg were comparable . The lack of an increase in stroke volume in the placebo group challenges the theory that uterine contraction causes autotransfusion of uterine blood , leading to an increase in preload Abstract Objective : To compare effectiveness and tolerability of carbetocin versus oxytocin in prevention of postpartum hemorrhage ( PPH ) after vaginal delivery . Methods : A prospect i ve double-blinded r and omized study conducted on 200 pregnant women r and omized into two groups : Group 1 ( 100 women ) received single 100 μg IM dose of carbetocin and Group 2 received of 5 IU oxytocin IM . Both groups received their drug after fetal and before placental delivery . Results : There was a statistically significant difference between the two study groups regarding amount of bleeding ( 337.73 ± 118.77 versus 378 ± 143.2 ) , occurrence of PPH ( 4 versus 16 % ) , need for other uterotonics ( 23 versus 37 % ) and hemoglobin difference between before and after delivery ( 0.55 ± 0.35 versus 0.96 ± 0.62 ) ( all being lower in carbetocin group ) and measured hemoglobin 24 h after delivery ( being higher in carbetocin group ) ; however , there was no significant difference between the two study groups regarding occurrence of major PPH and the need for blood transfusion . Women in carbetocin group showed a statistically significant lower systolic and diastolic blood pressure immediately after delivery and at 30 and 60 min than women in oxytocin group . There was no significant difference between the two study groups regarding occurrence of nausea , vomiting , flushing , dizziness , headache , shivering , metallic taste , dyspnea , palpitation and itching . Women in carbetocin group experienced tachycardia more than women in oxytocin group . Conclusions : Carbitocin is a better alternative to traditional oxytocin in prevention of PPH after vaginal delivery with minimal hemodynamic changes and similar side effects Purpose To determine , after Caesarean delivery , uterine contractility and blood pressure following intravenous ( iv ) and intramyometrial ( imy ) injection of oxytocin . Methods In a double-blind clinical trial 40 parturients scheduled for elective Caesarean section with spinal anaesthesia were r and omized into two equal groups . One litre Ringer ’s lactate was administerediv before intrathecal injection of 1.7 ml bupivacaine 0.75 % and 0.3 mg morphine . All patients received simultaneous iv and imy injections after removal of the placenta . Patients in Group 1 received 5 IU ( 10 IU·ml−1 ) oxytociniv and 2 ml salineimy ; Group 2 patients received 0.5 ml saline iv and 20 IU oxytocin into the myometrium . Baseline systolic blood pressure ( SBP ) and heart rate were measured before delivery and at one minute intervals for 15 min after injection of study solutions . Uterine contractility was assessed at 1 , 2 , 4 , 6 , 8 , 10 and 15 min after oxytocin injection . Haemoglobin concentration before surgery and on first post-operative day was also recorded . Results Mean decrease in systolic blood pressure ( SBP ) one minute after oxytocin was 8.4 mmHg in Group 1vs 14.6 mmHg in Group 2 ( P < 0.001 ) . Systolic blood pressure returned to baseline two minutes after oxytocin in Group 1 and after three minutes in Group 2 . Uterine contractility and change in haemoglobin concentration were similar in both groups . Conclusion Intramyometrial administration of 20 IU oxytocin after Caesarean delivery is associated with more severe hypotension than is iv injection of 5 IU oxytocin . Route of oxytocin injection did not affect uterine tone . RésuméObjectifDéterminer la contractilité utérine et la tension artérielle qui suivent une injection intraveineuse ( iv ) et intramyométriale ( imy ) d’ocytocine après un accouchement par césarienne . MéthodeLors d’un essai clinique en double aveugle , 40 parturientes devant subir une césarienne élective et recevoir une anesthésie péridurale ont été réparties de façon aléatoire en deux groupes égaux . Un litre de lactate de Ringer a été administré iv avant une injection intrathécale de 1,7 ml de bupivacaïne à 0,75 % et 0,3 mg de morphine . Toutes les patientes ont reçu des injections simultanées iv et imy après l ’ extraction du placenta . Les patientes du groupe 1 ont reçu 5 Ul ( 10 Ul·ml−1 ) d’ocytocine iv et 2 ml de solution salée imy ; les patientes du groupe 2 ont reçu 0,5 ml de solution salée iv et 20 Ul d’ocytocine imy . La tension artérielle systolique ( TAS ) de base et la fréquence cardiaque ont été mesurées avant l’accouchement et à intervalles d’une minute pendant 15 minutes après l’injection des solutions-test . La contractilité utérine a été évaluée à 1 , 2 , 4 , 6 , 8 , 10 et 15 minutes après l’injection d’ocytocine . On a aussi enregistré la concentration d’hémoglobine avant la chirurgie et le premier jour postopératoire . RésultatsLa baisse moyenne de la tension artérielle systolique ( TAS ) , une minute après l’injection d’ocytocine , était de 8,4 mmHg dans le groupe 1vs 14,6 mmHg dans le groupe 2 ( P < 0,001 ) . Également après l’ocytocine , il a fallu deux minutes pour le groupe 1 et trois minutes pour le groupe 2 avant de retrouver la tension artérielle de base . La contractilité utérine et le changement dans la concentration d’hémoglobine ont été similaires dans les deux groupes . Conclusion Ladministration intramyométriale de 20 Ul d’ocytocine après une césarienne est associée à une hypotension plus sévère qu’avec une injection iv de 5 Ul d’ocytocine . La voie d’administration de l’ocytocine n’a pas affecté la tonicité utérine OBJECTIVE To compare sublingual misoprostol with intramuscular oxytocin for prevention of postpartum hemorrhage ( PPH ) in low-risk vaginal birth . METHODS In a prospect i ve , r and omized , double-blind trial , 530 women without risk of PPH were r and omly allocated to receive either 400 μg of misoprostol sublingually or 10 units of oxytocin intramuscularly within 1minute of delivery . The outcome measures were incidence of PPH , postpartum blood loss , drop in hemoglobin level in 24 hours , need for additional uterotonic drug , incidence of adverse effects , and need for blood transfusion . Student t , χ(2 ) , Mann-Whitney U , and Fisher exact tests were used for comparison . RESULTS Incidence of postpartum hemorrhage ( ≥ 500 mL ) and postpartum blood loss in the misoprostol group were similar to those in the oxytocin group ( 6 % versus 5.7 % , P=0.85 ; 153 mL versus 146 mL , P=0.36 ) . Shivering and pyrexia were encountered more often in the misoprostol than in the oxytocin group ( shivering : 19 % versus 0.8 % , P<0.001 , relative risk [ RR ] 0.86 , 95 % confidence interval [ CI ] 0.82 - 0.90 ; pyrexia : 2.3 % versus 0 % , P=0.03 , RR 0.97 , 95 % CI 0.95 - 0.99 ) . CONCLUSION The efficacy of 400 μg of misoprostol administered sublingually was equivalent to that of 10 units of oxytocin given intramuscularly for prevention of PPH in low-risk vaginal delivery INTRODUCTION Postpartum hemorrhage ( PPH ) constitutes the main cause of delivery-related maternal mortality worldwide . Identification of the risk factors , as well as knowledge about preventive measures and adequate management , allow to limit blood loss . Oxytocin , carbetocin , methylergometrine , dinoprostone , suiprostone , and misoprostol are commonly used drugs in prevention of PPH . OBJECTIVES The aim of the study was to evaluate the efficacy of carbetocin and oxytocin in prevention of PPH after cesarean section . MATERIAL AND METHODS The study included 130 female patients after C-section who received 1 00 pg of carbetocin i.v . as a preventive agent after the surgery The control group consisted of 60 women who received 10 units of oxytocin i.v . In the study the risk factors for PPH were determined , and hemoglobin and hematocrit values before and 12 hours after birth , as well as blood loss and the need to use other prevyentfive and operational methods were evaluated . Results were compared between the groups . Statistical analysis was performed with the use of Statistica for hemoglobin and hematocrit values . The p-value of < or = 0.05 was considered as statistically significant . RESULTS Risk factors for PPH occurred in almost 100 % of the women with carbetocin and in 90 % of the women with oxytocin . The decrease in hemoglobin and hematocrit levels was not statistically significant , although a greater drop was detected in the group with oxytocin ( hemoglobin - 1.24 vs. 1.17 g% , hematocrit - 3.26 vs. 2.93 % ) . The decrease in hematological values was not statistically significant between both groups . In the group with'carbetocin , there was no need for additional pharmacological therapy or operative procedures . No adverse events in either of the groups were observed . CONCLUSIONS ( 1 . ) Carbetocin effectively prevents PPH after C-section . ( 2 . ) Carbetocin seems to have high efficiency in PPH prevention in pregnant women classified to the PPH risk group . ( 3 . ) Efficacy of Carbetocin in PPH prevention is higher than oxytocin BACKGROUND Globally 166 000 women die annually as a result of obstetric haemorrhage . More than 50 % of these deaths occur in sub-Saharan Africa . Uterine atony is the commonest cause of severe postpartum haemorrhage ( PPH ) . Bleeding at or after caesarean section ( CS ) is responsible for > 30 % of maternal deaths due to obstetric haemorrhage in South Africa ( SA ) . OBJECTIVE To compare oxytocin alone with oxytocin + ergometrine in terms of primary prophylaxis for PPH at the time of CS . METHODS This was a double-blind r and omised controlled interventional study comparing oxytocin with oxytocin + ergometrine administered during CS . Patients were r and omised to receive oxytocin alone intravenously as a bolus or oxytocin + ergometrine intramuscularly , with the placebo being an injection of sterile water . The study population consisted of women undergoing CS at Kalafong Provincial Tertiary Hospital in Atteridgeville , Gauteng , SA . RESULTS Five hundred and forty women were r and omised and data for 416 women , of whom 214 received oxytocin and 202 oxytocin + ergometrine , were available for analysis . In the oxytocin group 19 women ( 8.9 % ) required blood transfusion , compared with seven ( 3.5 % ) in the oxytocin + ergometrine group ( p=0.01 ; relative risk = 2.78 ; 95 % confidence interval 1.21 - 6.4 ) . There were no statistically significant differences in the mean estimated visual and mean calculated blood loss . CONCLUSIONS The overall need for blood transfusion was significantly reduced by about two-thirds in women receiving the oxytocin + ergometrine combination . Consideration should be given to using oxytocin + ergometrine for prophylaxis of PPH at CS Objective The objective of this study was to determine the optimal dose of intravenous oxytocin administered during cesarean delivery ( CD ) to decrease the amount of blood loss . Methods Out of a total of 226 women presenting for CD , 189 patients were r and omized into three groups by a computer‐generated r and om number sequence table . Low‐risk women with singleton term pregnancies undergoing scheduled CD were assigned to receive 20 , 30 , or 40 units ( U ) of oxytocin diluted in 500 mL of lactated Ringer solution intraoperatively . The primary outcome was the change in hemoglobin from pre‐CD to post‐CD . Results Overall , 63 women were assigned to each group . The primary outcome which was the drop in hemoglobin ( 1.4 ± 1.1 g/dL , 1.1 ± 0.8 g/dL , 1.0 ± 1.1 g/dL ; p = 0.097 ) and the total calculated blood loss ( 798.6 ± 298.3 mL , 794.4 ± 313.5 mL , 820.2 ± 316.2 mL ; p = 0.893 ) were not significantly different among the study groups . The incidence of intraoperative hypotension , postoperative systolic , and diastolic blood pressure changes was similar across the groups . Conclusion The amount of blood loss during CD was not significantly different among the three groups , thus the lowest dose of oxytocin infusion ( 20 U in 500 mL of lactated Ringer solution ) seems to be an appropriate regimen Objective To compare misoprostol with st and ard oxytocic regimens in the prevention of postpartum haemorrhage Postpartum hemorrhage ( PPH ) is the most common serious maternal complication of childbirth and the prophylactic use of uterotonic drugs is generally recommended to prevent this complication . Between February and March 2005 a prospect i ve r and omized clinical trial was conducted at the Gynecologic and Obstetric Department of F. Hached Hospital Sousse Tunisia to determine whether the use of oxytocin in the third stage of labor significantly reduced the postpartum blood loss . All women with singleton pregnancies at term who were expected to be delivered vaginally were included . Patients with placenta praevia antepartum hemorrhage noncephalic presentation intrauterine death parity greater than five uterine fibroids anticoagulation therapy and a history of PPH or cesarean delivery were excluded . The women were r and omly allocated to an active management or an expectant management group . In the active management group the women received an intravenous flash injection of 5 I of oxytocin at the time of delivery of the anterior shoulder . The third stage of labor was managed in the same way for all women : immediate clamping and cutting of the cord and delivery of the placenta by controlled cord traction with gentle fundal pressure when signs of placental separation appeared . Manual removal of placenta was used if hemorrhaging occurred and /or if the placenta was not delivered within 30 min of birth . ( excerpt Summary This r and omised controlled trial aim ed to compare the efficacy of intramuscular syntometrine with intravenous syntocinon , in preventing postpartum haemorrhage . A total of 686 women were r and omised into two groups ; one receiving intramuscular syntometrine and the other receiving intravenous syntocinon , as part of the active management of the third stage of labour . There was no difference in the mean blood loss between the two groups . However , there was an increased incidence of having a diastolic blood pressure of > 90 , 30 min after the delivery ( p = 0.004 ) , with intramuscular syntometrine . Therefore , it can be concluded that 1 ml of intramuscular syntometrine and 10 units of intravenous syntocinon are equally effective in preventing postpartum haemorrhage OBJECTIVE To determine the effectiveness of sustained uterine massage started before delivery of the placenta in reducing postpartum hemorrhage . METHODS A r and omized controlled trial conducted in Egypt and South Africa between September 2006 and February 2009 . A total of 1964 pregnant women were r and omly allocated to 1 of 3 treatment groups : intramuscular oxytocin , sustained uterine massage , or both treatments . Blood loss within 30 minutes of delivery was recorded . RESULTS The incidence of blood loss of 300 mL or more within 30 minutes of delivery was significantly higher in the massage group than in the massage plus oxytocin ( RR 1.88 ; 95 % CI , 1.29 - 2.74 in Assiut , and RR 1.3 ; 95 % CI , 1.00 - 1.68 in SA ) and the oxytocin only group ( RR 1.7 ; 95 % CI , 1.11 - 2.61 in Assiut , and RR 2.24 ; 95 % CI , 1.54 - 3.27 in SA ) . In both centers , use of additional uterotonics was significantly higher in the uterine massage group compared with the other 2 groups . CONCLUSION Uterine massage was less effective than oxytocin for reducing blood loss after delivery . When oxytocin was used , there was no additional benefit from uterine massage . The effectiveness of uterine massage in the absence of oxytocin was not studied . ACTRN : 12609000372280 Aim of the study To test that rectal misoprostol is effective for active management of third stage of labor , and probably with less side effects than oral misoprostol . Material s and methods As much as 658 patients were r and omly allocated to receive either 600 μg misoprostol orally or rectally 5 min after cord clamping and cutting . The primary outcome was incidence of postpartum hemorrhage . Secondary outcomes included amount of blood loss , duration of third stage of labor , incidence of side effects , pre- and post-delivery hemoglobin , and the use of additional uterotonics . Results A total of 331 patients received 600 μg of misoprostol orally , while 327 rectally . Both groups were comparable in demographic data and neonatal outcome . Oral misoprostol was associated with significantly more blood loss than rectal ( P = 0.016 ) . Shivering and pyrexia occurred in 161 ( 52.1 % ) and 86 ( 27.8 % ) women receiving oral misoprostol , and in 81 ( 26.2 % ) and 47 ( 15.2 % ) of those who received rectal misoprostol , respectively ( P = 0.000 and 0.001 ) . Conclusion Rectal misoprostol is effective in the management of third stage of labor , and with a significant decrease in side effects . Lesser dose and other routes could be explored in the future BACKGROUND Postpartum haemorrhage is a major cause of maternal mortality in the developing world . Although effective methods for prevention and treatment of such haemorrhage exist -- such as the uterotonic drug oxytocin -- most are not feasible in re source -poor setting s where many births occur at home . We aim ed to investigate whether oral misoprostol , a potential alternative to oxytocin , could prevent postpartum haemorrhage in a community home-birth setting . METHODS In a placebo-controlled trial undertaken between September , 2002 , and December , 2005 , 1620 women in rural India were r and omised to receive oral misoprostol ( n=812 ) or placebo ( n=808 ) after delivery . 25 auxiliary nurse midwives undertook the deliveries , administered the study drug , and measured blood loss . The primary outcome was the incidence of acute postpartum haemorrhage ( defined as > or = 500 mL bleeding ) within 2 h of delivery . Analysis was by intention-to-treat . The trial was registered with the US clinical trials data base ( http://www . clinical trials.gov ) as number NCT00097123 . FINDINGS Oral misoprostol was associated with a significant reduction in the rate of acute postpartum haemorrhage ( 12.0 % to 6.4 % , p<0.0001 ; relative risk 0.53 [ 95 % CI 0.39 - 0.74 ] ) and acute severe postpartum haemorrhage ( 1.2 % to 0.2 % , p<0.0001 ; 0.20 [ 0.04 - 0.91 ] . One case of postpartum haemorrhage was prevented for every 18 women treated . Misoprostol was also associated with a decrease in mean postpartum blood loss ( 262.3 mL to 214.3 mL , p<0.0001 ) . Postpartum haemorrhage rates fell over time in both groups but remained significantly higher in the placebo group . Women taking misoprostol had a higher rate of transitory symptoms of chills and fever than the control . INTERPRETATION Oral misoprostol was associated with significant decreases in the rate of acute postpartum haemorrhage and mean blood loss . The drug 's low cost , ease of administration , stability , and a positive safety profile make it a good option in re source -poor setting OBJECTIVE To determine the role of intraumbilical vein oxytocin reducing blood loss during and after one hour of delivery of placenta and its efficacy in reducing the frequency of retained placenta . STUDY DESIGN R and omized controlled trial . PLACE AND DURATION OF STUDY Combined Military Hospital , Multan , from June 2002 to October 2002 . METHODOLOGY Five hundred parturient women with low risk singleton term pregnancy were enrolled in the study . Two hundred and fifty women each were included in the study and control group after r and omization . The patients and health care providers both were blinded to the intervention . Primary outcome measures were kept as duration and amount of blood loss in third stage of labour . Secondary outcome measures included incidence of retained placenta , abdominal need for additional utero-tonics , frequency of postpartum pain , nausea and vomiting , fever , need for blood transfusion , establishment of breast feeding and total duration of hospital stay . RESULTS Women in study group who received intraumbilical vein syntocinon lost 234.03 ml of blood while the control group lost 276.51 ml ( p=0.001 ) . Mean duration of third stage was 2.59 minutes in the study group and 7.67 minutes in the control group ( p<0.001 ) . The frequency of retained placenta was 1.2 % , which involved only the control group . Abdominal pain was experienced by study group but the difference was not found statistically significant . Nausea and vomiting was more in study group ( p=0.001 ) . No discernible difference was found in length of hospital stay , the need for blood transfusion , fever and establishment of breast-feeding in both groups . CONCLUSION The addition of intraumbilical vein syntocinon 10 units result ed in marked reduction in amount of blood loss , duration of third stage and incidence of retained placenta in comparison to intravenous 5 IU oxytocin+0.5 mg ergometrine alone OBJECTIVE To determine the optimum time for misoprostol administration to minimize blood loss during and after elective cesarean delivery . METHODS A r and omized clinical trial was conducted at Mansoura University Hospital , Egypt , between January 1 , 2013 , and December 31 , 2014 . Eligible participants had full-term pregnancies , were scheduled to have a cesarean , and had normal fetal heart tracing . Patients were r and omly allocated into two equal groups using computer-generated tables and sealed opaque envelopes . Misoprostol ( 400μg , given rectally ) was given either before ( group 1 ) or after ( group 2 ) surgery . Patients , investigators , and data analysts were not masked to group assignment . The primary outcome was blood loss . RESULTS A total of 348 women were included ( 174 in each group ) . Blood loss was significantly lower in group 1 than in group 2 ( 570±240 vs 844±270mL ; P<0.001 ) . The frequency of maternal and neonatal adverse events did not differ between the groups . CONCLUSION Preoperative misoprostol ( 400μg , given rectally ) reduces blood loss to a greater extent than does postoperative misoprostol during elective cesarean delivery . The frequency of complications was not affected by time of administration Objective To assess the effectiveness of 600 μg oral misoprostol on postpartum haemorrhage ( PPH ) and postpartum anaemia in a low income country home birth situation OBJECTIVE To evaluate the uterotonic effect of carbetocin compared with oxytocin in emergency cesarean delivery . STUDY DESIGN Participants were r and omized to intravenous bolus injection of 100mcg carbetocin or 10IU oxytocin after cesarean delivery of the baby . The primary outcome is any additional uterotonic which may be administered by the blinded provider for perceived inadequate uterine tone with or without hemorrhage in the first 24hours after delivery . Secondary outcomes include operating time , perioperative blood loss , change in hemoglobin and hematocrit levels , blood transfusion and reoperation for postpartum hemorrhage . RESULTS Additional uterotonic rates were 107/276 ( 38.8 % ) vs. 155/271 ( 57.2 % ) [ RR 0.68 95 % CI 0.57 - 0.81 p<0.001 ; NNTb 6 95 % CI 3.8 - 9.8 ] , mean operating time 45.9±16.0 vs. 44.5±13.1minutes p=0.26 , mean blood loss 458±258 vs. 446±281ml p=0.6 , severe postpartum hemorrhage ( ≥1000ml ) rates 15/276 ( 5.4 % ) vs. 10/271 ( 3.7 % ) p=0.33 and blood transfusion rates 6/276 ( 2.2 % ) vs. 10/271 ( 3.7 % ) ; p=0.30 for carbetocin and oxytocin arms respectively . There was only one case of re-operation ( oxytocin arm ) . In the cases that needed additional uterotonic 98 % ( 257/262 ) was started intraoperatively and in 89 % ( 234/262 ) the only additional uterotonic administered was an oxytocin infusion over 6hours . CONCLUSION Fewer women in the carbetocin arm needed additional uterotonics but perioperative blood loss , severe postpartum hemorrhage , blood transfusion and operating time were not different The umbilical vein administration of oxytocin in saline was compared with umbilical vein saline alone and the traditional management of the third stage of labour . Seventy‐two women were r and omized to 3 groups . Group 1 received intraumbilical 20 IU of oxytocin diluted to 40 mL with saline . Group 2 received intraumbilical vein 40 mL of saline while subjects in group 3 were managed according to the st and ard protocol without any intraumbilical injection . No significant differences were found in terms of the length of the third stage , the blood loss in the third stage and postpartum haematocrit differences among the 3 groups . The administration of diluted oxytocin or saline do not seem to have any superiority to the traditional management of the third stage of labour In a prospect i ve , open-label , assessor-blind , r and omised parallel group study the efficacy and safety of Hemabate ( Pharmacia-Upjohn Pharmaceuticals , Milton Keynes , Buckinghamshire ) an analogue of 15-methyl-prostagl and in ( PGF2alpha ) analogue was compared with Syntometrine ( Alliance Pharmaceuticals , Chippenham , Wilts ) the st and ard combination of ergometrine and syntocinon used for the active management of the third stage of labour and the prevention of primary postpartum haemorrhage ( PPH ) . The study was set in a district general hospital with approximately 4,000 deliveries annually . The study was discontinued at the time of the interim analysis because of unacceptable gastrointestinal side effects . At the time of the interim analysis , a total of 529 women had completed the study with 263 r and omised to receive PGF2alpha and 266 to receive ergometrine and syntocinon . In a pre-specified subgroup analysis , women delivered vaginally were further subdivided into those considered to be at high or low risk of primary PPH . The measured blood loss and incidence of PPH was similar in both treatment groups whether delivered by caesarean section or vaginally independent of whether women were considered to be at high or low risk . Adverse gastrointestinal events were recorded more often in the Hemabate group . The most common symptom was diarrhoea which occurred in 21 % of women who received Hemabate compared to only 0.8 % of Syntometrine users . PGF2alpha is as effective as Syntometrine in the prophylaxis of primary PPH in all groups studied but there was a statistically significantly increased risk of diarrhoea among users of PGF2alpha OBJECTIVE Manual removal of placenta is performed in 1 - 3 % of cases , and although it is a well-established and relatively safe procedure , it is not without complications . We carried out this study to determine whether intraumbilical vein oxytocin injection reduces the need for manual removal of placenta and shortens the third stage of labor , in comparison with placebo . MATERIAL S AND METHODS In this r and omized clinical trial , 178 women with singleton pregnancy and normal delivery were studied in 1 year . Immediately after fetus delivery , oxytocin infusion ( 20 IU/L ) was started in both groups . Moreover , 10 IU oxytocin and 1 mL normal saline were injected into the umbilical vein of women in the experimental and control groups , respectively . The duration of third-stage labor , need for manual delivery of placenta , and drug side effects were evaluated in both groups . With regard to the mean level of hemoglobin before and after delivery , the two groups were compared using the Levene test and independent t test , and other qualitative variables of the two groups were compared using the χ(2 ) test . RESULTS The women who received intraumbilical vein oxytocin had a shorter third stage of labor as compared with the placebo group ( 4.24 ± 3.27 min vs. 10.66 ± 7.41 ) ( p < 0.001 ) and there was less need for manual delivery of placenta in the experiment group ( 1.1 % vs. 5.1 % ) ( p = 0.024 ) . CONCLUSION It was concluded that intraumbilical vein administration of 10 IU ( 1 mL ) oxytocin immediately after fetus delivery was clinical ly effective in shortening the third stage of labor OBJECTIVE To assess the effect of injecting an uterotonic agent in the umbilical vein during the third stage of labor in women with retained placentas . METHODS In this prospect i ve clinical study , 75 women with retained placentas received 20 mL of a 0.9 % saline solution with either 20 IU of oxytocin ( n=54 ) , 0.5 mg of carboprost tromethamine ( n=7 ) , or 0.2 mg of methylergometrine ( n=14 ) injected in the umbilical vein after clamping . The treatment success was determined by the clinical signs of placental ablation . RESULTS There were no statistically significant differences among the 3 therapeutic groups regarding age , parity , risk factors , pregnancy duration , type of delivery ( spontaneous , induced , or augmented ) , or possible early postpartum complications caused by the intraumbilical injection . The rates of therapeutic success were 76.9 % in the oxytocin group , 85.7 % in the synthetic prostagl and in group , and 64.2 % in the methylergometrine group . CONCLUSION The intraumbilical injection of uterotonics is a noninvasive , effective , and clinical ly safe method of shortening the third stage of labor in women with retained placentas Please cite this paper as : Elati A , Elmahaishi M , Elmahaishi M , Elsraiti O , Weeks A. The effect of misoprostol on postpartum contractions : a r and omised comparison of three sublingual doses . BJOG 2011;118:466–473 AIM The aim of this study was to evaluate the efficacy of adjunctive rectal misoprostol compared to oxytocin infusion in the prevention of primary postpartum hemorrhage after routine active management of the third stage of labor in women with identifiable risk factors for uterine atony . MATERIAL AND METHODS A double-blind r and omized controlled trial was carried out at Obafemi Awolowo University Teaching Hospitals Complex , Ile-Ife , Nigeria . A total of 264 parturients with known risk factors for postpartum hemorrhage were r and omized to receive either rectal misoprostol ( 600 µg ; n = 132 ) or oxytocin infusion ( 20 IU in 500 mL ; n = 132 ) after routine active management of the third stage of labor . Intrapartum blood loss was measured using a combination of the BRASSS-V calibrated drapes and differential pad weighing . Hematocrit was measured intrapartum and 24 h postpartum . RESULTS There was no significant difference ( P = 0.07 ) in the mean intrapartum blood loss between the misoprostol ( 387.28 ± 203.09 mL ) and oxytocin ( 386.73 ± 298.51 mL ) groups . There was also no difference in the requirement for additional intervention for uterine atony ( P = 0.74 ) . Postpartum hematocrit drop and blood transfusion were , however , significantly less in the misoprostol group . CONCLUSION Rectal misoprostol is as effective as oxytocin infusion as an adjunct for prevention of postpartum hemorrhage in women with risk factors for uterine atony and is associated with a lower hematocrit drop and blood transfusion postpartum . However , shivering , pyrexia and vomiting are more frequent with misoprostol , though usually self-limited Background : The aim of this study was to compare the efficacy and safety of oral misoprostol 400 µg with intramuscular syntometrine in the management of the third stage of labor . Material and Methods : This was a double-blind r and omized controlled trial conducted in a tertiary care hospital . Three hundred and fifty-five women r and omized to receive either oral misoprostol 400 µg or intramuscular syntometrine in the third stage of labor were studied . The change in hemoglobin level from before to 48 h after delivery , use of additional oxytocics and treatment related side effects were the main outcome measures . Results : There were no significant differences between the two groups in terms of the change in hemoglobin level and mean blood loss . The incidence of shivering was significantly higher in the misoprostol group whilst that of vomiting was significantly higher in the syntometrine group . There were no differences in the incidence of nausea , headache , diarrhea and pyrexia between the two groups . Conclusion : Orally administeredmisoprostol at a dose of 400 µg is an acceptable alternative in preventing post-partum blood loss , as measured by the peri-partum change in hemoglobin level and was not associated with an increased incidence of side effects Abstract Background and Objectives Postpartum hemorrhage is the single largest and leading cause of maternal morbidity and mortality not only in developing countries but also in developed countries . The present study is an attempt to evaluate the scope of using prophylactic intramuscular carboprost tromethamine 125 μg in comparison with intramuscular oxytocin 10 units for the active management of third stage of labor . Material s and Methods Two hundred pregnant women at term with spontaneous onset of labor were included in the study and were r and omly divided into 2 groups of 100 women each . Group A and group B were given injection oxytocin 10 units and injection carboprost tromethamine 125 μg intramuscularly , respectively , at the time of delivery of anterior shoulder . The main outcome measures with respect to third stage of labor were : duration , blood loss by volume , difference in hemoglobin , need for additional oxytocics and side effects . Results Subjects who received carboprost tromethamine 125 μg showed a significant reduction in duration of third stage of labor ( p < 0.05 ) and blood loss ( p < 0.01 ) when compared to the subjects who received oxytocin 10 units . Likelihood of occurrence of postpartum hemorrhage was reduced without significant side effects except for diarrhea . Additional need for other uterotonics after carboprost was significantly less compared to oxytocin . Conclusion Intramuscular carboprost 125 μg is a better cost-effective alternative as compared to 10 units intramuscular oxytocin in active management of third stage of labor OBJECTIVE To compare oral misoprostol with conventional oxytocics in the management of the third stage of labor . METHODS In a controlled trial , 1574 women were r and omized into four groups , as follows : Group 1 received intravenous infusion of oxytocin 10 IU plus oral misoprostol 400 μg , followed by two doses of oral misoprostol 100 μg 4 hours apart ; group 2 received oral misoprostol 400 μg , followed by two doses of oral misoprostol 100 μg 4 hours apart ; group 3 received intravenous infusion of oxytocin 10 IU ; and group 4 received intravenous infusion of oxytocin 10 IU plus intramuscular administration of methylergonovine maleate ( Methergine ) 0.2 mg . The incidence of postpartum hemorrhage and decrease in hemoglobin concentration from before delivery to 24 hours postpartum were the main outcome measures . RESULTS The primary outcome measures were similar in groups 2 and 3 . The incidence of postpartum hemorrhage was 9 % in group 2 , compared with 3.2 % in group 1 and 3.5 % in group 4 ( P < .01 , and P = .01 , respectively ) . There were no significant differences among the four groups regarding hemoglobin concentrations . Significantly more women needed additional oxytocin in group 2 , when compared with group 4 ( 5.9 % versus 2.2 % ; P = .01 ) . The proportion of women requiring additional methylergonovine maleate was 4.8 % in group 2 , compared with 0.7 % in group 1 and 1 % in group 4 ( P < .01 and P = .01 , respectively ) . CONCLUSION Oral misoprostol alone is as effective as oxytocin alone for the prevention of postpartum hemorrhage ; it is less effective than oxytocin plus methylergonovine maleate and oral misoprostol plus oxytocin OBJECTIVE To compare the effect of oxytocin and Syntometrine when used as part of active management of third stage of labour on postpartum haemorrhage , hypertension , nausea/vomiting and retained placenta . STUDY DESIGN A r and omised double blind trial was conducted in the Obstetric Unit of Corniche Hospital , Abu Dhabi in the United Arab Emirates . Between 1 January 1991 and 30 June 1991 , 2040 women were r and omly allocated either to the oxytocin ( n = 1017 ) or the Syntometrine ( n = 1023 ) group . Twelve patients had to be excluded from the trial ( oxytocin , 5 ; Syntometrine , 7 ) after r and omisation because they no longer fulfilled the inclusion criteria . All women in the trial received either oxytocin 10 units or Syntometrine 1 ml ( oxytocin 5 units+ergometrine ( ergonovine ) 0.5 mg ) by intramuscular injection with delivery of the anterior shoulder of the baby . Relative risk with 95 % confidence intervals was calculated for each variable . RESULTS Oxytocin ( 10 units ) alone was as effective as Syntometrine ( 1 ml ) in preventing post-partum haemorrhage without an increase in the incidence of retained placenta . Median blood loss was similar in both groups . The incidences of nausea , vomiting and headache were significantly lower in the oxytocin group , as was the occurrence of a mean rise in diastolic and systolic blood pressures of 20 and 30 mmHg or more , respectively . CONCLUSION Prophylactic administration of oxytocin 10 U in the third stage of labour , as part of active management , reduces the incidence of maternal nausea , vomiting , headache and rise in blood pressure than does Syntometrine 1 ml without adversely affecting the rate of post partum haemorrhage OBJECTIVE This study compares the efficacy of sublingual misoprostol versus intravenous oxytocin in reducing bleeding during and after cesarean delivery . MATERIAL S AND METHODS A r and omized clinical trial conducted on 120 pregnant women at term ( 37 - 40 weeks ) gestation scheduled for elective cesarean delivery , who were assigned to either sublingual misoprostol 400 μg or intravenous infusion of 20 units of oxytocin after delivery of the neonate . The main outcome measures were blood loss at and 2 hours after cesarean delivery , change in hematocrit value , need for any additional oxytocic drugs , and drug-related side effects . RESULTS The overall mean blood loss was significantly lower in the misoprostol group compared to the oxytocin group ( 490.75 ± 159.90 mL vs. 601.08 ± 299.49 mL ; p = 0.025 ) . However , changes in hematocrit level ( pre- and postpartum ) was comparable between both groups . There was a need for additional oxytocic therapy in 16.7 % and 23.3 % after use of misoprostol and oxytocin , respectively ( p = 0.361 ) . Incidence of side effects such as shivering and metallic taste were significantly higher in the misoprostol group compared to the oxytocin group ( p < 0.001 ) . CONCLUSIONS Sublingual misoprostol is more effective than intravenous infusion of oxytocin in reducing blood loss during and after cesarean delivery . However , occurrence of temporary side effects such as shivering and metallic taste was more frequent with the use of misoprostol Objective To compare the efficacy and side effects of misoprostol , compared with methylergometrine , for the prevention of postpartum haemorrhage Purpose The aim of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 95 % of women ( ED95 ) undergoing elective Cesarean delivery under spinal anesthesia . Methods One hundred and twenty term pregnant women at low risk for postpartum hemorrhage ( PPH ) undergoing elective Cesarean delivery under spinal anesthesia were r and omly allocated to receive carbetocin in doses of 20 , 40 , 60 , 80 , or 100 μg iv upon delivery of the fetus . The obstetrician evaluated the efficacy of uterine tone as satisfactory or unsatisfactory , and in case of unsatisfactory tone , additional uterotonics were administered as per routine institutional practice . The primary outcome measure was satisfactory uterine tone at two minutes after carbetocin administration , and the secondary outcomes were the estimated blood loss , need for additional uterotonic agents within 24 hr , and side effects . Results Overall satisfactory uterine tone at two minutes was observed in 94.2 % ( 113/120 ) of the women , and there was no difference across the different study groups . It was not possible to calculate the ED95 of carbetocin due to the even distribution of women with unsatisfactory uterine tone at two minutes across all dose groups ( P = 0.60 ) . Additional uterotonics within 24 hr were required in 13 % ( 16/120 ) of the women . Side effects were similar across all dose groups , with an overall 42.5 % incidence of hypotension following the administration of carbetocin . Conclusions In women at low risk for PPH undergoing elective Cesarean delivery under spinal anesthesia , carbetocin is similarly effective in doses of 20 - 100 μg . There is a high incidence of hypotension associated with carbetocin in these doses . Further dose-finding studies are warranted , including doses lower than 20 μg . This trial was registered at www . clinical trials.gov (NCT01428817).RésuméObjectifL’objectif de cette étude était de déterminer la dose intraveineuse de carbétocine nécessaire à produire une contraction utérine efficace chez 95 % des femmes ( DE95 ) subissant un accouchement par césarienne programmé sous rachianesthésie . MéthodeCent vingt femmes enceintes à terme et présentant un faible risque d’hémorragie postpartum ( HPP ) subissant un accouchement programmé par césarienne sous rachianesthésie ont reçu de façon aléatoire de la carbétocine à des doses de 20 , 40 , 60 , 80 ou 100 μg lors de la délivrance du fœtus . L’obstétricien a évalué l’efficacité du tonus utérin comme étant satisfaisante ou insatisfaisante et , en cas de tonus insatisfaisant , des agents utérotoniques supplémentaires ont été administrés selon la pratique habituelle de l’institution . Le critère d’évaluation principal était un tonus utérin satisfaisant deux minutes après l’administration de carbétocine , et les critères secondaires étaient la perte de sang estimée , le besoin d’agents utérotoniques supplémentaires au cours des 24 premières heures , et les effets secondaires . RésultatsUn tonus utérin globalement satisfaisant à deux minutes a été observé chez 94,2 % ( 113/120 ) des femmes , et il n’y a pas eu de différence entre les divers groupes à l’étude . Il n’a pas été possible de calculer la DE95 de la carbétocine en raison de la distribution égale des femmes présentant un tonus utérin insatisfaisant à deux minutes dans tous les groupes de doses ( P = 0,60 ) . Les effets secondaires étaient semblables dans tous les groupes , avec une incidence globale de 42,5 % d’hypotension suivant l’administration de carbétocine . Conclusion Chez les femmes courant un risque faible d’HPP et subissant un accouchement par césarienne programmé sous rachianesthésie , la carbétocine est aussi efficace à des doses de 20 - 100 μg . Il y a une forte incidence d’hypotension associée à la carbétocine à de telles doses . D’autres études d’évaluation de doses sont nécessaires , y compris avec des doses plus basses que 20 μg . Cette étude a été enregistrée au www . clinical trials.gov ( NCT01428817 ) OBJECTIVE : To estimate the efficacy of the routine use of intraumbilical vein injection of oxytocin with active management of the third stage of labor in reducing blood loss and length of the third stage . METHODS : In this prospect i ve , r and omized , double-blind trial , 412 women undergoing vaginal delivery who did not have risk factors for postpartum hemorrhage were r and omly allocated to receive either 20 international units oxytocin diluted with 26 mL saline ( n=207 ) or 30 mL saline ( n=205 ) by intraumbilical vein injection . Active management of the third stage of labor ( prophylactic injection of 10 international units oxytocin within 2 minutes of birth , early clamping of the umbilical cord , and controlled cord traction ) was used in both groups . The primary outcome was mean blood loss during the third and fourth stages of labor . RESULTS : The mean estimated blood loss was significantly lower in women treated with oxytocin compared with women in the placebo group ( 195.3±81.0 mL compared with 288.3±134.1 mL , respectively ; P<.001 ) . The third stage of labor was significantly shorter in the oxytocin group than in the placebo group ( 4.5±1.6 minutes compared with 7.9±3.4 minutes , respectively ; P<.001 ) . The percentages of placentas remaining undelivered beyond 15 minutes were 0 % in the oxytocin group and 4.4 % in the placebo group ( P=.002 ) . CONCLUSION : The use of intraumbilical injection of oxytocin with the active management of the third stage of labor significantly reduced postpartum blood loss and the duration of the third stage . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT01094028 . LEVEL OF EVIDENCE : OBJECTIVES A double-blind r and omized study involving pregnant women undergoing cesarean section was conducted to compare the effectiveness of a single 100 micrograms intravenous injection of the long-acting oxytocin analog , carbetocin , with that of a st and ard infusion of oxytocin with respect to intraoperative blood loss . The two treatments also were compared for safety and ability to maintain adequate uterine tone . STUDY DESIGN The study drug was administered to 57 women during elective cesarean section after placental delivery ; blood was collected until abdominal closure . Intraoperative blood loss was calculated with a sensitive colorimetric method . Position , tone of the fundus , and vital signs were assessed up to 24 hours after the operation . The need for additional uterotonic agents was recorded . RESULTS A single 100 micrograms intravenous injection of carbetocin was as effective as a continuous 16 hour infusion of oxytocin in controlling intraoperative blood loss after placental delivery . Mean blood loss after carbetocin administration was 29 ml less than after oxytocin administration ( p = 0.3 ) . Subset analysis deleting two patients who received oxytocic intervention in the operating room and one extreme outlier revealed a mean blood loss of 41 ml less in the carbetocin group ( p = 0.14 ) with lower variances ( p = 0.02 ) . The percentage of patients with blood loss of 200 ml or less was greater with carbetocin ( 79 % vs 53 % ; p = 0.041 ) . Carbetocin enhanced early postpartum uterine involution . The fundus was below the umbilicus in more patients who received carbetocin at 0 , 2 , 3 , and 24 hours on the ward ( p < 0.05 ) . There were no significant differences in uterine tone or type or amount of lochia . Additional oxytocin was used to treat three patients for postpartum hemorrhage or persistent uterine atony . All interventions were in the oxytocin group . Vital signs and hematologic values were comparable in each group , confirming similar safety profiles . CONCLUSIONS A single 100 micrograms intravenous injection of carbetocin is as effective and more reliable than a st and ard continuous infusion of oxytocin in maintaining adequate uterine tone and preventing excessive intraoperative blood loss during cesarean section after delivery of the placenta . Patients receiving carbetocin required less intervention . Carbetocin was well tolerated OBJECTIVE To compare the efficacy of rectally administered misoprostol with intravenous oxytocin infusion in preventing uterine atony and blood loss during cesarean delivery . METHODS In this prospect i ve , r and omized , double-blind trial , 200 women undergoing cesarean delivery who did not have risk factors for postpartum hemorrhage were r and omly allocated to receive either 800 microg of rectal misoprostol at the time of peritoneal incision or an intravenous infusion of oxytocin after delivery of the neonate . Primary outcome measures were estimated amount of intraoperative and postoperative ( 8 hours ) blood loss and changes in hemoglobin levels 24 hours after delivery . RESULTS A total of 96 and 94 women were analyzed in the misoprostol and oxytocin groups , respectively . Intraoperative and postoperative blood loss was significantly lower in the misoprostol group than in the oxytocin group ( 503 vs 592 mL , P=0.003 and 74 vs 114 mL , P=0.045 , respectively ) . The incidence of shivering was higher in the misoprostol group ( 8.3 % vs 1.1 % , P=0.018 ; RR 7.83 ; 95 % confidence interval , 0.99 - 61.42 ) . CONCLUSION Rectal misoprostol appears to be an effective alternative to intravenous oxytocin in preventing blood loss for routine use during cesarean delivery . CLINICAL TRIALS REGISTRATION CTRI/2009/091/000075 To determine whether intraumbilical oxytocin would shorten the third stage of labor , we enrolled 50 normal parturients into a r and omized , double-blind protocol . Either 10 U of oxytocin diluted to 20 mL in normal saline ( 25 subjects ) or 20 mL of normal saline alone ( 25 subjects ) was injected into the placental circulation within one minute after cord clamping . The mean ( ± SD ) duration of the third stage was 4.1 ± 2.0 minutes in saline-treated subjects and 4.6 ± 3.4 minutes in those treated with oxytocin . Intraumbilical oxytocin was not effective in shortening the normal third stage of labor OBJECTIVE To determine the most efficient route and timing of oxytocin administration for active management of the third stage of labor . METHODS A prospect i ve r and omized study was done at one center in Ankara , Turkey , between January and October 2010 . Women with a singleton pregnancy ( > 37 weeks ) who had a live vaginal birth were r and omly allocated to four groups : iv-A ( intravenous oxytocin after delivery of the fetus ) , iv-B ( when anterior shoulder seen ) , im-A ( intramuscular oxytocin after delivery ) , and im-B ( when anterior shoulder seen ) . Postpartum blood loss within the first hour , hemoglobin , hematocrit , and duration of the third stage were compared . RESULTS A total of 600 eligible women were recruited ; 150 were assigned to each group . Postpartum blood loss , prepartum and postpartum hemoglobin and hematocrit , and need for additional uterotonics were similar among groups ( P>0.05 ) . The duration of the third stage of labor and changes in hemoglobin and hematocrit were significantly reduced in group iv-B ( P<0.05 ) . Among women not exposed to oxytocin before delivery , postpartum blood loss was significantly lower in group iv-B ( P=0.019 ) . Labor augmentation was related to significantly increased postpartum blood loss in all groups except iv-A. CONCLUSION Although postpartum blood loss was similar in all groups , early intravenous administration seemed to have beneficial effects . Clinical Trials.gov : NCT01954186 Please cite this paper as : Bellad M , Tara D , Ganachari M , Mallapur M , Goudar S , Kodkany B , Sloan N , Derman R. Prevention of postpartum haemorrhage with sublingual misoprostol or oxytocin : a double‐blind r and omised controlled trial . BJOG 2012;119:975–986 Abstract Objective : We compared the efficacy of Carbetocin ( long-acting oxytocin receptor agonist ) versus Oxytocin given at non-elective caesarean section . Method : We performed a double-blind , r and omised , single-centre study . Eligible women were ≥37 weeks of gestation undergoing emergency caesarean section . Participants received either carbetocin of 100 μg or oxytocin 5 international units . The primary outcome was the need to administer additional uterotonics , as determined by the clinician . Secondary outcomes included estimated blood loss , haemoglobin drop pre – post operation and the need for a blood transfusion Results : From August 2012 to February 2013 , 114 women were enroled . Two were excluded from analysis as they received a general anaesthetic . Fifty-nine patients received 100-μg carbetocin ; 53 received 5 international units oxytocin . There was no statistically significant difference in the number of women requiring additional uterotonics between the two groups : Carbetocin group 22 % and Oxytocin group 13 % ( p = 0.323 ) . There were no significant differences in the fall in haemoglobin , estimated blood loss , rates of post-partum haemorrhage or blood transfusions . Conclusion : Oxytocin and carbetocin have similar requirements for additional uterotonics , estimated blood loss , haemoglobin drop and blood transfusions . There was a trend towards requiring additional uterotonics in patients receiving Carbetocin which was not statistically significant . This study found no benefits in using carbetocin over oxytocin This study aims to evaluate the efficacy and side-effects of 200 μg sublingual misoprostol vs 5 IU i.m . oxytocin , administered immediately following cord clamping in normal non-augmented vaginal delivery , in prevention of postpartum haemorrhage ( PPH ) . A total of 104 women were r and omised into three groups : misoprostol group ( 28 patients ) ; oxytocin group ( 37 patients ) and control group ( 39 patients ) . Misoprostol and oxytocin significantly minimised the blood loss during the third stage of labour and reduced the need for additional treatments for PPH as compared with the control group . Oxytocin was more effective than misoprostol in minimising blood loss and the need for additional uterotonic treatments . However , a significant decrease in systolic and diastolic blood pressure , associated with tachycardia was observed in the oxytocin group . In conclusion , sublingual misoprostol appears to be less effective than i.m . oxytocin in the prevention of PPH ; however , it has the potential advantages of being easily used , cost-effective and stable at room temperature . Therefore , sublingual misoprostol is still a feasible drug for routine management of third stage , especially in areas with limited medical facilities OBJECTIVE To determine the effect of nipple stimulation on uterine activity during the third stage of labor . METHODS R and omized controlled study comparing ; ( i ) 15 min of nipple stimulation ( n = 6 ) , ( ii ) routine syntometrine injection ( n = 3 ) , ( iii ) no action/control ( N = 5 ) . Uterine activity was continuously measured using the placenta as an in-situ hydrostatic bag connected to a pressure transducer . RESULTS Compared to controls uterine pressure was higher during nipple stimulation ( 103 mmHg vs. 70.8 mmHg , P = 0.04 ) . The duration of the third stage and blood loss tended to be reduced with nipple stimulation compared to controls ( 20.3 vs. 12.3 min ) and ( 257 vs. 166 ml ) respectively but was not significant . Similar differences were observed between syntometrine and control groups . CONCLUSIONS For women in developing countries where parenteral oxytocics are not available , nipple stimulation might reduce the incidence of postpartum hemorrhage . A larger trial now seems warranted OBJECTIVE To compare the effectiveness of 400 microg rectal misoprostol in 5 cm(3 ) of saline with oxytocin 10 IU , i.m . , in reducing bleeding during the third stage of labor . DESIGN A double blind , r and omized , clinical trial including 663 women with uncomplicated vaginal delivery who received misoprostol ( n=324 ) or oxytocin ( n=339 ) . MAIN OUTCOME MEASURES Changes in hemoglobin and hematocrit from before to 72 h postpartum ; blood loss during the third stage ; duration of the third stage of labor ; need for additional oxytocic drug ; frequency of requisition and of administration of blood ; changes in blood pressure ; and occurrence of side effects . RESULTS No significant differences were observed between groups , before and 72 h postpartum , in mean hemoglobin and hematocrit , on volume of blood loss and duration of third stage of labor . The incidence of shivering and mean temperature ( P<0.01 ) was significantly greater among women receiving misoprostol than oxytocin . CONCLUSIONS Misoprostol administered as a micro-enema , 400 microg in 5 ml of saline during the third stage of labor , appears to be as effective as oxytocin 10 IU , i.m . , but misoprostol produced more side effects than oxytocin OBJECTIVE We sought to identify risk factors for uterine atony or hemorrhage . STUDY DESIGN We conducted a secondary analysis of a 3-arm double-blind r and omized trial of different dose regimens of oxytocin to prevent uterine atony after vaginal delivery . The primary outcome was uterine atony or hemorrhage requiring treatment . In all , 21 potential risk factors were evaluated . Logistic regression was used to identify independent risk factors using 2 complementary predefined model selection strategies . RESULTS Among 1798 women r and omized to 10 , 40 , or 80 U of prophylactic oxytocin after vaginal delivery , treated uterine atony occurred in 7 % . Hispanic ( odds ratio [ OR ] , 2.1 ; 95 % confidence interval [ CI ] , 1.3 - 3.4 ) , non-Hispanic white ( OR , 1.6 ; 95 % CI , 1.0 - 2.5 ) , preeclampsia ( OR , 3.2 ; 95 % CI , 2.0 - 4.9 ) , and chorioamnionitis ( OR , 2.8 ; 95 % CI , 1.6 - 5.0 ) were consistent independent risk factors . Other risk factors based on the specified selection strategies were obesity , induction/augmentation of labor , twins , hydramnios , anemia , and arrest of descent . Amnioinfusion appeared to be protective against uterine atony ( OR , 0.53 ; 95 % CI , 0.29 - 0.98 ) . CONCLUSION Independent risk factors for uterine atony requiring treatment include Hispanic and non-Hispanic white ethnicity , preeclampsia , and chorioamnionitis OBJECTIVE To compare the efficacy of a single dose of 100 microg intramuscular carbetocin to a single dose of intramuscular syntometrine ( 0.5 mg ergometrine and 5IU oxytocin ) , in preventing post-partum hemorrhage ( PPH ) in high risk patients following vaginal delivery . METHODS A prospect i ve , r and omized controlled study was conducted in a tertiary hospital where 120 pregnant women with risk factors for PPH who delivered vaginally were r and omized into two groups : the study group where 100 microg intramuscular carbetocin was administered and the control group , who received intramuscular syntometrine . Outcome measures compared included changes in vital signs , amount of intrapartum blood loss , uterine fundal position , addition of another oxytocic agent , side-effects of the drugs , amount of lochia and hemoglobin drop after 24 hours post-partum . Incidence of PPH or other adverse events were also compared . RESULTS There were no significant differences in terms of requirement for additional oxytocic agents , time interval to well contracted uterus , blood transfusion requirements , adverse effects or complications . There was a significantly lower mean estimated blood loss in the carbetocin group compared to the syntometrine group ( 244 + /- 114 mL vs 343 + /- 143 mL , 95 % CI 52 - 146 mL ) . There was also a significantly reduced drop in hemoglobin in the carbetocin group compared to the syntometrine group ( 0.3 + /- 0.2 g/dL vs 0.4 + /- 0.2 g/dL , 95 % CI 0.1 - 0.2 g/dL ) . CONCLUSION Intramuscular carbetocin may be more effective than intramuscular syntometrine in reducing post-partum blood loss and the drop in hemoglobin level OBJECTIVE To compare rectally administered misoprostol to intravenously administered oxytocin for the management of third-stage labor . STUDY DESIGN Subjects were r and omized to receive two , 200-microg misoprostol tablets rectally ( study medication ) plus 2 mL saline in Ringer 's lactate intravenously or two lactose tablets rectally plus 20 units oxytocin in Ringer 's lactate intravenously ( control medication ) . Blood loss was determined by estimation , measurement , and change in hematocrit values from admission to postpartum day 1 . Subjects were excluded if cesarean delivery was required . RESULTS A total of 325 women underwent analysis . By estimation , 21 % of subjects and 15 % of controls had postpartum hemorrhage ( P = .17 ) . By using measured blood loss , we determined that 70 of 154 ( 46 % ) study subjects and 61 of 161 ( 38 % ) control subjects had postpartum hemorrhage ( P = .17 ) . For 36 ( 23 % ) misoprostol subjects and 18 ( 11 % ) oxytocin subjects at least one additional agent was required to control bleeding ( P = .004 ) . CONCLUSION Rectal misoprostol ( 400 microg ) was no more effective than intravenous oxytocin in preventing postpartum hemorrhage OBJECTIVE To evaluate the effect of Arnica Montana and Bellis perennis on postpartum blood loss . DESIGN Double blind , placebo-controlled , r and omized , clinical trial . SETTING Department of Gynecology , Shaare Zedek Medical Center , Jerusalem . INTERVENTIONS Forty parturients were r and omized to one of three groups : Arnica montana C6 and Bellis perennis C6 ( n=14 ) , Arnica montana C30 and Bellis perennis C30 ( n=14 ) , or double placebo ( n=12 ) . After 48 h the Arnica/placebo was halted , and patients continued the Bellis/placebo until cessation of lochia . MAIN OUTCOME MEASURES Hemoglobin levels ( Hb ) at 48 and 72 h postpartum . RESULTS At 72 h postpartum , mean Hb levels remained similar after treatment with homeopathic remedies ( 12.7 versus 12.4 ) as compared to a significant decrease in Hb levels in the placebo group ( 12.7 versus 11.6 ; p<0.05 ) , in spite of less favorable initial characteristics of the treatment group . The mean difference in Hb levels at 72 h postpartum was -0.29 ( 95 % CI -1.09 ; 0.52 ) in the treatment group and -1.18 ( 95 % CI -1.82 ; -0.54 ) in the placebo group ( p<0.05 ) . CONCLUSION Treatment with homeopathic Arnica montana and Bellis perennis may reduce postpartum blood loss , as compared with placebo OBJECTIVES To compare the efficacy of a single 100 micro g intramuscular ( IM ) carbetocin injection , a long-acting oxytocin agonist , to a 2-hour 10 IU oxytocin intravenous ( IV ) infusion , in reducing the incidence and severity of postpartum hemorrhage ( PPH ) in women at risk for this condition . METHODS A r and omized , double-blind , placebo-controlled study was conducted at 2 hospital centres , including 160 women with at least 1 risk factor for PPH . Eighty-three women received 100 microg carbetocin IM and an IV placebo immediately after placental delivery , while 77 women received placebo IM and oxytocin IV infusion . Complete blood count was collected at entry and 24 hours postpartum . All outcome measures , including the need for additional uterotonic agents or uterine massage , blood loss , and drop in hemoglobin and hematocrit , were analyzed using chi-square , Fisher exact , and Student t tests . RESULTS Population profile and risk factors for PPH were similar for each group . No significant difference was observed in the number of women requiring additional uterotonic medication ( 12 in each group ) . However , in the carbetocin group , 36 of the 83 women ( 43.4 % ) required at least 1 uterine massage compared to 48 of the 77 women ( 62.3 % ) in the oxytocin group ( P < .02 ) . Overall , uterotonic intervention was clinical ly indicated in 37 of the women ( 44.6 % ) receiving carbetocin compared to 49 of the women ( 63.6 % ) given an IV oxytocin infusion ( P < .02 ) . There were no differences in laboratory PPH indicators between the 2 groups OBJECTIVE To determine if high‐dose oxytocin reduces the need for additional uterotonic agents at cesarean . METHODS A r and omized , double‐masked trial of two oxytocin regimens was performed to prevent postpartum uterine atony in laboring women . The pharmacy prepared sequentially numbered oxytocin solutions containing either 10 U/500 mL or 80 U/500 mL of lactated Ringer 's solution infused over 30 minutes after cord clamping . The need for additional uterotonic agents was determined by the surgical team . Hypotension was diagnosed and treated with crystalloid or a pressor agent . To detect a 50 % decrease in the need for additional uterotonic agents and considering a βerror of 0.2 , 220 patients would be required in each group ( α = 0.05 , two‐tailed χ2 test ) . RESULTS The low‐dose group ( n = 163 ) received 333 mU/min , and the high‐dose group ( n = 158 ) received 2667 mU/min of oxytocin . The groups were similar with respect to risk factors for atony . Women in the low‐dose group received additional uterotonic medication significantly more often than those in the high‐dose group ( 39 % compared with 19 % , P < .001 , relative risk 2.1 , 95 % confidence interval 1.4 , 3.0 ) . Moreover , more women in the low‐dose group received methylergonovine , 15‐methyl prostagl and in F2α or both ( 9 % compared with 2 % , relative risk 4.8 , 95 % confidence interval 1.4 , 16 ) after additional oxytocin ( median 20 U ) had been added to the study solution . The incidence of hypotension was similar in both groups . CONCLUSION Compared with an infusion rate of 333 mU/min , oxytocin infused at 2667 mU/min for the first 30 minutes postpartum reduces the need for additional uterotonic agents at cesarean delivery AIM To compare vaginally administered misoprostol to rectally administered misoprostol and placebo in a prospect i ve r and omized placebo-controlled study . METHODS One hundred and fifty women with singleton vaginal deliveries were r and omized ( 50 women in each arm ) to receive 400-microg misoprostol tablets ( crushed and suspended in a microenema ) intravaginally , or 400-microg misoprostol tablets rectally , or two placebo lactose tablets rectally . The medication was administered immediately after delivery of the placenta . Women with profuse hemorrhage and delayed placental separation ( > 30 min ) were excluded . Our outcome measures were postpartum blood loss 1 h after administration , and change in hemoglobin and hematocrit values from baseline to postpartum day 1 . Analysis of variance and chi-squared tests were used to compare the outcome variables between groups . RESULTS One hundred and twenty-six women were available for analysis . Baseline characteristics were similar across the groups . The number of excluded subjects , the estimated blood loss , and the drop in hemoglobin and hematocrit values did not differ between the three groups ( P > 0.05 ) . CONCLUSIONS Misoprostol administered vaginally or rectally at a dosage of 400 microg following placental separation was not effective for decreasing postpartum bleeding in women without excessive hemorrhage In this study the effect of intraumbilical oxytocin on duration and amount of blood loss in third stage of labour was studied . Pregnant women were r and omized into 2 groups of 50 each . Group I was managed actively with 10 units of oxytocin diluted in 20 ml saline given through umbilical vein immediately after cord claming and Group II managed traditionally with oxytocin infusion 10 units in 250 ml of dexrose saline at rate of 125 ml/hr given after delivery of baby . In the study group there was a statistically significant decrease in duration of third stage of labour < 1.48 min vs 3.27 min > , fall in haemoglobin < 1.2 g/dl vs 1.96 g/dl > and fall in haematocrit < 3.88 % Vs 7.20%<. It was concluded that intraumbilical oxytocin appears to be a useful , safe and practical method for active management of third stage OBJECTIVE Postpartum hemorrhage ( PPH ) is one of the major preventable causes of maternal death in developing countries . Although the non-parenteral use of misoprostol is a big advantage especially in home births , its benefits in prevention of PPH is still debating . We aim ed to assess the effect and side-effects of prophylactic oral , rectal or vaginal misoprostol on preventing postpartum hemorrhage comparing with no-treatment option . PATIENTS AND METHODS In a r and omized clinical trial , during uncomplicated vaginal delivery , 248 women were assigned to receive one of the five treatment protocol s in the third stage of labor which was managed routinely by early cord clamping and controlled cord traction . Maternal hemoglobin and hematocrit values , the duration of the third stage , and the incidence of blood transfusion was recorded . RESULTS There was no statistically significant differences between the antepartum and postpartum values of hemoglobin or hematocrit between the groups . The mean duration ( 11.8 ± 4.5 min ) of the third stage of labor in oral+vaginal group was significantly shorter . Shivering was observed totally in 11 women and the differences were not significant between groups . CONCLUSIONS Despite misoprostol has benefit in treatment of postpartum hemorrhage , it has no remarkable effect in prophylaxis of atony-induced postpartum hemorrhage OBJECTIVE : Oxytocin is frequently used by intravenous bolus and infusion to minimize blood loss and prevent postpartum hemorrhage at cesarean delivery . Current dosing regimens are arbitrary whereas large doses may pose a serious risk to the mother . The purpose of this study was to estimate the minimum effective intravenous bolus dose of oxytocin ( ED90 ) required for adequate uterine contraction at elective cesarean in nonlaboring women . METHODS : A r and omized , single-blinded study was undertaken in 40 healthy term pregnant women presenting for elective cesarean under spinal anesthesia . Oxytocin was administered by bolus according to a biased coin up- and -down sequential allocation scheme with increments or decrements of 0.5 IU . Uterine contraction was assessed by the obstetrician , who was blinded to the dose of oxytocin , as either satisfactory or unsatisfactory . After achieving sustained uterine contraction , an infusion of 40 mU/min of oxytocin was started . Oxytocin-induced adverse effects and intraoperative complications were recorded and blood loss was estimated . Data were interpreted by parametric analysis based on logistic regression model and nonparametric analyses at 95 % confidence intervals ( CIs ) . RESULTS : The ED90 of oxytocin as determined by logistic regression model fitted to the data was estimated to be 0.35 IU ( 95 % CI 0.18–0.52 IU ) , with nonparametric estimates of 97.1 % ( 95 % CI 84.9–99.8 % ) response rate at 0.5 IU , and 100 % ( 95 % CI 92.2–100 % ) at 1.0 IU . The estimated blood loss was 693 ± 487 mL ( mean ± st and ard deviation ) . CONCLUSION : The bolus dose of oxytocin used at elective cesarean deliveries in nonlaboring women can be significantly reduced while maintaining effective uterine contraction . Alteration in practice will likely reduce the potential adverse effects of this drug when given in large bolus doses , but may require modification of the techniques to remove the placenta OBJECTIVE To compare the effectiveness of misoprostol ( 600 microg ) when administered sublingually with the same dose administered per rectum to patients , immediately after delivery in preventing postpartum hemorrhage ( PPH ) . METHODS This study was carried out in Al Thawra General Hospital , Sana'a , Yemen , from May 1 , 2007 to April 31 , 2008 . A total of 215 women were recruited , and divided into 2 groups in a quasi-r and om fashion . Group I comprised 118 women , and was given 600 ug misoprostol sublingually immediately after delivery . The other group comprised 97 women ( group II ) , and was given the same dose of misoprostol per rectum . The blood loss was measured , and the side effects of the misoprostol were assessed . The need for additional uterotonic agents , blood transfusion , and the length of the third stage labor were recorded . RESULTS Nine patients in group I , and 7 patients in group II had PPH . Of these patients , blood loss was > 1000 ml in 4 patients in group I , but < 1500 ml in 3 patients in group II , ( relative risk - 1.05 , 0.40 - 2.73 confidence interval [ 95 % ] . The mean blood loss was 362.3 + /- 170 ml in group I versus 342.3 + /- 154.7 ml in group II . Only 3 cases ( 3 % ) of the patients in group I were given additional uterotonic agents versus 2 cases ( 2 % ) in group II . CONCLUSION Postpartum use of 600 microg misoprostol by sublingual route has a comparable effect in reducing PPH , as that of rectal route . It was observed that severe PPH ( 1000 ml but < 1500 ml ) had been observed in 40 % of those who developed PPH in both groups Objective To compare the efficacy and safety of intravenous oxytocin with intramuscular syntometrine in the management of the third stage of Objective To assess and compare the efficacy and safety of a single intramuscular dose of carbetocin to a single intramuscular dose of syntometrine in managing the third stage of labor following vaginal delivery among women with low risk factors for postpartum hemorrhage . Study design Prospect i ve double-blind r and omized controlled study .Subjects and methods The study included 240 healthy women with viable normal singleton pregnancies achieving normal vaginal delivery at or beyond 37 weeks ’ gestation during the period from May 2009 to December 2009 at TAIBA Hospital in Kuwait . Women were r and omized to receive either a single dose of carbetocin or syntometrine intramuscularly following the delivery of the anterior shoulder of the baby . Outcome measures compared included postpartum hemorrhage requiring additional uterotonic therapy , incidence of postpartum hemorrhage , amount of intrapartum blood loss as well as adverse effects profile . Results There was a statistically highly significant difference in the estimated mean blood loss between the carbetocin and syntometrine groups , with a blood loss of 81.5 ml higher in the syntometrine group . The mean drop of hemoglobin concentration 24 h after delivery was 0.8 g/dl in carbetocin group and 1.1 g/dl in syntometrine group , and the difference was statistically highly significant . Women in the carbetocin group were less likely to experience nausea and vomiting . ConclusionS ingle dose of intramuscular carbetocin 100 μg may be more effective as compared to a single intramuscular dose of syntometrine in reducing postpartum blood loss with a smaller drop in hemoglobin levels and less adverse effects OBJECTIVES To compare oral misoprostol versus intramuscular oxytocin in the management of third stage of labour . METHODS The quasi-experimental study was conducted at the Obstetrics and Gynaecology Unit II , Civil Hospital , Karachi , from June 20 to December 19 , 2006 . A total of 70 patients diagnosed in active phase of labour who fulfilled the inclusion criteria were selected by non-probability convenience sampling . These patients were divided into 2 groups of 35 patients each , for Oxytocin ( Group 1 ) and misoprostol ( Group 2 ) . Main and secondary outcome measures were analysed . SPSS 10 was used for statistical analysis . RESULTS Average amount of blood loss(ml ) was 267.14 + /- 140.35 with Oxytocin versus 302.86 + /- 160.4 , with Misoprostol , this difference was statistically insignificant ( p = 0.236 ) . Average drop in haemoglobin concentration ( g/dl ) with Oxytocin was 1.55 + /- 0.38 vs 1.66 + /- 0.61 with Misoprostol ( p = 0.684 ) . Drop in haematocrit ( % ) was 4.18 + /- 0.64 with Oxytocin vs. 4.50 + /- 0.92 with Misoprostol ( p = 0.133 ) . There was also insignificant difference in duration of third stage of labour , between oxytocin and Misoprostol groups ( 5.37 + /- 2.20 vs. 5.23 + /- 2.46 , p = 0.451 ) Shivering , in Misoprostol group occured in n = 11 ( 31.4 % ) vs n = 3 ( 8.6 % ) with Oxytocin ( p = 0.017 ) and pyrexia in n = 6 ( 17.1 % ) with misoprostol vs n = 0 , with oxytocin ( p = 0.025 ) thus significantly higher in misoprostol group . CONCLUSION There were no major differences in oral misoprostol and intramuscular oxytocin in the management of third stage of labour OBJECTIVE To compare the effectiveness of intramuscular oxytocin against intravenous oxytocin against intravenous traditional oxytocin infusion , in the active management of the third period of the delayed impingement labor work and controlled cord traction . METHODS R and omized controlled blinded clinical trial . In women age 14 to 40 with full term pregnancy , childbirth attended by ISSSTE 's Regional Hospital " Gral . Ignacio Zaragoza " , in the period from August to December 2015 . RESULTS 152 deliveries were attended , from which 66 fulfill with selection criteria . Group 1 = 22 patients , group 2 = 21 patients and Group 3 = 23 patients . The total age average was 26.92 + 5.8 . For blood volume , statistical differences were significant among the three groups ( p = 0.000 ) . Adverse reactions were presented in 1 .5 % , without difference between the groups . ( P = 0.337 ) . The differences in hemoglobin values and final and initial hematocrit presented differences with statistical significance ( p = 0.000 for both ) . CONCLUSIONS Nonetheless , the differences obtained in the analysis of the diverse variables among the three types of treatment , the three schemes are effective on the obstetrical hemorrhage prevention OBJECTIVE : To evaluate the effectiveness and safety of misoprostol administered simultaneously with oxytocin as part of the active management of the third stage of labor . METHODS : This multicenter , double-blind , r and omized , placebo-controlled trial recruited women in the first stage of labor with expected vaginal deliveries at 36–42 weeks of gestation . Exclusion criteria were multiple pregnancies , hypersensitivity to misoprostol , and cesarean delivery . Participants received routine intravenous oxytocin and were r and omly allocated to receive 400 micrograms misoprostol or placebo orally immediately after delivery of the newborn . The primary outcome was postpartum hemorrhage ( 500 mL or greater within 2 hours of birth ) . Secondary outcomes included severe postpartum hemorrhage ( 1,000 mL or greater ) and adverse maternal events such as fever , shivering , and nausea . Two groups of 1,550 women were required to demonstrate a 33 % decrease of postpartum hemorrhage according to a two-tailed & agr ; at 0.05 with 80 % power . An interim analysis was planned after 50 % enrollment . RESULTS : Participant enrollment occurred from April 2010 to September 2013 . Baseline characteristics were similar in the two groups . The study was discontinued after the planned interim analysis including 1,721 patients showed that misoprostol was not effective and was associated with significantly more adverse effects . The rate of postpartum hemorrhage was 8.4 % ( 68/806 ) in the misoprostol and 8.3 % ( 66/797 ) in the placebo group ( P=.98 ) , and rates of severe postpartum hemorrhage were 1.8 % and 2.4 % , respectively ( P=.57 ) . Maternal adverse events occurred significantly more frequently in the misoprostol group ( for fever 30.4 % in the misoprostol group compared with 6.3 % in the placebo group , P<.001 ; for shivering 10.8 % in the misoprostol group compared with 0.6 % in the placebo group , P<.001 ) . CONCLUSION : Misoprostol administered with prophylactic routine oxytocin did not reduce the rate of postpartum hemorrhage risk and increased the rate of adverse events . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , https:// clinical trials.gov , NCT01113229 Aim . To assess the efficacy and safety of tranexamic acid in reducing blood loss at caesarian section ( CS ) . Method . A prospect i ve r and omised study conducted on 90 primiparas divided into two groups who underwent CS . The study group , 45 women , received tranexamic acid immediately before CS , whereas the control group , 45 women received placebo . Blood loss volume was measured from the end of CS to 2 h postpartum and compared between the two groups . Hemoglobin ( Hb ) and hematocrit ( Hct ) were tested 24 h after CS and compared between the two groups . Results . Tranexamic acid significantly reduced the blood loss from the end of CS to 2 h postpartum ; 28.02 ± 5.53 mL in the tranexamic group versus 37.12 ± 8.97 mL in the control group ( p = 0.000 ) . Hb 24 h after CS was significantly greater in tranexamic group than control group ( 12.57 ± 1.33 in the tranexamic group and 11.74 ± 1.14 in the control group , p = 0.002 ) . No complications or side effects were reported in either group . Conclusions . Tranexamic acid statistically reduces blood loss from end to 2 h after CS and its use was not associated with any side effects or complications . Consequently , tranexamic acid can be used safely and effectively to reduce bleeding result ing from CS The objective of this study was to compare a Tibetan traditional medicine ( the uterotonic Zhi Byed 11 [ ZB11 ] ) to oral misoprostol for prophylaxis of postpartum hemorrhage ( PPH ) . We conducted a double-blind r and omized controlled trial at three hospitals in Lhasa , Tibet , People 's Republic of China . Women ( N = 967 ) were r and omized to either ZB11 or misoprostol groups . Postpartum blood loss was measured in a calibrated blood collection drape . The primary combined outcome was incidence of PPH , defined as measured blood loss ( MBL ) > or = 500 mL , administration of open label uterotonics , or maternal death . We found that the rate of the combined outcome was lower among the misoprostol group ( 16.1 % versus 21.8 % for ZB11 ; P = .02 ) . Frequency of PPH was lower with misoprostol ( 12.4 % versus 17.4 % ; P = .02 ) . There were no significant differences in MBL > 1000 mL or mean or median MBL . Fever was significantly more common in the misoprostol group ( P = .03 ) . The rate of combined outcome was significantly lower among women receiving misoprostol . However , other indices of obstetric hemorrhage were not significantly different Postpartum haemorrhage accounts for nearly 28 % of maternal mortality in developing countries . Syntometrine is an effective and commonly used oxytocic in preventing postpartum haemorrhage , but it requires a controlled storage environment and i.m . administration . Misoprostol is an orally active uterotonic agent . A total of 2058 patients having a singleton pregnancy , low risk for postpartum haemorrhage and vaginal delivery were r and omized to receive either 1 ml syntometrine or 600 microgram misoprostol for the management of the third stage of labour . There were no significant differences between the two groups in the mean blood loss , the incidence of postpartum haemorrhage and the fall in haemoglobin concentration . The need for additional oxytocic injection was significantly higher in the misoprostol group [ relative risk ( RR ) 1.62 , 95 % confidence interval ( CI ) 1.34 - 1.96 ] , but that of manual removal of placenta was reduced ( RR 0.29 , 95 % CI 0.09 - 0.87 ) . Shivering and transient pyrexia were more common in the misoprostol group . Oral misoprostol might be used in the management of the third stage , especially in situations where the use of syntometrine is contraindicated and facilities for storage and parenteral administration of oxytocics are limited We sought to determine the efficacy and safety of tranexamic acid ( TA ) in reducing blood loss during elective cesarean section ( CS ) . We performed a r and omized , double-blind , placebo-controlled study of 660 women who underwent elective CS . The patients were r and omly selected to receive an intravenous infusion of either TA ( 1 g/10 mL in 20 mL of 5 % glucose ; N = 330 ) or 30 mL 5 % glucose prior to surgery . The primary outcome was the estimated blood loss following CS . No demographic difference was observed between groups . The mean estimated blood loss was significantly lower in women treated with TA compared with women in the placebo group ( 499.9 ± 206.4 mL versus 600.7 ± 215.7 mL , respectively ; P < 0.001 ) , and the proportion of women in the TA group who had an estimated blood loss > 1000 mL was significantly lower than in the placebo group ( 7 [ 2.1 % ] versus 19 [ 5.8 % ] , respectively ; relative risk [ RR ] 2.7 ; 95 % confidence interval [ CI ] 1.1 to 6.3 ; P < 0.03 ) . Furthermore , more women in the placebo group than in the TA group required additional uterotonic agents ( 48 [ 14.5 % ] versus 28 [ 8.5 % ] , respectively ; RR 1.7 ; 95 % CI 1.1 to 2.6 ; P = 0.02 ) . Maternal and neonatal outcomes did not differ significantly . TA significantly reduced bleeding during CS , the percentage of patients with blood loss > 1000 mL , and the need for additional uterotonic agents . Furthermore , the incidence of thromboembolic events did not increase . Our results suggest that TA can be used safely and effectively to reduce CS bleeding OBJECTIVE To compare the effectiveness of sublingual misoprostol administered immediately after delivery of the neonate at cesarean section , with intravenous oxytocin infusion in prevention of uterine atony and thereby reducing blood loss at cesarean section . METHODS One hundred women with singleton term pregnancy undergoing elective or emergency lower segment cesarean section under spinal anesthesia were included in this study . They were r and omly allocated to receive either misoprostol 400 mug sublingually or intravenous infusion of 20 units of oxytocin soon after delivery of the neonate . The main outcome measures were blood loss at cesarean section , change in hemoglobin levels , need for additional oxytocics and drug related side effects . RESULTS The mean blood loss estimated was significantly lower in misoprostol group compared to oxytocin group ( 819 ml versus 974 ml ; p = 0.004 ) . The number of women who had blood loss exceeding 500 ml and the change in hemoglobin , however , was comparable between the two groups . There was a need for additional oxytocic therapy in 16 % and 18 % after use of misoprostol and oxytocin respectively ( p = 0.673 ) . The incidence of side effects such as pyrexia , shivering and metallic taste was significantly higher in misoprostol group compared to oxytocin group . CONCLUSION Sublingual misoprostol appears to be as effective as intravenous infusion of oxytocin in reducing blood loss at cesarean section . However , occurrence of transient side effects such as shivering and pyrexia were noted more frequently with the use of misoprostol OBJECTIVES Delivery-induced hemorrhage is defined as a blood loss greater than 500 ml within the first 24 hours after delivery . Loss of more than 1000 ml is a sign of gravity . For certain authors , 40 % of these hemorrhages could be avoided with systematic preventive measures using uterotonic agents to control the third phase of labor . The aim of our work was to assess the preventive efficacy of active management measures during the third phase of labor and to determine which agents are most effective . PATIENTS AND METHODS We compared two protocol s for controlled deliver : a conventional method using ocytocin ( 2.5 IU i.v . bolus ) , and a more recent method using a prostagl and in E1 analog : misoprostol ( Cytotec , 3 tablets per os ) . We compared the two methods with a control group where no preventive measures were used , the st and ard procedure in our maternity unit . RESULTS Six hundred two women participated in the study . They were divided into 3 homogeneous groups ( ocytocin group misoprostol group , control group ) . There was a 46 % reduction in delivery-induced hemorrhage in the ocytocin group but only a minimal preventive effect against severe hemorrhage . Misoprostol did not demonstrate any efficacy in our study . DISCUSSION It would appear appropriate to take preventive measures against delivery-induced hemorrhage for all deliveries . A bolus intravenous injection of ocytocin immediately after delivery should bed used . The dose should be greater than that used in this study in order to prevent the development of severe hemorrhage . The most satisfactory results can be obtained with 5 IU ( 1 ampoule of Syntocinon ) . It is important to obtain a precise quantification of excessive blood loss in order to institute appropriate care rapidly . Misoprostol should be assessed with other prospect i ve studies because of its easy administration , its low cost and easy storage , important advantages in countries with limited re sources OBJECTIVE To determine whether serial oral misoprostol shortens the third stage of labor in second‐trimester pregnancy loss . METHODS This was a r and omized , double‐blind , placebo‐controlled study of women between 13 and 28 weeks ' gestation admitted for spontaneous or induced pregnancy termination . Subjects were r and omized to receive either misoprostol ( 200 μg ) or placebo orally every hour for a maximum of three doses if the placenta had not delivered spontaneously within 10 minutes of the fetus . A dilute oxytocin infusion was given to women in both groups . The patients were managed expectantly until intervention was required or up to 6 hours when curettage was scheduled . RESULTS One hundred eighteen women were r and omized to misoprostol and 119 r and omized to placebo . Fifty‐eight ( 49 % ) and 55 ( 46 % ) of the misoprostol and placebo groups , respectively , did not receive their medication ( P = .65 , χ2 test ) . There was no difference between the groups with regard to demographic features , method of pregnancy termination , or gestational age . Sixty‐seven ( 57 % ) and 62 ( 52 % ) of the misoprostol and placebo groups , respectively , completed the third stage of labor within 2 hours ( P = .47 , χ2 test ) . There was no statistically significant difference in the median time from fetus to placenta ( 60 versus 91 minutes in the misoprostol versus placebo group , P = .57 , Mann‐Whitney U test ) . There was no difference between the groups in the incidence of hemorrhage , need for transfusion , or curettage rate . CONCLUSION The therapeutic use of oral misoprostol in the third stage of labor in second‐trimester pregnancy loss does not reduce the time to complete spontaneous placental delivery Abstract Objective : To assess the effect of sublingual misoprostol compared to intravenous oxytocin for blood loss during cesarean delivery in women living at high altitude . Study design : In a r and omized trial , conducted in Quito , Ecuador ( 2800 m above sea level ) , 100 women received either sublingual misoprostol ( 400 µg ) or intravenous oxytocin ( 10 IU ) . Results : Bleeding in the misoprostol was no different than in the oxytocin group . Shivering was reported in 66 % of women in the misoprostol group . Conclusion : Sublingual misoprostol might be a valid alternative to oxytocin reduce intra-operative blood loss during cesarean section in women living at high altitude OBJECTIVE The purpose of this double-blind prospect i ve r and omized trial was to determine whether high-dose intraumbilical vein oxytocin injection shortens the third stage of labor in midtrimester pregnancy losses . STUDY DESIGN Patients ( n = 50 ) with spontaneous or induced midtrimester pregnancy losses ( 14 to 26 weeks ' gestation ) were r and omized to receive either 100 IU of oxytocin in 20 ml of normal saline solution or 20 ml of normal saline solution alone as a placebo . The umbilical vein was injected as soon as the cord was clamped . Outcome data were collected . RESULTS Of the 50 patients r and omized , 45 completed the study . Five were excluded after r and omization because of either cesarean delivery ( 1 patient ) or en caul delivery ( 4 patients ) . Twenty-one patients received oxytocin , and 14 received placebo . Ten patients who were not injected because of technical failure were evaluated separately . There were no differences between the three groups with regard to gestational age , fetal weight , length of the third stage , blood loss , or need for operative removal of the placenta . CONCLUSION Injection of high-dose oxytocin into the umbilical vein in second-trimester pregnancy losses does not shorten the third stage of labor or decrease the need for surgical intervention because of retained placenta OBJECTIVE To assess the effects of 400-μg sublingual misoprostol plus routine uterotonics on postpartum hemorrhage . METHODS A double-blind , placebo-controlled , r and omized study was performed . After delivery of the child , eligible women received routine uterotonics and were r and omly allocated to receive 400-μg misoprostol or placebo sublingually . The primary outcome measure was blood loss of at least 500 mL within 1 hour of taking the trial tablets . RESULTS In total , 672 women received misoprostol and 673 received placebo . The baseline data were similar for both groups . Misoprostol plus routine uterotonics reduced postpartum blood loss , but the effect was not significant for blood loss of at least 500 mL ( relative risk [ RR ] 0.96 ; 95 % confidence interval [ CI ] , 0.63 - 1.45 ) or blood loss of at least 1000 mL ( RR 0.50 ; 95 % CI , 0.15 - 1.66 ) . Misoprostol also reduced the need for non-routine oxytocin , manual removal of the placenta , and hysterectomy , but these differences were not significant either . Misoprostol was associated with pyrexia and moderate/severe shivering . There was no death in either group . CONCLUSION Misoprostol plus routine uterotonics result ed in modest reductions of blood loss in the third stage of labor , but the effects did not reach statistical significance . Larger studies are recommended OBJECTIVE The purpose of this study was to assess the efficacy of buccal misoprostol to decrease uterine atony , hemorrhage , and the need for additional uterotonic agents during cesarean delivery . STUDY DESIGN Patients who underwent cesarean delivery were assigned r and omly to either 200-microg misoprostol or placebo placed in the buccal space . A dilute intravenous oxytocin infusion was given to all patients at delivery of the placenta . The primary outcome variable was the need for additional uterotonic agents . RESULTS A total of 352 women received r and om assignments . Demographic and intrapartum characteristics were similar between the groups . More women in the placebo group required 1 additional uterotonic agent ( 43 % vs 26 % ; P < .01 ; relative risk , 1.3 ; 95 % CI , 1.10 , 1.50 ) . There was not a difference between the groups in the incidence of postpartum hemorrhage or a difference in preoperative and postoperative hemoglobin level . CONCLUSION Buccal misoprostol reduces the need for additional uterotonic agents during cesarean delivery Objective : The objective of this study was to compare the administration of oxytocin at the beginning and end of the third stage of labor for the prevention of postpartum hemorrhage . Methods : Patients with documented singleton pregnancies were r and omly assigned to two groups . The first received 10 units of oxytocin intramuscularly at delivery of the anterior shoulder of the fetus and an identical appearing placebo injection following delivery of the placenta . The second received the opposite medication sequence . The study was double blinded . Blood loss was measured by weighing all fluids collected , visual estimation , and serial blood counts . Results : 27 women received oxytocin at the delivery of the fetal shoulder and 24 after the placenta . Oxytocin given after placenta delivery result ed in lower blood loss ( 345 vs. 400 ml , p = 0.28 ) , lower collection bag weight ( 763 vs. 833 g , p = 0.55 ) , lower change in HgB ( –1.26 vs. –1.32 g , p = 0.86 ) , lower ΔHCT ( –3.43 vs. –3.64 % , p = 0.85 ) , and a shorter third stage of labor duration ( 8.6 vs. 9.2 min , p = 0.75 ) . The incidence of postpartum hemorrhage , defined as estimated blood loss > 500 ml ( 0 vs. 14.8 % ) was significantly lowered with oxytocin following placental delivery ( p = 0.049 ) . Conclusions : In our study , postpartum hemorrhage was less frequent when oxytocin administration was delayed until after placenta delivery 30 women received an intramuscular injection of 0.2 mg of methylergobasine immediately after delivery and then 3 tablets of 1 mg of ergotamine tartrate per mouth daily for 6 days post-partum . 28 women received no treatment after delivery . The selection of the two groups was r and om . The treatment with rye ergot derivatives did not have a significant effect on the quantity of milk that the infant took , nor on the infant 's weight gain in the 6 first days of life Objective This prospect i ve r and omized controlled study was carried out with the purpose of assessing the efficacy of sublingual misoprostol in decreasing intraoperative blood loss and the need for additional uterotonic agents at cesarean delivery . Methods One hundred seventy-four women undergoing elective or emergency cesarean delivery were assigned r and omly to receive either 400 μg misoprostol or placebo sublingually at the time of cord clamping . An intravenous infusion of 20 units of oxytocin was started in all women at the same time . The primary outcome measures were intraoperative blood loss , need for additional uterotonic agents , and perioperative hemoglobin ( Hb ) fall . Results The maternal demographic factors , indications for cesarean delivery , and high-risk factors were similar between the two groups . Mean intraoperative blood loss was significantly less in misoprostol group as compared with placebo group ( 595 ± 108 vs. 651 ± 118 ml , P = 0.025 ) . Fewer women needed additional uterotonic agents in misoprostol group ( 22.2 vs. 42.8 % ; P = 0.0035 ; RR 0.52 , 95 % CI 0.33–0.82 ) . Perioperative Hb fall was significantly less in misoprostol group ( 0.87 ± 0.29 vs. 1.01 ± 0.26 g , P = 0.0018 ) . ConclusionS ublingual misoprostol decreases intraoperative blood loss and the need for additional uterotonic agents at cesarean delivery Blood loss and the incidence of emetic sequelae were assessed in 148 patients undergoing midcavity forceps delivery under continuous lumbar extradural analgesia . Five units of oxytocin i.v . was found to be as effective as ergometrine 0.5 mg i.v . in reducing blood loss at delivery . Nausea , retching or vomiting occurred in 35 ( 46 % ) of the mothers who received ergometrine and in none of those who received i.v . oxytocin . The cardiovascular side-effects of ergometrine and oxytocin are review ed and compared with special reference to patients with hypertension and heart disease . It is suggested that 5 units of oxytocin i.v . should be preferred in these high-risk patients . Because of the absence of an emetic action , i.v . oxytocin is preferable to i.v . ergometrine for patients receiving extradural analgesia OBJECTIVE To compare the effectiveness of oral misoprostol and intravenous oxytocin in reducing blood loss in women undergoing indicated or elective cesarean delivery ( CD ) under spinal anesthesia . METHODS In this prospect i ve , double-blind pilot study , 56 parturients who received 5 IU of intravenous oxytocin after cord clamping were r and omized to further receive either misoprostol orally and a placebo infusion intravenously or placebo orally and an oxytocin infusion intravenously . RESULTS After adjustment was made for the sonographically estimated amniotic fluid volume , there was no statistical difference in blood loss between the 2 groups ( mean+/-S.D. , 1083+/-920 mL in the oxytocin group vs. 970+/-560 mL in the misoprostol group ; P=.59 ) . CONCLUSION Oxytocin followed by oral misoprostol is as effective as an oxytocin injection followed by an oxytocin infusion in reducing postoperative blood loss after CD , and the protocol may be a safe , valuable , and cost-effective alternative to oxytocin alone . Visual estimation of intraoperative blood loss undervalues the effective value of misoprostol use by 30 % Objectives To compare oral misopostol 600 mcg with 10 IU units oxytocin i.m . in the active management of the third stage of labor . Material s and Methods A total of 200 pregnant women of 34–42 weeks of gestation delivering vaginally in the Rajendra Institute of Medical Sciences , Ranchi , were selected for study . Hundred women received oral misoprostol 600 mg and 100 women received i.m . oxytocin 10 IU immediately after delivery of the baby and cord clamping by the method of r and omization . Results In the misoprostol group , mean blood loss is 145 ml , mean duration of the third stage of labor is 3.76 min , and mean fall in hemoglobin is 0.55 g/dl . In the oxytocin group , mean blood loss in 125.6 ml , mean duration of the third stage of labor in 3.50 min , and mean fall in hemoglobin is 0.48 g/dl . There was no significant difference between the two groups with regard to the above-mentioned factors . There were 8 cases of PPH in the misoprostol group and 6 cases in the oxytocin group . Twenty-two cases in the misoprostol group and 16 cases in the oxytocin group required additional oxytocics . Adverse effects like shivering and pyrexia were more in the misoprostol group . Conclusion Oral misoprostol is as effective as oxytocin in AMTSL and can be used safely in vaginal deliveries for prevention of PPH , especially in non-institutional deliveries and in places of low re source setting Objective To compare oral misoprostol 400 μg with placebo in the routine management of the third stage of labour Objective To select the misoprostol dose to be used in a large multicentre r and omised trial comparing misoprostol with oxytocin in the routine management of the third stage of labour AIM The effects of oxytocics on thoracic epidural pressure during cesarean section were studied in 60 parturients , ( American Society of Anesthesiologist physical status , class I or II ) after obtaining informed consent . METHODS The subjects were r and omized to either a ergometrine ( n = 30 ) or oxytocin treatment group ( n = 30 ) . The subjects were anesthetized with 11 - 12 mg of intrathecal isobaric bupivacaine ( 0.5 % ) , and an epidural catheter was placed at Th 11/12 , and was connected to a pressure transducer to continuously monitor thoracic epidural pressure . We analyzed epidural pressure , blood pressure , and heart rate 5 min after administering intrathecal bupivacaine ( SAB5 m ) , immediately before skin incision ( pre-incision ) , immediately after delivery of the placenta ( placenta-del ) , and 5 min after delivery of the fetus ( CS5 m ) . RESULTS In both groups , epidural pressures were found to be elevated after delivery compared with their levels before the skin incisions were made , ( P < 0.0001 ) . Epidural pressures at placenta-del ( P = 0.0055 ) and CS5 m ( P < 0.0001 ) were higher than at SAB5 m in the ergometrine group . Epidural pressures at placenta-del were also higher than at SAB5 m in the oxytocin group ( P < 0.0001 ) . Epidural pressures at placenta-del were lower in the ergometrine group compared with the oxytocin group ( P = 0.0122 ) , but epidural pressures at CS5 m were higher in the ergometrine group compared with the oxytocin group ( P < 0.0001 ) . CONCLUSIONS We conclude that there is an increase in thoracic epidural pressure after fetal delivery , which appears to be associated with uterine contraction BACKGROUND The optimal dose of oxytocin at Caesarean section is unclear . Oxytocin may cause adverse cardiovascular effects , including tachycardia and hypotension , whereas an inadequate dose can result in increased uterine bleeding . We compared the effects of two doses of oxytocin in a r and omized double-blind trial . METHODS Eighty patients undergoing elective Caesarean section received an i.v . bolus of either 2 or 5 units ( u ) of oxytocin after delivery , followed by an oxytocin infusion of 10 u h(-1 ) . All received combined spinal-epidural anaesthesia with arterial pressure maintained by a phenylephrine infusion . We compared changes in heart rate ( HR ) , mean arterial pressure ( MAP ) , blood loss , uterine tone , the need for additional uterotonic drugs , and emetic symptoms . RESULTS There was a greater increase in mean ( sd ) HR in patients who received 5 u of oxytocin [ 32 ( 17 ) beats min(-1 ) ] than in those who received 2 u [ 24 ( 13 ) beats min(-1 ) ] ( P=0.015 ) . There was a larger decrease in MAP in patients who received 5 u [ 13 ( 15 ) mm Hg ] than in those who received 2 u [ 6 ( 10 ) mm Hg ] ( P=0.030 ) . The frequency of nausea and antiemetic use was higher after 5 u ( 32.5 % ) than 2 u ( 5 % ) ( P=0.003 ) . There were no differences in blood loss , uterine tone , or requests for additional uterotonic drugs ( 17.5 % in both groups ) . CONCLUSIONS In elective Caesarean section , a 2 u bolus of oxytocin results in less haemodynamic change than 5 u , with less nausea and no difference in the need for additional uterotonics OBJECTIVE To determine the optimal dose of oxytocin to be injected intraumbilically after fetal delivery for active management of the third stage of labor . METHODS A prospect i ve r and omized study was carried out with 125 primigravidas to compare the duration of the third stage of labor following the intraumbilical administration of 50 mL of a normal saline solution alone ( in a control group ) , or with 10 IU , 20 IU , or 30 IU of oxytocin . The volumes of blood lost were also compared . RESULTS Compared with the control group , the duration of the third stage of labor was significantly reduced in the 3 study groups ( P<0.001 ) , and the maximum reduction was in the group that received 30 IU of oxytocin . Blood loss and hematocrit values followed the same pattern . CONCLUSION Administering 30 IU of oxytocin intraumbilically in 50 mL of a normal saline solution after fetal delivery is a simple , noninvasive , and effective method for active management of the third stage of labor Postpartum hemorrhage ( PPH ) is a major cause of morbidity and mortality in both developed and developing countries . Various pharmacologic agents including oxytocin ergot preparations and prostagl and in analogues such as 15-methyl prostagl and in F2a and prostagl and in E2 have been found to prevent PPH . However they are expensive associated with adverse effects and require parenteral administration . Misoprostol is a prostagl and in E1 analogue shown in several r and omized controlled trials to be effective in preventing PPH because of its strong uterotonic effects . Moreover misoprostol is inexpensive stable at room temperature and easy to administer . The present study compared the efficacy and side effects of 400 µg of rectal misoprostol with 125 µg of 15-methyl prostagl and in F2a in the prevention of PPH . ( excerpt OBJECTIVE To compare the efficacy of intravenous ergometrine , intramuscular oxytocin , and oral misoprostol in the control of postpartum hemorrhage . METHODS Mean blood loss , rates of blood loss between 500 and 1000 ml , hematocrit fall greater than 10 % , and need for additional oxytocic agents and nature and rates of adverse effects were assessed in this prospect i ve , r and omized , controlled study . RESULTS All outcomes were similar in the 3 groups . The main adverse effects in the misoprostol group were temperatures higher than 99 degrees F , which normalized within 2 h and shivering , which was mild and self-limiting . CONCLUSIONS Oral misoprostol is as effective as conventional oxytocic agents in preventing postpartum hemorrhage and can be recommended for use in low-re source setting BACKGROUND The aim of this study was to determine the lowest effective bolus dose of oxytocin to produce adequate uterine tone ( UT ) during elective Caesarean delivery ( CD ) . METHODS Seventy-five pregnant patients undergoing elective CD under spinal anaesthesia were r and omized to receive oxytocin ( 0.5 , 1 , 3 , 5 units ) or placebo . UT was assessed by a blinded obstetrician as either adequate or inadequate , and using a verbal numerical scale score ( 0 - 10 ; 0 , no UT ; 10 , optimal UT ) at 2 , 3 , 6 , and 9 min after oxytocin administration . Minimum effective doses of oxytocin were analysed ( ED(50 ) and ED(95 ) ) using logistic regression . Oxytocin-related side-effects ( including hypotension ) were recorded . RESULTS There were no significant differences in the prevalence of adequate UT among the study groups at 2 min ( 73 % , 100 % , 93 % , 100 % , and 93 % for 0 , 0.5 , 1 , 3 , and 5 units oxytocin , respectively ) . The high prevalence of adequate UT after placebo and low-dose oxytocin precluded determination of the ED(50 ) and ED(95 ) . UT scores were significantly lower in patients receiving 0 unit oxytocin at 2 and 3 min compared with 3 and 5 units oxytocin ( P<0.05 , respectively ) . The prevalence of hypotension was significantly higher after 5 units oxytocin vs 0 unit at 1 min ( 47 % vs 7 % ; P=0.04 ) . CONCLUSIONS The routine use of 5 units oxytocin during elective CD can no longer be recommended , as adequate UT can occur with lower doses of oxytocin ( 0.5 - 3 units ) OBJECTIVE To compare the effectiveness and safety of carbetocin , misoprostol , and oxytocin for the prevention of postpartum hemorrhage following cesarean deliveries . METHODS A double-blind r and omized controlled trial enrolled patients with a singleton pregnancy scheduled for an elective cesarean delivery at a maternity hospital in Cairo , Egypt , between October 1 , 2012 and June 30 , 2013 . Participants were r and omized using a computer-generated sequence to receive treatment with carbetocin , misoprostol , or oxytocin . The primary outcome was the occurrence of uterine atony necessitating additional uterotonics . Per- protocol analyses were performed . Patients , investigators , and data analysts were masked to treatment assignments . RESULTS The present study enrolled 263 patients ; data were analyzed from 88 patients treated with carbetocin , 89 treated with misoprostol , and 86 women treated with oxytocin . Further uterotonics were needed for the treatment of 5 ( 6 % ) patients who were treated with carbetocin , 20 ( 22 % ) patients treated with misoprostol , and 11 ( 13 % ) patients treated with oxytocin . In the prevention of uterine atony , carbetocin was comparable with oxytocin ( RR 0.41 , 95%CI 0.14 - 1.25 ) and superior to misoprostol ( RR 0.21 , 95%CI 0.07 - 0.58 ) . CONCLUSION Additional uterotonics were needed less frequently by patients treated with carbetocin . Carbetocin was comparable to oxytocin and superior to misoprostol in the prevention of uterine atony following an elective cesarean delivery . Clinical Trials.gov : NCT02053922 BACKGROUND AND OBJECTIVES Misoprostol would reduce the uterine bleeding after cesarean delivery without harmful effects on either mother or baby . We aim ed to evaluate the effects of preoperative misoprostol on maternal blood loss , uterine tone , and the need for additional oxytocin after cesarean delivery under isoflurane anesthesia . METHODS After ethical approval , 366 patients scheduled for elective cesarean delivery were r and omly allocated to receive either sublingual misoprostol 400μg ( n=179 ) or placebo tablet ( n=187 ) after intubation . Anesthesia was maintained with 0.5 - 0.7 MAC isoflurane with nitrous oxide . All patients received intravenous infusion of 10IU of oxytocin after placental delivery . Perioperative estimated blood loss , uterine tone , need for supplementary oxytocin , hematocrit , Apgar scores at 1 and 5 min and adverse effects were recorded . RESULTS After induction , patients receiving sublingual misoprostol had significant less perioperative estimated blood loss ( 202±383.1 vs. 708±204.3mL , p<0.001 ) , need for oxytocin ( p<0.001 ) , higher hematocrit levels ( p<0.001 ) and uterine tone ( p<0.02 ) . The incidence of shivering was higher in the misoprostol group ( p=0.04 ) . There were no differences between the two groups as regarding Apgar scores , nausea and vomiting , gastrointestinal disturbances and pyrexia . CONCLUSION Preoperative administration of sublingual misoprostol 400μg is safe and effective in attenuating the maternal bleeding and uterine atony from isoflurane anesthesia for cesarean delivery OBJECTIVE Postpartum hemorrhage ( PPH ) , a major cause of maternal mortality and morbidity in low-income countries , can occur unpredictably . This study examined the sociodemographic , clinical , and perinatal characteristics of low-risk women who experienced PPH . METHODS This analysis was conducted using data on 1620 women from a r and omized trial testing oral misoprostol for prevention of PPH in rural India . RESULTS Of the women , 9.2 % experienced PPH . No maternal or sociodemographic factors and few perinatal factors differed between women with PPH and those without , other than treatment with misoprostol . Having fewer than 4 prenatal visits and lack of iron supplementation increased the risk for PPH ( P<0.001 and P=0.037 , respectively ) . Several factors unknown until the second stage of labor ( perineal tear and birth weight ) were also associated ( P=0.003 ) . CONCLUSIONS Among women at low risk for PPH , there were few factors associated with further risk . Given that PPH can occur without warning , rural communities should consider ways to increase both primary prevention ( iron supplementation , AMTSL ) and secondary prevention of PPH ( availability of obstetric first aid , availability of transport , and availability of emergency obstetric care ) OBJECTIVE : To assess the efficacy of buccal misoprostol to decrease bleeding after vaginal delivery . METHODS : This was a r and omized study of patients between 22 weeks and 42 weeks of gestation with anticipated vaginal delivery . Patients were given either a 200-μg misoprostol tablet or placebo in the buccal space at the time of cord clamping . A continuous dilute intravenous oxytocin infusion was given to all patients at delivery of the placenta . Postpartum hemorrhage was defined as blood loss exceeding 500 mL. Sample size calculations based on previous studies assumed a 13 % incidence of postpartum hemorrhage in the control group . To show a statistically significant reduction of postpartum hemorrhage a total of 1,604 patients would be required in each group . RESULTS : A total of 848 patients were enrolled and 756 r and omly assigned , 377 in the misoprostol group and 379 in the placebo group . Demographic , antepartum , and intrapartum characteristics were similar between the groups . The incidence of postpartum hemorrhage , 3 % compared with 5 % , ( relative risk 0.65 , 95 % confidence interval 0.33–1.29 , P = .22 ) , mean estimated blood loss , 322 compared with 329 mL , ( P = .45 ) , and mean minutes of the third stage of labor , 6.7 compared with 6.9 ( P = .52 ) were similar between the groups , misoprostol and placebo , respectively . Hemoglobin difference before and after delivery , need for second or third uterotonic agent , and all measured neonatal variables including birth weights , and umbilical cord pH were similar between the groups . CONCLUSION : Buccal misoprostol at cord clamping is no more effective than placebo in reducing postpartum hemorrhage . LEVEL OF EVIDENCE : Please cite this paper as : Jangsten E , Mattsson L , Lyckestam I , Hellström A , Berg M. A comparison of active management and expectant management of the third stage of labour : a Swedish r and omised controlled trial . BJOG 2011;118:362–369 BACKGROUND Oxytocin administration to prevent uterine atony following cesarean delivery is associated with adverse effects including hypotension , tachycardia , and nausea . Calcium chloride increases mean arterial pressure , systemic vascular resistance , and uterine smooth muscle contractility . This study evaluated whether the co-administration of calcium chloride with oxytocin following cesarean delivery could alter maternal hemodynamics . Secondary outcomes included uterine tone and blood loss . METHODS Sixty healthy parturients with singleton , term , vertex pregnancies undergoing elective cesarean delivery under spinal anesthesia were r and omized to one of three study solutions given intravenously immediately after umbilical cord clamping : ( 1 ) placebo , oxytocin 5U alone ; ( 2 ) CA-200 , oxytocin 5U+calcium chloride 200 mg ; or ( 3 ) CA-400 , oxytocin 5U+calcium chloride 400 mg . Blood pressure , heart rate , uterine tone , vasopressor or alternate uterotonic use and the incidence of nausea or vomiting were recorded . Baseline and intraoperative plasma concentration of ionized calcium and hematocrit were measured . RESULTS Plasma concentration of ionized calcium was elevated in both study groups compared with placebo ( P=0.001 ) . Blood pressure decreased and heart rate increased in all groups ( P < 0.0001 ) , with no differences between groups . No differences were observed between groups in uterine tone , vasopressor use , hematocrit change , estimated blood loss , incision-to-delivery interval , delivery-to-skin closure interval , total intravenous fluid administered or incidence of nausea . CONCLUSIONS The decrease in blood pressure associated with oxytocin administration following cesarean delivery was not attenuated with co-administration of calcium chloride at the doses evaluated . Vasopressor use , uterine tone , and blood loss were also unaffected OBJECTIVE To determine whether buccal misoprostol during cesarean delivery in conjunction with active management of the third stage of labor reduces the need for additional uterotonic drugs . METHOD A double-blind , r and omized , placebo-controlled trial was performed in Monterrey , Mexico , between February 2008 and December 2013 . Eligible women had risk factors for uterine atony and were to undergo cesarean delivery under epidural block . Using a computer-generated sequence and blocks of six , patients were r and omly assigned to receive 400μg misoprostol or 800μg placebo buccally after cord clamping . Both groups received an intravenous oxytocin infusion . The primary outcome was the need for additional uterotonic drugs . Analyses were performed per protocol . Patients , investigators , and data analysts were masked to group assignment . RESULTS A total of 120 women were included in analyses ( 60 in each group ) . At least one additional uterotonic drug was required in 24 ( 40 % ) women in the placebo group versus 6 ( 10 % ) women in the misoprostol group ( relative risk 0.16 ; 95 % confidence interval 0.06 - 0.44 ) . No adverse effects due to misoprostol were recorded . CONCLUSION Buccal misoprostol during cesarean delivery reduced the need for additional uterotonic drugs to treat uterine atony . Clinical Trials.gov : NCT01733329 Background : IV bolus oxytocin is used routinely during cesarean delivery to prevent postpartum hemorrhage . Its adverse hemodynamic effects are well known , result ing in a recent change in dose from 10 IU to 5 . Whether a 5 IU bolus has any advantages over infusion alone is unclear . We tested the hypothesis that a 5 IU IV bolus of oxytocin before the initiation of a continuous infusion decreases the need for additional uterotonic drugs in the first 24 hours after delivery in women with risk factors for uterine atony undergoing cesarean delivery , compared with infusion alone . Methods : A prospect i ve , r and omized , double-blind , controlled trial was conducted in 143 subjects undergoing cesarean delivery with at least 1 risk factor for uterine atony . Subjects received 5 IU bolus of oxytocin or normal saline IV over 30 seconds after umbilical cord clamping . All subjects received an infusion of 40 IU oxytocin in 500 mL normal saline over 30 minutes , followed by 20 IU in 1 L over 8 hours . The primary outcome was the need for additional uterotonics in the first 24 hours after delivery . Secondary outcomes included uterine tone as assessed by the surgeon ( 5-point Likert scale : 0 = “ floppy , ” 4 = “ rock hard ” ) , estimated blood loss , side effects of bolus administration , and the oxytocin bolus – placental delivery interval . Results : There was no difference in the need for additional uterotonic drugs in the first 24 hours between groups . There was a significant difference in uterine tone immediately after placental delivery ( P < 0.01 ) ( 2.8 in the oxytocin group [ 95 % confidence interval 2.6–3.0 ] vs 2.2 in the saline group [ 95 % confidence interval 1.8–2.5 ] ) , which disappeared after 5 minutes . There were no differences in observed or reported side effects between groups . Conclusions : We found that a 5 IU IV bolus of oxytocin added to an infusion did not alter the need for additional uterotonic drugs to prevent or treat postpartum hemorrhage in the first 24 hours in women undergoing cesarean delivery with risk factors for uterine atony , despite causing an initial stronger uterine contraction . Our study was not powered to find a difference in side effects between groups . These results suggest that an oxytocin infusion may be adequate without the need for a bolus , even in high-risk patients Abstract Objective : To compare effectiveness and tolerability of carbetocin versus syntometrine in prevention of postpartum hemorrhage ( PPH ) after cesarean section ( CS ) . Methods : A double-blind r and omized study conducted on 300 pregnant subjected r and omly either to single 100 μg IV dose of carbetocin ( 150 women ) or combination of 5 IU oxytocin and 0.2 mg ergometrine ( 150 women ) after fetal extraction and before placental removal . Primary outcome parameter was the occurrence of PPH . Other parameters were hemoglobin and hematocrit changes , the need of additional oxytocic , hemodynamic changes and occurrence of side effects . Results : There was no significant difference between the two study groups regarding hemoglobin and hematocrit at start of CS and after 2 days of surgery and mean blood loss during the operation ( p > 0.05 ) . There was a highly significant difference between the two study groups regarding incidence of primary PPH ( 2.7 % versus10 % ) and the need of additional oxytocic ( 3.3 % versus17.3 % ) . Women in oxytocin group showed a statistically significant lower systolic and diastolic blood pressure at 1 , 5 and 30 min than women in carbetocin group . Women in carbetocin group experienced more metallic taste , flushing , headache , dizziness , dyspnea and itching , while women in oxytocin methergine group experienced more palpitations . Conclusions : Carbetocin is a reasonable effective alternative to syntometrine in prevention of PPH after cesarean delivery AIM To compare the efficacy and safety of intramuscular oxytocin with intramuscular ergometrine in the management of postpartum hemorrhage during the third stage of labor . METHODS Women who had been pregnant for more than 35 weeks and delivered cephalic singletons vaginally without predelivery administration of oxytocics were included . The cases considered to be at high risk were excluded , such as those who had uterine fibroids , a previous cesarean section , previous postpartum hemorrhage , or severe anemia . Five units of oxytocin or 0.2 mg of methylergometrine were administered intramuscularly immediately after delivery of the baby . RESULTS Compared with intramuscular ergometrine , the use of intramuscular oxytocin was associated with a significant reduction in mean total postpartum blood loss ( 288.16 g vs 354.42 g , P = 0.004 ) , frequency of postpartum hemorrhage ( > or=500 mL : 10.9 % vs 20.32 % , relative risk [ RR ] = 0.54 , 95 % confidence interval [ CI ] = 0.32 - 0.91 ) , and need for therapeutic oxytocics ( 5.13 % vs 12.3 % , RR = 0.42 , 95 % CI = 0.19 - 0.91 ) . There were no differences between the groups in terms of the mean duration of the third stage , the mean level of hemoglobin on the second postpartum day , and the frequency of postpartum hemorrhage ( > or = 1000 mL ) , or manual removal of placenta . Few side-effects were found , with no significant differences between the groups . CONCLUSIONS The routine use of intramuscular oxytocin is more effective than the use of intramuscular ergometrine for prevention of postpartum hemorrhage in the third stage of labor Our objective was to compare oral misoprostol with intramuscular oxytocin in the prevention of postpartum haemorrhage . Four hundred and ninety-six women were r and omised to receive either 600 µg misoprostol orally or 10 IU oxytocin intramuscularly after delivery . There were no significant differences between the misoprostol and oxytocin groups with regard to the incidence of postpartum haemorrhage ( 1 % vs. 0 % respectively , relative risk ( RR ) 3.02 , 95 % confidence interval ( CI ) 0.32 - 28.88 ) or drop in haemoglobin concentration ( 0.71 g/dl vs. 0.68 g/dl , respectively , P = 0.699 ) . The length of the third stage of labour and the percentage of women requiring manual removal of placenta , further oxytocics or blood transfusion were also similar . Shivering was significantly higher with misoprostol ( 57 % vs. 14 % ; RR 4.06 , CI 2.93 - 5.62 ) , but there were no differences in other side effects . We conclude that oral misoprostol can replace intramuscular oxytocin in reducing postpartum haemorrhage in low-risk women , in developing countries , especially as it is administered orally and it is thermostable in tropical conditions The influence of intramyometrial injection of 125 micrograms of 15-s-15-methyl prostagl and in F2 alpha ( carboprost tromethamine , Prostin/15 M ) versus 20 U of oxytocin immediately after delivery of placenta on blood loss at cesarean section was investigated by means of a double-blinded , r and omized trial . Hematocrit decrease from the day before operation to the third postoperative day was used as an index of blood loss . Decreases in hematocrit were comparable for the oxytocin and carboprost tromethamine groups . Excess blood loss ( hematocrit decrease more than 6 vol . % ) was significantly associated with the indication for cesarean section ( three of four for cephalopelvic disproportion versus 9 of 42 others , p less than 0.01 ) , but not with age , parity , number of prior cesarean sections , or birthweight . Carboprost tromethamine does not appear to be more effective than oxytocin when given by intramyometrial injection at this dose for routine cesarean section ; its prophylactic utility in higher doses or in cases at risk for hemorrhage from uterine atony remains to be investigated BACKGROUND Access to injectable uterotonics for management of postpartum haemorrhage remains limited in Senegal outside health facilities , and misoprostol and oxytocin delivered via Uniject have been deemed viable alternatives in community setting s. We aim ed to compare the efficacy of these drugs when delivered by auxiliary midwives at maternity huts . METHODS We did an unmasked cluster-r and omised controlled trial at maternity huts in three districts in Senegal . Maternity huts with auxiliary midwives located 3 - 21 km from the closest referral centre were r and omly assigned ( 1:1 ; via a computer-generated r and om allocation overseen by Gynuity Health Projects ) to either 600 μg oral misoprostol or 10 IU oxytocin in Uniject ( intramuscular ) , stratified by reported previous year clinic volume ( deliveries ) and geographical location ( inl and or coastal ) . Maternity huts that had been included in a previous study of misoprostol for prevention of postpartum haemorrhage were excluded to prevent contamination . Pregnant women in their third trimester were screened for eligibility either during community outreach or at home-based prenatal visits . Only women delivered by the auxiliary midwives in the maternity huts were eligible for the study . Women with known allergies to prostagl and ins or pregnancy complications were excluded . The primary outcome was mean change in haemoglobin concentration measured during the third trimester and after delivery . This study was registered with Clinical Trials.gov , number NCT01713153 . FINDINGS 28 maternity hut clusters were r and omly assigned-14 to the misoprostol group and 14 to the oxytocin group . Between June 6 , 2012 , and Sept 21 , 2013 , 1820 women were recruited . 647 women in the misoprostol group and 402 in the oxytocin group received study drug and had recorded pre-delivery and post-delivery haemoglobin concentrations , and overall 1412 women delivered in the study maternity huts . The mean change in haemoglobin concentrations was 3·5 g/L ( SD 16·1 ) in the misoprostol group and 2·7 g/L ( SD 17·8 ) in the oxytocin group . When adjusted for cluster design , the mean difference in haemoglobin decreases between groups was not significant ( 0·3 g/L , 95 % CI -8·26 to 8·92 , p=0·71 ) . Both drugs were well tolerated . Shivering was common in the misoprostol group , and nausea in the oxytocin group . Postpartum haemorrhage was diagnosed in one woman allocated to oxytocin , who was referred and transferred to a higher-level facility for additional care , and fully recovered . No other women were transferred . INTERPRETATION In terms of effects on haemoglobin concentrations , neither oxytocin nor misoprostol was significantly better than the other , and both drugs were safe and efficacious when delivered by auxiliary midwives . The programmatic limitations of oxytocin , including short shelf life outside the cold chain , mean that misoprostol could be more appropriate for community-level prophylaxis of postpartum haemorrhage . FUNDING Bill & Melinda Gates Foundation Objective : To compare the effectiveness of carbetocin with oxytocin with respect to maintain adequate uterine tone and to reduce the incidence and severity of postpartum haemorrhage . Moreover safety , adverse effects and the need of additional medications were evaluated . Methods : Prospect i ve controlled clinical trial . We compared the effect of a single dose of carbetocin ( n = 55 ) with oxytocin infusion ( n = 55 ) in a women population undergoing to elective caesarean section with regional subarachnoid anaesthesia with at least one risk factor for postpartum haemorrhage . Results : The mean ± SD of postoperative pain in the day of surgery in carbetocin group was significantly lower than in oxytocin group and remained significant till the third day after caesarean section . In the day of surgery and the first day after surgery , women of carbetocin group who needed analgesic drugs were significantly lower than women of oxytocin group . The differences of diuresis and of diuretic drugs need were not statistically significant between the two groups . Conclusions : A single carbetocin injection is efficacious and safe on the maintenance of uterine tone and on the limitation of blood losses , in peri- and in postoperative period . In addition , carbetocin was able to reduce pain perception during postoperative days improving quality life of women Background . To compare sublingual misoprostol with intravenous syntometrine use during third stage of labor by measuring the blood loss Summary : A r and omized controlled study of 112 women with singleton pregnancies at term , and no antenatal complications , admitted in spontaneous labour were r and omized to receive either an intramuscular injection of 0.5 mg of Syntometrine or an intramuscular injection of 125 ug of prostagl and in 15‐methyl F2 alpha at delivery of the anterior shoulder of the baby . Blood lost in the first 2 hours , and subsequent 22 hours postdelivery were collected separately and measured by colourimetric measurement of haemoglobin content . Other parameters in the third stage were measured , including need for transfusion of blood or blood products , length of the third stage , and change in haemoglobin concentration before and 24 hours after delivery . The incidence of side‐effects with administration of either prostagl and in 15‐methyl F2 alpha or Syntometrine were documented . The prophylactic use of intramuscular prostagl and in 15‐methyl F2 alpha ( Carboprost ) in the active management of the third stage of labour gave similar results to prophylactic intramuscular Syntometrine in terms of length of the third stage of labour , incidence of postpartum haemorrhage and total blood loss in the first 2 hours and subsequent 22 hours after delivery . However it has the disadvantage of higher cost , as well as statistically significant increase in the incidence of profuse and frequent diarrhoea . Based on these results intramuscular injection of prostagl and in 15‐methyl F2 alpha offers no advantage over intramuscular Syntometrine for routine prophylactic use to reduce blood loss in the third stage of labour AIMS The aim of this study was to compare the effectiveness and safety of sublingual misoprostol with i.v . oxytocin infusion administered after delivery in reducing blood loss at cesarean section in Nigeria . MATERIAL S AND METHODS One hundred women with term singleton pregnancy undergoing elective or emergency cesarean section under spinal anesthesia in Nigeria were r and omly allocated to receive either misoprostol 400 µg sublingually or i.v . infusion of 20 units oxytocin soon after delivery of the baby . Estimated blood loss at surgery and within the first 4 h post-operation were measured in both groups . RESULTS No significant difference was found in mean blood loss between the oxytocin and misoprostol groups . Similarly , no significant difference occurred between preoperative and postoperative hematocrit levels in both groups . The need for additional oxytocin was similar in both groups . There was significantly less blood loss in the first 4 h after surgery in the misoprostol group than in the oxytocin group ( 58.2 ± 20.7 vs 80.5 ± 26.8 ; P-value = 0.02 ) . The incidence of adverse effects like shivering/pyrexia was significantly higher in the misoprostol group than in the oxytocin group ( 27/50 vs 1/50 , P < 0.001 ) . CONCLUSION Sublingual misoprostol was as effective as i.v . oxytocin infusion in reducing blood loss at cesarean section . It offers several advantages over oxytocin , including long shelf life , stability at room temperature , and oral administration , which make it a suitable uterotonic agent in low-re source areas OBJECTIVE To compare , at the community level , the cost-effectiveness of oxytocin and misoprostol for the prevention of postpartum hemorrhage ( PPH ) . METHODS The present cost-effectiveness study used data collected during a r and omized trial that compared the prophylactic effectiveness of misoprostol and oxytocin for the prevention of PPH in a rural setting in Senegal between June 6 and September 21 2013 . The two interventions were compared , with referral to a higher level facility owing to PPH being the outcome measure . The costs and effects were calculated for two hypothetical cohorts of patients delivering during a 1-year period , with each cohort receiving one intervention . A comparison with a third hypothetical cohort receiving the current st and ard of care was included . A sensitivity analysis was performed to estimate the impact of variations in model assumptions . RESULTS The cost per PPH referral averted was US$ 38.96 for misoprostol and US$ 119.15 for oxytocin . In all the scenarios modeled the misoprostol intervention dominated , except in the worst-case scenario , where the oxytocin intervention demonstrated slightly better cost-effectiveness . CONCLUSION The use of misoprostol for PPH prophylaxis could be cost effective and improve maternal outcomes in low-income setting ObjectOur purpose in conducting this study was to determine the efficacy of tranexamic acid ( TXA ) in reducing blood loss in patients after cesarean section ( CS ) . Method A r and omized , double-blind , case-controlled study was conducted on 174 primipara undergoing CS . 88 of them given 10 mg/kg TXA immediately before CS were compared with 86 others to whom TXA was not given . Blood loss was calculated from blood collected and measured during two periods : the first period was from placental delivery to end of CS and the second from the end of CS to 2 h postpartum . Vital signs such as BP , HR , RP , hemoglobin , platelet count , postoperative PT and PPT were tested in the two groups . Results Blood loss in the period between the end of CS and 2 h postpartum was significantly lower ( p < 0.01 ) in the TXA group ( 46.6 ± 42.7 ) than in the control group ( 84.7 ± 80.2 ) . The quantity of total blood from placental delivery to 2 h postpartum was also significantly reduced ( p = 0.02 ) in the TXA group ( 379.2 ± 160.1 ) than in the control group ( 441.7 ± 189.5 ) . However , the amount of blood loss in the period from placental delivery to the end of CS did not differ between the TXA and control groups ( p = 0.17 ) . PPH stopped in 65 women ( 75.6 % ) in the control group and in 81 ( 92.0 % ) in the TXA group ( p < 0.01 ) . No significant abnormal vital signs were observed after TXA administration . Mild , transient side effects occurred more often in the TXA group than in the control group . Conclusion Treatment with TXA is effective in reducing blood loss in patients undergoing CS . Although the study was not adequately powered to address safety issues , the observed side effects were mild and transient OBJECTIVE To compare efficacy and adverse effects of 200μg and 400μg misoprostol for prevention of postpartum hemorrhage ( PPH ) . METHODS In a r and omized control trial , women with term singleton pregnancies in active labor attending University College Hospital , Ibadan , Nigeria , were enrolled between July 2011 and February 2012 . Participants were r and omly assigned using r and om numbers ( block size four ) to receive 200μg or 400μg sublingual misoprostol after delivery of the anterior shoulder , alongside intravenous oxytocin . Investigators were masked to group assignment , but participants were not . The primary outcomes were blood loss up to 1h after delivery , PPH ( blood loss ≥500mL ) , and adverse effects . RESULTS Overall , 62 patients were assigned to each group . No significant differences between the 200-μg and 400-μg groups were recorded in mean peripartum blood loss ( 307±145mL vs 296±151mL ; P=0.679 ) and PPH occurrence ( 5 [ 8.1 % ] vs 6 [ 9.7 % ] women ; P=0.752 ) . Noticeable adverse effects were reported by 16 ( 25.8 % ) women in the 200-μg group and 42 ( 67.7 % ) in the 400-μg group ( P<0.001 ) . Risk of shivering was significantly lower with 200μg than 400μg ( relative risk 0.33 , 95 % confidence interval 0.19 - 0.58 ) . CONCLUSION Blood loss and PPH occurrence did not differ by misoprostol dose , but a 200-μg dose was associated with a reduction in adverse effects . Pan Africa Clinical Trials Registry : PACTR201505001107182 OBJECTIVE To determine if the timing of the administration of prophylactic oxytocin influences the incidence of postpartum hemorrhage caused by uterine atony , retained placenta , and third-stage duration . STUDY DESIGN Parturients who presented for vaginal delivery were r and omized in a double-blinded fashion to receive oxytocin , 20 units in a 500-mL crystalloid intravenous bolus , beginning upon delivery of either the fetal anterior shoulder or placenta . For all patients , the third stage of labor was managed with controlled cord traction until placental expulsion , followed by at least 15 seconds of fundal massage . Patients were excluded if they had a previous cesarean section , multiple gestation , antepartum hemorrhage , or bleeding disorder . RESULTS A total of 1486 patients were enrolled : 745 in the before-placenta group and 741 in the after-placenta group . The groups were similar with respect to gestational age , fetal weight , labor duration , maternal age , parity , and ethnicity . The incidence of postpartum hemorrhage did not differ significantly between the two groups ( 5.4 % vs 5.8 % ; crude OR , 0.92 ; 95 % CI , 0.59 to 1.43 ) . There were no significant differences between the two groups with respect to incidence of retained placenta ( 2.4 % vs 1.6 % ; OR , 1.49 ; 95 % CI , 0.72 to 3.08 ) , or third-stage duration ( 7.7 minutes vs 8.1 minutes ; P = .23 ) . CONCLUSIONS The administration of prophylactic oxytocin before placental delivery does not reduce the incidence of postpartum hemorrhage or third-stage duration , when compared with giving oxytocin after placental delivery . Early administration , however , does not increase the incidence of retained placenta A r and omized , double-blind , placebo-controlled study evaluated the influence of umbilical vein administration of oxytocin on the third stage of labor . Five minutes after delivery , 37 women received 10 units of oxytocin diluted in physiologic saline solution to a total volume of 20 ml ; 41 women received 20 ml of saline solution alone . There was no significant difference between groups in mean ( + /- SD ) injection-placental expulsion interval ( 9 + /- 7 versus 10 + /- 8 minutes ) OBJECTIVE To compare the efficacy of oral misoprostol with that of oxytocin for active management of the third stage of labor ( AMTSL ) . METHODS A double-blind r and omized control trial was undertaken at a center in Ilorin , Nigeria , between January and June 2013 . Every other eligible patient ( in the first stage of labor at term , to have a spontaneous vaginal delivery , and no/low risk of postpartum hemorrhage [ PPH ] ) were r and omly assigned with computer-generated r and om numbers to receive oral misoprostol ( 600μg ) plus placebo injection or oral placebo plus oxytocin injection ( 1mL of 10IU ) in the third stage of labor . The primary outcome was amount of blood loss during delivery . RESULTS Mean postpartum blood loss was 325.85±164.72mL in the 100 patients given misoprostol and 303.95±163.33mL in the 100 patients given oxytocin ( P=0.391 ) . PPH ( ≥500mL blood loss ) was recorded in 15 ( 15.0 % ) patients given misoprostol and 14 ( 14.0 % ) given oxytocin ( P=0.841 ) . Shivering , pyrexia , and diarrhea were all significantly more common in the misoprostol group ( P<0.01 for all ) . CONCLUSION The efficacy of oral misoprostol was similar to that of intramuscular oxytocin . Adverse effects associated with misoprostol were transient and self-limiting . Thus , oral misoprostol is efficacious and a good alternative to oxytocin for AMTSL . Pan African Clinical Trials Registry : PACTR201407000825227 We aim ed to show to patients the benefit of post‐partum haemorrhage prophylaxis treatment and the effectiveness as a uterotonic agent of the combined use of methylergonovine and oxytocin infusion in the prevention of haemorrhage during and after Caesarean section , by comparison with a control group which received oxytocin infusion only . Two groups of patients undergoing Caesarean section at the same clinic were included in the study . A combination of methylergonovine and oxytocin was administered to the first group during the intra‐operative and post‐operative periods . The second group did not receive methylergonovine and was administered only with oxytocin infusion in the intra‐operative and post‐operative periods . Pre‐operative and post‐operative haemogram readings were taken for all patients in each of the groups for comparison . No difference was found between the two groups with regard to mean ages and pre‐operative haemogram values . The decrease in post‐operative haemoglobin values for the group administered with methylergonovine maleate and oxytocin was found to be significantly greater than for the group administered with oxytocin only . Results indicated that prophylactic methylergonovine treatment was clearly successful for the patients and no adverse side effects were found . The routine use of methylergonovine and oxytocin infusion in combination during the intra‐operative period of Caesarean section reduced the level of post‐partum haemorrhage considerably . We believe that this procedure will also reduce the risk of uterine atony , but clearly , prospect i ve studies will be necessary in future to confirm this assumption OBJECTIVE In patients with severe preeclampsia there is an increased risk of postpartum hemorrhage , but the hemodynamic changes associated with severe preeclampsia make the management of any kind of bleeding particularly troublesome . There are many pharmacological options for the management of postpartum hemorrhage , oxytocin being the first line of treatment . There is as yet no evidence about the safety and efficacy of using carbetocin , an oxytocin agonist , in these patients . We aim ed to compare oxytocin with carbetocin for the routine prevention of postpartum hemorrhage in patients with severe preeclampsia . METHODS We performed a prospect i ve double-blind r and omized controlled trial in 60 women with severe preeclampsia , recruited between July and September 2010 . The women were r and omized to receive either oxytocin or carbetocin during the third stage of labour . The primary outcome measure was postpartum hemorrhage requiring additional uterotonics , and the secondary outcome measures were the difference in hemoglobin levels between groups , the development of oliguria , and hemodynamic status ( mean arterial pressure and heart rate ) after administration of the drug . RESULTS Carbetocin was as effective as oxytocin in the prevention of postpartum hemorrhage in women with severe preeclampsia . Carbetocin had a safety profile similar to that of oxytocin , and it was not associated with the development of oliguria or hypertension in this cohort . CONCLUSIONS Carbetocin is an appropriate alternative to oxytocin for the prevention of postpartum hemorrhage in women with severe preeclampsia . Considering that it appears not to have a major hemodynamic effect in women with severe preeclampsia and that it uses a lower volume per dose than oxytocin , it should be considered a valid option in the management of the third stage of labour in women with hypertensive disorders of pregnancy Background . Oxytocics are routinely used in an attempt to prevent excessive blood loss during cesarean section . Misoprostol , a potent uterotonic agent , has been reported to be useful in the prevention and treatment of postpartum hemorrhage by several investigators but its use during cesarean section has not been described . The objective of this study was to r and omly compare the effectiveness of oral misoprostol with intravenous syntocinon on blood loss during elective cesarean sections under regional anesthesia Abstract Objective : To assess and compare the effectiveness and safety of single IV polus dose of carbetocin , versus IV oxytocin infusion in the prevention of PPH in obese nulliparous women undergoing emergency Cesarean Delivery . Methods : A double-blinded r and omized-controlled trial was conducted on 180 pregnant women with BMI > 30 . Women were r and omized to receive either oxytocin or carbetocin during C.S. The primary outcome measure was major primary PPH > 1000 ml within 24 h of delivery as per the definition of PPH by the World Health Organization Secondary outcome measures were hemoglobin and hematocrit changes pre- and post-delivery , use of further ecobolics , uterine tone 2 and 12-h postpartum and adverse effects . Results : A significant difference in the amount of estimated blood loss or the incidence of primary postpartum haemorrhage ( > 1000 ml ) in both groups . Haemoglobin levels before and 24-h postpartum was similar . None from the carbetocin group versus 71.5 % in oxytocin group needed additional utrotonics ( p < 0.01 ) . The uterine contractility was better in the carbetocin group at 2 , and 12-h postpartum ( p < 0.05 ) . Conclusions : A single 100-µg IV carbetocin is more effective than IV oxytocin infusion for maintaining adequate uterine tone and preventing postpartum bleeding in obese nulliparous women undergoing emergency cesarean delivery , both has similar safety profile and minor hemodynamic effect OBJECTIVE To compare the effect of rectal misoprostol with intramuscular oxytocin in the routine management of the third stage in a rural developing country . METHODS A r and omized controlled trial was performed at two district hospitals in Ghana , West Africa . Four hundred fifty women in advanced labour were enrolled . The only exclusion criterion was a known medical contraindication to prostagl and in administration . Women were r and omized to receive rectal misoprostol 800 microg or intramuscular oxytocin 10 IU with delivery of the anterior shoulder . The main outcome measure was change in hemoglobin concentration from before to after delivery . Secondary outcomes included the need for additional uterotonics , estimated blood loss , transfusion , and medication side effects . RESULTS Demographic characteristics were similar in each treatment group . There was no significant difference between treatment groups in change in hemoglobin ( misoprostol 1.19 g/dL and oxytocin 1.16 g/dL ; relative difference 2.6 % ; 95 % confidence intervals [CI]-16.8 % to 19.4 % ; P = 0.80 ) . The only significant secondary outcome was shivering , which was more common in the misoprostol group ( misoprostol 7.5 % vs. oxytocin 0.9 % ; relative risk 8.0 ; 95 % CI 1.86 - 34.36 ; P = 0.001 ) . CONCLUSION Rectal misoprostol 800 microg is as effective as 10 IU intramuscular oxytocin in minimizing blood loss in the third stage of labour . Rectal misoprostol has a lower incidence of side effects than the equivalent oral dose . This confirms the utility of misoprostol as a safe and effective uterotonic for use in the rural and remote areas of developing nations where other pharmacologic agents may be less feasible OBJECTIVE To compare active management with physiological management of the third stage of labour in women at low risk of postpartum haemorrhage . DESIGN R and omised allocation of women in labour at low risk of postpartum haemorrhage to either physiological or active management of the third stage . SETTING Labour ward in a district general hospital . PATIENTS 193 Women with spontaneous vaginal delivery at term completed the study . Exclusion criteria were induction or augmentation of labour , antepartum or previous postpartum haemorrhage , premature rupture of membranes , previous caesarean section , raised blood pressure , cervical lacerations and third degree tears . INTERVENTIONS Active management with syntometrine and controlled cord traction ; or physiological management , where the cord was not clamped and the placenta was delivered by maternal effort . MEASUREMENTS Blood loss was measured subjectively at delivery and estimated objective ly by comparing the haemoglobin in labour with that on the third postpartum day . The duration of the third stage was also measured as was the incidence of retained placenta and blood transfusion . RESULTS There was no significant difference in the estimated blood loss or haemoglobin drop between the two groups ( P > 0.5 ) . In addition the duration of the third stage was significantly longer in the physiological group ( P < 0.001 ) . Out of 90 women having physiological management , 7 received oxytocics for presumed postpartum haemorrhage . Only one case in the active group required further oxytocics and one other case in this group required a manual removal of placenta . CONCLUSIONS This preliminary study confirms that active management results in a reduction in the length of the third stage of labour . However , it suggests that active management does not reduce blood loss when compared to physiological management in the woman at low risk of postpartum haemorrhage OBJECTIVE To assess the effect of intravenous tranexamic acid on blood loss during and after cesarean delivery . METHODS One hundred pregnant women were r and omized to receive either 10 mg/kg of tranexamic acid or placebo intravenously 20 minutes before incision in a double-blind controlled study . Postplacental delivery blood loss , postoperative hemorrhage 2 hours after surgery , and oxytocin administration were recorded . RESULTS The patients ' mean age , weight , and duration of surgery were similar between the 2 groups . Mean blood loss was significantly less in the tranexamic acid group compared with the control group for both intraoperative bleeding ( 262.5 ± 39.6 vs 404.7 ± 94.4 mL ) and postoperative bleeding ( 67.1 ± 6.5 vs 141.0 ± 33.9 mL ; P<0.001 ) , respectively . Oxytocin administration was significantly less in the tranexamic acid group compared with the control group ( 39 ± 5.8 vs 43 ± 5.4 units ; P=0.001 ) . CONCLUSION Intravenous tranexamic acid decreased intra- and postoperative blood loss and oxytocin administered in patients delivered by cesarean In the last five years , the number of publications on metabolomics in neonatology and pediatrics has greatly increased [ 1 ] . This is a subject not only of great scientific interest , but also one that may have strong repercussions on clinical practice in the coming five years [ 2 ] . It is an evolution , perhaps a silent revolution , that promises to become a consoli date d discipline with which neonatologists and pediatricians will have to come to grips in the immediate future and which will become part of our world : we are thus of the opinion that the time is ripe to propose the neologisms neonatomics and childomics present in the title of our supplement . On this subject , we wish to thank the Editor-in-Chief of the Journal of Maternal Fetal Neonatal Medicine , Prof. Gian Carlo di Renzo , who continues to host us this year as well , with a supplement dedicated completely to the Italian metabolomic network and its national and international ramifications , on the occasion of the 10th International Workshop on Neonatology to be held in Cagliari ( October , 21st–25th , 2014 ) . The lesson that David Barker prophetically taught us is that the life of every individual is a continuum from prenatal life to that of the adult , and that early events may cause qualitative and quantitative metabolic changes having a permanent effect on the phenotype and important long-term consequences for the individual [ 3 ] . It is from this assumption that comes the subject of the works presented here , which start from obstetrics ( the diagnosis of childbirth ) and cover the entire field of neonatology , to arrive at the autistic child . To underst and what triggers the time of delivery , what series of events and metabolites press the button of no return , that is , the beginning of delivery , is a challenge that may lead to unimaginable advantages and it is no coincidence that important obstetricians of global renown are pressing on the accelerator of metabolomics [ 4 ] . This technique seems of outst and ing impact on perinatology [ 5 ] . Connected with pregnancy is the contribution of urinary metabolomics at birth of babies with weights that are ‘ ‘ not enough ’ ’ or ‘ ‘ too much ’ ’ [ 6 ] . A key role appears to be played by myoinositol and we know from the literature that inositol administered to pregnant women at risk of gestational diabetes greatly reduces its incidence [ 7 ] . This part of nutri-metabolomics has been investigated both with NMR and GC-MS . The knowledge acquired may lead to new advances towards a better underst and ing of the epidemic of diabesity that has recently characterized babies and adolescents [ 8,9 ] . The hard core of the works presented in this supplement is in any case represented by neonatology and the topics , among others , concern two most important themes : nutrition ( metabolomic analysis of breast milk ) [ 10 ] and infections [ 11 ] , which are the cause of approximately one million neonatal deaths every year . The composition of the milk of mothers with preterm delivery has been monitored up to the fortieth week of postconception age . Sample s of formula milk have also been analyzed . From the explorative analysis it emerges that breast milk differs from artificial milk . The artificial milk formulated for preterms is instead more similar to natural milk . It is to be noted that in the sample s collected in the first week of lactation there is a clear difference between the milk of ‘ ‘ early preterm ’ ’ deliveries ( between the 23rd and 25th weeks of gestation ) and that of all the others ( 29th weeks of gestation ) , thus showing that the metabolites analyzed tend to become uniform around the 30th week after conception . From the results obtained we can also see other differences between breast milk and artificial milk , especially in lactose , present in greater concentrations in breast milk , and galactose 1-phosphate and maltose , which instead are present in greater concentrations in formula . Such results may contribute to determining the ideal metabolic profile of formula for neonates at the different gestational ages [ 12 ] . As concerns infections , a review is presented on today ’s metabolomic knowledge of viral infections [ 13 ] ; another original paper focuses on the diagnosis and monitoring of fungal sepsis in the single neonate . The latter study fits perfectly in the fields of predictive , prospect i ve and personalized medicine [ 14 ] . A truly innovative preliminary datum , compared with the current literature [ 15,16 ] , that emerges from one of the studies presented concerns pulmonary bronchodysplasia , which appears to be a congenital disease ( genetics and intrauterine epigenetics ) and the most the neonatologist can do is limit its severity , but not its presence or absence . All appears to occur on the basis of a genetic predisposition inside the womb , J M at er n Fe ta l N eo na ta l M ed D ow nl oa de d fr om in fo rm ah ea lth ca re .c om b y U ni ve rs ity o f T or on to o n 02 /0 2/ OBJECTIVE To evaluate cutaneous blood flow , as identified by Doppler fluximetry , to underst and the etiology of shivering associated with the postpartum use of oral misoprostol . METHODS Eligible participants were recruited from a group of women who were enrolled in an ongoing r and omized trial comparing 400 microg of oral misoprostol to 5 IU of intravenous oxytocin for postpartum hemorrhage prophylaxis . The laser Doppler fluximeter was used to noninvasively measure changes in peripheral tissue perfusion ( flux ) . A skin probe attached to the upper arm recorded flux and skin temperature . Baseline levels were obtained before delivery and for 30 minutes postpartum ( maximum flux ) after the women received the study drug . Continuous variables were analyzed with Student t-test or paired t-test , with the Wilcoxon signed rank test used for non-parametric ordinal data . Categoric data were analyzed with the chi-square test or Fisher 's exact test . RESULTS Sixteen women were enrolled , and 10 women had a vaginal delivery and received the study drugs . Among these 10 women , a significant difference between baseline and maximum flux levels was demonstrated for both women treated with oxytocin ( P = .04 ) and for those treated with misoprostol ( P = .04 ) . Women treated with oxytocin also had a significant change in skin temperature ( P = .04 ) . Maximum flux levels were not significantly different between the women receiving misoprostol compared with those receiving oxytocin ( P = .42 ) . CONCLUSIONS Shivering associated with oral misoprostol may not be due to a re setting of the hypothalamic thermoregulatory centre . Further study is needed to determine whether shivering associated with oral misoprostol is dose-dependent or related to locally mediated phenomena Please cite this paper as : Moertl M , Friedrich S , Kraschl J , Wadsack C , Lang U , Schlembach D. Haemodynamic effects of carbetocin and oxytocin given asintravenous bolus on women undergoing caesarean delivery : a r and omised trial . BJOG 2011;118:1349–1356 OBJECTIVE : Higher-dose oxytocin is more effective than lower-dose regimens to prevent postpartum hemorrhage after cesarean delivery . We compared two higher-dose regimens ( 80 units and 40 units ) to our routine regimen ( 10 units ) among women who delivered vaginally . METHODS : In a double-masked r and omized trial , oxytocin ( 80 units , 40 units , or 10 units ) was administered in 500 mL over 1 hour after placental delivery . The primary outcome was a composite of any treatment of uterine atony or hemorrhage . Prespecified secondary outcomes included outcomes in the primary composite and a decline of 6 % or more in hematocrit . A sample size of 600 per group ( N=1,800 ) was planned to compare each of the 80-unit and 40-unit groups to the 10-unit group . At planned interim review ( n=1,201 ) , enrollment in the 40-unit group was stopped for futility and enrollment continued in the other groups . RESULTS : Of 2,869 women , 1,798 were r and omized as follows : 658 to 80 units ; 481 to 40 units ; and 659 to 10 units . Most characteristics were similar across groups . The risk of the primary outcome in the 80-unit group ( 6 % ; relative risk [ RR ] 0.93 , 95 % confidence interval [ CI ] 0.62–1.40 ) or the 40-unit group ( 6 % ; RR 0.94 , 95 % CI 0.61–1.47 ) was not different compared with the 10-unit group ( 7 % ) . Treatment with additional oxytocin after the first hour was less frequent with 80 units compared with 10 units ( RR 0.41 , 95 % CI 0.19–0.88 ) , as was a 6 % or more decline in hematocrit ( RR 0.83 , 95 % CI 0.69–0.99 ) ; both outcomes declined with increasing oxytocin dose . Outcomes were similar between the 40-unit and 10-unit groups . CONCLUSION : Compared with 10 units , 80 units or 40 units of prophylactic oxytocin did not reduce overall postpartum hemorrhage treatment when administered in 500 mL over 1 hour for vaginal delivery . Eighty units decreased the need for additional oxytocin and the risk of a decline in hematocrit of 6 % or more . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00790062 . LEVEL OF EVIDENCE : OBJECTIVE To compare haemodynamic changes , measured noninvasively using the USCOM monitor , after combined spino-epidural anaesthesia and after administration of two different uterotonic drugs , oxytocin and carbetocin , in a population of pregnant women during elective caesarean delivery . METHODS Haemodynamic measurements were obtained with the USCOM system , by positioning a probe at maternal suprasternal notch ( SSN ) until the aortic valve flow 's profile was optimally identified . Evaluations of the haemodynamic profile were obtained in seven different moments : before anaesthesia ; during skin incision ; 60 , 180 and 300s after administration of uterotonic drug , at closure of the uterus , at closure of the skin . Doses of uterotonic drugs were : Oxytocin 5UI in 500cc NaCl eV , Carbetocin 100mcg in bolus eV. Main measured parameters were : heart rate , mean blood pressure , stroke volume , cardiac output and total vascular resistance . RESULTS We enrolled 32 pregnant women . Patients were r and omized in two groups : oxytocin and carbetocin . A reduction in mean blood pressure , a reduction of total vascular resistance and an increase of cardiac output and of stroke volume were seen , while heart rate values remained stable in both treatment groups . No statistically significant differences were found . DISCUSSION Administration of carbetocin is associated with a substantial global haemodynamic stability in patients undergoing elective caesarean section without any difference with oxytocin . This observation allows us to consider carbetocin comparable to oxytocin , with minimum haemodynamic impact on the maternal circulation . This minimal effect on global haemodynamic stability might extend the use of this uterotonic drug in patients at high haemorrhagic risk with preeclampsia Serum prolactin concentration was measured by radioim- munoassay in 29 women , In the first 1½ hours postpartum . Fourteen women received 0.2 mg methylergonovine maleate ( Methergine ) intramuscularly after the delivery of the placenta . Fifteen women who served as controls received only saline . The rise in serum prolactin concentration seen in the control women ( 266.4 ng/ml ± 40.8 SE ) was significantly greater than that seen in methylergonovine-treated patients ( 141.0 ng/ml ± 29.0 SE ) BACKGROUND The effects of intravenous oxytocics on blood loss and uterine contraction during cesarean section were studied in 136 parturients . METHODS The subjects were r and omized to receive either methylergometrine 0.2 mg bolus ( MEM group ; n = 34 ) , oxytocin 10 IU over 30 seconds ( OX 30 s group ; n = 34 ) , oxytocin 10 IU over 5 minutes ( OX 5 m group ; n = 34 ) or oxytocin 10 IU over 15 minutes ( OX 15 m group ; n = 34 ) . The subjects received spinal anesthesia with 11 - 12 mg of intrathecal isobaric bupivacaine ( 0.5 % ) . Additional intramyometrial prostagl and in F2alpha ( PGF2alpha ) was administered when obstetrician diagnosed uterine atony . We analyzed total amount of blood loss including amniotic fluid and number of parturients that received additional intramyometrial PGF2alpha to evaluate uterine contraction . RESULTS The amounts of blood loss in the OX 30 s and OX 5 m groups were significantly lower than in the MEM group , and the numbers of parturients received additional PGF2alpha in all the oxytocin treat ment groups were significantly lower than in the MEM group ( P < 0.05 ) . There were no significant differences in blood loss and uterine contractior among the oxytocin treatment groups . CONCLUSIONS Intravenous oxytocin 10 IU over 30 seconds to 15 minutes was effective to decrease blood loss and uterine contraction than intravenous methylergometrine 0.2 mg bolus OBJECTIVE This study investigated the effectiveness of rectal misoprostol in preventing postpartum hemorrhage . STUDY DESIGN In a r and omized , placebo-controlled study , 550 women were r and omly allocated to rectally receive 400 microg misoprostol or nonidentical placebo after normal vaginal delivery . Any excessive bleeding was actively managed with conventional oxytocic agents . Blood loss was measured directly . RESULTS The baseline variables were similar . Blood loss of > or = 1000 mL occurred in 4.8 % ( 13/270 ) of the misoprostol group and 7 % ( 19/272 ) of the placebo group . Additional oxytocic therapy was required by 3.3 % and 4.7 % , respectively . No predominance of side effects , particularly shivering , was noted in the misoprostol group . CONCLUSIONS Postpartum use of 400 microg rectal misoprostol was well tolerated and associated with a statistically nonsignificant trend toward less postpartum hemorrhage . The early active management of excessive bleeding with conventional oxytocic agents may have reduced the potential of the study to detect differences between the groups OBJECTIVE To determine the effectiveness of tranexamic acid ( TXA ) in reducing blood loss during and after caesarean section ( CS ) , as well as its safety . STUDY DESIGN A r and omized double-blind placebo controlled study . PLACE AND DURATION OF STUDY The Lyari General Hospital , Karachi , from March 2009 till April 2011 . METHODOLOGY Women undergoing lower segment caesarean section ( LSCS ) were enrolled . The patients were r and omized to receive either injection TXA or distilled water just before the surgery . Blood loss was collected and measured . First from the time of placental delivery to the end of LSCS and later from the end of LSCS to two hours postpartum . Haemoglobin , urine analysis , liver and renal functions were tested in both the groups . Mean values blood loss were compared using t-test with significance at p < 0.05 . RESULTS Tranexamic acid significantly reduced the quantity of blood loss from placental delivery to the end of LSCS which was 356.44 ± 143.2 ml in the TXA group versus 710.22 ± 216.72 ml in the placebo group ( p < 0.001 ) . It also reduced the quantity of blood loss from the end of LSCS to 2 hours postpartum which was 35.68 ± 23.29 ml in the TXA group versus 43.63 ± 28.04 ml in the placebo group ( p = 0.188 ) , was not significant . No complications or side effects were reported in either group . CONCLUSION Tranexamic acid significantly reduced the amount of blood loss during the LSCS , but it did not reduce the blood loss significantly after the caesarean section . Its use was not associated with any side effects or complication like thrombosis . TXA can be used safely and effectively in women undergoing LSCS to reduce intraoperative blood loss OBJECTIVE To compare the efficacy and side effects of sublingual misoprostol and intravenous methylergometrine for active management of third stage of labor . METHOD One hundred twenty low risk pregnant women at term with spontaneous onset of labor were included in the study . The women were r and omized to receive either two tablets of misoprostol ( 200 microg/tablet ) sublingually or 1 ml of methylergometrine ( 200 microg ) intravenous injection , after the delivery of the anterior shoulder of the baby . The main outcome measures were : need for additional oxytocic drugs , blood loss > or=500 ml , change in hemoglobin levels and side effects . RESULTS Postpartum hemorrhage as defined by hemorrhage > or=500 ml occurred in 3.1 % of the women in the sublingual misoprostol group but none of the women in the methylergometrine group ( P > 0.05 ) . There was a need for additional oxytocic drugs in 5.0 % and 8.3 % after methylergometrine and misoprostol , respectively ( P > 0.05 ) . The change in hemoglobin levels at 24 h postpartum were 0.8 and 0.7 gm% in methylergometrine and misoprostol group , respectively(P > 0.05 ) . In the misoprostol group , 6.6 % women developed fever > or=38 degrees C and 21.6 % had shivering while in methylergometrine group none experienced these side effects . However , the incidence of other side effects like nausea , vomiting , headache and giddiness were similar in both groups . CONCLUSION Sublingual misoprostol appears to be as effective as intravenous methylergometrine in the prevention of postpartum hemorrhage . However , larger r and omized studies are needed to advocate its routine use OBJECTIVES A double blind r and omized controlled trial was performed at the tertiary hospital in Harare , Zimbabwe to compare oral misoprostol with intramuscular oxytocin in the management of third stage of labor . METHODS A total of 499 women were r and omized to receive either 400 microg misoprostol orally or 10 IU oxytocin intramuscularly . The incidences of postpartum hemorrhage and side effects were examined . RESULTS The demographic and labor characteristics were comparable . Postpartum hemorrhage occurred in 15.2 % of women given misoprostol and in 13.3 % of those given oxytocin ( P=0.534 ) . Measured blood loss of more than 1000 ml occurred in 3.7 % of the misoprostol group compared with 2 % in the oxytocin group ( P=0.237 ) . There was no significant difference in the need for additional oxytocic drugs or blood transfusion in women given misoprostol ( P values 0.137 and 0.600 , respectively ) . Significant side effects of misoprostol were shivering [ RR=1.32 ( 95 % CI 1.11 - 1.58 ) ; P=0.002 ) and a rise in temperature [ RR=2.02 ( 95 % CI 1.75 - 2.33 ) ; P<0.001 ] . CONCLUSIONS Oral misoprostol is as effective as intramuscular oxytocin in the prevention of PPH . Shivering and transient pyrexia were specific side effects of misoprostol . Misoprostol has potential in reducing the high incidence of PPH in developing countries OBJECTIVE To compare the blood loss at elective lower segment caesarean section with administration of oxytocin 5IU bolus versus oxytocin 5IU bolus and oxytocin 30IU infusion and to establish whether a large multi-centre trial is feasible . STUDY DESIGN Women booked for an elective caesarean section were recruited to a pilot r and omised controlled trial and r and omised to either oxytocin 5IU bolus and placebo infusion or oxytocin 5IU bolus and oxytocin 30IU infusion . We wished to establish whether the study design was feasible and acceptable and to establish sample size estimates for a definitive multi-centre trial . The outcome measures were total estimated blood loss at caesarean section and in the immediate postpartum period and the need for an additional uterotonic agent . RESULTS A total of 115 women were r and omised and 110 were suitable for analysis ( 5 protocol violations ) . Despite strict exclusion criteria 84 % of the target population were considered eligible for study participation and of those approached only 15 % declined to participate and 11 % delivered prior to the planned date . The total mean estimated blood loss was lower in the oxytocin infusion arm compared to placebo ( 567 ml versus 624 ml ) and fewer women had a major haemorrhage ( > 1000 ml , 14 % versus 17 % ) or required an additional uterotonic agent ( 5 % versus 11 % ) . A sample size of 1500 in each arm would be required to demonstrate a 3 % absolute reduction in major haemorrhage ( from baseline 10 % ) with > 80 % power . CONCLUSION An additional oxytocin infusion at elective caesarean section may reduce blood loss and warrants evaluation in a large multi-centre trial The objective of this trial was to investigate whether 500 ug oraJ misoprostol given immediately after delivery of the neonate at Caesarean section is as effective as a bolus intravenous injection of 10 iu Syntocinon in stimulating uterine contractions and thereby reducing blood loss OBJECTIVE To compare the impact of a dinoprostone vaginal insert and intravenous oxytocin in reducing blood loss of women undergoing vaginal or cesarean delivery . METHODS This study was conducted among term singleton pregnancies delivered vaginally or by elective cesarean section . In the vaginally delivered cases , active management of the third stage of labor was conducted . During cesarean delivery , 20 IU of intravenous oxytocin was administered . Women , who either delivered via the vaginal or abdominal route , were then r and omly allocated to receive 10 mg vaginal dinoprostone insert for 12 hours ( group I , n : 100 ) or intravenous oxytocin ( group II , n : 100 ) , respectively . RESULTS Mean blood loss and need for additional uterotonics and postpartum hemoglobin and hematocrit levels at 24 and 36 hours after delivery did not differ between the two groups . Women allocated to the dinoprostone vaginal insert arm experienced more nausea and vomiting . CONCLUSION Dinoprostone vaginal insert was as effective as intravenous oxytocin in the prevention of postpartum blood loss OBJECTIVE The purpose of this study to compare breast milk pharmacokinetics between misoprostol 200 mug and methylergometrine 250 mug after single oral dosing in women who require postpartum uterotonic therapy . STUDY DESIGN Open prospect i ve r and omized phase I study measuring misoprostol and methylergometrine on postpartum days 3 to 6 in milk 0.5 , 1 , 2 , 3 , 4 , and 5 hours postdose , and in maternal serum at 0.5 and 1 hours ( misoprostol ) and 1 and 2 hours ( methylergometrine ) in 10 lactating women per group . RESULTS Milk misoprostol levels rose and declined rapidly , which gave a milk elimination half-life of less than one half that of methylergometrine ( mean + /- SE , 1.1 + /- 0.3 hours [ median , 0.6 hours ] vs 2.33 + /- 0.3 hours [ median , 1.9 hours ] ; P = .003 ) . Milk/plasma ratios for misoprostol were one third of those for methylergometrine at 1 hour ( P < .0001 ) and 2 hours ( P < .0015 ) . CONCLUSION Misoprostol warrants further investigation as an alternative to postpartum methylergometrine because it enters and leaves breast milk at twice the rate , with one third of the milk/plasma ratio , which significantly lowers infant exposure and facilitates a timed dosing regimen OBJECTIVE To compare the efficacy and adverse effects of sublingual misoprostol , intravenous oxytocin , and intravenous methylergometrine in active management of the third stage of labor ( AMTSL ) . METHODS A double-blind r and omized trial of 300 women with a healthy singleton pregnancy allocated into 4 groups to receive either : 400 microg or 600 microg of sublingual misoprostol , 5 IU of intravenous oxytocin , or 200 microg of intravenous methylergometrine . The primary outcome measure was blood loss in the third and fourth stage of labor ; secondary measures were duration of the third stage of labor , changes in hemoglobin levels , and adverse effects . RESULTS Patients who received 600 microg of misoprostol had the lowest blood loss ( 96.05+/-21.1 mL ) , followed by 400 microg of misoprostol ( 126.24+/-49.3 mL ) , oxytocin ( 154.7+/-45.7 mL ) , and methylergometrine ( 223.4+/-73.7 mL ) ( P<0.01 ) . Shortest mean duration of the third stage of labor ( 5.74 minutes ) was with 600 microg of misoprostol , while methylergometrine had the longest ( 6.83 minutes ) ( P<0.05 ) . Pyrexia was observed in the misoprostol groups , and raised blood pressure in the methylergometrine group ( P<0.001 ) . The 24-hour postpartum hemoglobin level was similar among the groups ( P>0.05 ) . CONCLUSION Administration of 600 microg of sublingual misoprostol was more effective than 400 microg of misoprostol , intravenous oxytocin , and intravenous methylergometrine for AMTSL OBJECTIVE To assess whether a combination of misoprostol and oxytocin is more beneficial than oxytocin alone in reducing blood loss after vaginal delivery among women with known risk factors for postpartum hemorrhage ( PPH ) . METHODS A r and omized , double-blind trial was conducted in a medical college in eastern India among women aged at least 18 years who had known high-risk factors for PPH . Using a computer-generated r and om number sequence ( block size 6 - 8 ) , participants were r and omly assigned to receive 400 μg misoprostol or matched placebo tablets sublingually , in addition to 10 units of oxytocin , after vaginal delivery . The primary outcomes were postpartum blood loss at 1 hour and frequency of PPH . Analyses were by intention to treat . RESULTS Both groups contained 144 participants . Postpartum blood loss at 1 hour after delivery was significantly lower among women who received misoprostol than among those who received placebo ( 225.8±156.7 mL vs 302.4±230.3 mL ; P<0.001 ) . The frequency of moderate PPH ( 500 - 999 mL ) was significantly lower in the group receiving misoprostol than in the placebo group ( 5 [ 3.5 % ] vs 15 [ 10.4 % ] participants ; P=0.03 ) . CONCLUSION As compared with oxytocin alone , misoprostol with oxytocin more effectively reduced blood loss after vaginal delivery among women at risk of PPH . Clinical Trial Registry India : CTRI/2014/03/004491 OBJECTIVE : To test whether an oxytocin challenge test raises neonatal levels of copeptin , the C-terminal portion of proarginine vasopressin , a sensitive stress marker elevated in neonates born by vaginal delivery as opposed to elective cesarean delivery . METHODS : In a r and omized controlled trial in women with a singleton pregnancy undergoing elective cesarean delivery at greater than 36 weeks of gestation and no contractions or rupture of membranes , we compared arterial umbilical cord plasma concentrations of copeptin between neonates exposed to an oxytocin challenge test before elective cesarean delivery and those administered saline infusion ( placebo group ) . Women r and omized to an oxytocin challenge test received 5 international units/500 mL oxytocin Ringer lactate infused at a rate of 12 mL/h and doubled every 10 minutes until it induced three uterine contractions per 10-minute interval , at which point it was discontinued . Neonatal copeptin levels were the primary endpoint . Secondary endpoints included biochemical and physiologic parameters of fetal and maternal well-being . RESULTS : From January 2012 to October 2012 and from September 2013 to January 2015 , 78 women underwent an oxytocin challenge test and 78 placebo infusion , of whom 12 and 11 , respectively , were excluded as a result of insufficient blood sample volume for analysis . Umbilical cord plasma copeptin levels [ median ( range ) ] were higher in neonates who underwent an oxytocin challenge test than those who underwent placebo infusion : 22.2 ( 3.22–2,319 ) compared with 7.39 ( 2.5–344.6 ) pmol/L ( P<.001 ) . There were no statistically significant differences between the two groups in secondary outcomes . CONCLUSION : Oxytocin challenge test-induced contractions before elective cesarean delivery trigger fetal copeptin release . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , https:// clinical trials.gov , NCT01962701 OBJECTIVE To determine whether rectally administered misoprostol can induce intestinal motility compared with oxytocin infusion when used to prevent primary postpartum hemorrhage after cesarean delivery . METHODS In a prospect i ve r and omized double-blind study in Nigeria , 218 parturients undergoing cesarean delivery who had risk factors for primary postpartum hemorrhage were enrolled between July 1 , 2010 , and March 31 , 2011 . Participants received 600 μg of rectal misoprostol or 20 intravenous units of oxytocin for 4 hours after surgery . The primary outcome was time until passage of flatus . Adverse effects , need for additional analgesic , and length of hospital stay were also assessed . RESULTS The misoprostol group had a significantly shorter mean postoperative interval to passage of flatus ( 20.27 ± 7.77 hours versus 38.34 ± 10.98 hours ; P<0.001 ) and commencement of regular diet ( 21.08 ± 7.69 hours versus 39.13 ± 10.94 hours ; P<0.001 ) . Gastrointestinal adverse effects were more frequent , albeit not significantly , in the misoprostol group : nausea , 6.4 % versus 1.8 % ; vomiting , 7.3 % versus 2.8 % ; and abdominal distension , 3.7 % versus 2.8 % . The need for additional analgesic was the same in the 2 groups . CONCLUSION After cesarean delivery , rectal misoprostol had the added benefit of inducing intestinal motility . Misoprostol might be considered in a clinical setting where postoperative ileus is anticipated OBJECTIVE To evaluate whether a combination of misoprostol and oxytocin more effectively reduces blood loss during and after cesarean delivery than does oxytocin alone among women with known risk factors for postpartum hemorrhage ( PPH ) . METHODS A prospect i ve , r and omized , double-blind , placebo-controlled trial was performed at a tertiary care center in Kolkata , India , between October 2012 and December 2013 . Women were eligible if they were undergoing emergency cesarean under spinal anesthesia and were at high risk for PPH . Participants were r and omly assigned ( 1:1 ) to receive 400 μg misoprostol or matched placebo sublingually after delivery of the newborn using a computer-generated r and om number sequence ( block size eight ) . Participants and providers were masked to assignment . All participants received 20 IU oxytocin . The primary outcomes were intraoperative and postoperative blood loss . RESULTS Both groups contained 198 women . Mean intraoperative blood loss was significantly lower in the misoprostol group ( 505.4±215.5 mL ) than in the placebo group ( 587.3±201.5 mL ; P<0.001 ) . Mean postoperative blood loss was slightly lower in the misoprostol group ( 96.9±57.3 mL ) than in the placebo group ( 103.4±58.4 mL ; P=0.07 ) . Shivering and pyrexia were more frequently associated with misoprostol ( P<0.05 for both ) . CONCLUSION Misoprostol as an adjunct to oxytocin seemed to more effectively reduce blood loss than did oxytocin alone . Clinical Trial Registry India : CTRI/2013/05/003645 OBJECTIVE To study the efficacy and safety of preoperative intravenous tranexamic acid to reduce blood loss during and after elective lower-segment cesarean delivery . METHODS A single-blind , r and omized placebo-controlled study was undertaken of women undergoing elective lower-segment cesarean delivery of a full-term singleton pregnancy at a center in Cairo , Egypt , between November 2013 and November 2014 . Patients were r and omly assigned ( 1:1 ) using computer-generated r and om numbers to receive either 1 g tranexamic acid or 5 % glucose 15 minutes before surgery . Preoperative and postoperative complete blood count , hematocrit values , and maternal weight were used to calculate the estimated blood loss ( EBL ) during cesarean , which was the primary outcome . Analyses included women who received their assigned treatment , whose surgery was 90 minutes or less , and who completed follow-up . RESULTS Analyses included 100 women in each group . Mean EBL was significantly higher in the placebo group ( 700.3 ± 143.9 mL ) than in the tranexamic acid group ( 459.4 ±7 5.4 mL ; P<0.001 ) . Only six women , all in the placebo group , experienced an EBL of more than 1000 mL. There were no reports of thromboembolic events up to 4 weeks postoperatively . CONCLUSION Preoperative administration of tranexamic acid safely reduces blood loss during elective lower-segment cesarean delivery . Australian New Zeal and Clinical Trials Registry : ACTRN12615000312549 BACKGROUND The aim of this study was to determine serum oxytocin concentrations following different regimens of prophylactic oxytocin administration in women undergoing elective caesarean delivery . METHODS Thirty healthy pregnant patients were r and omized , after clamping of the umbilical cord , to receive intravenous oxytocin in one of the following groups : G1 ( n=9 ) , 10 IU of oxytocin infused over 30 min ( 0.33 IU/min ) ; G2 ( n=11 ) , 10 IU of oxytocin infused over 3 min and 45 s ( 2.67 IU/min ) ; and G3 ( n=10 ) , 80 IU of oxytocin infused over 30 min ( 2.67 IU/min ) . Both patient and surgeon were blinded to allocation . Uterine tone was assessed by surgical palpation . Serum oxytocin concentration was determined by enzyme immunoassay before anaesthesia ( T0 ) and at 5 ( T5 ) , 30 ( T30 ) and 60 ( T60 ) min after the start of oxytocin infusion . RESULTS Serum oxytocin concentrations ( mean±st and ard error , ng/mL ) were not significantly different in the groups at T0 ( 0.06±0.02 , 0.04±0.02 and 0.07±0.04 , respectively , P=0.76 ) , and T60 ( 0.65±0.26 , 0.36±0.26 and 0.69±0.26 , respectively , P=0.58 ) . G3 showed higher concentrations than G1 at T5 ( 3.65±0.74 versus 0.71±0.27 , P=0.01 ) and at T30 ( 6.19±1.19 versus 1.17±0.37 , P<0.01 ) , and were higher than G2 at T30 ( 6.19±1.19 versus 0.41±0.2 , P<0.01 ) . Haemodynamic data and uterine tone were considered satisfactory and similar in all groups . No additional uterotonic agents were needed . CONCLUSION Serum oxytocin measurements made using enzyme immunoassay in healthy pregnant women undergoing elective caesarean delivery showed that administration of 80 IU oxytocin over 30 min result ed in higher serum oxytocin levels after 5 and 30 min than the two other regimens . The concentrations did not differ between groups at 60 min Please cite this paper as : Attilakos G , Psaroudakis D , Ash J , Buchanan R , Winter C , Donald F , Hunt L , Draycott T. Carbetocin versus oxytocin for the prevention of postpartum haemorrhage following caesarean section : the results of a double‐blind r and omised trial . BJOG 2010;117:929–936 Background Postpartum haemorrhage ( PPH ) is the leading cause of maternal mortality in low-income countries and contributes to nearly a quarter of maternal deaths globally . The current available interventions for prevention of postpartum haemorrhage , oxytocin and carbetocin , are limited by their need for refrigeration to maintain potency , as the ability to maintain a cold chain across the drug distribution and storage network is inconsistent , thus restricting their use in countries with the highest burden of maternal mortality . We describe a r and omized , double-blind non-inferiority trial comparing a newly developed room temperature stable formulation of carbetocin to the st and ard intervention ( oxytocin ) for the prevention of PPH after vaginal birth . Methods / design Approximately 30,000 women delivering vaginally will be recruited across 22 centres in 10 countries . The primary objectives are to evaluate the non-inferiority of room temperature stable carbetocin ( 100 μg intramuscular ) versus oxytocin ( 10 IU intramuscular ) in the prevention of PPH and severe PPH after vaginal birth . The primary endpoints are blood loss ≥500 mL or the use of additional uterotonics ( composite endpoint required by drug regulatory authorities ) and blood loss ≥1,000 mL ( WHO requirement ) . Non-inferiority will be assessed using a two-sided 95 % confidence interval for the relative risk of the above endpoints for room temperature stable carbetocin versus oxytocin . The upper limit of the two-sided 95 % confidence interval for the relative risk for the composite endpoint of blood loss ≥500 mL or the use of additional uterotonics , and for the endpoint of blood loss ≥1,000 mL , will be compared to a non-inferiority margin of 1.16 and 1.23 , respectively . If the upper limit is below the corresponding margin , non-inferiority will have been demonstrated . The safety analysis will include all women receiving treatment . Safety and tolerability will be assessed by a review of adverse events , by conducting inferential testing with significance levels for between-group comparisons . Discussion If the results of the study show that room temperature stable carbetocin is a safe and effective alternative to oxytocin , this could have a substantial impact on the prevention of postpartum haemorrhage and maternal survival worldwide . Trial registration ACTRN12614000870651 ( 14 August 2014 Abstract Purpose To compare the effect of combined oxytocin – misoprostol versus oxytocin and misoprostol alone in reducing blood loss at cesarean delivery . Methods One hundred fifty patients of 18–40 years with singleton term pregnancies scheduled for cesarean section under spinal anesthesia were recruited in a prospect i ve double-blind r and omized clinical trial to one of the three following groups to receive 20 IU infusion of oxytocin ( group O ) , 400-µg sublingual misoprostol tablets ( group M ) or 200-µg misoprostol plus 5 IU bolus intravenous oxytocin ( group MO ) after delivery . The hemoglobin level before surgery and 24 h after surgery , the need for additional oxytocic therapy , and the incidence of adverse effects were recorded . Results The mean blood loss during surgery was significantly lower in group MO compared to other groups ( P = 0.04 ) . Comparison of mean arterial pressure ( P = 0.38 ) and heart rate ( P = 0.23 ) changes during spinal anesthesia and surgery failed to reveal any statistically significant differences between all groups through repeated measure analysis . Conclusion The use of combined lower dose of misoprostol – oxytocin significantly reduced the amount of blood loss during and after the lower segment cesarean section compared to higher dose of oxytocin and misoprostol alone , and its use was not associated with any serious side effects |
13,215 | 28,806,470 | Finally , we found no significant differences between sugammadex and neostigmine regarding risk of serious adverse events ( RR 0.54 , 95 % CI 0.13 to 2.25 ; I2= 0 % ; 10 studies , n = 959 ; GRADE : low quality ) .Application of trial sequential analysis ( TSA ) indicates superiority of sugammadex for outcomes such as recovery time from T2 to TOFR > 0.9 , adverse events , and overall signs of postoperative residual paralysis .
AUTHORS ' CONCLUSIONS Review results suggest that in comparison with neostigmine , sugammadex can more rapidly reverse rocuronium-induced neuromuscular block regardless of the depth of the block .
With an NNTB of 8 to avoid an adverse event , sugammadex appears to have a better safety profile than neostigmine . | BACKGROUND Acetylcholinesterase inhibitors , such as neostigmine , have traditionally been used for reversal of non-depolarizing neuromuscular blocking agents .
However , these drugs have significant limitations , such as indirect mechanisms of reversal , limited and unpredictable efficacy , and undesirable autonomic responses .
Sugammadex is a selective relaxant-binding agent specifically developed for rapid reversal of non-depolarizing neuromuscular blockade induced by rocuronium .
Its potential clinical benefits include fast and predictable reversal of any degree of block , increased patient safety , reduced incidence of residual block on recovery , and more efficient use of healthcare re sources .
OBJECTIVES The main objective of this review was to compare the efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade caused by non-depolarizing neuromuscular agents in adults . | Background Acetylcholinesterase inhibitors can not rapidly reverse profound neuromuscular block . Sugammadex , a selective relaxant binding agent , reverses the effects of rocuronium and vecuronium by encapsulation . This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia . Methods Patients aged ≥18 years , American Society of Anesthesiologists class 1 - 4 , scheduled to undergo surgery under general anesthesia were enrolled in this phase III , multicenter , r and omized , safety-assessor blinded study . Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation , with maintenance doses of 0.015 mg/kg as required . Patients were r and omized to receive sugammadex 4 mg/kg or neostigmine 70 μg/kg with glycopyrrolate 14 μg/kg at 1 - 2 post-tetanic counts . The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9 . Safety assessment s included physical examination , laboratory data , vital signs , and adverse events . Results Eighty three patients were included in the intent-to-treat population ( sugammadex , n = 47 ; neostigmine , n = 36 ) . Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex ( 4.5 minutes ) compared with neostigmine ( 66.2 minutes ; p < 0.0001 ) ( median , 3.3 minutes with sugammadex versus 49.9 minutes with neostigmine ) . No serious drug-related adverse events occurred in either group . Conclusions Recovery from profound vecuronium-induced block is significantly faster with sugammadex , compared with neostigmine . Neostigmine did not rapidly reverse profound neuromuscular block ( Trial registration number : NCT00473694 ) Backround Sugammadex is a reversal agent with well known advantages but it ’s effects on haemostasis and bleeding have been a topic of interest . Septoplasty is a common surgical procedure with postoperative respiratory complications and bleeding . The aim of this study is to investigate the effects of sugammadex on postoperative coagulation parameters and bleeding after septoplasty procedure . Material / Methods In this r and omized controlled study , fifty patients were grouped into two groups ; neostigmine ( Group N ) vs. sugammadex ( Group S ) . For the evaluation of PT , aPTT and INR , blood sample s were taken for at the postoperative 120th minutes and alteration of these values with respect to preoperative values were documented . Postoperative bleeding was measured by evaluating the amount of blood absorbed on the nasal tip dressing during 3 hours postoperatively . Results Postoperative bleeding amount was significantly higher in the Group S compared to Group N ( p=0.013 ) . No significant difference was observed between two groups according to coagulation parameters ( PT ; p=0.953 , aPTT ; p=0.734 , INR ; p=0.612 ) . Conclusions Sugammadex was associated with higher amount of postoperative bleeding than neostigmine in septoplasty patients . In surgical procedures having high risk of bleeding the safety of sugammadex need to be verified BACKGROUND : Sugammadex , a specifically design ed & ggr;-cyclodextrin , is a selective relaxant binding drug that rapidly reverses rocuronium-induced and , to a lesser extent , vecuronium-induced neuromuscular blockade . In this study , we compared the efficacy of sugammadex and neostigmine for the reversal of vecuronium-induced neuromuscular blockade in patients scheduled for elective surgery . METHODS : Patients aged ≥18 yr , ASA Class I – III , and scheduled for a surgical procedure under sevoflurane/opioid anesthesia received an intubating dose of vecuronium ( 0.1 mg/kg ) and maintenance doses of 0.02–0.03 mg/kg at reappearance of the second twitch ( T2 ) of train-of-four ( TOF ) if required . Neuromuscular blockade was monitored using acceleromyography ( TOF-Watch ® SX , Schering-Plough Irel and , Dublin , Irel and ) . At end of surgery , at reappearance of T2 after the last dose of vecuronium , patients were r and omized to receive either sugammadex ( 2 mg/kg ) or neostigmine ( 50 & mgr;g/kg ) plus glycopyrrolate ( 10 & mgr;g/kg ) IV . The primary efficacy end-point was time from start of administration of sugammadex or neostigmine to recovery of TOF ratio to 0.9 . RESULTS : The geometric mean time to recovery of the TOF ratio to 0.9 was significantly faster with sugammadex compared with neostigmine ( 2.7 min [ 95 % confidence interval { CI } ] : 2.2–3.3 ) versus 17.9 min [ 95 % CI : 13.1–24.3 ] , respectively ; P < 0.0001 ) . The mean recovery times to a TOF ratio of 0.8 and 0.7 were also significantly shorter with sugammadex . No serious adverse events or unexpected side effects were reported with either drug . CONCLUSION : Sugammadex provided significantly faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine Background This study compared efficacy and safety of the selective relaxant binding agent sugammadex ( 2 mg/kg ) with neostigmine ( 50 μg/kg ) for neuromuscular blockade ( NMB ) reversal in Chinese and Caucasian subjects . Methods This was a r and omized , active-controlled , multicenter , safety-assessor-blinded study ( NCT00825812 ) in American Society of Anesthesiologists Class 1 - 3 subjects undergoing surgery with propofol anesthesia . Rocuronium 0.6 mg/kg was administered for endotracheal intubation , with 0.1–0.2 mg/kg maintenance doses given as required . NMB was monitored using TOF-Watch ® SX . At second twitch reappearance , after last rocuronium dose , subjects received sugammadex 2 mg/kg or neostigmine 50 μg/kg plus atropine 10–20 μg/kg , according to r and omization . Primary efficacy variable was time from sugammadex/neostigmine to recovery of the train-of-four ( TOF ) ratio to 0.9 . Results Overall , 230 Chinese subjects ( sugammadex , n = 119 , neostigmine , n = 111 ) ; and 59 Caucasian subjects ( sugammadex , n = 29 , neostigmine , n = 30 ) had evaluable data . Geometric mean ( 95 % CI ) time to recovery to TOF ratio 0.9 was 1.6 ( 1.5–1.7 ) min with sugammadex vs 9.1 ( 8.0–10.3 ) min with neostigmine in Chinese subjects . Corresponding times for Caucasian subjects were 1.4 ( 1.3–1.5 ) min and 6.7 ( 5.5–8.0 ) min , respectively . Sugammadex 2 mg/kg was generally well tolerated , with no serious adverse events reported . There was no residual NMB or recurrence of NMB . Conclusion Both Chinese and Caucasian subjects recovered from NMB significantly faster after sugammadex 2 mg/kg vs neostigmine 50 μg/kg , with a ~5.7 times ( p < 0.0001 ) faster recovery with sugammadex vs neostigmine in Chinese subjects . Sugammadex was generally well tolerated . Trial registration Clinical Trials.gov Identifier : NCT00825812 Background Rapid and complete reversal of neuromuscular blockade ( NMB ) is desirable at the end of surgery . Sugammadex reverses rocuronium-induced NMB by encapsulation . It is well tolerated in Caucasian patients , providing rapid reversal of moderate ( reappearance of T2 ) rocuronium-induced NMB . We investigated the efficacy and safety of sugammadex versus neostigmine in Korean patients . Methods This r and omized , safety assessor-blinded trial ( NCT01050543 ) included Korean patients undergoing general anesthesia . Rocuronium 0.6 mg/kg was given prior to intubation with maintenance doses of 0.1 - 0.2 mg/kg as required . Patients received sugammadex 2.0 mg/kg or neostigmine 50 µg/kg with glycopyrrolate 10 µg/kg to reverse the NMB at the reappearance of T2 , after the last rocuronium dose . The primary efficacy endpoint was the time from sugammadex or neostigmine administration to recovery of the train-of-four ( TOF ) ratio to 0.9 . The safety of these medications was also assessed . Results Of 128 r and omized patients , 118 had evaluable data ( n = 59 in each group ) . The geometric mean ( 95 % confidence interval ) time to recovery of the TOF ratio to 0.9 was 1.8 ( 1.6 , 2.0 ) minutes in the sugammadex group and 14.8 ( 12.4 , 17.6 ) minutes in the neostigmine group ( P < 0.0001 ) . Sugammadex was generally well tolerated , with no evidence of residual or recurrence of NMB ; four patients in the neostigmine group reported adverse events possibly indicative of inadequate NMB reversal . Conclusions Sugammadex was well tolerated and provided rapid reversal of moderate rocuronium-induced NMB in Korean patients , with a recovery time 8.1 times faster than neostigmine . These results are consistent with those reported for Caucasian patients The frequency and duration of postoperative residual neuromuscular block on arrival of 150 patients in the recovery ward following the use of vecuronium ( n = 50 ) , atracurium ( n = 50 ) and rocuronium ( n = 50 ) were recorded . Residual block was defined as a train‐of‐four ratio of < 0.8 . An additional group of 10 patients received no neuromuscular blocking drugs during anaesthesia . The incidence of postoperative residual neuromuscular block was 64 % , 52 % and 39 % after the use of vecuronium , atracurium and rocuronium , respectively . Similar numbers of patients were not able to maintain a sustained head or leg lift for 5 s on arrival in the recovery ward . The mean [ range ] times to attaining a train‐of‐four ratio of ≥0.8 after arrival in the recovery ward were 9.2 [ 1–61 ] , 6.9 [ 1–24 ] and 14.7 [ 1.5–83 ] min for vecuronium , atracurium and rocuronium , respectively . None of the 10 patients who did not receive neuromuscular blocking drugs had train‐of‐four ratios < 0.8 on arrival in the recovery ward . It is concluded that a large proportion of patients arrive in the recovery ward with a train‐of‐four ratio < 0.8 , even with the use of intermediate‐acting neuromuscular blocking drugs . Although the residual block is relatively short lasting , it may occasionally be prolonged , requiring close observation and monitoring of such patients in the recovery ward BACKGROUND Sugammadex is a selective relaxant binding agent design ed to encapsulate the neuromuscular blocking agent , rocuronium . The sugammadex-rocuronium complex is eliminated by the kidneys . This trial investigated the pharmacokinetics ( PKs ) of sugammadex and rocuronium in patients with renal failure and healthy controls . METHODS Fifteen ASA class II-III renal patients [ creatinine clearance ( CL(CR ) ) < 30 ml min(-1 ) ] and 15 ASA I-II controls ( CL(CR ) > or = 80 ml min(-1 ) ) were included . After induction of anaesthesia , a single i.v . dose of rocuronium 0.6 mg kg(-1 ) was given , followed by a single i.v . dose of sugammadex 2.0 mg kg(-1 ) at reappearance of the second twitch of the train-of-four response . Plasma concentrations of rocuronium and sugammadex were estimated and PK variables determined using non-compartmental analyses . Percentages of sugammadex and rocuronium excreted in the urine were measured . RESULTS PK data were obtained from 26 patients . Mean total plasma clearance ( CL ) of sugammadex was 5.5 ml min(-1 ) in renal patients and 95.2 ml min(-1 ) in controls ( P<0.05 ) . Rocuronium CL was 41.8 ml min(-1 ) in renal patients and 167 ml min(-1 ) in controls ( P<0.05 ) . The median amount of sugammadex and rocuronium excreted in the urine over 72 h in renal patients was 29 % and 4 % , respectively , and 73 % and 42 % over 24 h in controls . CONCLUSIONS Large differences in the PKs of sugammadex and rocuronium between patients with renal failure and healthy controls were observed . The effect of renal impairment on the PK variables of rocuronium was less than with sugammadex . Urinary excretion of both drugs was reduced in renal patients Background Sugammadex is a novel neuromuscular reversal agent , but its associated hypersensitivity reaction and high cost have been obstacles to its widespread use . In the interest of reducing the necessary dosage of sugammadex , the reversal time of the combined use of sugammadex and neostigmine from moderate neuromuscular blockade were investigated . Methods The patients enrolled ranged in age from 18 to 65 years old with American Society of Anesthesiologists class 1 or 2 . The subjects were r and omly assigned into one of the four groups ( Group S2 , S1 , SN , and N ; n = 30 per group ) . The reversal agents of each groups were as follows : S2 - sugammadex 2 mg/kg , S1 - sugammadex 1 mg/kg , SN - sugammadex 1 mg/kg + neostigmine 50 µg/kg + glycopyrrolate 10 µg/kg , N - neostigmine 50 µg/kg + glycopyrrolate 10 µg/kg . The time to recovery of the train-of-four ( TOF ) ratio was checked in each group . Results The time to 90 % recovery of TOF ratio was 182.6 ± 88.9 , 371.1 ± 210.4 , 204.3 ± 103.2 , 953.2 ± 379.7 sec in group S2 , S1 , SN and N , respectively . Group SN showed a significantly shorter recovery time than did group S1 and N ( P < 0.001 ) . However , statistically significant differences between the S2 and SN groups were not be observed ( P = 0.291 ) . No hypersensitivity reactions occurred in all groups . Conclusions For the reversal from rocuronium-induced moderate neuromuscular blockade , the combined use of sugammadex and neostigmine may be helpful to decrease the recovery time and can also reduce the required dosage of sugammadex . However , the increased incidence of systemic muscarinic side effects must be considered CONTEXT Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected , but direct evidence of such bias is currently limited to case reports . OBJECTIVE To study empirically the extent and nature of outcome reporting bias in a cohort of r and omized trials . DESIGN Cohort study using protocol s and published reports of r and omized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg , Denmark , in 1994 - 1995 . The number and characteristics of reported and unreported trial outcomes were recorded from protocol s , journal articles , and a survey of trialists . An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta- analysis . Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias . Protocol s and published articles were also compared to identify discrepancies in primary outcomes . MAIN OUTCOME MEASURES Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes ; consistency between primary outcomes defined in the most recent protocol s and those defined in published articles . RESULTS One hundred two trials with 122 published journal articles and 3736 outcomes were identified . Overall , 50 % of efficacy and 65 % of harm outcomes per trial were incompletely reported . Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy ( pooled odds ratio , 2.4 ; 95 % confidence interval [ CI ] , 1.4 - 4.0 ) and harm ( pooled odds ratio , 4.7 ; 95 % CI , 1.8 - 12.0 ) data . In comparing published articles with protocol s , 62 % of trials had at least 1 primary outcome that was changed , introduced , or omitted . Eighty-six percent of survey responders ( 42/49 ) denied the existence of unreported outcomes despite clear evidence to the contrary . CONCLUSIONS The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocol s. Published articles , as well as review s that incorporate them , may therefore be unreliable and overestimate the benefits of an intervention . To ensure transparency , planned trials should be registered and protocol s should be made publicly available prior to trial completion Background : We aim ed to compare clinical effects of sugammadex versus combination of anticholinergic-anticholinesterase agents for reversing of nondepolarizing neuromuscular block in pediatric patients . Material s and Methods : A total of 60 pediatric patients whom should be performed general anesthesia in the supine position were enrolled to this r and omized double-blinded clinical trial . Fentanyl 1 μg/kg , propofol 2 mg/kg , rocuronium 0.6 mg/kg were used in induction and sevofluran , 50 % O2 - 50 % N2O in maintenance of anesthesia . Neuromuscular conductions were assessed by train of four (TOF)-Watch SX ( Organon , Schering-Plough , Irel and ) acceleromyograph . Patients were intubated at the moment of TOF 0 . At the end of the operation emergence of T2 point was replied by 2 mg/kg sugammadex administration in group 1 and 0.06 mg/kg neostigmine + 0.02 mg/kg atropine in group 2 . At the moment of T0.9 inhalation , gases were ceased , and patients were extubated . Hemodynamic alterations , access to T0.9 , extubation time , recovery parameters , drug consumptions and adverse effects were recorded . Results : Train of four scores showed a lesser increase in group 2 than group 1 from 15th s to 30th min during post reverse period ( from 6.9 ± 6.4 to 91.7 ± 7.2 in group 2 vs. from 35.4 ± 21.4 to 99.5 ± 1.0 in group 1 ) ( p < 0.0004 ) . Group 1 patients exhibited much more complete muscle strength rates than group 2 ( P < 0.001 ) . T0.9 and extubation times were significantly longer in group 2 than group 1 ( P < 0.001 ) . Comparison of adverse effects yielded no difference . Conclusion : Sugammadex can be considered as a safe agent in order to reverse neuromuscular block in pediatric patients Background : The subjective experience of residual neuromuscular blockade after emergence from anesthesia has not been examined systematic ally during postanesthesia care unit ( PACU ) stays . The authors hypothesized that acceleromyography monitoring would diminish unpleasant symptoms of residual paresis during recovery from anesthesia by reducing the percentage of patients with train-of-four ratios less than 0.9 . Methods : One hundred fifty-five patients were r and omized to receive intraoperative acceleromyography monitoring ( acceleromyography group ) or conventional qualitative train-of-four monitoring ( control group ) . Neuromuscular management was st and ardized , and extubation was performed when defined criteria were achieved . Immediately upon a patient 's arrival to the PACU , the patient 's train-of-four ratios were measured using acceleromyography , and a st and ardized examination was used to assess 16 symptoms and 11 signs of residual paresis . This examination was repeated 20 , 40 , and 60 min after PACU admission . Results : The incidence of residual blockade ( train-of-four ratios less than 0.9 ) was reduced in the acceleromyography group ( 14.5 % vs. 50.0 % control group , with the 99 % confidence interval for this 35.5 % difference being 16.4–52.6 % , P < 0.0001 ) . Generalized linear models revealed the acceleromyography group had less overall weakness ( grade d on a 0–10 scale ) and fewer symptoms of muscle weakness across all time points ( P < 0.0001 for both analyses ) , but the number of signs of muscle weakness was small from the time of arrival in the PACU and did not differ between the groups at any time . Conclusion : Acceleromyography monitoring reduces the incidence of residual blockade and associated unpleasant symptoms of muscle weakness in the PACU and improves the overall quality of recovery BACKGROUND Reversal of the residual effect of rocuronium or cisatracurium by neostigmine may be slow and associated with side-effects . This r and omized , safety-assessor-blinded study compared the efficacy of sugammadex , a selective relaxant binding agent for reversal of rocuronium-induced neuromuscular block , with that of neostigmine for reversal of cisatracurium-induced neuromuscular block . The safety of sugammadex and neostigmine was also evaluated . METHODS Adult surgical patients ( ASA class I-III ) were r and omized to sugammadex 2.0 mg kg(-1 ) for reversal of block induced by rocuronium 0.6 mg kg(-1 ) , or neostigmine 50 microg kg(-1 ) for reversal of block induced by cisatracurium 0.15 mg kg(-1 ) . Anaesthesia was induced and maintained using i.v . propofol and remifentanil , fentanyl , or sufentanil . Neuromuscular function was monitored using acceleromyography ( TOF-Watch SX ) . Sugammadex or neostigmine was administered at reappearance of T(2 ) . The primary efficacy variable was time for recovery of the train-of-four ( TOF ) ratio to 0.9 . RESULTS Eighty-four patients were r and omized , 73 of whom received sugammadex ( n=34 ) or neostigmine ( n=39 ) . Time from start of administration of reversal agent to recovery of the TOF ratio to 0.9 was 4.7 times faster with sugammadex than with neostigmine ( geometric mean=1.9 vs 9.0 min , P<0.0001 ) . Reversal of block was sustained in all patients . There were no serious adverse effects from either reversal agent and no significant changes in any measure of safety , except for similar elevations in urinary N-acetyl glucosaminidase in both groups . CONCLUSIONS Sugammadex 2.0 mg kg(-1 ) administered at reappearance of T(2 ) was significantly faster in reversing rocuronium-induced blockade than neostigmine was in reversing cisatracurium-induced block BACKGROUND This study aim ed to investigate whether reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade and facilitated operating room discharge readiness . METHODS Adult patients undergoing abdominal surgery received rocuronium , followed by r and omized allocation to sugammadex ( 2 or 4 mg kg(-1 ) ) or usual care ( neostigmine/glycopyrrolate , dosing per usual care practice ) for reversal of neuromuscular blockade . Timing of reversal agent administration was based on the providers ' clinical judgement . Primary endpoint was the presence of residual neuromuscular blockade at PACU admission , defined as a train-of-four ( TOF ) ratio < 0.9 , using TOF-Watch ® SX . Key secondary endpoint was time between reversal agent administration and operating room discharge-readiness ; analysed with analysis of covariance . RESULTS Of 154 patients r and omized , 150 had a TOF value measured at PACU entry . Zero out of 74 sugammadex patients and 33 out of 76 ( 43.4 % ) usual care patients had TOF-Watch SX-assessed residual neuromuscular blockade at PACU admission ( odds ratio 0.0 , 95 % CI [ 0 - 0.06 ] , P<0.0001 ) . Of these 33 usual care patients , 2 also had clinical evidence of partial paralysis . Time between reversal agent administration and operating room discharge-readiness was shorter for sugammadex vs usual care ( 14.7 vs. 18.6 min respectively ; P=0.02 ) . CONCLUSIONS After abdominal surgery , sugammadex reversal eliminated residual neuromuscular blockade in the PACU , and shortened the time from start of study medication administration to the time the patient was ready for discharge from the operating room . CLINICAL TRIAL REGISTRATION Clinical trials.gov : NCT01479764 Background The primary outcome of sugammadex reversal for rocuronium-induced neuromuscular block ( NMB ) is a train-of-four ratio ( TOFR ) of 0.9 , not first twitch ( T1 ) height . We investigated whether the recovery of TOFR or T1 differs based on the reversal of NMB with neostigmine or sugammadex . Methods The acceleromyographic responses from 0.6 mg/kg of rocuronium were monitored supramaximally in 80 patients after induction of anesthesia . The TOFR and T1 height were recorded , and saved in a personal computer using TOF-Watch SX Monitor software in all patients . Patients were r and omly assigned to 2 groups to receive either neostigmine 50 µg/kg with glycopyrrolate 10 µg/kg ( neostigmine group , n = 40 ) or sugammadex 2.0 mg/kg ( sugammadex group , n = 40 ) . The primary objective was to determine the difference of recovery time between TOFR to 0.9 and T1 to 0.9 after sugammadex or neostigmine administration during moderate rocuronium-induced NMB . Results The recovery pattern of the TOFR 2 min after sugammadex administration was 1.0 or more , but that of T1 was less than 90 % ( T1 / control value ) up to 6 min after drug was injected . The recovery pattern of TOFR and T1 was similar during the 20 min after reversal with neostigmine . Conclusions If you have not performed the T1 monitoring , both TOFR and T1 should be considered to confirm suitable recovery during the 6 min after reversal with sugammadex during rocuronium-induced moderate NMB BACKGROUND Sugammadex is a modified γ-cyclodextrin with a novel mechanism of action for reversing the steroidal neuromuscular blocking agent rocuronium . Bispectral index ( BIS ) is an EEG-derived measure which can be sensitive to frontal electromyographic ( EMG ) artifacts . We compared BIS values before and after sugammadex or neostigmine neuromuscular block ( NMB ) reversal in patients with or without high EMG activity . METHODS During stable propofol/remifentanil anaesthesia and rocuronium-induced block , 48 patients were r and omly allocated to receive sugammadex 4 mg kg(-1 ) or neostigmine 50 μg kg(-1)/glycopyrrolate 10 μg kg(-1 ) , 10 min after the end of surgery . RESULTS Five minutes after sugammadex administration , mean BIS 50.1 ( 10.3 ) increased ( P=0.018 ) to 61.7 ( 7.9 ) in 11 patients with high EMG activity . In contrast , BIS 49.3 ( 4.9 ) remained at 51.9 ( 5.4 ) in 13 patients who had no EMG activity . Fifteen minutes after neostigmine administration , mean BIS 51.9 ( 8.1 ) increased ( P=0.007 ) to 63.9 ( 8.1 ) in 13 patients who had reappearance of muscle activity . However , in 11 patients who had no EMG activity , BIS 52.3 ( 7.4 ) remained at 53.3 ( 6.8 ) . There was no significant difference between the sugammadex and neostigmine groups over time . CONCLUSIONS We have shown that reversal of NMB with sugammadex or neostigmine increased BIS values dependent on the presence of EMG activity . Thus , the effect of muscle activity reappearance during rocuronium NMB reversal spuriously increasing the BIS value should be taken into consideration when relying on BIS monitoring for evaluating propofol/remifentanil recovery BACKGROUND Complete and fast recovery of neuromuscular function is very important in morbidly obese patients because of the possible influence of postoperative residual curarization ( PORC ) on respiratory function in the postoperative period . Recent reports underline incidences of the residual influence of neuromuscular blocking agents . METHODS Seventy morbidly obese ( BMI > 40 kg m(-2 ) ) patients requiring general anaesthesia and receiving rocuronium for muscle relaxation were r and omly assigned into two groups : at the end of the anaesthetic procedure , one group received sugammadex 2 mg kg(-1 ) of corrected body weight ( Group SUG ) and the other group received neostigmine 0.05 mg kg(-1 ) of CBW ( Group NEO ) . At the end of surgery and when response reached a train-of-four ( TOF ) score of 2 , patients received the study drugs . The neuromuscular function was recorded and time to achieve 90 % of TOF ( safe extubation ) was measured . Patients were examined directly after arrival to the post-anaesthesia care unit ( PACU ) by a blinded investigator for the presence of PORC . RESULTS Thirty-five patients received sugammadex and 35 neostigmine . Mean dose of rocuronium was 87.9 vs 85.6 mg ( P>0.05 ) , mean time to 90 % of TOF was 2.7 vs 9.6 min ( P<0.05 ) , and TOF at the PACU was 109.8 % vs 85.5 % ( P<0.05 ) in Groups SUG and NEO , respectively . CONCLUSIONS Administration of sugammadex provides fast recovery of neuromuscular function and prevents PORC in the morbidly obese , however neostigmine does not BACKGROUND To avoid postoperative residual neuromuscular block there is a need for a change in clinician 's attitude towards monitoring and reversal . This study aims to evaluate changes of perioperative neuromuscular block management during the last decade in our institution and to quantify the incidence of postoperative residual neuromuscular block . METHODS Patients receiving intermediate-acting neuromuscular blocking agents for scheduled surgical procedures during 3-month periods in 1995 ( n=435 ) , 2000 ( n=130 ) , 2002 ( n=101 ) , and in 2004 ( n=218 ) were prospect ively and successively enrolled in our study . The management of neuromuscular block in the operating room and the adequacy of the recovery were at the discretion of the anaesthesiologist . An attempt was made between each study period to promote a change in the management of neuromuscular block . In the post-anaesthesia care unit , train-of-four ( TOF ) stimulations were used to assess the presence of a residual neuromuscular block . RESULTS Between 1995 and 2004 quantitative measurement and reversal of neuromuscular block in the operating room increased from 2 to 60 % and from 6 to 42 % , respectively ( P<0.001 ) . During the same time , the incidence of residual neuromuscular block defined as a TOF ratio less than 0.9 decreased from 62 to 3 % ( P<0.001 ) . Use of objective neuromuscular monitoring and /or anticholinesterase drugs was less likely in patients with an inadequate recovery ( P<0.001 ) . CONCLUSIONS During the last decade the incidence of residual neuromuscular block strongly decreased in our institution . It confirms the positive impact of neuromuscular monitoring and reversal of neuromuscular block in routine anaesthetic practice BACKGROUND The routine use of neuromuscular blocking agents reduces the occurrence of unacceptable surgical conditions . In some surgeries , such as retroperitoneal laparoscopies , deep neuromuscular block ( NMB ) may further improve surgical conditions compared with moderate NMB . In this study , the effect of deep NMB on surgical conditions was assessed . METHODS Twenty-four patients undergoing elective laparoscopic surgery for prostatectomy or nephrectomy were r and omized to receive moderate NMB ( train-of-four 1 - 2 ) using the combination of atracurium/mivacurium , or deep NMB ( post-tetanic count 1 - 2 ) using high-dose rocuronium . After surgery , NMB was antagonized with neostigmine ( moderate NMB ) , or sugammadex ( deep NMB ) . During all surgeries , one surgeon scored the quality of surgical conditions using a five-point surgical rating scale ( SRS ) ranging from 1 ( extremely poor conditions ) to 5 ( optimal conditions ) . Video images were obtained and 12 anaesthetists rated a r and om selection of images . RESULTS Mean ( st and ard deviation ) SRS was 4.0 ( 0.4 ) during moderate and 4.7 ( 0.4 ) during deep NMB ( P<0.001 ) . Moderate block result ed in 18 % of scores at the low end of the scale ( Scores 1 - 3 ) ; deep block result ed in 99 % of scores at the high end of the scale ( Scores 4 and 5 ) . Cardiorespiratory conditions were similar during and after surgery in both groups . Between anaesthetists and surgeon , there was poor agreement between scores of individual images ( average κ statistic 0.05 ) . CONCLUSIONS Application of the five-point SRS showed that deep NMB results in an improved quality of surgical conditions compared with moderate block in retroperitoneal laparoscopies , without compromise to the patients ' peri- and postoperative cardiorespiratory conditions . Trial registration The study was registered at clinical trials.gov under number NCT01361149 Introduction : Sugammadex effectively and rapidly reverses deep to moderate rocuronium-induced neuromuscular block . However , the required dose of sugammadex for smaller degrees of residual block is unknown . Therefore we investigated the efficacy of sugammadex and neostigmine at a train-of-four ( TOF ) ratio of 0.5 . Methods : After ethics committee ( Munich , Germany ) approval and written informed consent were obtained , 99 patients were anesthetized with propofol , remifentanil , and rocuronium . Neuromuscular monitoring was performed by calibrated electromyography . At recovery of the TOF ratio to 0.5 , patients r and omly received sugammadex ( 0.0625 , 0.125 , 0.25 , 0.5 , or 1.0 mg/kg ) , neostigmine ( 5 , 8 , 15 , 25 , or 40 & mgr;g/kg ) , or saline . The time between study drug injection , at TOF ratio of 0.5 , and postoperative TOF ratio of 0.9 was measured . The dose-response relationship was analyzed with a biexponential model using the dose as the independent variable and the logarithm of the recovery time as the dependent variable . Effective doses were interpolated from regression models . Results : Sugammadex , 0.22 mg/kg , is able to reverse a TOF ratio of 0.5 to 0.9 or higher in an average time of 2 min . Within 5 min , 95 % of patients reach this TOF ratio . Neostigmine , 34 & mgr;g/kg , is able to reverse a TOF ratio of 0.5 to 0.9 or higher within 5 min . No recurarization was observed . Conclusions : Sugammadex , 0.22 mg/kg , and neostigmine , 34 & mgr;g/kg , effectively and comparably reverse a rocuronium-induced shallow residual neuromuscular block at a TOF ratio of 0.5 In a r and omised , controlled , double‐blind , multicentre trial in 338 patients , we assessed the incidence of residual paralysis following administration of cisatracurium or rocuronium . The incidence at the end of surgery was significantly lower in patients treated with rocuronium ( 62 of 142 patients , 44 % ) than in those given cisatracurium ( 99 of 175 patients , 57 % ) ( p < 0.05 ) . In contrast , with rocuronium the mean ( SD ) time between skin closure and extubation was 28 ( 28 ) min vs 18 ( 19 ) min for cisatracurium , and the duration 0.9 ( time from administration of last top‐up dose to recovery of the train‐of‐four ratio to 0.9 ) was significantly longer and more variable for rocuronium than for cisatracurium . Thus , after repeated administration , the duration and variability of duration of action are greater with rocuronium compared with cisatracurium . These pharmacodynamic differences do not necessarily translate into a higher incidence of residual paralysis , because clinicians compensate for the longer duration of action and variability of rocuronium by terminating administration of the neuromuscular blocking earlier Background : Acetylcholinesterase inhibitors are widely used for the reversal of neuromuscular blocking agents . However , acetylcholinesterase inhibitors have several side effects and are not effective during profound block . Org 25969 is a modified & ggr;-cyclodextrin that encapsulates the neuromuscular blocking agent , rocuronium bromide ( Esmeron ® /Zemuron ® , NV Organon , Oss , The Netherl and s ) , forming a tightly bound complex with an association constant of approximately 107 m−1 . Chemical encapsulation of rocuronium promotes dissociation of rocuronium from the acetylcholine receptor , thereby reversing the neuromuscular block without the side effects associated with acetylcholinesterase inhibitors . Methods : Twenty-nine healthy male volunteers were enrolled to investigate the safety , pharmacokinetics , and efficacy of Org 25969 . In part 1 , Org 25969 or placebo was administered to 19 subjects during one to three treatment periods each . In part 2 , a further 10 subjects received general anesthesia on two separate occasions , using an intubating dose of 0.6 mg/kg rocuronium . Three minutes after rocuronium administration , Org 25969 or placebo was given in r and om order . Six doses of 0.1–8.0 mg/kg Org 25969 were evaluated . Neuromuscular block was measured using an acceleromyograph , the TOF-Watch-SX ® ( NV Organon , Oss , The Netherl and s ) . Results : All adverse events related to Org 25969 treatment were of limited duration and mild intensity , except for a period of paresthesia , seen in one patient receiving 8 mg/kg Org 25969 , which was of moderate intensity . No adverse events required any treatment , and all subjects recovered from them . When 8 mg/kg Org 25969 was given , the train-of-four ratio returned to 0.9 within 2 min after its administration . No signs of recurarization were observed . Conclusions : Org 25969 was both well tolerated and effective in reversing neuromuscular block induced by rocuronium in 29 human volunteers Deep neuromuscular blockade during certain surgical procedures may improve operating conditions . Sugammadex can be used to reverse deep neuromuscular blockade without waiting for spontaneous recovery . This r and omised study compared recovery times from neuromuscular blockade induced by rocuronium 0.6 mg.kg−1 , using sugammadex 4 mg.kg−1 administered at 1–2 post‐tetanic count ( deep blockade ) or neostigmine 50 μg.kg−1 ( plus atropine 10 μg.kg−1 ) administered at the re‐appearance of the second twitch of a train‐of‐four stimulation ( moderate blockade ) , in patients undergoing laparoscopic surgery . The primary efficacy variable was the time from the start of sugammadex/neostigmine administration to recovery of the train‐of‐four ratio to 0.9 . Patients receiving sugammadex recovered 3.4 times faster than patients receiving neostigmine ( geometric mean ( 95 % CI ) recovery times of 2.4 ( 2.1–2.7 ) and 8.4 ( 7.2–9.8 ) min , respectively , p < 0.0001 ) . Moreover , 94 % ( 62/66 ) of sugammadex‐treated patients recovered within 5 min , vs 20 % ( 13/65 ) of neostigmine‐treated patients , despite the difference in the depth of neuromuscular blockade at the time of administration of both drugs . The ability to provide deep neuromuscular blockade throughout the procedure but still permit reversal at the end of surgery may enable improved surgical access and an enhanced visual field BACKGROUND Electronic neuromuscular monitoring is not widely used to determine either the reversal requirements for neuromuscular block before extubation of the trachea , or to determine if there is any subsequent postoperative residual neuromuscular block ( PORNB ) . OBJECTIVES To investigate the incidence of PORNB using acceleromyography after spontaneous recovery of rocuronium-induced block and to compare this with the administration of sugammadex , neostigmine or a placebo . DESIGN Partially r and omised , partially r and omised , placebo-controlled , double-blind , four-group parallel-arm study . SETTING Single-centre study performed between October 2013 and December 2015 in a university hospital . PATIENTS Of the 134 eligible patients , 128 gave their consent and 125 of these completed the study . INTERVENTIONS Patients received general anaesthesia with propofol , sevoflurane , fentanyl and rocuronium . Neuromuscular transmission was measured by acceleromyography ( TOF-Watch-SX ; Organon Teknika B.V. , Boxtel , the Netherl and s ) but the anaesthetist was blind to the results . If the anaesthetist deemed pharmacological reversal to be necessary before extubation of the trachea then patients were assigned r and omly to receive either sugammadex ( 2.0 mg kg−1 ) , neostigmine ( 0.05 mg kg−1 ) or a placebo . In the postanaesthesia care unit , an independent anaesthetist , unaware of the treatment given , assessed the neuromuscular function using acceleromyography . MAIN OUTCOME MEASURES The incidence of a normalised train-of-four ratio less than 0.9 on arrival in the recovery room . RESULTS In total , 125 patients were recruited . Neuromuscular block was allowed to recover spontaneously in 50 patients , whereas the remainder received either sugammadex ( 27 ) , neostigmine ( 26 ) or placebo ( 22 ) . The number of cases with PORNB were one ( 3.7 % ) , four ( 15 % ) , 13 ( 26 % ) and 10 ( 45 % ) after sugammadex , neostigmine , spontaneous recovery and placebo , respectively . Sugammadex and neostigmine were more effective than placebo [ odds ratio ( OR ) : 0.05 , 95 % confidence interval ( CI ) : 0.005 to 0.403 , P = 0.005 ; OR : 0.22 , 95 % CI : 0.056 to 0.85 , P = 0.028 , respectively ] . Sugammadex performed better than spontaneous recovery ( OR : 0.11 , 95 % CI : 0.014 to 0.89 , P = 0.039 ) unlike neostigmine ( OR : 0.52 , 95 % CI : 0.15 to 1.79 , P = 0.297 ) . Yet , antagonism ( pooled data ) was more effective than spontaneous recovery ( OR : 0.3 , 95 % CI : 0.1 to 0.9 , P = 0.03 ) . CONCLUSION Although pharmacological reversal based on clinical signs was superior to spontaneous recovery it did not prevent PORNB , irrespective of the reversal agent . TRIAL REGISTRATION The study is registered under EUDRACT number 2013 - 001965 - 17 BACKGROUND : Adequate recovery from neuromuscular block ( NMB ) is imperative for the patient to have full control of pharyngeal and respiratory muscles . The train-of-4 ( TOF ) ratio should return to at least 0.90 to exclude potentially clinical ly significant postoperative residual block . Fade can not be detected reliably with a peripheral nerve stimulator ( PNS ) at a TOF ratio > 0.4 . The time gap between loss of visual fade by using a PNS until objective TOF ratio has returned to > 0.90 can be considered “ the potentially unsafe period of recovery . ” According to our hypothesis the duration of this period would be significantly shorter with sugammadex than with neostigmine . METHODS : Fifty patients received volatile anesthetics , opioids , and a rocuronium-induced NMB . TOF-Watch ® without a preload was used , but the anesthesiologist relied on visual evaluation of the TOF responses only . At end of operation , patients were r and omized to receive either neostigmine 50 & mgr;g/kg or sugammadex 2 mg/kg , when 2 twitch responses were detected after the last dose of rocuronium . Timing of tracheal extubation was based on PNS and clinical data . Duration of the potentially unsafe period of recovery after reversal by either neostigmine or sugammadex was analyzed . Mann – Whitney U test and Pearson & khgr;2 test were used for statistical analysis . RESULTS : The times [ mean ± SD ( range ) ] from loss of visual fade to TOF ratio > 0.90 were 10.3 ± 5.5 ( 1.3 to 26.0 ) minutes and 0.3 ± 0.3 ( 0.0 to 1.0 ) minutes in the neostigmine and sugammadex groups , respectively ( P < 0.001 ) . The times from reversal by neostigmine or sugammadex to TOF ratio > 0.90 were 13.3 ± 5.7 ( 3.5 to 28.9 ) and 1.7 ± 0.7 ( 0.7 to 3.5 ) minutes , respectively ( P < 0.001 ) . The values of TOF ratios at the time of loss of visual fade were 0.34 ± 0.14 ( 0.00 to 0.56 ) in patients given neostigmine and 0.86 ± 0.11 ( 0.64 to 1.04 ) in patients given sugammadex ( P < 0.001 ) . CONCLUSIONS : There is a significant time gap between visual loss of fade and return of TOF ratio > 0.90 after reversal of a rocuronium block by neostigmine . Sugammadex in comparison with neostigmine allows a safer reversal of a moderate NMB when relying on visual evaluation of the TOF response Background : Morbid obese ( MO ) population is increasing every year worldwide , and laparoscopic bariatric surgery ( LBS ) has a central role in their treatment . The postoperative period of MO is not free from complications . The introduction of sugammadex has brought huge developments in patient ’s safety and nowadays LBS is performed with better care and quality . However , the effect of this agent in postoperative pain is still unknown . Material s and Methods : A controlled trial enrolling 88 MO su bmi tted to LBS under general anesthesia using muscle relaxation , r and omly assigned into 2 groups : one received sugammadex ( SUG group ) at the end of surgery and the other neostigmine ( NEO group ) . In the postanesthetic care unit ( PACU ) , we evaluated pain using the visual analogue scale in 4 different moments : arrival in the PACU , 30 minutes after arrival , 60 minutes after arrival , and immediately before leaving the PACU . We also recorded the presence of postoperative nausea and vomits ( PONV ) and the duration of the PACU stay before discharge to the ward . Results : Forty-four patients received sugammadex and 44 received neostigmine . We found lower visual analogue scale pain scores in the SUG group at 30 and 60 minutes after arriving to the PACU ( P<0.05 ) . We also had less PONV in the SUG group and these patients were also discharged earlier . Conclusions : Sugammadex is associated with less pain felt in the PACU . This “ opioid-sparing ” effect , combined with less PONV and a faster discharge from the PACU , makes sugammadex an indispensable drug in this type of patients and allows fast-track surgery in the MO Purpose : To examine the influence of continuing administration of sevoflurane or isoflurane during reversal of rocuronium induced neuromuscular block with neostigmine . Methods : one hundred and twenty patients , divided into three equal groups , were r and omly allocated to maintenance of anesthesia with sevoflurane , isoflurane or propofol . Neuromuscular block was induced with rocuronium and monitored using train-of-four ( TOF ) stimulation of the ulnar nerve and recording the force of contraction of the adductor pollicis muscle . Neostigmine was administered when the first response in TOF had recovered to 25 % . At this time the volatile agent administration was stopped or propofol dosage reduced in half the patients in each group ( n=20 in each group ) . The times to attain TOF ratio of 0.8 , and the number of patients attaining this end point within 15 min were recorded . Results : The times ( mean±SD ) to recovery of the TOF ratio to 0.8 were 12.0±5.5 and 6.8±2.3 min in the sevoflurane continued and sevoflurane stopped groups , 9.0±8.3 and 5.5±3.0 min in the isoflurane continued and isoflurane stopped groups , and 5.2 ±2.8 and 4.7±1.5 min in the propofol continued and propofol stopped groups ( P<0.5–0.1 ) . Only 9 and 15 patients in the sevoflurane and isoflurane continued groups respectively had attained a TOF ratio of 0.8 within 15 min ( P<0.001 for sevoflurane ) . Conclusions : The continued administration of sevoflurane , and to a smaller extent isoflurane , results in delay in attaining adequate antagonism of rocuronium induced neuromuscular block . RésuméObjectife : Examiner l’influence de l’administration continue de sévoflurane ou d’isoflurane pendant le renversement d’un bloc neuromusculaire induit avec du rocuronium et de la néostigmine . Méthode : Cent vingt patients , répartis en trois groupes égaux , ont reçu au hasard du sévoflurane , de l’isoflurane ou du propofol pour le maintien de l’anesthésie . Le bloc neuromusculaire a été induit avec du rocuronium et placé sous monitorage d’une stimulation en train-dequatre ( TDQ ) du nerf cubital et d’un enregistrement de la force de contraction du muscle adducteur du pouce . La néostigmine a été administrée au moment de la première réponse en TDQ d’une récupération à 25 % . À ce moment . l’administration de l’anesthésique volatil a été stoppée , ou le propofol réduit , chez la moitié des patients de chaque groupe ( n=20 dans chaque groupe ) . Le temps nécessaire pour atteindre un ratio de 0,8 du TDQ et le nombre de patients qui atteignent cette mesure cible en moins de 15 min ont été enregistrés . Résultats : Le temps ( moyenne±écart type ) de récupération du ratio de 0,8 du TDQ a été de 12,0±5,5 et de 6,8±2,3 min avec le sévoflurane continu et stoppé ; 9.0±8,3 et 5,5±3,0 min avec l’isoflurane continu et stoppé ; 5,2±2,8 et 4,7±1,5 min avec le propofol continue et stoppé ( P<0,5−01 ) . Seulement 9 et 15 patients ayant reçu du sévoflurane et de l’isoflurane en administration continue ont atteint le ratio de 0,8 du TDQ en moins de 15 min ( P<0,001 pour le sévoflurance ) . Conclusion : L’administration continue de sévoflurane et , dans une moindre mesure , d’isoflurane , a retardé le renversement d’un bloc neuromusculaire induit avec du rocuronium BACKGROUND : Rocuronium for cesarean delivery under general anesthesia is an alternative to succinylcholine for rapid-sequence induction of anesthesia because of the availability of sugammadex for reversal of neuromuscular blockade . However , there are no large well-controlled studies in women undergoing general anesthesia for cesarean delivery . The aim of this noninferiority trial was to determine whether rocuronium and sugammadex confer benefit in time to tracheal intubation ( primary outcome ) and other neuromuscular blockade outcomes compared with succinylcholine , rocuronium , and neostigmine in women undergoing general anesthesia for cesarean delivery . METHODS : We aim ed to enroll all women undergoing general anesthesia for cesarean delivery in the 2 participating university hospitals ( Brno , Olomouc , Czech Republic ) in this single-blinded , r and omized , controlled study . Women were r and omly assigned to the ROC group ( muscle relaxation induced with rocuronium 1 mg/kg and reversed with sugammadex 2–4 mg/kg ) or the SUX group ( succinylcholine 1 mg/kg for induction , rocuronium 0.3 mg/kg for maintenance , and neostigmine 0.03 mg/kg for reversal of the neuromuscular blockade ) . The interval from the end of propofol administration to tracheal intubation was the primary end point with a noninferiority margin of 20 seconds . We recorded intubating conditions ( modified Viby-Mogensen score ) , neonatal outcome ( Apgar score < 7 ; umbilical artery pH ) , anesthesia complications , and subjective patient complaints 24 hours after surgery . RESULTS : We enrolled 240 parturients . The mean time to tracheal intubation was 2.9 seconds longer in the ROC group ( 95 % confidence interval , −5.3 to 11.2 seconds ) , noninferior compared with the SUX group . Absence of laryngoscopy resistance was greater in the ROC than in the SUX groups ( ROC , 87.5 % ; SUX , 74.2 % ; P = 0.019 ) , but there were no differences in vocal cord position ( P = 0.45 ) or intubation response ( P = 0.31 ) between groups . No statistically significant differences in incidence of anesthesia complications or in neonatal outcome were found ( 10-minute Apgar score < 7 , P = 0.07 ; umbilical artery pH , P = 0.43 ) . The incidence of postpartum myalgia was greater in the SUX group ( ROC 0 % ; SUX 6.7 % ; P = 0.007 ) . The incidence of subjective complaints was lower in the ROC group ( ROC , 21.4 % ; SUX , 37.5 % ; P = 0.007 ) . CONCLUSIONS : We conclude that rocuronium for rapid-sequence induction is noninferior for time to tracheal intubation and is accompanied by more frequent absence of laryngoscopy resistance and lower incidence of myalgia in comparison with succinylcholine for cesarean delivery under general anesthesia The present study employed train-of-four ( TOF ) stimulation at à current of 20 mA to assess the incidence and degree of residual neuromuscular blockade in 64 r and omly selected Post Anesthesia Care Unit ( PACU ) patients . Group C ( Control , n = 10 ) had received anaesthesia without nondepolarizing muscle relaxant ; Group V ( n = 25 ) had received vecuronium ; and Group P ( n = 29 ) had received pancuronium . At the end of surgery , each patient had been considéréd by his anaesthetist to have adequate neuromuscular function on the basis of clinical signs and tactile or visual evaluation of responses to TOF stimulation . However , upon testing in the PACU 15 min later , 45 % ( 13 of 29 ) of Group P patients and 8 % ( 2 of 25 ) of Group V patients had à TOF ratio < 0.70 . This study indicates that residual curarization may be commonly encountered following long-acting relaxants despite qualitative intraoperative TOF monitoring . The present incidence , detected at à current of 20 mA , is consistent with previous reports which employed supramaximal TOF stimulation . We conclude that despite intraoperative monitoring , residual curarization following long-acting nondepolarizing agents is common and that it may be detected with TOF at à low stimulating current ( 20 mA).RésuméLa présente étude à utilisé l’ondée-de-quatre ( TOF ) avec des courants de 20 mA afin d’évaluer l’incidence et le degré de blocage neuromusculaire résiduel chez 64 patients choisis au hasard dans l’unité des soins postanesthésiques ( PACU ) . Le groupe C ( Contrôle , n = 10 ) à reçu de l’anesthésie sans relaxant musculaire nondépolarisant ; le Groupe V ( n = 25 ) à reçu du vécuronium ; et le Groupe P ( n = 29 ) à reçu du pancuronium . A la fin de la chirurgie , chaque patient fut considéré par son anesthésiste comme ayant une fonction neuromusculaire adéquate sur la base des signes cliniques tacliles et les évaluations visuelles des réponses de la stimulation avec une ondée-de-quatre . Cependant , lors de la stimulation au PACU 15 minutes plus tard , 45 % ( 13 de 29 ) du Groupe de patients P et 8 % ( 2 de 25 ) avaient un ratio de TOF < 0,70 . Cette étude indique que la curarisation résiduelle peut survenir fréquémment après les relaxants à tongue action malgré une surveillance qualitative intraopératoire du TOF . L ’ incidence trouvée , détectée avec un courant de 20 mA , est en accord avéc des études antérieures qui émploient la stimulation supramaximale de TOF . On conclut que malgré une surveillance intraopératoire , la curarisation résiduelle après des agents non-dépolarisants à longue action est fréquente et qu’elle pourrait être détectée par une stimulation avec un TOF avec un courant de 20 Sugammadex is design ed to antagonize neuromuscular blockade ( NMB ) induced by rocuronium or vecuronium . In clinical practice , we have noticed a rise in the numerical values of bispectral index ( BIS ) and Entropy , two electroencephalogram ( EEG ) – based depth of anesthesia monitors , during the reversal of the NMB with sugammadex . The aim of this prospect i ve , r and omized , double‐blind study was to test this impression and to compare the effects of sugammadex and neostigmine on the BIS and Entropy values during the reversal of the NMB Background and objective Sugammadex , a modified γ-cyclodextrin , is a selective relaxant-binding agent design ed to reverse the effects of the steroidal neuromuscular blocking agents rocuronium or vecuronium . This study compared the efficacy of sugammadex and neostigmine for reversal of neuromuscular blockade induced by rocuronium for facilitating elective surgery . Methods This r and omised , multicentre , parallel-group trial included 98 adult patients . Patients received intravenous propofol for induction followed by sevoflurane maintenance anaesthesia . Neuromuscular blockade was monitored using acceleromyography and a train-of-four ( TOF ) mode of stimulation . Patients were r and omly allocated to receive sugammadex 2.0 mg kg−1 or neostigmine 50 μg kg−1 ( with glycopyrrolate 10 μg kg−1 ) at reappearance of the second response of the TOF ( mean 16 % twitch height of first response ) after the last dose of rocuronium . Safety was evaluated by assessing adverse events , laboratory variables and vital signs . Results Time to recovery of the TOF ratio of 0.9 after sugammadex compared with neostigmine was significantly shorter ( P < 0.0001 ) , being 1.5 versus 18.6 min ( geometric means ) . Predictability of response was greater with sugammadex than neostigmine : with 98 % of sugammadex patients versus 11 % of neostigmine patients recovering to a TOF ratio of 0.9 within 5 min . There were no clinical events related to residual neuromuscular blockade or reoccurrence of blockade . Serious adverse events were observed in two sugammadex-treated patients and in three neostigmine-treated patients , respectively , but none were considered related to study drugs . Conclusion Sugammadex achieved significantly faster recovery of neuromuscular function after rocuronium to a TOF ratio of 0.9 compared with neostigmine ( Clinical trials.gov identifier : NCT00451217 ) STUDY OBJECTIVE To compare sugammadex with conventional reversal of neuromuscular block in terms of postoperative gastrointestinal motility . DESIGN Double blinded , r and omized , controlled clinical trial . SETTING Operating room , postoperative recovery area . PATIENTS Seventy-two patients with ASA physical status I or II , scheduled for total thyroid surgery were studied . INTERVENTIONS When 4 twitches were observed on train-of-four stimulation , neuromuscular block was reversed conversatively in the control group , and with sugammadex in the study group . MEASUREMENTS Time to first flatus and feces , incidence of postoperative nausea , vomiting , diarrhea and constipation were collected . MAIN RESULTS Median time of first flatus was 24 hours ( 18 - 32 [ 10 - 36 ] ) in the neostigmine group , and 24 ( 18 - 28 [ 12 - 48 ] ) in the sugammadex group ( P > .05 ) . Median ( IQR ) time of first feces was 24 hours ( 18 - 36 [ 10 - 48 ] ) in neostigmine group , 32 hours ( 28 - 36 [ 12 - 72 ] ) in sugammadex group ( P > .05 ) . There were no occurrences of nausea , vomiting , diarrhea , or constipation . CONCLUSIONS Sugammadex may be safely used in cases where postoperative ileus is expected OBJECTIVE To investigate the potential effect of sugammadex on anti-Xa anticoagulantactivity of enoxaparin and the activated partial thromboplastin time ( APTT ) of unfractionated heparin ( UFH ) . METHODS This two-part , r and omized , double-blind , placebocontrolled , four-period cross-over study was performed in healthy males ( 18 - 45 years ) . In each period , subjects received 40 mg enoxaparin ( in part 1 ) , 5,000 units UFH ( in part 2 ) , or placebo followed by 4 or 16 mg/kg sugammadex , or placebo . Treatments were separated by ≥ 4 days . Primary endpoints were anti-Xa activity and APTT both time-averaged from 3 to 30 minutes post-dose . Geometric mean ratios ( GMRs ) and their two-sided 90 % confidence limits were calculated for anticoagulant plus sugammadex ( 4 or 16 mg/kg ) vs. anticoagulant plus placebo . The pre-specified threshold for a potential effect of clinical relevance was a 90 % upper confidence limit ( UCL ) > 1.50 . RESULTS In part 1 ( n = 13 ) , the 90 % UCLs were 1.07 and 1.08 for GMRs of anti-Xa activity after dosing with 4 and 16 mg/kg sugammadex , respectively . In part 2 ( n = 43 ) , the 90 % UCLs for GMRs of APTT were 1.06 and 1.15 . Neither sugammadex dose produced a treatment effect that met the pre-specified criterion for potential clinical relevance . Treatments were generally well tolerated . CONCLUSIONS In healthy subjects , treatment with 4 mg/kg and 16 mg/kg sugammadex did not change either anti-Xa activity or APTT to a clinical ly meaningful extent following pretreatments with enoxaparin or UFH STUDY OBJECTIVE To determine whether the new selective binding agent sugammadex causes less postoperative nausea and vomiting ( PONV ) than the cholinesterase inhibitor neostigmine . DESIGN Prospect i ve , r and omized , double-blinded study . SETTING University-affiliated hospital . PATIENTS One hundred American Society of Anesthesiologists physical status 1 and 2 patients scheduled for extremity surgery . INTERVENTIONS Patients were r and omly assigned to neostigmine ( 70 μg/kg ) and atropine ( 0.4 mg per mg neostigmine ) or sugammadex 2 mg/kg for neuromuscular antagonism at the end of anesthesia , when 4 twitches in response to train-of-four stimulation were visible with fade . MEASUREMENTS We recorded PONV , recovery parameters , antiemetic consumption , and side effects . MAIN RESULTS Nausea and vomiting scores were lower in the sugammadex patients upon arrival in the postanesthesia care unit ( med : 0 [ min-max , 0 - 3 ] vs med : 0 [ min-max , 0 - 3 ] ; P < .05 ) , but thereafter low and comparable . Postoperative antiemetic and analgesic consumption were similar in each group . Extubation ( median [ interquartile range ] , 3 [ 1 - 3.25 ] vs 4 [ 1 - 3.25 ] ; P < .001 ) first eye opening ( 4 [ 3 - 7.25 ] vs 7 [ 5 - 11 ] ; P < .001 ) , and head lift ( 4 [ 2 - 7.25 ] vs 8 [ 11 - 25 ] ; P < .001 ) in minutes were shorter in patients given sugammadex . Postoperative heart rates were significantly lower in all measured times patients given neostigmine . CONCLUSIONS Nondepolarizing neuromuscular blocking antagonism with sugammadex speeds recovery of neuromuscular strength but only slightly and transiently reduces PONV compared with neostigmine and atropine Background : Reversal of rocuronium-induced neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex , a modified & ggr;-cyclodextrin derivative . This study investigated the efficacy and safety of sugammadex in reversing rocuronium-induced profound neuromuscular blockade at 5 min in American Society of Anesthesiologists physical status I and II patients . Methods : Forty-five American Society of Anesthesiologists physical status I and II patients ( aged 18–64 yr ) scheduled to undergo surgical procedures ( anticipated anesthesia duration ≥ 90 min ) were r and omly assigned to a phase II , multicenter , assessor-blinded , placebo-controlled , parallel , dose-finding study . Anesthesia was induced and maintained with propofol and an opioid . Profound neuromuscular blockade was induced with 1.2 mg/kg rocuronium bromide . Sugammadex ( 2.0 , 4.0 , 8.0 , 12.0 , or 16.0 mg/kg ) or placebo ( 0.9 % saline ) was then administered 5 min after the administration of rocuronium . Neuromuscular function was monitored by acceleromyography , using train-of-four nerve stimulation . Recovery time was the time from the start of administration of sugammadex or placebo , to recovery of the train-of-four ratio to 0.9 . Safety assessment s were performed on the day of the operation and during the postoperative and follow-up period . Results : A total of 43 patients received either sugammadex or placebo . Increasing doses of sugammadex reduced the mean recovery time from 122 min ( spontaneous recovery ) to less than 2 min in a dose-dependent manner . Signs of recurrence of blockade were not observed . No serious adverse events related to sugammadex were reported . Two adverse events possibly related to sugammadex were reported in two patients ( diarrhea and light anesthesia ) ; however , both patients recovered without sequelae . Conclusions : Sugammadex rapidly and effectively reversed profound rocuronium-induced neuromuscular blockade in humans and was well tolerated Background : Doses of sugammadex required to reverse deep , moderate , and shallow rocuronium-induced neuromuscular blockade have been established . However , no adequate doses for the reversal of reappearance of four twitches of train-of-four ( TOF ) stimulation ( threshold TOF-count-four ) have been established . Methods : This single-center , r and omized , controlled , double-blind , four-groups parallel-arm study included 80 patients undergoing general anesthesia with propofol , sevoflurane , fentanyl , and rocuronium . Neuromuscular monitoring was performed with calibrated acceleromyography . Once rocuronium-induced neuromuscular blockade recovered spontaneously to threshold TOF-count-four , patients r and omly received 0.5 , 1.0 , 2.0 mg/kg of sugammadex or 0.05 mg/kg of neostigmine . The time between study drug injection and reversal of TOF ratios to 1.0 was measured . Rapid reversal ( ⩽2.0 min average , upper limit of 5.0 min ) was the primary endpoint and slower reversal ( ⩽5.0 min average , upper limit of 10 min ) was the secondary endpoint of the study . Results : Sugammadex , in doses of 1.0 and 2.0 mg/kg , reversed threshold TOF-count-four to TOF ratios of 1.0 in 2.1 ± 0.8 min ( mean ± SD ) and 1.8 ± 0.9 min , respectively . Sugammadex , 0.5 mg/kg , induced a similar degree of reversal in 4.1 ± 1.9 min ( P < 0.001 vs. 1.0 and 2.0 mg/kg ) . Neostigmine , 0.05 mg/kg , reversed TOF ratios to 1.0 in 8.5 ± 3.5 min ( P < 0.001 vs. sugammadex groups ) . Conclusion : Sugammadex , 1.0 mg/kg , rapidly and effectively reverses rocuronium-induced block that has recovered spontaneously to a threshold TOF-count-four . A dose of 0.5 mg/kg was equally effective , but satisfactory antagonism took as long as 8 min to take place Background : Residual neuromuscular block caused by vecuronium alters pharyngeal function and impairs airway protection . The primary objectives of this investigation were to radiographically evaluate the swallowing act and to record the incidence of and the mechanism behind pharyngeal dysfunction during partial neuromuscular block . The secondary objective was to evaluate the effect of atracurium on pharyngeal function . Methods : Twenty healthy volunteers were studied while awake during liquid-contrast bolus swallowing . The incidence of pharyngeal dysfunction was studied by fluoroscopy . The initiation of the swallowing process , the pharyngeal coordination , and the bolus transit time were evaluated . Simultaneous manometry was used to document pressure changes at the tongue base , the pharyngeal constrictor muscles , and the upper esophageal sphincter . After control recordings , an intravenous infusion of atracurium was administered to obtain train-of-four ratios ( T4/T1 ) of 0.60 , 0.70 , and 0.80 , followed by recovery to a train-of-four ratio of more than 0.90 . Results : The incidence of pharyngeal dysfunction was 6 % during the control recordings and increased ( P < 0.05 ) to 28 % , 17 % , and 20 % at train-of-four ratios 0.60 , 0.70 , and 0.80 , respectively . After recovery to a train-of-four ratio of more than 0.90 , the incidence was 13 % . Pharyngeal dysfunction occurred in 74 of 444 swallows , the majority ( 80 % ) result ing in laryngeal penetration . The initiation of the swallowing reflex was impaired during partial paralysis ( P = 0.0081 ) . The pharyngeal coordination was impaired at train-of-four ratios of 0.60 and 0.70 ( P < 0.01 ) . A marked reduction in the upper esophageal sphincter resting tone was found , as well as a reduced contraction force in the pharyngeal constrictor muscles . The bolus transit time did not change significantly . Conclusion : Partial neuromuscular paralysis caused by atracurium is associated with a four- to fivefold increase in the incidence of misdirected swallowing . The mechanism behind the pharyngeal dysfunction is a delayed initiation of the swallowing reflex , impaired pharyngeal muscle function , and impaired coordination . The majority of misdirected swallows result ed in penetration of bolus to the larynx Background : Sugammadex reverses the neuromuscular blocking effects of rocuronium by chemical encapsulation . The efficacy , safety , and pharmacokinetics of sugammadex for reversal of profound rocuronium-induced neuromuscular blockade were evaluated . Methods : Ninety-eight male adult patients were r and omly assigned to receive sugammadex ( 1 , 2 , 4 , 6 , or 8 mg/kg ) or placebo at 3 , 5 , or 15 min after 0.6 mg/kg rocuronium . Patients were anesthetized with propofol and fentanyl . The primary endpoint of the study was the time to achieve a recovery of train-of-four ratio to 0.9 . Neuromuscular blockade was measured using acceleromyography . Concentrations of rocuronium and sugammadex were determined in venous blood and urine sample s. A population pharmacokinetic model using NONMEM ( GloboMax LLC , Hanover , MD ) was applied . Results : The mean time to recovery of the train-of-four ratio to 0.9 after dosing at 3 , 5 , and 15 min decreased from 52.1 , 51.7 , and 35.6 min , respectively , after administration of placebo to 1.8 , 1.5 , and 1.4 min , respectively , after 8 mg/kg sugammadex . Sugammadex was safe and well tolerated . However , 20.4 % of patients showed signs of inadequate anesthesia after its administration . The median cumulative excretion of rocuronium in the urine over 24 h was 26 % in the placebo group and increased to 58–74 % after 4–8 mg/kg sugammadex . The mean plasma clearances of sugammadex and rocuronium were 0.084 and 0.26 l/min , respectively . Conclusions : In male subjects , sugammadex safely reversed profound neuromuscular blockade induced by 0.6 mg/kg rocuronium in a dose-dependent manner . Sugammadex enhanced the renal excretion of rocuronium , and its clearance is approximately one third that of rocuronium Background : Previous studies show a prolongation of activated partial thromboplastin time and prothrombin time in healthy volunteers after treatment with sugammadex . The authors investigated the effect of sugammadex on postsurgical bleeding and coagulation variables . Methods : This r and omized , double-blind trial enrolled patients receiving thromboprophylaxis and undergoing hip or knee joint replacement or hip fracture surgery . Patients received sugammadex 4 mg/kg or usual care ( neostigmine or spontaneous recovery ) for reversal of rocuronium- or vecuronium-induced neuromuscular blockade . The Cochran – Mantel – Haenszel method , stratified by thromboprophylaxis and renal status , was used to estimate relative risk and 95 % confidence interval ( CI ) of bleeding events with sugammadex versus usual care . Safety was further evaluated by prespecified endpoints and adverse event reporting . Results : Of 1,198 patients r and omized , 1,184 were treated ( sugammadex n = 596 , usual care n = 588 ) . Bleeding events within 24 h ( classified by an independent , blinded Adjudication Committee ) were reported in 17 ( 2.9 % ) sugammadex and 24 ( 4.1 % ) usual care patients ( relative risk [ 95 % CI ] , 0.70 [ 0.38 to 1.29 ] ) . Compared with usual care , increases of 5.5 % in activated partial thromboplastin time ( P < 0.001 ) and 3.0 % in prothrombin time ( P < 0.001 ) from baseline with sugammadex occurred 10 min after administration and resolved within 60 min . There were no significant differences between sugammadex and usual care for other blood loss measures ( transfusion , 24-h drain volume , drop in hemoglobin , and anemia ) , or risk of venous thromboembolism , and no cases of anaphylaxis . Conclusion : Sugammadex produced limited , transient ( < 1 h ) increases in activated partial thromboplastin time and prothrombin time but was not associated with increased risk of bleeding versus usual care Background : Postoperative recurarization remains a risk following the use of the conventional neuromuscular blocking agents . In addition , none of the commonly used reversal agents , such as neostigmine or edrophonium are capable of reliably reversing profound blockade . The present comparative and r and omized study investigated the use of sugammadex for reversing profound neuromuscular blockade ( NMB ) in pediatric neurosurgical patients undergone posterior fossa tumor excision . Patients and Methods : Forty pediatric patients undergoing elective craniotomy for posterior fossa tumor excision were r and omly divided into either of neostigmine or sugammadex group in which muscle relaxant was reversed at the end of anesthesia either with neostigmine 0.04 mg/kg added to atropine 0.02 mg/kg or sugammadex 4 mg/kg alone , respectively . The primary endpoint was the time from the administration of sugammadex or neostigmine to recovery of the train of four ( TOF ) ratio to 90 % after rocuronium-induced neuromuscular block . Unpaired t-test was used to compare continuous variables between groups . Meanwhile , repeated ANOVA was used to detect intragroup differences . Results : Patients in sugammadex group attained a TOF ratio 90 % in statistically shorter time ( 1.4 ± 1.2 min ) than those in neostigmine group ( 25.16 ± 6.49 min ) for reversal of the rocuronium . Mean arterial pressure and heart rate were significantly higher in neostigmine group at 2 , 5 and 10 min after administration of the reversal agents and returned nonsignificantly different after that . With no recurarization in any patient throughout the study period . Conclusion : Sugammadex rapidly and effectively reverses rocuronium-induced NMB in pediatric patients undergoing neurosurgery when administered at reappearance of T2 of TOF at dose 4 mg/kg STUDY OBJECTIVE The aim of this study is to compare the hemodynamic effects of neostigmine-atropine combination and sugammadex in patients with cardiac problems undergoing noncardiac surgery . DESIGN Prospect i ve r and omized study . SETTING In the operating room . PATIENTS Ninety patients with a class 2 or 3 cardiovascular disease according to the New York Heart Association classification and aged between 18 and 75 years undergoing noncardiac surgery were r and omized . INTERVENTIONS Group N ( n = 45 ) received 0.03 mg/kg IV neostigmine when T2 appeared as measured with a nerve muscle stimulator . When heart rate was 5 beats/min ( ±10 beats/min ) lower than the heart rate before administration of the medication , 0.5 mg IV atropine sulfate was given . Group S ( n = 45 ) received 3 mg/kg IV sugammadex when T2 appeared as measured with a nerve muscle stimulator . MEASUREMENTS Heart rate , mean systolic and diastolic blood pressures , and electrocardiographic alterations including the QTc ( QT Fredericia and QT Bazett ) were recorded . MAIN RESULTS There were no significant differences between and within the groups in terms of QTc values . Sugammadex group had a significant decrease on heart rate 1 minute after the medication when compared to the measurement before the medication ( P < .05 ) . Heart rate and systolic blood pressure increased in neostigmine group 3 minutes after the medication and during postoperative measurements ( P < .05 ) . Sugammadex group had lower systolic , diastolic , and mean blood pressures and heart rate when compared to neostigmine group ( P < .05 ) . CONCLUSIONS We suggest that sugammadex might be preferred as it provides more hemodynamic stability compared to neostigmine-atropine combination to reverse rocuronium-induced neuromuscular blockage in cardiac patients undergoing noncardiac surgery Background The rapid recovery from mivacurium-induced neuromuscular block has encouraged omission of its reversal . The purpose of this study was to determine , in children and in adults , whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit . Methods In 50 children , aged 2 - 12 yr , and 50 adults , aged 20 - 60 yr , anesthesia was induced and maintained with propofol and fentanyl , and neuromuscular block was achieved by an infusion of mivacurium , to maintain one or two visible responses to train-of-four ( TOF ) stimulation of the ulnar nerve . At the end of surgery , mivacurium infusion was stopped , and 10 min later , reversal was attempted with saline or 0.5 mg * symbol * kg sup -1 edrophonium by r and om allocation . On arrival in the postanesthesia care unit , a blinded observer assessed patients clinical ly and by stimulation of the ulnar nerve with a Date x electromyogram in the uncalibrated TOF mode . Results Children arrived in the postanesthesia care unit 8.2 + /-3.4 min after reversal of neuromuscular block and showed no sign of weakness , either clinical ly or by TOF stimulation . Although TOF ratio was greater in children who had received edrophonium ( 1.00 + /-0.05 vs. 0.93+/-0.01 , P < 0.01 ) , TOF was > 0.7 in all children . Adults arrived in the postanesthesia care unit 12.9+/- 5.3 min after reversal of neuromuscular block ( P < 0.01 vs. children ) . Six in the saline group demonstrated weakness ( two required immediate reversal of neuromuscular block , and TOF was < 0.7 in four others ) , compared with TOF < 0.7 in only one of the edrophonium group ( P < 0.05 ) . Conclusions This study demonstrated that , in adults , failure to reverse mivacurium neuromuscular block was associated with an increased incidence of residual block . Such weakness was not observed in children receiving similar anesthetic and neuromuscular blocking regimens BACKGROUND The use of neuromuscular blocking agents has been associated with severe postoperative respiratory morbidity . Complications can be attributed to inadequate reversal , and reversal agents may themselves have adverse effects . OBJECTIVE To compare the electromyographic activity of the diaphragm ( EMGdi ) during recovery from neuromuscular blockade using neostigmine and sugammadex . The hypothesis was that there would be better neuromuscular coupling of the diaphragm when sugammadex was used . DESIGN A r and omised , controlled , parallel-group , single-centre , double-blinded study . SETTING District general hospital in Belgium . PARTICIPANTS Twelve healthy male volunteers . INTERVENTIONS Individuals were anaesthetised with propofol and remifentanil . After rocuronium 0.6 mg kg−1 , a transoesophageal electromyography ( EMG ) recorder was inserted . For reversal of neuromuscular blockade , volunteers received sugammadex 2 mg kg−1 ( n = 6 ) or neostigmine 70 & mgr;g kg−1 ( n = 6 ) . MAIN OUTCOME MEASURES EMGdi , airway pressure and flow were continuously measured during weaning from the ventilator until tracheal extubation . Arterial blood gas sample s were obtained for PaO2 and PaCO2 analysis at the first spontaneous breathing attempt and after tracheal extubation . RESULTS During weaning , 560 breaths were retained for analysis . The median ( 95 % CI ) peak EMGdi was 1.1 ( 0.9 to 1.5 ) & mgr;V in the neostigmine group and 1.6 ( 1.3 to 1.9 ) & mgr;V in the sugammadex group ( P < 0.001 ) . Individuals in the neostigmine group had 125 of 228 ( 55 % ) breaths with associated EMGdi at least 1 & mgr;V vs. 220 of 332 ( 66 % ) breaths in the sugammadex group ( P = 0.008 ) . The median ( 95 % CI ) tidal volume was 287 ( 256 to 335 ) ml after neostigmine and 359 ( 313 to 398 ) ml after sugammadex ( P = 0.013 ) . The median ( 95 % CI ) PaO2 immediately after extubation was 30.5 ( 22.8 to 37.1 ) kPa after sugammadex vs. 20.7 ( 12.9 to 27.5 ) kPa after neostigmine ( P = 0.03 ) . CONCLUSION EMGdi , tidal volume and PaO2 following tracheal extubation were increased after sugammadex compared with neostigmine , reflecting diaphragm-driven inspiration after sugammadex administration . Sugammadex may free more diaphragmatic acetylcholine receptors than neostigmine , which has an indirect effect . TRIAL REGISTRATION EudraCT ref : 2013 - 002078 - 30 Background : After anaesthesia involving pancuronium a high incidence of both residual neuromuscular block and postoperative pulmonary complications ( POPC ) has been reported . The aim of this study was to compare the incidence of POPC following the use of pancuronium , atracurium , and vecuronium , and to examine the effect of residual neuromuscular block on the incidence of POPC OBJECTIVE To compare the effects of neostigmine/atropine combination and sugammadex on intraocular pressure during tracheal extubation period . METHODS The single-blind prospect i ve r and omised controlled study was conducted at Ordu University Research and Training Hospital from August to October 2014 , and comprised patients who were r and omly assigned to 2 groups according to the agent used for reversal of neuromuscular blockade . Group N received 0.05mgkg-1 neostigmine and 0.02 mgkg-1 atropine and the patients in Group S received 2mgkg-1 sugammadex intravenously . Heart rate , mean arterial pressure and intraocular pressure were measured at baseline , before the induction ( T1 ) , after the application of reversal agent ( T2 ) , and 1 ( T3 ) , 3 ( T4 ) , 5 ( T5 ) and 10 ( T6 ) minutes after the extubation . SPSS 16 was used for statistical analysis . RESULTS There were 36 patients in the study ; 18(50 % ) in each group . There was no significant difference between the groups in terms of age , gender and body mass index ( p>0.05 each ) . Intraocular pressure was significantly higher when the baseline level was compared with all measurement intervals in Group N ( p<0.05 each ) . In Group S , it showed no significant difference at T2 ( p>0.05 ) whereas it was significantly higher at all other measurement intervals ( p<0.05 each ) . Intergroup comparisons showed statistically significant difference in heart rate and mean arterial pressure levels at T2 interval which were higher in Group N ( p<0.01 ) . Intraocular pressure levels at T2 and T3 intervals were significantly higher in Group N ( p<0.01 ) . CONCLUSIONS Lower end-extubation intraocular pressure levels were obtained when sugammadex was used as a neuromuscular block reversal agent in comparison with neostigmine-atropine combination . Sugammadex may be a better option for the reversal of neuromuscular blockade and intraocular pressure increase should be avoided in patients with glaucoma or penetrating eye injury Background A previous study has demonstrated a decrease in the hypoxic ventilatory response in volunteers partially paralyzed with vecuronium . However , in this study , hypocapnia was allowed to occur . Because hypocapnia counteracts the ventilatory response to hypoxia during partial vecuronium-induced neuromuscular block and isocapnia , the hypoxic ventilatory response ( HVR ) was tested in 10 awake volunteers . Methods To avoid hypocapnia , the resting hyperoxic control end-tidal PCO2 was increased to 43.3 ± 2.4 mmHg , raising inspiratory minute ventilation ( & OV0312;1 ) to 140 ml·kg-1·min-1·Hypoxic ventilatory response ( Δ&OV0312;1 /ΔSpO2 , L·min-1·%-1 ) was measured during a 5-min isocapnic step reduction to a mean arterial hemoglobin oxygen saturation ( SpO2 ) of 84.8 ± 1.4 % . Immediately thereafter , hypercapnic ventilatory response ( HCVR ; δ&OV0312;1/ΔPetCO2 , L·min-1·mmHg-1 ) was determined at the end of a 6-min step increase of PetCO2 to 50.5 ± 2.7 mmHg . During a subsequent 30–40-min pause , an intravenous infusion of vecuronium was adjusted to reduce the adductor pollicis train-of-four ratio to 0.70 , as monitored using mechanomyography . Ventilatory parameters , HVR and HCVR , were then re-determined . Results Resting & OV0312;1 , PetCO2 , and SpO2 were unchanged by drug infusion . Hypoxic ventilatory response decreased from control ( a ) of 0.97 ± 0.43 to 0.74 ± 0.41 L·min-1·%-1 ( P < 0.02 ) during drug infusion ( b ) , while HCVR was unchanged ( a = 1.91 ± 0.82 , b = 1.62 ± 0.46 L·min-1·mmHg-1 ; NS ) . To correct HVR for possible vecuronium-induced respiratory muscle weakness or otherwise altered central nervous system reactivity , the drug/control ratio ( HVRb/a ) was divided by the associated HCVRb/a ratio . This HVR index , FHVR was 0.84 ± 0.12 ( P < 0.01 ) . Conclusions We conclude that a vecuronium-induced partial neuromuscular block impairs HVR more than it does HCVR In humans , suggesting an effect of vecuronium on carotid body hypoxic chemosensitivity Background : Sugammadex ( Org 25969 ) forms a complex with steroidal neuromuscular blocking agents , thereby reversing neuromuscular block . This study investigated the dose – response relation , safety , and pharmacokinetics of sugammadex to reverse rocuronium-induced block . Methods : Twenty-seven male surgical patients aged 18–64 yr were r and omly assigned to receive placebo or sugammadex ( 0.5 , 1.0 , 2.0 , 3.0 , or 4.0 mg/kg ) for reversal of 0.6 mg/kg rocuronium – induced neuromuscular block . Anesthesia was induced and maintained using intravenous fentanyl and propofol . Neuromuscular function was assessed using acceleromyography . Sugammadex or placebo was administered at reappearance of T2 of the train-of-four . The primary efficacy variable was the time required for recovery to a train-of-four ratio of 0.9 . Results : Sugammadex decreased median recovery time in a dose-dependent manner from 21.0 min in the placebo group to 1.1 min in the group receiving 4.0 mg/kg sugammadex . Doses of sugammadex of 2.0 mg/kg or greater reversed rocuronium-induced neuromuscular block within 3 min . A median of 59–77 % of sugammadex was excreted unchanged in the urine within 16 h , mostly in the first 8 h. Sugammadex increased the proportion of the rocuronium dose excreted unchanged in the urine ( from a median of 19 % in the placebo group to 53 % in the 4.0-mg/kg group within 16 h ) . Sugammadex was safe and well tolerated . No evidence of recurarization was observed in any patient . Conclusion : At doses of 2.0 mg/kg or greater , sugammadex safely reversed 0.6 mg/kg rocuronium – induced neuromuscular block in a dose-dependent manner . Sugammadex enhanced renal excretion of rocuronium and was excreted unchanged by the kidneys BACKGROUND The aim of this dose-finding study was to evaluate the dose-response relationship of sugammadex and neostigmine to reverse a commonly observed level of incomplete recovery from rocuronium-induced neuromuscular block , that is , a train-of-four ratio ( TOFR ) ≥0.2 . METHODS Ninety-nine anaesthetized patients received rocuronium 0.6 mg kg(-1 ) i.v . for tracheal intubation and , if necessary , incremental doses of 0.1 - 0.2 mg kg(-1 ) . Neuromuscular monitoring was performed by calibrated electromyography . Once the TOFR recovered to 0.2 , patients were r and omized to receive sugammadex ( 0.25 , 0.5 , 0.75 , 1.0 , or 1.25 mg kg(-1 ) i.v . ) , neostigmine ( 10 , 25 , 40 , 55 , or 70 µg kg(-1 ) i.v . ) , or saline ( n=9 per group ) . Primary and secondary end points were the doses necessary to restore neuromuscular function to a TOFR≥0.9 with an upper limit of 5 and 10 min for 95 % of patients , respectively . RESULTS Neostigmine was not able to fulfil the end points . Based on the best-fitting model , the sugammadex dose estimation for recovery to a TOFR≥0.9 for 95 % of patients within 5 and 10 min was 0.49 and 0.26 mg kg(-1 ) , respectively . CONCLUSION A residual neuromuscular block of a TOFR of 0.2 can not be reversed reliably with neostigmine within 10 min . In the conditions studied , substantially lower doses of sugammadex than the approved dose of 2.0 mg kg(-1 ) may be sufficient to reverse residual rocuronium-induced neuromuscular block at a recovery of TOFR≥0.2 . CLINICAL TRIAL REGISTRATION NCT01006720 During surgery , changes in intraocular pressure ( IOP ) can be observed result ing from several factors , such as airway manipulations and drugs used . We aim ed to investigate the effects of sugammadex and neostigmine on IOP , hemodynamic parameters , and complications after extubation . Our study comprised 60 patients , aged 18 - 65 years , with a risk status of the American Society of Anesthesiologists I-II who underwent arthroscopic surgery under general anesthesia . The patients were r and omly assigned into two groups . At the end of the surgery , the neuromuscular block was reversed using neostigmine ( 50 μg/kg ) plus atropine ( 15 μg/kg ) in Group 1 , and sugammadex ( 4 mg/kg ) in Group 2 . Neuromuscular blockade was monitored using acceleromyography and a train-of-four mode of stimulation . IOP was measured before induction and at 30 seconds , 2 minutes , and 10 minutes after extubation . A Tono-Pen XL applanation tonometer was used to measure IOP . This showed that elevation in IOP of patients reversed using sugammadex was similar to that recorded in patients reversed using neostigmine-atropine . When heart rate was compared , there was a significant difference between basal values and those obtained at 30 seconds and 10 minutes after extubation in the neostigmine-atropine group . Extubation time ( time from withdrawal of anesthetic gas to extubation ) was significantly shorter in the sugammadex group ( p = 0.003 ) than in the neostigmine-atropine group . The postextubation IOP values of the sugammadex group were similar to the neostigmine-atropine group . Extubation time ( time from withdrawal of anesthetic gas to extubation ) was significantly shorter in the sugammadex group ( p = 0.003 ) than in the neostigmine-atropine group Background : Traditionally , reversal of nondepolarizing neuromuscular blocking agents was achieved using acetylcholinesterase inhibitors , but these are unable to adequately reverse profound blockade . Sugammadex is a novel reversal agent , reversing the effects of rocuronium by encapsulation . This study assessed the efficacy and safety of sugammadex versus neostigmine for reversal of profound rocuronium-induced neuromuscular blockade . Methods : This phase III , r and omized study enrolled surgical patients , aged 18 yr or older with American Society of Anesthesiologists physical status I – IV . Patients were r and omized to receive sugammadex ( 4.0 mg/kg ) or neostigmine ( 70 & mgr;g/kg ) plus glycopyrrolate ( 14 & mgr;g/kg ) . Anesthetized patients received an intubating dose of rocuronium ( 0.6 mg/kg ) , with maintenance doses ( 0.15 mg/kg ) as required . Neuromuscular monitoring was performed by acceleromyography . Sugammadex or neostigmine was administered at reappearance of 1–2 posttetanic counts ( profound neuromuscular blockade ) . The primary efficacy parameter was the time from sugammadex or neostigmine – glycopyrrolate administration to return of the train-of-four ratio to 0.9 . Results : In the intent-to-treat population ( n = 37 in each group ) , geometric mean time to recovery to a train-of-four ratio of 0.9 with sugammadex was 2.9 min versus 50.4 min with neostigmine – glycopyrrolate ( P < 0.0001 ) ( median , 2.7 min vs. 49.0 min ) . Most sugammadex patients ( 97 % ) recovered to a train-of-four ratio of 0.9 within 5 min after administration . In contrast , most neostigmine patients ( 73 % ) recovered between 30 and 60 min after administration , with 23 % requiring more than 60 min to recover to a train-of-four ratio of 0.9 . Conclusions : Recovery from profound rocuronium-induced neuromuscular blockade was significantly faster with sugammadex versus with neostigmine , suggesting that sugammadex has a unique ability to rapidly reverse profound rocuronium neuromuscular blockade Context Residual paralysis is associated with post-operative pulmonary complications , including critical respiratory events . Objective We determined the incidence of critical respiratory events , such as hypoxaemia , in patients with minimal residual neuromuscular blockade and compared these data with those from patients with full recovery of blockade . Design R and omised , prospect i ve , placebo-controlled trial . Setting Single centre ; Rostock , Germany , from January 2007 to February 2008 . Patients One hundred and thirty-two adult patients , aged 18–80 years , with the American Society of Anesthesiology I – III physical status , undergoing orthopaedic surgery under general anaesthesia , including rocuronium to produce neuromuscular blockade ; 114 patients were r and omised to one of two groups : neostigmine group ( neostigmine 20 & mgr;g kg−1 ) or placebo group ( saline ) . Interventions In the patients in the neostigmine group , the tracheal tube was removed at a train-of-four ( TOF ) ratio of 1.0 ; in the patients in the placebo group , the trachea was extubated at a TOF ratio less than 1.0 , but without fade in TOF and double-burst stimulation ( DBS ) . Neuromuscular monitoring was assessed simultaneously with qualitative TOF/DBS monitoring , and with quantitative calibrated acceleromyography . Critical respiratory events , such as hypoxaemia , were assessed in the post-anaesthesia care unit . Main outcome measures Forty-five patients ( 39.5 % ) became hypoxaemic ( SaO2 < 93 % ) ; there was a significant difference between the groups ( 29 patients in the placebo group versus 16 in the neostigmine group ; P = 0.021 ) . Results In the neostigmine group , all patients were extubated at a TOF ratio of 1.0 . In the placebo group , the median TOF ratio was 0.7 ( range : 0.46–0.9 ; P < 0.001 ) . The median time for spontaneous recovery in the placebo group was 16 min ( range 3–49 min ) . Neostigmine 20 & mgr;g kg−1 was effective in antagonising rocuronium-induced blockade without fade in TOF and DBS . Conclusion In this r and omised , prospect i ve , placebo-controlled trial , minimal residual block was associated with hypoxaemia in the post-anaesthesia care unit . Neostigmine 20 & mgr;g kg−1 was effective in antagonising rocuronium-induced ( minimal ) blockade |
13,216 | 10,796,247 | REVIEW ER 'S CONCLUSIONS Both ampicillin and first generation cephalosporins have similar efficacy in reducing postoperative endometritis .
There does not appear to be added benefit in utilizing a more broad spectrum agent or a multiple dose regimen . | BACKGROUND Prophylactic antibiotics for cesarean section have been shown to reduce the incidence of maternal postoperative infectious morbidity .
Many different antibiotic regimens have been reported to be effective .
OBJECTIVES The objective of this review was to determine which antibiotic regimen is most effective in reducing the incidence of infectious morbidity in women undergoing cesarean section . | In an ongoing prospect i ve study at 2 hospitals , 114 cesarean section patients were studied to determine whether giving ampicillin after umbilical cord clamping is as effective as perioperative ampicillin in reducing maternal postoperative morbidity . The same patients have also been studied to determine the effect of prophylactic cesarean section ampicillin on the newborn . Results have shown that prophylactic ampicillin initiated after cord clamping is as effective in reducing maternal morbidity as ampicillin initiated prior to the surgery . There is also no evidence from our study that the transplacental passage of prophylactic ampicillin increases immediate or delayed neonatal infections A prospect i ve r and omized clinical trial was conducted to test the effectiveness of long-term and short-term prophylaxis with cefuroxime in preventing morbidity after cesarean section . Sixty patients who required emergency cesarean section were r and omly assigned to one of three treatment groups : a control group of 20 patients receiving no prophylactic antibiotics ; a group of 20 patients receiving 24 hours of cefuroxime prophylaxis ( 0.75 gm 30 to 60 minutes before surgery and at 8 hours and 16 hours after surgery ) ; and a group of 20 patients receiving five days of cefuroxime prophylaxis ( 0.75 gm three times a day , the first dose being given postoperatively ) . The short-term and long-term prophylaxes were equally effective in reducing morbidity , assessed by postoperative temperatures , presence or absence of endometritis , and duration of postoperative hospital stay The effectiveness of a single prophylactic dose of two broad spectrum antibiotics , during Caesarean section , was compared and evaluated . In 119 consecutive cases at the Cantonal Hospital in Winterthur , Switzerl and , either 1 g i.v . cefotaxime or 1,2 g amoxicillin plus clavulanic acid were administered after clamping the umbilical cord during Caesarean section . The study shows that single dose prophylaxis of either regimen provides adequate cover in preventing morbidity in Caesarean section , in both high-risk and low-risk groups In a prospect i ve , r and omized trial , the efficacy of a single-dose , first-generation , long-acting cephalosporin was compared with a three-dose regimen in a group of 100 women undergoing cesarean section who were at high risk for postoperative febrile morbidity . Fifty women received a single 1 gm intravenous dose of cefazolin and 50 received 1 gm of the drug followed by two additional doses , 8 hours apart , to complete a three-dose regimen . Another 50 women , considered to be at low risk for postoperative febrile morbidity , were not given antibiotic prophylaxis . Outcomes of febrile morbidity ( 18 % vs 12 % ) and particularly morbidity caused by endometritis ( 6 % vs 8 % , respectively ) were similar for single-dose and three-dose groups . In the untreated low-risk group there were no cases of endometritis and the febrile morbidity was comparable to that of the prophylactically treated groups ( 14 % vs 15 % ) . Single-dose cefazolin prophylaxis appears to be comparable to multidose prophylaxis in reducing febrile morbidity after cesarean section The use of antibiotics for prophylaxis against infection among women undergoing nonelective cesarean section has become the st and ard of care in the United States . Many different antibiotics have been used successfully . Single-dose regimens administered after the cord is clamped have proven just as effective as multiple-dose regimens . Although the most frequently used class of antibiotics is the cephalosporin family , the single best agent has not been determined . This study was a double-blind , r and omized trial in which we compared a narrow-spectrum cephalosporin ( cefazolin ; n = 63 ) with an exp and ed-spectrum cephamycin ( cefoxitin ; n = 66 ) and with a broad-spectrum cephalosporin ( cefotaxime ; n = 60 ) used as a single-dose prophylaxis in patients undergoing a nonelective cesarean section . Of the 194 patients enrolled in the study , 189 were evaluable . There was no significant difference between the groups in mean age , gravidity , parity , duration of labor , duration of ruptured membranes , number of vaginal examinations , or socioeconomic status ( socioeconomic status was defined by third-party coverage ) . There was no significant difference among the antibiotics in the incidence of immediate or delayed postoperative infections . These data indicate that a less expensive , narrow-spectrum cephalosporin is as effective as more expensive , broader-spectrum cephamycins and cephalosporins as prophylaxis for patients undergoing nonelective cesarean section This study compared the efficacy of a single intravenous dose of Cefazolin alone or combined with an antibiotic containing preclosure-irrigation solution in patients undergoing cesarean section . A total of 308 patients were prospect ively assigned to two groups by r and omization . Group I received two grams of Cefazolin IV and abdomino-peritoneal irrigation with saline . Group II received one gram of Cefazolin IV and one gram in the saline irrigation solution . The rate of total postoperative morbidity was 2.3 times higher in Group I compared to Group II ( 16/154 or 10.4 % vs 7/154 or 4.5 % ) and morbidity at the operative site was six times higher ( 13/154 or 8.4 % vs 2/154 or 1.3 % ) A r and omized , prospect i ve , double-blind study was design ed to compare intravenous administration with intrauterine irrigation using an extended half-life ( tl/2=three hours ) cephalosporin , ceforanide . Patients included in the study had a nonelective cesarean section with rupture of membranes for three hours or longer . Sixty-four patients received a single dose of ceforanide immediately after clamping the umbilical cord . Patients were similar in both groups in age , weight , length of labor , and duration of ruptured membranes . The group receiving the intravenous ceforanide had a significantly shorter duration of surgery than the patients receiving the intrauterine ceforanide . Endometritis infection rates were similar , 11.8 % ( intravenous ) versus 11.1 % ( intrauterine ) , P>.1 . Serum levels were as much as tenfold higher in the intravenous group versus the intrauterine group . Intrauterine irrigation with an antimicrobial agent provided no advantage over systemic administration A prospect i ve and r and omized study was undertaken to determine the safety and efficacy of low price and discouraging bacterial resistance agents , given for 12 hours versus 72 hours , as prophylaxis at cesarean section . Ninety six patients received penicillin ( ten million units ) intravenously and tetracycline ( 0.25 g ) intramuscularly at cord clamping and 12 hours postoperatively ( table I ) . Among them 14 % of febrile morbidity was recorded ( table II ) . Eighty seven patients received the same treatment followed by oral ampicillin ( 2 g ) and tetracycline ( 1.5 g ) per day , for a further 60 hours ( table I ) . Maternal febrile morbidity was not further reduced by the oral additional treatment ( table II ) . This regiment prophylactic effect is comparable to previous reported data concerning other protocol s , and even better , while expenses are reduced and efficacy for important pathogens such as chlamydia and mycoplasma is obtained . No side effects of the drugs were recorded To study the effectiveness of anaerobic coverage in prevention of postpartum endometritis in women undergoing nonelective cesarean sections , we conducted a r and omized prospect i ve double-blind study of women undergoing cesarean sections and requiring antibiotic prophylaxis from April 1 , 1989 , through December 31 , 1990 . Ninety-four patients were enrolled in the study . Forty-five patients received ampicillin alone and 46 received ampicillin in conjunction with sulbactam . All patients were evaluated prior to surgery and in the postoperative period . Ninety-one patients completed the study and their records were analyzed . Patients were divided into two groups depending on the presence or absence of ruptured membranes . Seventy-five percent of patients had ruptured membranes . Failure of prophylaxis and subsequent endometritis was documented in 8.8 % of patients who received ampicillin and sulbactam and 35.3 % of patients who received ampicillin alone . This difference was statistically significant ( p < 0.02 ) . In conclusion , single-dose ampicillin and sulbactam provides better prophylaxis than single-dose ampicillin in women undergoing cesarean section with rupture of membranes A prospect i ve r and omized study was undertaken in 100 patients undergoing cesarean section to evaluate the efficacy of cefotaxime when given as a single-dose versus the more traditional triple-dose regimen for prophylaxis . Analysis of the results demonstrated no significant differences in febrile morbidity ( 14 versus 20 % ) or postoperative endometritis ( 10 versus 14 % between the single- and triple-dose groups , respectively . Pretherapy aerobic and anaerobic placental cultures were positive in 60 % of the overall study population . In those patients who subsequently developed endometritis , seven ( 58 % ) had a positive placental culture , suggesting that this technique is relatively nonspecific as a screening procedure . Results of transcervical culture in the endometritis patients most often demonstrated a polymicrobial picture . Several of the organisms cultured were found to be resistant to cefotaxime , supporting the need to better guide antimicrobial therapy by routine endometrial culturing in patients who fail prophylaxis . The results of the present study suggest that single-dose administration of cefotaxime is equally effective as triple-dose therapy in reducing postcesarean section endometritis The purpose of this prospect i ve investigation was to compare a single intravenous dose of cefazolin to a single dose of cefonicid as prophylaxis for women having unscheduled cesarean delivery . In a double-blind , r and omized design , 96 patients were assigned to receive a 1-g dose of cefazolin and 103 patients were design ated to receive a 1-g dose of cefonicid . The antibiotics were administered after delivery of the infant . The two groups were comparable with respect to recognized risk factors for postcesarean infection . There were no statistically significant differences between the groups in the incidence of st and ard febrile morbidity , endomyometritis , urinary tract infection , wound infection , and bacteremia . There were also no significant differences between the groups in the fever index or the duration of hospitalization . We conclude that cefazolin and cefonicid provide a similar degree of prophylaxis against infection in patients having unscheduled cesarean delivery This study included 207 patients in a double-blind , prospect i ve r and omized trial of cefazolin veisus cefam and ole single-dose prophylaxis by both intravenous ( IV ) and lavage routes in patients laboring with ruptured membranes who eventually had nonelective cesareans . No significant differences ( P < .05 ) were noted in the rates of infectious morbidity ( cefazolin IV : six of 47 , 13 % ; cefazolin lavage : nine of 59 , 15 % ; cefam and ole IV : six of 47 , 13 % ; cefam and ole lavage : six of 54 , 11 % ) . The incidence of operative complications in the patients developing endometritis ( eight of 22 , 36 % ) was significantly different ( P < .004 ) from that in the group who did not develop endometritis ( 21 of 185 , 11 % ) . Cefazolin by IV and lavage routes of administration appears to be as effective as cefam and ole by either route of administration A study comparing the efficacy of cefotetan versus cefoxitin for prophylaxis in patients undergoing cesarean section was carried out at the University of Iowa . After institutional review , 36 subjects who met the study criteria and agreed to participate were entered into the study ; of these , 29 were evaluable for efficacy . Twenty subjects received a single 2 gm dose of cefotetan , and nine subjects received three 2 gm doses each of cefoxitin . Both antibiotics were administered intravenously at the time the umbilical cord was clamped . The subsequent doses of cefoxitin were given intravenously at four and eight hours after the initial dose . Clinical and bacteriologic responses were evaluated ; there were no statistically significant differences between the two groups , and both antibiotics provided effective prophylaxis against infection . It appears that cefotetan is a satisfactory antibiotic choice for cesarean section prophylaxis . Further , in this small study it appears that a single dose of cefotetan is as effective as three doses of cefoxitin . This implies that cefotetan would not only decrease administration time and supplies but would decrease the cost to the patient while maintaining very acceptable infection rates Despite the increasing popularity of antibiotic prophylaxis to reduce febrile morbidity in patients who undergo cesarean delivery , little is known of the pharmacokinetics of antibiotics in the patient at term gestation . This study was design ed to eluci date the pharmacokinetics of cefoxitin when administered intravenously or by uterine and peritoneal lavage at cesarean section . Significant differences were found in the values for total body clearance area under the serum concentration-time curve ( AUC ) , and K21 of cefoxitin administered intravenously to pregnant patients at term gestation compared to values for these parameters observed in nonpregnant patients . The concentration of cefoxitin in decidual tissue after uterine and peritoneal lavage with the antibiotic was 92.5 + /- 10.1 micrograms/gm ( mean + /- SEM ) , whereas the concentration of cefoxitin in decidual tissue after intravenous administration of the antibiotic was 36.9 + /- 10.5 micrograms/gm ( mean + /- SEM ) . This difference is statistically significant ( p less than 0.05 ) . We conclude that the pharmacokinetics of cefoxitin are altered in the pregnant patient as evidence d by the increased rapidity of clearance of the antibiotic ( total body clearance for cefoxitin in pregnant patients , 20.41 L/hr ) . Moreover , uterine and peritoneal lavage results in significant tissue concentrations of antibiotic , which is of potential importance since the decidua is a presumed site of initiation of bacterial infection after cesarean section Seven antibiotics , administered in 10 different regimens for prophylaxis , were r and omly assigned to 1580 patients who were delivered by cesarean section . Cefazolin 1 gm , administered for three doses , served as the control group . Cefazolin 1 gm , cefazolin 2 gm , cefoxitin 1 gm , cefoxitin 2 gm , cefonicid 1 gm , cefotetan 1 gm , ceftizoxime 1 gm , ampicillin 2 gm , and piperacillin 4 gm were all administered in a single dose . Four antibiotics proved to be superior in preventing postpartum endometritis : ampicillin 2 gm ( p = 0.03 ) , cefazolin 2 gm ( p = 0.005 ) , piperacillin 4 gm ( p = 0.0007 ) , and cefotetan 1 gm ( p = 0.0001 ) . Single-dose cephalosporin antibiotic prophylaxis was found to result in approximately a twofold increase in Enterococcus faecalis colonization of the vagina ( p less than 0.01 ) . This may be significant in patients in whom postpartum endometritis develops and who have failure of initial treatment with a broad-spectrum cephalosporin , e.g. , cefoxitin or cefotetan , or a combination such as clindamycin or metronidazole plus an aminoglycoside . Rupture of amniotic membranes for a half hour or more was associated with an increased risk for postpartum endometritis . The use of internal fetal monitoring was associated with an increased risk of soft tissue pelvic infection The present study was undertaken to determine the minimal effective antibiotic dosage in caesarean section prophylaxis . The study was conducted at the Academisch Ziekenhuis der Vrije Universiteit in Amsterdam ( Amsterdam Free University Hospital ) to compare the efficacy of one dose of cefoxitin ( 2 g ) with three administrations of 2 , 1 and 1 g respectively . In this prospect i ve and double-blind study , 66 patients were given one dose and 72 patients received three doses . In terms of febrile morbidity , endometritis , wound infection , urinary tract infection and need for postoperative antibiotic therapy , the three-dose group showed fewer postoperative infections : as to wound infections ( p less than 0.05 ) and therapeutic antibiotic use ( p less than 0.025 ) these differences were statistically significant . The numbers of days of hospitalization after the caesarean section also showed differences : 10.6 + /- 2.6 versus 9.8 + /- 1.5 days in the one- and three-dose groups respectively ( p less than 0.05 ) . It is concluded that , contrary to several reports in the literature , prophylaxis consisting of three administrations of cefoxitin is to be preferred . No significant allergic or adverse reactions were observed in our patients A study to compare the prophylactic efficacy of a single 2 g dose of cefotetan with multiple 2 g doses of cefoxitin in reducing the incidence of postcesarean section infection was evaluated in a multicenter trial of 269 women . No significant differences in clinical or bacteriologic response were detected between the two groups . A successful clinical response rate was achieved in 139 of 162 of the evaluable subjects given cefotetan ( 86 percent ) and in 71 of 79 patients ( 90 percent ) given cefoxitin . The respective satisfactory bacteriologic response rates were 91 percent ( 135 of 148 patients ) and 93 percent ( 68 of 73 patients ) . The incidences of endometritis for cefotetan and cefoxitin ( 12 percent and 5 percent , respectively ) and of postoperative wound infection ( 3 percent and 5 percent , respectively ) were also not significantly different . Bactericidal levels of cefotetan were maintained in plasma in the immediate postpartum period . Both drugs were well tolerated . Single-dose prophylaxis with cefotetan was comparable to multiple doses of cefoxitin in reducing infectious morbidity in women undergoing cesarean section At Parkl and Memorial Hospital a group of women at high risk for infection following cesarean delivery was identified . These included nulliparas who underwent cesarean section for cephalopelvic disproportion 6 or more hours following membrane rupture . During the puerperium , uterine infection developed in 85 to 95 % of such women , and one third of this high-risk group had associated complications . The authors have previously reported the efficacy of antimicrobial agents given to these women at the time of cesarean section and continued for 4 days . The present prospect i ve study was design ed to assess the efficacy of a shorter course of perioperative antimicrobial therapy for these high-risk women . Three doses of antimicrobial agents were given perioperatively to 305 women r and omly assigned to 1 of 3 treatment regimens : 115 were given penicillin plus gentamicin , 82 received 2,1 , and 1 g of cefam and ole , respectively , and the remaining 108 were given 2 , 2 , and 2 g of cefam and ole , respectively . The incidence of uterine infection in these 305 women was 24 % and associated complications were identified in 7 % of all women . Based upon a comparison of results with the progenitor study , the authors conclude that 3-dose perioperative antimicrobial therapy is preferred to 4 days of treatment for women at high risk for infection following cesarean delivery A total of 120 patients who were to be delivered by cesarean section and who were at high risk of postoperative infection received three doses of either cefam and ole , cephalothin or placebo perioperatively . Maternal serum levels for both antibiotics were in the therapeutic range . Although both drugs reduced the incidence of febrile morbidity and endometritis , only cefam and ole significantly reduced the fever index . Risk factors for postoperative infections were the presence of ruptured membranes , labor , and internal fetal monitoring . Cefam and ole beneficially influenced all risk factors while cephalothin was able to reduce only the risk of ruptured membranes . When a new method for obtaining endometrial tissue was utilized , 50 % of cultures were negative . There was no difference in the organisms isolated from patients with and without endometritis We conducted a prospect i ve , double-blind , r and omized , placebo-controlled study of cefoxitin perioperative prophylaxis in 386 women having cesarean sections after labor or rupture of membranes . Private patients constituted 70 % of subjects . Cefoxitin was chosen for its low toxicity and its broad spectrum against common obstetric pathogens including Bacteroides fragilis . Cefoxitin-treated women received 2 mg of drug intravenously at umbilical cord clamping and at 6 and 12 hours after surgery . Demographic and obstetric variables did not differ between the 190 placebo-treated women and the 196 cefoxitin-treated women . The morbidity rate from infection was significantly reduced by cefoxitin prophylaxis . Seven factors were significantly correlated with increased risk of infection after cesarean section : maternal age , socioeconomic status , race , gestational age , duration of internal fetal monitoring , use of intrauterine pressure catheter , and obesity . Cefoxitin prophylaxis result ed in significant decreases in infection incidence in women with one , two , and three risk factors , respectively , but the reduction was not significant in women with no risk factors . Length of hospital stay was not significantly reduced by cefoxitin prophylaxis but antibiotic use was decreased 24 % To determine the efficacy of perioperative cefoxitin in preventing infections after primary cesarean section , a r and omized placebo-controlled , double-blind clinical trial was performed . Among 266 participants , those who received three perioperative 2 gm doses of cefoxitin ( 138 ) had significantly fewer serious infections ( 19.5 % vs. 4.3 % ) , fewer urinary tract infections ( 10.7 % vs. 4.4 % ) , less st and ard febrile morbidity ( 9.4 % vs. 3.6 % ) , and fewer courses of antibiotics postoperatively ( 23.4 % vs. 11.6 % ) . There was no reduction in the length of hospitalization . Use of perioperative cefoxitin umbilical cord is clamped are safe and efficacious in preventing infection after primary cesarean section One hundred fifty patients undergoing cesarean section were evaluated prospect ively for the effect of prophylactic antibiotics on postoperative morbidity . The postoperative infection rate was significantly reduced , being 30 % , 16 % , and 50 % in the ampicillin , the cephalothin , and the control groups , respectively . The results are favorably compared with the results achieved in previously reported studies where the antibiotic treatment was started preoperatively . Our study confirms experimental studies that postoperative infection can be reduced by using prophylactic antibiotics in the immediate postoperative period . By this regimen , undesired placental transfer of the antibiotics to the fetus can be avoided To compare the efficacy of antibiotic prophylaxis through uterine lavage in women undergoing cesarean section in labor to the efficacy of the more st and ard , perioperative intravenous method , we prospect ively r and omized 100 women to receive either 2 g of cefotaxime in 1,000 mL of normal saline with a lavage protocol or 1 g of cefotaxime intravenously after cord clamping followed by 1-g doses 6 and 12 hours later . The two groups were similar with respect to age , gestational age , race , weight , length of labor and of ruptured membranes , use of internal monitoring , blood loss and number of vaginal examinations . St and ard febrile morbidity and postpartum endomyometritis requiring antibiotic therapy occurred in 18 % and 12 % , respectively , of the lavage group and in 16 % and 12 % , respectively , of the intravenous group . Before the routine use of prophylactic antibiotics for cesarean section in labor on our service , the febrile morbidity and endomyometritis rates were 36 % and 32 % , respectively . The results confirm the benefit of prophylactic antibiotics for cesarean section in labor and demonstrate that the lavage and intravenous methods are similar with respect to efficacy Intrauterine irrigation with a cefazolin solution at cesarean section was compared with intravenous cefazolin administration for prophylaxis against post-cesarean-section endomyometritis in a r and omized , controlled , prospect i ve fashion . There were no statistically significant differences in the incidence of infection between the lavage and intravenous groups . The incidence of endomyometritis was 37 % in the lavage group and 29 % in the intravenous ( P = NS ) . Intrauterine cefazolin lavage is safe , effective , time saving and more cost effective than intravenous cefazolin in preventing post-cesarean-section endomyometritis This prospect i ve study was undertaken in an effort to evaluate the role of systemic antibiotic prophylaxis in elective abdominal delivery . Eighty-two patients undergoing elective cesarean section who were not in labor and who did not have ruptured membranes were assigned on a r and omized , double-blind basis to receive a three-dose perioperative course of either placebo or ampicillin . Postoperatively , patients were evaluated for the development of infection-related complications . Patients in the antibiotic group experienced less febrile morbidity , had lower fever indices and developed fewer operative-site infections than did patients in the control group . No patient in either group , however , developed a potentially life-threatening infection , and all infected patients responded promptly to parenteral antibiotic therapy . Because of the limited morbidity associated with elective cesarean section in this patient population , it is concluded that the theoretical risks of antibiotic prophylaxis outweigh the expected benefits We studied 212 patients undergoing emergency cesarean section at an urban hospital . Four techniques of antibiotic prophylaxis were used , including single-dose and triple-dose parenteral therapy , parenteral and lavage therapy , and lavage therapy alone . One agent , mezlocillin , was used for all patients . There was no significant difference in surgically related infectious morbidity among the groups . This antibiotic proved efficacious when related to historical controls , and was the most economical of the modalities of administration studied The effectiveness of antibiotic irrigation in reducing post-cesarean section infectious morbidity was studied in a prospect i ve , r and omized , double-blind trial . One hundred twenty-eight patients were divided into three groups and irrigated with either cefoxitin solution , cephapirin solution , or saline . Following delivery of the placenta , the uterine cavity and incision , bladder flap , pelvic gutters , and subcutaneous tissue of the patients were irrigated . There was a significant reduction in total infectious morbidity ( p less than 0.02 ) and wound infection ( p less than 0.04 ) when antibiotic use was compared to the saline control . No statistical difference in the effectiveness of the two antibiotics could be demonstrated . No adverse effects were noted . Antibiotic irrigation is a safe and effective method in reducing infectious morbidity of the parturient patient A r and omized , prospect i ve study compared a long-acting , second-generation cephalosporin , cefonicid ( Monocid ) , with a short-acting , second-generation cephalosporin , cefoxitin ( Mefoxin ) , for cesarean section prophylaxis . One hundred thirty-nine patients were enrolled , with 81 receiving a 1-g intravenous dose of cefonicid after cord clamping and 58 receiving a 2-g dose of intravenous cefoxitin after cord clamping and at 6 , 12 and 18 hours postpartum . In those patients receiving cefonicid prophylaxis , endometritis incidence was 17.3 % ( 14 of 81 ) . This finding was not statistically significant ( P less than .397 ) when compared to the 12.1 % incidence of endometritis ( 7 of 58 ) with cefoxitin . In addition , the febrile morbidity incidence for cefonicid prophylaxis was 23.5 % ( 19 of 81 ) as compared to 15.5 % ( 9 of 58 ) for cefoxitin ( P less than .25 ) . Because the two drugs appear to be equally efficacious , cefonicid may be the better choice because of its markedly lower cost A prospect i ve , blinded , placebo-controlled study was performed to determine the minimum effective duration of short-term antibiotic prophylaxis following cesarean section . Cefoxitin was selected as the study drug , and 189 women at high risk for postoperative infectious morbidity were r and omly assigned to three cohorts , each receiving intravenous infusions at cord clamping and at 4 and 8 hours postoperatively . The incidence of endometritis in the placebo group was 29.3 % versus 9.4 % in patients receiving one dose of cefoxitin ( 2 gm ) at cord clamping and 5.0 % in patients receiving three doses of cefoxitin ( p less than 0.0001 ) . Cefoxitin prophylaxis significantly reduced the incidence of endometritis in patients with postoperative anemia . There were no serious complications or drug reactions in the treated groups The efficacy of intraoperative irrigation with cefam and ole nafate at cesarean section was evaluated in a prospect i ve , r and omized double-blind study . Two hundred and eight patients were treated with antibiotic irrigation and intravenous placebo or with perioperative intravenous cefam and ole and irrigated with normal saline . The rate endometritis was 10.9 % in the irrigation group and 14 % the intravenous group , but the difference was not statistically significant . The rate of any infection , the number days with fever , additional hospitalization days , and number of antibiotics used for treatment were similar in the two groups . It thus was concluded that irrigation with antibiotic is equal but not superior to perioperative intravenous antibiotics Despite recent enthusiasm for antibiotic prophylaxis by uterine irrigation at the time of cesarean section , no data exists comparing the efficacy of this technique with st and ard intravenous antibiotic administration . Therefore , 124 patients about to undergo cesarean section were entered into a prospect i ve , r and omized , double-blind evaluation of uterine irrigation versus intravenous administration of either normal saline or cefoxitin . All women were considered to be at increased risk for postoperative infection because of the presence of labor or ruptured membranes . The incidence of endometritis and the fever index in patients receiving intravenous cefoxitin ( 3.2 % , 4.6 degree hours ) was significantly less than in patients receiving intravenous normal saline ( 21.2 % , 22.3 degree hours ) . There was no significant difference between the use of intravenous normal saline and uterine irrigation with either cefoxitin ( 18.9 % , 16.6 degree hours ) or normal saline ( 17.4 % , 24.6 degree hours ) . These results suggest that intravenous infusion is the most effective means of administering cefoxitin as a prophylactic antibiotic A prospect i ve , double-blind study was performed to evaluate the comparative efficacy of single- and multiple-dose antimicrobial prophylaxis for preventing infection in high-risk patients undergoing cesarean section . One hundred fifty-eight patients were r and omly assigned to receive either a single perioperative dose of mezlocillin , three doses of mezlocillin or three doses of cefoxitin . The incidence of endometritis was 5.9 % , 4.0 % and 4.0 % , respectively . The incidence of febrile morbidity was 5.9 % , 2.0 % and 6.1 % , respectively . These differences are not statistically significant . The single perioperative dose of mezlocillin was as effective as the three-dose regimen of either mezlocillin or cefoxitin Cefoxitin , a second-generation cephalosporin , was compared with cefazolin , a first-generation cephalosporin , and a placebo in a prospect i ve , double-blind study of antibiotic prophylaxis in women undergoing nonelective cesarean section . In the groups that received cefazolin or the placebo there eas no statistically significant change in colonization of the cervix by aerobic bacteria by the fourth day after the operation , but there was a statistically significant increase in colonization by anaerobes . Cefoxitin had the opposite effect . Of the 14 postoperative infections in 11 patients , significantly more were in patients who had received the placebo ; the numbers were too small to show a difference in effectiveness between the two antibiotics . Of the microorganisms implicated as the infectious agents , group B Streptococcus was the most frequent aerobe , and Peptostreptococcus and Bacteroides bivius were the most frequent anaerobes . Among the 15 patients for whom at least one perioperative specimen yielded positive culture results , a postoperative infection developed in 5 of the 6 who received the placebo , 2 of the 4 who received cefazolin and 1 of the 5 who received cefoxitin A prospect i ve , r and omized double-blind study was undertaken to determine the safety and efficacy of single-dose versus multiple-dose piperacillin for primary cesarean operation prophylaxis . After informed consent was obtained , patients received either 4 gm of piperacillin intravenously as a single dose or three 2 gm doses of piperacillin intravenously 4 hours apart . One hundred sixteen patients were evaluated for response ; postoperative infection at the operative site was prevented in 52/60 ( 86.6 % ) who received the single dose and 53/56 ( 94.6 % ) who received multiple doses . The types of postoperative infections that occurred were similar in those patients in each group who developed infection and all responded well to therapeutic drugs . No adverse reactions to piperacillin were noted . Demographic characteristics and risk factors for infection were comparable for the two groups . These data support the efficacy of single-dose prophylaxis with an appropriate antibiotic agent The effectiveness of intraoperative irrigation with cefoxitin was compared prospect ively with that of a short course of intravenous cefoxitin as prophylaxis against endometritis . One hundred three patients who underwent primary cesarean at University Hospital , Jacksonville , Florida , were r and omized into two study groups . The first group received intraoperative cefoxitin irrigation . The second group received a short course of intravenous cefoxitin prophylaxis and intraoperative saline irrigation . The result ing incidence of endometritis was 3.8 % and 4 % , respectively . There was no statistically significant difference between the use of the cefoxitin solution and the short course of intravenous cefoxitin To compare the effectiveness of three doses and of a single dose of cefoxitin , a second-generation cephalosporin , in preventing infection after nonelective cesarean section , we carried out a prospect i ve study in 255 women who underwent the procedure between March 1983 and February 1985 . The rate of postoperative infection was 7 % in the group that received three doses and 8 % in the one-dose group . The sensitivity and specificity of perioperative cultures were low . The rate of asymptomatic bacteriuria was high , at 20 % , but few symptomatic urinary tract infections were found . Routine antibiotic prophylaxis with a single dose is suggested for all nonelective cesarean sections The purpose of this investigation was to determine whether an extended-spectrum antibiotic with a long duration of action was more effective for prophylaxis for cesarean delivery than a limited-spectrum agent with a shorter duration of action . Patients were eligible for the study if they were in labor or had ruptured membranes at the time of surgery . In a r and omized , double-blind manner , 377 women were assigned to receive 2 g of cefazolin ( 192 ) or 2 g of cefotetan ( 185 ) intravenously immediately after the infant 's umbilical cord was clamped . There were no significant differences between groups with respect to the frequency of febrile morbidity ( 22.4 versus 21.6 % ) , the mean fever index ( 15.8 versus 14.9 degree-hours ) , the frequency of endometritis ( 19.3 versus 21.1 % ) , or the mean duration of postoperative hospitalization ( 3.8 versus 3.9 days ) . Among patients who became infected despite prophylaxis , enterococcus was isolated with disproportionate frequency . This organism was responsible for 89 % of the postoperative urinary tract infections and all three cases of bacteremia . It was also the second most common isolate in women with endometritis . A single dose of cefazolin is comparable in effectiveness to cefazolin . In view of the cost difference between the two antibiotics , there is no justification for use of the more expensive , extended-spectrum agent The efficacy of perioperative antibiotic prophylaxis in cesarean section with a single dose of ceftriaxone , a long-acting cephalosporin not widely used for prophylaxis , was tested . Ceftriaxone as a single dose of 1 g i.v . versus three doses of cefoxitin 1 g i.v . respectively were used in a prospect i ve , r and omized , controlled study consisting of 1052 patients undergoing cesarean section . Postoperative infection rate as measured by fever , endometritis and wound infection was 6.5 % with ceftriaxone and 6.4 % with cefoxitin . Urinary tract infections were significantly more frequent in the cefoxitin than in the ceftriaxone group ( 17.8 % vs. 9.7 % , p < 0.001 ) . Enterococci and Escherichia coli accounted for urinary tract infections 1.86- , respectively , 4.3-fold more frequently with cefoxitin than with ceftriaxone . The time of hospitalization in patients with urinary tract infections was significantly lower with ceftriaxone than with cefoxitin ( 11 vs. 12 days , p < 0.05 ) . The tolerance in both groups was equally satisfactory . A single dose of ceftriaxone , which is simple , reliable ( compliance ) , well tolerated , inexpensive ( fewer urinary tract infections and therefore fewer treatment costs than with cefoxitin ) and safe ( no overgrowth of pathogens ) in our opinion is the antibiotic regimen of choice for prophylaxis in cesarean section in the described circumstances Two hundred sixty-three patients were r and omly assigned to receive either piperacillin or cefoxitin for prophylaxis in cesarean section . Although both drugs were considered effective , piperacillin achieved a level of 98 percent satisfactory prophylaxis compared with only 91 percent for cefoxitin . Costs of prophylactic failure in cesarean section were calculated and then assessed for four different antibiotic regimens ( based on 100 patients ) . Because of its high failure rate , ampicillin was the most expensive antibiotic ; piperacillin was the least expensive . It was suggested that highly effective prophylaxis with an antibiotic agent such as piperacillin can result in significant cost savings when used for high-risk patients undergoing cesarean section Abstract Sixty-one patients were prospect ively evaluated as to the worth of prophylactic antibiotics in cesarean section . Ampicillin , kanamycin , and methicillin were administered in double-blind fashion before and 2 and 8 hours after operation . The patients were evaluated for morbidity . An over-all 27 per cent infection rate was found in the antibiotic group as compared to a 61 per cent rate in the placebo group . No correlation was noted in age , hospital stay , organism , or rupture of membranes . The repeat sections in the antibiotic group have a statistically significant lower infection rate A single 2-g dose of ampicillin or a placebo identical in appearance was administered intravenously in a r and omized , prospect i ve , double-blind manner to 71 patients undergoing cesarean section . The solutions were given either on call to the operating room or during the intraoperative period . Postoperative morbidity from infection occurred in 59.4 % of patients receiving placebo and in 14.7 % of those receiving ampicillin ( P<.0001 ) . In those individuals undergoing primary cesarean section the incidence of infection with placebo was 65 % and with ampicillin 6.3 % ( P<.0004 ) . In patients undergoing repeat cesarean section the incidence was 53 % in the placebo group and 22 % in the treatment group ( P>.05 ) . There were no differences in the effectiveness of the drug whether given preoperatively or intraoperatively . Serious infections and wound infections were not encountered in patients receiving ampicillin In a multicenter , open , r and omized , comparative trial , 308 women undergoing cesarean section were given a single 1 gm dose of cefotetan or three 2 gm doses of cefoxitin after cord clamping to reduce the incidence of postoperative infectious morbidity . Of the 286 evaluable patients , 195 received cefotetan and 91 received cefoxitin . Most patients were in active labor and one third had ruptured membranes . Microorganisms cultured from the endocervix or intraoperatively from the endometrium or abdominal wall operative sites were comparable for the two groups . In this multicenter study , the difference between the percentage of patients receiving cefotetan who did not develop clinical signs and symptoms of infection ( 93 % ) and the percentage of patients receiving cefoxitin ( 85 % ) considered clinical successes was statistically significant ( p = 0.02 , chi 2 ) . The bacteriologic response rate for patients taking cefotetan was also significantly higher than that for patients taking cefoxitin ( 93 % versus 85 % , p = 0.03 ) . Isolates recovered from the endocervix , endometrium , or operative site were comparable for the two groups . Both drugs were well tolerated . In this evaluation , cefotetan administered in a single dose of 1 gm was more effective as a prophylactic agent than multiple 2 gm doses of cefoxitin in the reduction of infectious morbidity in this large series of patients undergoing cesarean section Summary . In a double‐blind r and omized controlled study 232 patients undergoing elective lower segment caesarean section were r and omly allocated to receive a pre‐operative prophylactic dose of a combination of crystalline penicillin and chloramphenicol or a placebo . The two groups were comparable in terms of patient characteristics and operation variables . The group receiving antibiotics had significantly fewer febrile and infectious morbid events and thus spent fewer days in hospital than the group receiving the placebo A prospect i ve , r and omized , open trial of a single intravenous dose of a new broad-spectrum and long-acting cephalosporin was compared with the effect of three doses of cefoxitin in a group of 70 women undergoing cesarean section who were at high risk for postoperative endomyometritis and wound infection . All patients either had ruptured membranes or were in active labor , or both , without clinical ly detectable chorioamnionitis at the time of prophylaxis . Forty-six women received a single 2 gm dose of cefotetan and 24 received 2 gm of cefoxitin every 4 hours to complete a three-dose regimen . Outcomes of infectious febrile morbidity due to endomyometritis ( 15 % versus 8 % ) , wound erythema ( 4 % versus 12 % ) , and other parameters were similar for cefotetan and cefoxitin , respectively . Both agents were well tolerated in this high-risk population . Within the limits of this study , single-dose cefotetan chemoprophylaxis appears to be comparable to multidose cefoxitin administration in reducing morbidity in operative site infections after cesarean section |
13,217 | 29,351,865 | The study from Syria reported that a communication skills training intervention for resident doctors was not associated with higher satisfaction reported by women .
In the UK study , patient-actors ' ( experienced midwives ) perceptions of safety and communication significantly improved for postpartum haemorrhage scenarios after training with patient-actors in local hospitals , compared with training using manikins in simulation centres , but no differences were identified for other scenarios .
KEY CONCLUSIONS AND IMPLICATION S FOR PRACTICE the review identified a lack of evidence on impact of interventions to support effective communication between maternity care staff and healthy women during labour and birth .
Very low quality evidence was found on effectiveness of communication training of maternity care staff . | OBJECTIVES the objectives of this review were ( 1 ) to assess whether interventions to support effective communication between maternity care staff and healthy women in labour with a term pregnancy could improve birth outcomes and experiences of care ; and ( 2 ) to synthesize information related to the feasibility of implementation and re sources required . | Objective : To explore the effect of training on patient-actor perception of care during simulated obstetric emergencies . Method : A sub analysis from a prospect i ve r and omised controlled trial in six UK hospitals and the Bristol Medical Simulation Centre , UK . Midwives and doctors working in participating hospitals were eligible for inclusion . 140 participants ( 22 junior and 23 senior doctors , 47 junior and 48 senior midwives ) were r and omised to one of four obstetric emergency training interventions : 1-day course at local hospitals ; 1-day course at simulation centre ; 2-day course with teamwork training at local hospitals ; and 2-day course with teamwork training at simulation centre . Local training used patient-actors and low-fidelity part-task trainers whereas simulation centre training used full-bodied computerised manikins and high-fidelity part-task trainers . Three weeks before and after the training , the participants managed three simulated obstetric emergencies . Patient-actors scored their care after each simulation using a patient-actor perception score ( communication , safety , respect ) . Results : The following numbers of scores were awarded : 139 and 132 participant and 46 and 48 team scenarios , before and after training , respectively . There was a significant improvement in all scores in all scenarios after the training ( p = 0.017 to > 0.001 ) . Perception of safety and communication during postpartum haemorrhage was significantly improved following training with patient-actors compared with training with manikins ( safety p = 0.048 , communication p = 0.035 ) . Teamwork training offered no additional benefit to patient-actors ’ perception of their care . Conclusions : All multiprofessional training improved patient-actor perception of care . Training using a patient-actor may be better at improving perception of safety and communication than training with a computerised manikin simulator Objectives To determine the effect of training residents in interpersonal and communication skills on women ’s satisfaction with doctor – woman relationship in labour and delivery rooms . Design A stepped wedge cluster r and omised trial . Setting 4 tertiary care teaching maternity hospitals in Damascus , Syria . Participants 2000 women who gave birth to a living baby in the four study hospitals and consented to participate in the intervention took part in the study . Women with difficult labour and high-risk pregnancies were excluded . All were interviewed at home after discharge . Interventions A specially design ed training package in communication skills was delivered to all resident doctors at the four hospitals . Primary outcome measures The main outcome measure was women ’s satisfaction with interpersonal relationships in labour and delivery rooms measured via a series of questions on a Likert scale modified from the Medical Interview Satisfaction Scale . Results At the individual level , the mean for the average satisfaction score was 3.23 ( SD 0.72 ) of a possible score of 5 in the control group and 3.42 ( SD 0.73 ) in the intervention group . Using generalised linear mixed models , we were unable to detect a difference between the mean for the average satisfaction score of women in the intervention arm and that of women in the control arm ; the 95 % CI associated with the effect of the intervention ranged from –0.08 to 0.15 . Conclusions Despite slight changes in the observed residents ’ communication skills , the training package in communication skills does not seem to be associated with higher satisfaction scores of women . This raises the question of whether training individuals without further structural changes in the delivery of care and without further reinforcement of the training can have an impact on improving the quality of doctor – patient communication . Trial Registration Number IS RCT Background To assess the student perspective on acceptability , realism , and perceived effect of communication training with peer role play ( RP ) and st and ardised patients ( SP ) . Methods 69 prefinal year students from a large German medical faculty were r and omly assigned to one of two groups receiving communication training with RP ( N = 34 ) or SP ( N = 35 ) in the course of their paediatric rotation . In both groups , training addressed major medical and communication problems encountered in the exploration and counselling of parents of sick children . Acceptability and realism of the training as well as perceived effects and applicability for future parent-physician encounters were assessed using six-point Likert scales . Results Both forms of training were highly accepted ( RP 5.32 ± .41 , SP 5.51 ± .44 , n.s . ; 6 = very good , 1 = very poor ) and perceived to be highly realistic ( RP 5.60 ± .38 , SP 5.53 ± .36 , n.s . ; 6 = highly realistic , 1 = unrealistic ) . Regarding perceived effects , participation was seen to be significantly more worthwhile in the SP group ( RP 5.17 ± .37 , SP 5.50 ± .43 ; p < .003 ; 6 = totally agree , 1 = do n't agree at all ) . Both training methods were perceived as useful for training communication skills ( RP 5.01 ± .68 , SP 5.34 ± .47 ; 6 = totally agree ; 1 = do n't agree at all ) and were considered to be moderately applicable for future parent-physician encounters ( RP 4.29 ± 1.08 , SP 5.00 ± .89 ; 6 = well prepared , 1 = unprepared ) , with usefulness and applicability both being rated higher in the SP group ( p < .032 and p < .009 ) . Conclusions RP and SP represent comparably valuable tools for the training of specific communication skills from the student perspective . Both provide highly realistic training scenarios and warrant inclusion in medical curricula . Given the expense of SP , deciding which method to employ should be carefully weighed up . From the perspective of the students in our study , SP were seen as a more useful and more applicable tool than RP . We discuss the potential of RP to foster a greater empathic appreciation of the patient perspective |
13,218 | 23,439,426 | There is evidence that maximal isometric contractions and prolonged static stretching ( > 5 min ) of the triceps surae complex cause an immediate decrease in AT stiffness , whereas prolonged running and hopping have minimal effect .
Limited but consistent evidence exists , indicating that AT hysteresis is reduced after prolonged static stretching .
Consistent evidence supports a reduction in free AT diameter ( anterior-posterior ) after dynamic ankle exercise , and this change appears most pronounced in the healthy tendon and after eccentric exercise .
The mechanical and morphological properties of the AT in vivo are affected by acute exercise in a mode- and dose-dependent manner .
Transient changes in AT stiffness , hysteresis , and diameter after unaccustomed exercise modes and doses may expose the tendon to increased risk of strain injury and impact on the mechanical function of the triceps surae muscle-tendon unit | INTRODUCTION Underst and ing the mechanical and morphological adaptation of the Achilles tendon ( AT ) in response to acute exercise could have important implication s for athletic performance , injury prevention , and rehabilitation .
The purpose of this study was to conduct a systematic review and critical evaluation of the literature to determine the immediate effect of a single bout of exercise on the mechanical and morphological properties of the AT in vivo . | In the present experiment we obtained the tensile properties of the human gastrocnemius tendon , a high-stressed tendon suitable for spring-like action during locomotion . Measurements were taken in vivo in six men . The gastrocnemius tendon elongation during tendon loading-unloading induced by muscle contraction-relaxation was measured using real-time ultrasonography . Tendon forces were calculated from the moment generated during isometric plantarflexion contraction , using tendon moment arm length data obtained in vivo with the tendon travel method . Tendon stiffness data were calculated from the slope of the tendon force-elongation curve , and were then normalized to the tendon 's original dimensions , obtained from morphometric analysis of sonographs , to estimate the tendon Young 's modulus . Mechanical hysteresis values were obtained from area calculations by numerical integration . The elongation of the tendon increased curvilinearly with the force acting upon it , from 1.7+/-1 mm ( 0.8+/-0.3 % strain ) at 87.5+/-8.5 N to 11.1+/-3.1 mm ( 4.9+/-1 % strain ) at 875+/-85 N. The tendon Young 's modulus and mechanical hysteresis were 1.16+/-0.15 GPa and 18+/-3 % , respectively . These values fall within the range of values obtained from in vitro experiments and are very similar to the respective values recently obtained from in vivo measurements in the less highly stressed human tibialis anterior tendon ( 1.2 GPa and 19 % ) , thus indicating that the material properties of tendon are independent of physiological loading and function . Combining the present tendon force-elongation data with previously reported Achilles tendon force data recorded during walking indicates that the gastrocnemius tendon would provide approximately 6 % of the total external work produced by the locomotor system . This estimate illustrates the contribution of passive elastic mechanisms on the economy and efficiency of walking . The contributions would be greater in more active exercise such as running The aim of the present study was to investigate the behavior of human muscle fascicles during dynamic contractions . Eight subjects performed maximal isometric dorsiflexion contractions at six ankle joint angles and maximal isokinetic concentric and eccentric contractions at five angular velocities . Tibialis anterior muscle architecture was measured in vivo by use of B-mode ultrasonography . During maximal isometric contraction , fascicle length was shorter and pennation angle larger compared with values at rest ( P < 0.01 ) . During isokinetic concentric contractions from 0 to 4.36 rad/s , fascicle length measured at a constant ankle joint angle increased curvilinearly from 49.5 to 69.7 mm ( 41 % ; P < 0.01 ) , whereas pennation angle decreased curvilinearly from 14.8 to 9.8 degrees ( 34 % ; P < 0.01 ) . During eccentric muscle actions , fascicles contracted quasi-isometrically , independent of angular velocity . The behavior of muscle fascicles during shortening contractions was believed to reflect the degree of stretch applied to the series elastic component , which decreases with increasing contraction velocity . The quasi-isometric behavior of fascicles during eccentric muscle actions suggests that the series elastic component acts as a mechanical buffer during active lengthening The aim of this study was to determine the effects of 14 wk of plyometric training on mechanical properties of the Achilles tendon . Nineteen subjects were r and omly assigned to trained or control group . Cross-sectional area ( CSA ) , stiffness , and dissipation coefficient of the Achilles tendon were measured before and after the training period . In the trained group , a decrease in dissipation coefficient ( -35.0 % ; P<0.05 ) and an upward trend in stiffness ( + 24.1 % ) of the Achilles tendon was found , without any changes in Achilles tendon CSA ( P>0.05 ) . Plyometric training enhances the muscular tension transmission mainly through a reduction in energy dissipated by the tendon . The lack of changes in the Achilles tendon CSA indicates that changes in mechanical properties would mainly result from a qualitative change in tendinous tissues rather than from changes in the geometry of the Achilles tendon While microgravity exposure is known to cause deterioration of skeletal muscle performance , little is known regarding its effect on tendon structure and function . Hence , the aims of this study were to investigate the effects of simulated microgravity on the mechanical properties of human tendon and to assess the effectiveness of resistive counter measures in preventing any detrimental effects . Eighteen men ( aged 25 - 45 yr ) underwent 90 days of bed rest : nine performed resistive exercise during this period ( BREx group ) , and nine underwent bed rest only ( BR group ) . Calf-raise and leg-press exercises were performed every third day using a gravity-independent flywheel device . Isometric plantar flexion contractions were performed by using a custom-built dynamometer , and ultrasound imaging was used to determine the tensile deformation of the gastrocnemius tendon during contraction . In the BR group , tendon stiffness estimated from the gradient of the tendon force-deformation relation decreased by 58 % ( preintervention : 124 + /- 67 N/mm ; postintervention : 52 + /- 28 N/mm ; P < 0.01 ) , and the tendon Young 's modulus decreased by 57 % postintervention ( P < 0.01 ) . In the BREx group , tendon stiffness decreased by 37 % ( preintervention : 136 + /- 66 N/mm ; postintervention : 86 + /- 47 N/mm ; P < 0.01 ) , and the tendon Young 's modulus decreased by 38 % postintervention ( P < 0.01 ) . The relative decline in tendon stiffness and Young 's modulus was significantly ( P < 0.01 ) greater in the BR group compared with the BREx group . Unloading decreased gastrocnemius tendon stiffness due to a change in tendon material properties , and , although the exercise counter measures did attenuate these effects , they did not completely prevent them . It is suggested that the total loading volume was not sufficient to completely prevent alterations in tendon mechanical properties Architectural properties of the triceps surae muscles were determined in vivo for six men . The ankle was positioned at 15 degrees dorsiflexion ( -15 degrees ) and 0 , 15 , and 30 degrees plantar flexion , with the knee set at 0 , 45 , and 90 degrees . At each position , longitudinal ultrasonic images of the medial ( MG ) and lateral ( LG ) gastrocnemius and soleus ( Sol ) muscles were obtained while the subject was relaxed ( passive ) and performed maximal isometric plantar flexion ( active ) , from which fascicle lengths and angles with respect to the aponeuroses were determined . In the passive condition , fascicle lengths changed from 59 , 65 , and 43 mm ( knee , 0 degrees ; ankle , -15 degrees ) to 32 , 41 , and 30 mm ( knee , 90 degrees ankle , 30 degrees ) for MG , LG , and Sol , respectively . Fascicle shortening by contraction was more pronounced at longer fascicle lengths . MG had greatest fascicle angles , ranging from 22 to 67 degrees , and was in a very disadvantageous condition when the knee was flexed at 90 degrees , irrespective of ankle positions . Different lengths and angles of fascicles , and their changes by contraction , might be related to differences in force-producing capabilities of the muscles and elastic characteristics of tendons and aponeuroses Plyometric training is commonly used to improve athletic performance ; however , it is unclear how each component of the muscle – tendon complex ( MTC ) is affected by this intervention . The effects of 14 weeks of plyometric training on the passive stiffness of the gastrocnemii muscles and Achilles tendon was determined simultaneously to assess possible local adaptations of elastic properties . The passive force – length relationship of the gastrocnemii MTC and elongation of the gastrocnemii muscles were determined using ultrasonography during passive cyclic stretching in 19 subjects divided into trained ( n = 9 ) and control ( n = 10 ) groups . An upward trend in stiffness of the gastrocnemii MTC ( P = 0.09 ) and a significant increase in the intrinsic gastrocnemii muscle stiffness were found ( P < 0.05 ) . In contrast , no significant change in gastrocnemii tendon stiffness , or in muscle and tendon geometry , was determined ( P > 0.05 ) . Considering the lack of change in gastrocnemii muscle geometry , the change in the gastrocnemii muscle stiffness may be mainly due to a change in the intrinsic mechanical properties of the muscular tissues Objective : To prospect ively investigate tendon thickness and tendon structure by ultrasonography in patients treated with eccentric calf muscle training for painful chronic Achilles tendinosis located at the 2–6 cm level in the tendon . Methods : The patients were examined with grey scale ultrasonography before and 3.8 years ( mean ) after the 12 week eccentric training regimen . At follow up , a question naire assessed present activity level and satisfaction with treatment . Results : Twenty six tendons in twenty five patients ( 19 men and six women ) with a mean age of 50 years were followed for a mean of 3.8 years ( range 1.6–7.75 ) . All patients had a long duration of painful symptoms ( mean 17.1 months ) from chronic Achilles tendinosis before treatment . At follow up , 22 of 25 patients were satisfied with treatment and active in Achilles tendon loading activities at the desired level . Ultrasonography showed that tendon thickness ( at the widest part ) had decreased significantly ( p<0.005 ) after treatment ( 7.6 ( 2.3 ) v 8.8 ( 3 ) mm ; mean ( SD ) ) . In untreated normal tendons , there was no significant difference in thickness after treatment ( 5.3 ( 1.3 ) mm before and 5.9 ( 0.8 ) mm after ) . All tendons with tendinosis had structural abnormalities ( hypoechoic areas and irregular structure ) before the start of treatment . After treatment , the structure was normal in 19 of the 26 tendons . Six of the seven patients with remaining structural abnormalities experienced pain in the tendon during loading . Conclusions : Ultrasonographic follow up of patients with mid-portion painful chronic Achilles tendinosis treated with eccentric calf muscle training showed a localised decrease in tendon thickness and a normalised tendon structure in most patients . Remaining structural tendon abnormalities seemed to be associated with residual pain in the tendon Background : Controversy exists on stretching and warm-up in injury prevention . We hypothesized that warm up has a greater effect on Achilles tendon biomechanics than static stretching . This study investigated static stretching and warm-up on Achilles tendon biomechanics in recreational athletes , in vivo . Material s and Methods : Ten active , healthy subjects , 5 males , 5 females , With a mean age of 22.9 years with no previous Achilles tendon injuries were recruited . Typical stretching and warm-up routines were created . Testing was performed in a r and omized cross-over design . A custom-built dynamometer was utilized to perform controlled isometric plantarflexion . A low profile ultrasound probe was utilized to visualize the musculotendinous junction of the medial gastrocnemius . An eight-camera motion capture system was used to capture ankle motion . Custom software calculated Achilles tendon biomechanics . Results : Achilles tendon force production was consistent . No statistically significant differences were detected in stretch , stiffness , and strain between pre- , post-stretching , and post-warm-up interventions . Conclusion : Stretching or warm-up alone , and combined did not demonstrate statistically significant differences . Stretching and warm-up may have an equivalent effect on Achilles tendon biomechanics . Prolonged and more intense protocol s may be required for changes to occur . Clinical Relevance : Stretching and warm-up of the Achilles before exercise are commonly practice d. Investigating the effect of stretching and warm-up may shed light on potential injury prevention PURPOSE Many studies have been undertaken to define the effects of static and ballistic stretching . However , most research ers have focused their attention on joint range-of-motion measures . The objective of the present study was to investigate whether static- and ballistic-stretching programs had different effects on passive resistive torque measured during isokinetic passive motion of the ankle joint and tendon stiffness measured by ultrasound imaging . METHODS Eighty-one healthy subjects were r and omized into three groups : a static-stretch group , a ballistic-stretch group , and a control group . Both stretching groups performed a 6-wk stretching program for the calf muscles . Before and after this period , all subjects were evaluated for ankle range of motion , passive resistive torque of the plantar flexors , and the stiffness of the Achilles tendon . RESULTS The results of the study reveal that the dorsiflexion range of motion was increased significantly in all groups . Static stretching result ed in a significant decrease of the passive resistive torque , but there was no change in Achilles tendon stiffness . In contrast , ballistic stretching had no significant effect on the passive resistive torque of the plantar flexors . However , a significant decrease in stiffness of the Achilles tendon was observed in the ballistic-stretch group . CONCLUSION These findings provide evidence that static and ballistic stretching have different effects on passive resistive torque and tendon stiffness , and both types of stretching should be considered for training and rehabilitation programs We prospect ively studied the effect of heavy-load eccentric calf muscle training in 15 recreational athletes ( 12 men and 3 women ; mean age , 44.3 7.0 years ) who had the diagnosis of chronic Achilles tendinosis ( degenerative changes ) with a long duration of symptoms despite conventional nonsurgical treatment . Calf muscle strength and the amount of pain during activity ( recorded on a visual analog scale ) were measured before onset of training and after 12 weeks of eccentric training . At week 0 , all patients had Achilles tendon pain not allowing running activity , and there was significantly lower eccentric and concentric calf muscle strength on the injured compared with the noninjured side . After the 12-week training period , all 15 patients were back at their preinjury levels with full running activity . There was a significant decrease in pain during activity , and the calf muscle strength on the injured side had increased significantly and did not differ significantly from that of the noninjured side . A comparison group of 15 recreational athletes with the same diagnosis and a long duration of symptoms had been treated conventionally , i.e. , rest , nonsteroidal antiinflammatory drugs , changes of shoes or orthoses , physical therapy , and in all cases also with ordinary training programs . In no case was the conventional treatment successful , and all patients were ultimately treated surgically . Our treatment model with heavy-load eccentric calf muscle training has a very good short-term effect on athletes in their early forties PURPOSE To evaluate the tendon response after acute strength training in chronic Achilles tendinosis using magnetic resonance imaging ( MRI ) . METHODS Twenty-two patients ( 44 Achilles tendons , 15 males , 8 patients with bilateral symptoms ) with a median age of 45 yr ( range 28 - 57 yr ) were included in the study . In all patients , both Achilles tendons were examined with MRI before and immediately after a st and ardized training program . The most painful side underwent 6 sets and 15 repetitions of heavy-loaded eccentric training . The contralateral tendons underwent only concentric loading during the training program . The tendon volume and the intratendinous signal were evaluated and calculated by MRI using a seed-growing technique . RESULTS The immediate response of eccentric loading on the symptomatic tendons result ed in a 12 % increase of the tendon volume , evident on T2-WI , from 7.8 + /- 2.0 to 8.8 + /- 2.7 cm3 ( P < 0.001 ) , and a 31 % increase of the intratendinous signal evident on PD-WI , from 221 + /- 74 to 278 + /- 78 signal units ( SU ) ( P < 0.001 ) . The corresponding sequences on the contralateral concentrically loaded tendons showed an increase of 17 % of tendon volume , from 6.1 + /- 1.5 to 7.0 + /- 1.6 cm3 ( P < 0.001 ) , and an increase of 27 % of the intratendinous signal , from 170 + /- 55 to 211 + /-57 SU ( P < 0.001 ) . There was no significant difference of the mean of the increased tendon volume and the intratendinous signal between the eccentrically heavily loaded symptomatic tendons and the concentrically loaded contralateral tendons . CONCLUSIONS Both eccentric and concentric loading of the Achilles tendon result ed in increased total tendon volume and intratendinous signal . This increase may be explained by a higher water content and /or hyperemia in the Achilles tendon during and /or immediately after strength training of the gastrocnemius-soleus complex PURPOSE Eccentric exercise has become the treatment of choice for Achilles tendinopathy . However , little is known about the acute response of tendons to eccentric exercise or the mechanisms underlying its clinical benefit . This research evaluated the sonographic characteristics and acute anteroposterior ( AP ) strain response of control ( healthy ) , asymptomatic , and symptomatic Achilles tendons to eccentric exercise . METHODS Eleven male adults with unilateral midportion Achilles tendinopathy and nine control male adults without tendinopathy participated in the research . Sagittal sonograms of the Achilles tendon were acquired immediately before and after completion of a common eccentric rehabilitation exercise protocol and again 24 h later . Tendon thickness , echogenicity , and AP strain were determined 40 mm proximal to the calcaneal insertion . RESULTS Compared with the control tendon , both the asymptomatic and symptomatic tendons were thicker ( P < 0.05 ) and hypoechoic ( P < 0.05 ) at baseline . All tendons decreased in thickness immediately after eccentric exercise ( P < 0.05 ) . The symptomatic tendon was characterized by a significantly lower AP strain response to eccentric exercise compared with both the asymptomatic and control tendons ( P < 0.05 ) . AP strains did not differ in the control and asymptomatic tendons . For all tendons , preexercise thickness was restored 24 h after exercise completion . CONCLUSIONS These observations support the concept that Achilles tendinopathy is a bilateral or systemic process and structural changes associated with symptomatic tendinopathy alter fluid movement within the tendon matrix . Altered fluid movement may disrupt remodeling and homeostatic processes and represents a plausible mechanism underlying the progression of tendinopathy This study compared the effects of static stretching ( ST ) and repeated muscle contractions ( CON ) on the viscoelastic properties of tendon structures in vivo . Eight male subjects performed ST ( passively flexed to 35 of dorsiflexion ) for 5 min and 50 repetitions of isometric maximum voluntary contraction ( MVC ) for 3 s each with 3 s relaxation . Before and after each task , the elongation of the tendon and aponeurosis of the medial gastrocnemius muscle ( MG ) was directly measured by ultrasonography , while the subjects performed ramp isometric plantar flexion up to MVC , followed by a ramp relaxation . The relationship between the estimated muscle force ( Fm ) and tendon elongation ( L ) during the ascending phase was applied to a linear regression , the slope of which was defined as stiffness of the tendon structures . The percentage of the area within the Fm-L loop to the area beneath the curve during the ascending phase was calculated as an index representing hysteresis . The ST protocol significantly decreased the stiffness ( -8 % ) and hysteresis ( 29 % ) . , respectively . In contrast , the CON protocol significantly decreased the stiffness , but not the hysteresis . These results suggested that the stretching and repeated contractions would make the tendon structures more complaint , and further decreased the hysteresis of the tendon structures |
13,219 | 26,321,114 | Conclusions Digoxin is associated with a neutral effect on mortality in r and omised trials and a lower rate of admissions to hospital across all study types . | Objective To clarify the impact of digoxin on death and clinical outcomes across all observational and r and omised controlled trials , accounting for study design s and methods . | Background and Purpose — It is often thought that elderly patients in particular would benefit from endovascular aneurysm treatment . The aim of this analysis was therefore to compare the efficacy and safety of endovascular coiling ( EVT ) with neurosurgical clipping ( NST ) in the subgroup of elderly SAH patients in the International Subarachnoid Aneurysm Trial ( ISAT ) . Methods — In the ISAT cohort 278 SAH patients , 65 years or older , were enrolled . The patients were r and omly allocated EVT ( n=138 ) or NST ( n=140 ) . The primary outcome was the proportion of patients with a modified Rankin scale score of 0 to 2 ( independent survival ) at 1 year after the SAH . The rates of procedural complications and adverse events were also recorded . Results — 83 of 138 ( 60.1 % ) patients allocated EVT were independent compared to 78 of 140 ( 56.1 % ) allocated NST ( N.S. ) . 36 of 50 ( 72.0 % ) patients with internal carotid and posterior communicating artery aneurysms allocated EVT were independent compared to 26 of 50 ( 52.0 % ) allocated NST ( P<0.05 ) . 10 of 22 ( 45.5 % ) patients with middle cerebral artery aneurysms allocated EVT were independent compared to 13 of 15 ( 86.7 % ) allocated NST ( P<0.05 ) . The epilepsy frequency was 0.7 % in the EVT group compared to 12.9 % in the NST group ( P<0.001 ) . Conclusions — In good grade elderly SAH patients with small anterior circulation aneurysms , EVT should probably be the favored treatment for ruptured internal carotid and posterior communicating artery aneurysms , whereas elderly patients with ruptured middle cerebral artery aneurysms appear to benefit from NST . EVT result ed in a lower epilepsy frequency than NST We retrospectively performed stepwise logistic regression analysis on 1,509 patients with chronic heart failure in 4 multicenter United States studies and 1 Australia-New Zeal and study to examine the effect of digoxin in patients r and omized to carvedilol or placebo . Patients receiving digoxin had more advanced heart failure , the incidence of hospitalization for any cause and the combination of all-cause death and all-cause hospitalization were the same in the digoxin versus no-digoxin groups AIMS To determine the effects of digoxin on all-cause mortality and heart failure ( HF ) hospitalizations , regardless of ejection fraction , accounting for serum digoxin concentration ( SDC ) . METHODS AND RESULTS This comprehensive post-hoc analysis of the r and omized controlled Digitalis Investigation Group trial ( n=7788 ) focuses on 5548 patients : 1687 with SDC , drawn r and omly at 1 month , and 3861 placebo patients , alive at 1 month . Overall , 33 % died and 31 % had HF hospitalizations during a 40-month median follow-up . Compared with placebo , SDC 0.5 - 0.9 ng/mL was associated with lower mortality [ 29 vs. 33 % placebo ; adjusted hazard ratio ( AHR ) , 0.77 ; 95 % confidence interval ( CI ) , 0.67 - 0.89 ] , all-cause hospitalizations ( 64 vs. 67 % placebo ; AHR , 0.85 ; 95 % CI , 0.78 - 0.92 ) and HF hospitalizations ( 23 vs. 33 % placebo ; AHR , 0.62 ; 95 % CI , 0.54 - 0.72 ) . SDC > or = 1.0 ng/mL was associated with lower HF hospitalizations ( 29 vs. 33 % placebo ; AHR , 0.68 ; 95 % CI , 0.59 - 0.79 ) , without any effect on mortality . SDC 0.5 - 0.9 reduced mortality in a wide spectrum of HF patients and had no interaction with ejection fraction > 45 % ( P=0.834 ) or sex ( P=0.917 ) . CONCLUSIONS Digoxin at SDC 0.5 - 0.9 ng/mL reduces mortality and hospitalizations in all HF patients , including those with preserved systolic function . At higher SDC , digoxin reduces HF hospitalization but has no effect on mortality or all-cause hospitalizations Objectives This study aims to assess whether digoxin has a different effect on mortality risk for women than it does for men in patients with heart failure ( HF ) . Design This study uses the UK-based The Health Information Network population data base in a cohort study of the impact of digoxin exposure on mortality for men and women who carry the diagnosis of HF . Digoxin exposure was assessed based on prescribing data . Multivariable Cox proportional hazards models were used to assess whether there was an interaction between sex and digoxin affecting mortality hazard . Setting The setting was primary care outpatient practice s. Participants The study cohort consisted of 17 707 men and 19 227 women with the diagnosis of HF who contributed only time without digoxin exposure and 9487 men and 10 808 women with the diagnosis of HF who contributed time with digoxin exposure . Main outcome measures The main outcome measure was all-cause mortality . Results The primary outcome of this study was the absence of a large interaction between digoxin use and sex affecting mortality . For men , digoxin use was associated with a HR for mortality of 1.00 , while for women , the HR was also 1.00 ( p value for interaction 0.65 ) . The results of sensitivity analyses were consistent with those of the primary analysis . Conclusion Observational data do not support the concern that there is a substantial increased risk of mortality due to the use of digoxin in women . This finding is consistent with previous observational studies but discordant with results from a post hoc analysis of a r and omised controlled trial of digoxin versus placebo The propensity score is the probability of treatment assignment conditional on observed baseline characteristics . The propensity score allows one to design and analyze an observational ( nonr and omized ) study so that it mimics some of the particular characteristics of a r and omized controlled trial . In particular , the propensity score is a balancing score : conditional on the propensity score , the distribution of observed baseline covariates will be similar between treated and untreated subjects . I describe 4 different propensity score methods : matching on the propensity score , stratification on the propensity score , inverse probability of treatment weighting using the propensity score , and covariate adjustment using the propensity score . I describe balance diagnostics for examining whether the propensity score model has been adequately specified . Furthermore , I discuss differences between regression-based methods and propensity score-based methods for the analysis of observational data . I describe different causal average treatment effects and their relationship with propensity score analyses Background — There is a paucity of international data on the various types of atrial fibrillation ( AF ) outside the highly selected population s from r and omized trials . This study aim ed to describe patient characteristics , risk factors , comorbidities , symptoms , management strategy , and control of different types of AF in real-life practice . Methods and Results — Real-life global survey evaluating patients with atrial fibrillation ( RealiseAF ) was a contemporary , large-scale , cross-sectional international survey of patients with AF who had ≥1 episode in the past 12 months . Investigators were r and omly selected to avoid bias . Among 9816 eligible patients from 831 sites in 26 countries , 2606 ( 26.5 % ) had paroxysmal , 2341 ( 23.8 % ) had persistent , and 4869 ( 49.6 % ) had permanent AF . As AF progressed from paroxysmal to persistent and permanent forms , the prevalence of comorbidities , such as heart failure ( 32.9 % , 44.3 % , and 55.6 % ) , coronary artery disease ( 30.0 % , 32.9 % , and 34.3 % ) , cerebrovascular disease ( 11.7 % , 10.8 % , and 17.6 % ) , and valvular disease ( 16.7 % , 21.2 % , and 35.8 % ) , increased , and the prevalence of lone AF decreased . Similarly , there was an increase in mean CHADS2 [ cardiac failure , hypertension , age , diabetes , stroke ( doubled ) ] score ( 1.7 , 1.8 , and 2.2 ) , and more than half of patients ( 51.0 % , 56.7 % , and 67.3 % ) qualified for oral anticoagulants . Almost 90 % of patients received ≥1 antiarrhythmic drug , but > 60 % had European Heart Rhythm Association symptom scores from II to IV . Furthermore , 40.7 % of persistent and 49.8 % of permanent AF patients were still in AF with a heart rate > 80 beats per minute . Conclusions — This survey disclosed high cardiovascular risks and an unmet need in daily practice for patients with any type of AF , especially those with the permanent form BACKGROUND The Atrial Fibrillation Follow-up Investigation of Rhythm Management trial showed that digoxin was associated with increased mortality in patients with atrial fibrillation . OBJECTIVES To assess the association of digoxin with cardiovascular ( CV ) morbidity and mortality in patients with permanent atrial fibrillation enrolled in the Dutch Rate Control Efficacy in Permanent AF : A Comparison Between Lenient Versus Strict Rate Control II trial as well as to assess the role of digoxin to achieve heart rate targets . METHODS The primary outcome was a composite of CV morbidity and mortality . Secondary outcomes included CV hospitalization and all-cause mortality or heart failure ( HF ) hospitalization . Of the 614 patients , 608 ( 99 % ) completed the dose-adjustment phase . Outcome events were analyzed from the end of the dose-adjustment phase until the end of follow-up . The median follow-up period was 2.9 years ( interquartile range 2.7 - 3.0 years ) . RESULTS In total , 284 patients ( 46.7 % ) used digoxin after the dose-adjustment phase ( median dosage 0.250 mg ; interquartile range 0.0625 - 0.750 mg ) . These patients were more often women , previously admitted for HF , had an increased left ventricular end-systolic diameter , and more often r and omized to strict rate control . By using Cox proportional hazards regression analysis , the use of digoxin was not associated with an increased risk for the primary and secondary outcomes . For the primary outcome , the 3-year estimated cumulative incidence was 12.9 % vs 13.4 % in the digoxin group vs the no-digoxin group ( unadjusted hazard ratio [ HR ] 0.97 ; 95 % confidence interval [ CI ] 0.62 - 1.52 ) . Incidence was 19.4 % vs. 19.5 % for CV hospitalization ( unadjusted HR 1.00 ; 95 % CI 0.69 - 1.45 ) and 6.6 % vs. 9.9 % for all-cause mortality or HF hospitalization ( unadjusted HR 0.62 ; 95 % CI 0.34 - 1.13 ) in the digoxin group vs the no-digoxin group . CONCLUSION The use of digoxin was not associated with increased morbidity and mortality Increased mortality in digoxin-treated subjects has been demonstrated in patients with recent myocardial infa rct ion . Those with congestive heart failure ( CHF ) due to causes other than myocardial infa rct ion seem to be free from this effect . No information is currently available concerning mortality in elderly people who are frequently prescribed digitalis even in the absence of CHF . The aim of this study was to investigate whether subjects improperly receiving digoxin were worse off than those not receiving this drug . This analysis is a part of CASTEL , a population -based prospect i ve study that has enrolled a cohort of 2,254 subjects aged > or = 65 years . CHF was diagnosed in 187 subjects and atrial fibrillation ( AF ) in 90 . The remaining 1,977 were free from CHF and in sinus rhythm , but 447 were treated with digitalis . Cumulative mortality and morbid events by digitalis treatment were calculated in all these categories . Among subjects free from CHF and AF ( improper use ) , all-cause and cardiovascular mortality was significantly higher among those taking digitalis than in those who did not . Non-fatal events including CHF were also more apparent in the former than in the latter . Cox analysis confirmed digitalis as a predictor of mortality in these subjects . No effect of digitalis on survival was found in patients with CHF or AF ( proper use ) . In elderly subjects without atrial fibrillation or CHF , the use of digitalis worsens morbidity and mortality To determine whether treatment with digitalis is associated with decreased survival after acute myocardial infa rct ion ( AMI ) , data from 504 patients who were enrolled in a postinfa rct ion natural history study were analyzed . At the time of discharge , 229 patients ( 45 % ) were taking digitalis . After 3 years of follow-up , the cumulative survival rate for patients discharged on a regimen of digitalis was 66 % , compared with 87 % for those not treated ( p less than 0.001 ) . Univariate analysis showed that statistically significant differences existed between the 2 groups with respect to age , previous AMI , left ventricular failure in the coronary care unit , atrial fibrillation in the coronary care unit , peak creatine kinase levels , enlarged heart and pulmonary vascular congestion on the discharge chest x-ray , ventricular arrhythmias and treatment with diuretic , antiarrhythmic and beta-blocking drugs . Survival analysis using Cox 's regression model showed that the association between digitalis and decreased survival was of borderline significance after adjustment for atrial fibrillation and left ventricular failure . Serum digoxin concentration was measured in 83 % of the patients who took digitalis . Survival was inversely and significantly related to serum digoxin , i.e. , the higher the serum digoxin concentration , the lower the long-term survival rate . After adjusting for atrial fibrillation and left ventricular failure , serum digoxin was not significantly related to survival . Taken together with the results of 3 other large , nonr and omized studies of digitalis treatment after AMI , this study suggests that digitalis treatment may have adverse effects on survival during follow-up . ( ABSTRACT TRUNCATED AT 250 WORDS The Multicenter Diltiazem Postinfa rct ion Trial ( MDPIT ) reported no consistent diltiazem effect on new or worsened congestive heart failure ( CHF ) during 12 - 52 months ' follow-up after acute myocardial infa rct ion . This was puzzling in light of the observation that patients with findings suggesting left ventricular dysfunction ( LVD ) at baseline on diltiazem had more cardiac events ( cardiac mortality or recurrent nonfatal infa rct ion ) than such patients on placebo . We hypothesized that diltiazem increased the frequency of late CHF as well as of cardiac events , but only in patients predisposed by LVD . Using the same characterizing variables as the primary MDPIT analysis , we found that patients with pulmonary congestion , anterolateral Q wave infa rct ion , or reduced ejection fraction ( EF ) at baseline were more likely to have CHF during follow-up than those without these markers of LVD . CHF was particularly frequent in the patients with LVD who were r and omized to diltiazem . Among those with a baseline EF of less than 0.40 , late CHF appeared in 12 % ( 39/326 ) receiving placebo and 21 % ( 61/297 ) receiving diltiazem ( p = 0.004 ) . Life table analysis in patients with an EF of less than 0.40 confirmed more frequent late CHF in those taking diltiazem ( p = 0.0017 ) . In addition , the diltiazem-associated rise in the frequency of late CHF was progressively greater with increasingly severe decrements in baseline EF . This diltiazem effect was absent in patients with pulmonary congestion at baseline but an EF of 0.40 or more , suggesting a unique association between diltiazem-related late CHF and systolic LVD . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The role of cardiac glycosides in treating patients with chronic heart failure and normal sinus rhythm remains controversial . We studied the effect of digoxin on mortality and hospitalization in a r and omized , double-blind clinical trial . METHODS In the main trial , patients with a left ventricular ejection fraction of 0.45 or less were r and omly assigned to digoxin ( 3397 patients ) or placebo ( 3403 patients ) in addition to diuretics and angiotensin-converting-enzyme inhibitors ( median dose of digoxin , 0.25 mg per day ; average follow-up , 37 months ) . In an ancillary trial of patients with ejection fractions greater than 0.45 , 492 patients were r and omly assigned to digoxin and 496 to placebo . RESULTS In the main trial , mortality was unaffected . There were 1181 deaths ( 34.8 percent ) with digoxin and 1194 deaths ( 35.1 percent ) with placebo ( risk ratio when digoxin was compared with placebo , 0.99 ; 95 percent confidence interval , 0.91 to 1.07 ; P=0.80 ) . In the digoxin group , there was a trend toward a decrease in the risk of death attributed to worsening heart failure ( risk ratio , 0.88 ; 95 percent confidence interval , 0.77 to 1.01 ; P=0.06 ) . There were 6 percent fewer hospitalizations overall in that group than in the placebo group , and fewer patients were hospitalized for worsening heart failure ( 26.8 percent vs. 34.7 percent ; risk ratio , 0.72 ; 95 percent confidence interval , 0.66 to 0.79 ; P<0.001 ) . In the ancillary trial , the findings regarding the primary combined outcome of death or hospitalization due to worsening heart failure were consistent with the results of the main trial . CONCLUSIONS Digoxin did not reduce overall mortality , but it reduced the rate of hospitalization both overall and for worsening heart failure . These findings define more precisely the role of digoxin in the management of chronic heart failure Summary Controversy surrounds the safety of digoxin use in patients recovering from acute myocardial infa rct ion . Previous observations yielded contradictory conclusions . To determine whether digoxin therapy is associated with increased mortality in patients recovering from acute myocardial infa rct ion , we analyzed data from 1731 survivors of acute myocardial infa rct ion enrolled in the Secondary Prevention Reinfa rct ion Israeli Nifedipine Trial ( SPRINT ) , from which patients with severe heart failure were excluded . At the time of hospital discharge , 175 patients ( 10 % ) were taking digoxin . Mortality over 1 year after infa rct ion was significantly higher in patients treated with digoxin than in patients who were not receiving digoxin [ 27 of 175 ( 15 % ) vs. 60 of 1556 ( 4 % ) ; p<0.0001 ] . Digoxin administration was associated with increased mortality in several subsets of patients . Since patients treated with digoxin had baseline characteristics predictive of mortality more frequently than their counterparts , we adjusted for these differences . Multivariate analysis performed by the Cox proportional hazards model identified treatment with digoxin as an independent determinant associated with increased death during the first year after myocardial infa rct ion [ relative risk ( RR ) 2.8 ; 90 % confidence interval ( CI ) 1.8–4.2 ] . Subgroup multivariate analysis indicated digoxin as an independent predictor of first year death in 464 patients who developed heart failure during their hospital stay ( RR 2.3 ; 90 % CI 1.3–4.0 ) , as well as among 1267 patients who did not ( RR 3.4 ; 90 % CI 1.7–6.9 ) . The present study suggests a significant excess mortality associated with digoxin therapy after myocardial infa rct ion . The increased mortality risk may be related to unidentified variables associated with the severity of disease in patients treated with digoxin . However , our findings raise concern that the administration of digoxin may contribute to increased mortality in survivors of acute myocardial infa rct ion The influence of digitalis therapy on survivors of acute myocardial infa rct ion was examined in the placebo-treated patients from the Beta-Blocker Heart Attack Trial ( BHAT ) . Two hundred fifty ( 13 % ) of the 1,921 placebo-treated patients were receiving digitalis at the time of r and omization . Patients receiving digitalis differed from those not receiving digitalis in such baseline characteristics as age , prior history of heart failure , prior myocardial infa rct ion and angina pectoris . They also experienced a higher proportion of in-hospital complications including pulmonary edema , persistent hypotension , atrial fibrillation and heart failure in addition to a greater prevalence of complex ventricular premature beats . The total mortality rate over a mean 25 month follow-up period for digitalis-treated patients was 20.4 % compared with 8.2 % for patients not receiving digitalis ; the odds ratio was 2.87 ( p less than 0.05 ) . When the mortality rates were adjusted for heart failure and ventricular premature beat complexity , patients receiving digitalis again demonstrated a higher mortality rate , although the adjusted odds ratio was now lower ( 1.70 ) . When the patients receiving or not receiving digitalis were compared by a multiple logistic regression analysis adjusting for 17 independent variables predictive of mortality , the use of digitalis was no longer independently predictive of total mortality ( adjusted odds ratio 1.07 ) . These data indicate that patients receiving digitalis had more extensive cardiovascular disease and greater morbidity than patients not receiving digitalis . Their subsequent higher mortality rate was probably related to these factors rather than to digitalis therapy BACKGROUND Some evidence s suggest that the use of digoxin may be harmful inatrial fibrillation ( AF ) patients . The aim of the study was to investigate in a " real world " of AF patients receiving vitamin K antagonists ( VKAs ) , the relationship between digoxin use and mortality . METHODS Prospect i ve single-center observational study including 815 consecutive non-valvular AF patients treated with VKAs . Total mortality was the primary outcome of the study . We also performed a sub- analysis considering only cardiovascular ( CV ) deaths . Time in therapeutic range ( TTR ) was used for anticoagulation quality . RESULTS Median follow-up was 33.2months ( 2460 person-years ) ; 171 ( 21.0 % ) patients were taking digoxin . Compared to those without , patients on digoxin were older ( p=0.007 ) , with a clinical history of HF ( p<0.001 ) and at higher risk of thromboembolic events ( p<0.001 ) . No difference in TTR between the two groups was registered ( p=0.598 ) . During the follow-up , 85 deaths occurred : 47 CV and 38 non-CV deaths ; 35 deaths occurred in digoxin users ( 20.6 % ) . A significant increased rate of total mortality was observed in digoxin-treated patients ( p<0.001 ) . Multivariable analysis showed that digoxin was associated with total mortality ( hazard ratio [ HR ] : 2.224 , p<0.001 ) and CV death ( HR : 4.686 , p<0.001 ) . A propensity score-matched analysis confirmed that digoxin was associated with total mortality ( HR : 2.073 , p=0.0263 ) and CV death ( HR : 4.043 , p=0.004 ) . CONCLUSIONS In AF patients on good anticoagulation control with VKAs , digoxin use was associated with a higher rate of total and CV mortality INTRODUCTION AND OBJECTIVES We aim ed to assess and compare the effect of digoxin on clinical outcomes in patients with atrial fibrillation vs those under beta-blockers or none of these drugs . METHODS AFBAR is a prospect i ve registry study carried out by a team of primary care physicians ( n=777 patients ) . Primary endpoints were survival , survival free of admission due to any cause , and survival free of admission due to cardiovascular causes . The mean follow up was 2.9 years . Four groups were analyzed : patients receiving digoxin , beta-blockers , or digoxin plus beta-blockers , and patients receiving none of these drugs . RESULTS Overall , 212 patients ( 27.28 % ) received digoxin as the only heart control strategy , 184 received beta-blockers ( 23.68 % ) , 58 ( 7.46 % ) were administered both , and 323 ( 41.57 % ) received none of these drugs . Digoxin was not associated with all-cause mortality ( estimated hazard ratio=1.42 ; 95 % confidence interval , 0.77 - 2.60 ; P=.2 ) , admission due to any cause ( estimated hazard ratio=1.03 ; 95 % confidence interval , 0.710 - 1.498 ; P=.8 ) , or admission due to cardiovascular causes ( estimated hazard ratio=1.193 ; 95 % confidence interval , 0.725 - 1.965 ; P=.4 ) . No association was found between digoxin use and all-cause mortality , admission due to any cause , or admission due to cardiovascular causes in patients without heart failure . There was no interaction between digoxin use and sex in all-cause mortality or in survival free of admission due to any cause . However , an association was found between sex and admission due to cardiovascular causes . CONCLUSIONS Digoxin was not associated with increased all-cause mortality , survival free of admission due to any cause , or admission due to cardiovascular causes , regardless of underlying heart failure AIMS Digoxin is recommended for long-term rate control in paroxysmal , persistent , and permanent atrial fibrillation ( AF ) . While some analyses suggest an association of digoxin with a higher mortality in AF , the intrinsic nature of this association has not been examined in propensity-matched cohorts , which is the objective of the current study . METHODS AND RESULTS In Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) , 4060 patients with paroxysmal and persistent AF were r and omized to rate ( n = 2027 ) vs. rhythm ( n = 2033 ) control strategies . Of these , 1377 received digoxin as initial therapy and 1329 received no digoxin at baseline . Propensity scores for digoxin use were estimated for each of these 2706 patients and used to assemble a cohort of 878 pairs of patients receiving and not receiving digoxin , who were balanced on 59 baseline characteristics . Matched patients had a mean age of 70 years , 40 % were women , and 11 % non-white . During the 3.4 years of the mean follow-up , all-cause mortality occurred in 14 and 13 % of matched patients receiving and not receiving digoxin , respectively [ hazard ratio ( HR ) associated with digoxin use : 1.06 ; 95 % confidence interval ( CI ) : 0.83 - 1.37 ; P = 0.640 ] . Among matched patients , digoxin had no association with all-cause hospitalization ( HR : 0.96 ; 95 % CI : 0.85 - 1.09 ; P = 0.510 ) or incident non-fatal cardiac arrhythmias ( HR : 0.90 ; 95 % CI : 0.37 - 2.23 ; P = 0.827 ) . Digoxin had no multivariable-adjusted or propensity score-adjusted associations with these outcomes in the pre-match cohort . CONCLUSIONS In patients with paroxysmal and persistent AF , we found no evidence of increased mortality or hospitalization in those taking digoxin as baseline initial therapy Estimating the causal effect of some exposure on some outcome is the goal of many epidemiological studies . This article review s a formal definition of causal effect for such studies . For simplicity , the main description is restricted to dichotomous variables and assumes that no r and om error attributable to sampling variability exists . The appendix provides a discussion of sampling variability and a generalisation of this causal theory . The difference between association and causation is described — the redundant expression “ causal effect ” is used throughout the article to avoid confusion with a common use of “ effect ” meaning simply statistical association— and shows why , in theory , r and omisation allows the estimation of causal effects without further assumptions . The article concludes with a discussion on the limitations of r and omised studies . These limitations are the reason why methods for causal inference from observational data are needed We examined the effects of digitalis therapy on postinfa rct ion mortality throughout a 24-month to 48-month follow-up in 867 patients who survived an acute myocardial infa rct ion . During follow-up , 145 patients died ( 16.7 % mortality ) . At the time of hospital discharge , 31 % of the patients were taking digitalis . The digitalis-treated patients were older , had more medical-cardiac risk factors , and had a higher mortality rate throughout the follow-up than the nondigitalis-treated patients . Statistical techniques were used to adjust for clinical imbalances between the digitalis-treated patients and nondigitalis-treated patients . The survival analysis ( n=728 patients ) utilized the Cox regression model , and the digitalis-associated mortality risk was identified only after all significant covariates were allowed , so that mortality could be predicted as accurately as possible . Digitalis therapy was associated with a significantly increased postinfa rct ion mortality risk after adjustment for the predictor covariates ( relative risk 2.3 , 95 % confidence interval 1.4–3.7 , p<0.001 ) . The findings from this large multicenter study suggest that it would be prudent to exercise caution in the use of digitalis in postinfa rct ion patients We r and omly assigned 230 patients in sinus rhythm with moderately severe heart failure to treatment with digoxin , milrinone , both , or placebo . The effects of each were compared during a 12-week , double-blind trial . Treatment with milrinone or digoxin significantly increased treadmill exercise time as compared with placebo ( by 82 and 64 seconds respectively ; 95 percent confidence limits , 44 and 123 , and 30 and 100 ) . Both treatments reduced the frequency of decompensation from heart failure , from 47 percent with placebo to 34 percent with milrinone ( P less than 0.05 ; 95 percent confidence limits , 22 and 46 ) and 15 percent with digoxin ( P less than 0.01 ; 95 percent confidence limits , 7 and 26 ) . However , the clinical condition of 20 percent of the patients taking milrinone deteriorated within two weeks after treatment was begun , as compared with only 3 percent of those taking digoxin ( P less than 0.05 ) . The left ventricular ejection fraction at rest was not significantly changed by milrinone ( + 0.2 percent ; 95 percent confidence limits , -1.5 and 1.9 ) , but it was increased by digoxin ( + 1.7 percent ; P less than 0.01 ; 95 percent confidence limits , -0.03 and 3.4 ) and decreased by placebo ( -2.0 percent ; 95 percent confidence limits , -3.8 and -0.1 ) . Three-month survival was related inversely to the base-line ejection fraction . Analysis of mortality from all causes according to the intention to treat suggested an adverse effect of milrinone ( P = 0.064 ) . After adjustment for an excess of patients with lower ejection fractions r and omly assigned to receive milrinone , this trend was not significant ( P = 0.26 ) . Increased ventricular arrhythmias occurred more frequently in patients who received milrinone than in those who did not ( 18 vs. 4 percent ; P less than 0.03 ) . We conclude that milrinone significantly increased exercise tolerance and reduced the frequency of worsened heart failure . However , in the population of patients studied , milrinone or the combination of milrinone and digoxin offered no advantage over digoxin alone . Furthermore , our data suggest that milrinone may aggravate ventricular arrhythmias BACKGROUND The use of digitalis is recommended for the treatment of heart failure to reduce hospitalization . Recent data suggest that digitalis treatment may adversely affect survival in women but not in men . We studied patients with left ventricular dysfunction enrolled in the Studies of Left Ventricular Dysfunction ( SOLVD ) to determine whether there was a gender-based survival difference in patients treated with digitalis . METHODS AND RESULTS Symptomatic ( n = 2569 ) and asymptomatic ( n = 4228 ) patients with left ventricular ejection fraction < or = 0.35 were studied . Digitalis use was assessed at baseline and baseline demographic variables were catalogued and compared . A multivariate analysis , incorporating known covariates of risk for adverse cardiovascular events , was used to examine the association of digitalis with all-cause mortality , cardiovascular death , death from heart failure , and arrhythmic death , with , or without , worsening heart failure in women compared with men . Analysis for an interaction between digitalis and gender on mortality was also performed . No interaction between gender and digitalis treatment on survival was found , and there was no significant difference in the hazard ratios for men and women on digitalis either with respect to all-cause mortality , cardiovascular mortality , heart failure mortality , or arrhythmic death with worsening heart failure . When mortality for arrhythmic death without worsening heart failure was adjusted for the probability of being treated with digitalis ( propensity analysis ) , women fared better than men . CONCLUSION Data from the SOLVD trials suggest that digitalis treatment of heart failure does not result in a difference in survival between men and women . Because a r and omized trial to definitively answer the question is unlikely , and perhaps inappropriate , examination of other heart failure population s for a gender-digitalis interaction is indicated Previous reports have yielded contradictory conclusions regarding the safety of digoxin therapy in patients with acute myocardial infa rct ion . The purpose of our study was to determine whether digoxin therapy is associated with increased mortality in patients with chronic coronary artery disease . We analyzed data from 8173 patients who were screened for participation in the Bezafibrate Infa rct ion Prevention ( BIP ) trial and who survived an acute myocardial infa rct ion at least 6 months prior to the study . Three-year overall mortality of the 451 ( 15.5 % ) patients receiving digoxin ( according to the judgement of their treating physician ) at the time of screening for BIP participation , was 22.4 % compared to 8.3 % in the patients who did not receive digoxin . Cardiac mortality was 16.2 % in the digoxin-treated group , compared to 4.9 % in the non-treated patients . The increased risk associated with digoxin remained statistically significant when patients were stratified according to sex , age groups , functional capacity and the presence of hypertension , diabetes or angina . The administration of digoxin to survivors of an acute myocardial infa rct ion in the chronic phase of their disease , is statistically associated with a 30 - 50 % increase in the risk of overall and cardiac mortality during long-term follow-up . A propensity of increased risk of arrhythmias in ischemic coronary patients may explain this finding BACKGROUND The Digitalis Investigation Group ( DIG ) clinical train r and omized 6800 congestive heart failure patients ( ejection fraction > or = 45 % ) to a daily regimen of either digoxin or placebo . At 37 months average follow-up , patients in both groups had similar mortality . We determined the incremental costs associated with the use of digoxin in this high-risk population . METHODS AND RESULTS Hospitalizations and medical costs were compared by using a societal perspective . Hospitalizations were assigned Medicare DRG codes by using descriptive information from the clinical trial . Digoxin use was assigned a cost by using the 1998 average wholesale price as reported by Red Book . On average , there were fewer hospitalizations in digoxin-treated patients . These patients had lower heart failure yet higher non-heart failure hospitalization costs than placebo patients . Digoxin therapy was cost saving versus placebo in only 27 % of 1000 bootstrap sample s using Medicare costs ( mean costs 12,648 dollars vs. 12,362 dollars ) and in 44 % of sample s using commercial carrier costs ( mean costs 17,400 dollars vs. 17,306 dollars ) . How ever , digoxin was cost saving in > 50 % of sample s for several higher-risk patient subgroups . CONCLUSIONS The use of digoxin therapy versus placebo was associated with reduced hospitalizations . Moreover , the result ing cost-savings could cover the costs of this inexpensive therapy in selected subgroups of higher-risk patients . In the remainder , there is a modest cost associated with this therapy Background —Elevated serum digoxin concentration can cause toxicity , including death . Dronedarone increases digoxin concentration by P-glycoprotein interaction . In Permanent Atrial Fibrillation Outcome Study Using Dronedarone On Top Of St and ard Therapy Trial ( PALLAS ) , dronedarone was associated with both increased cardiovascular death and heart failure in patients with permanent atrial fibrillation . The present analysis examines whether the dronedarone – digoxin interaction might explain these adverse outcomes . Methods and Results —Subgroup analysis was performed to compare outcomes of patients on digoxin at baseline or not . In PALLAS , 1619 patients were r and omized to dronedarone and 1617 to placebo , of whom 544 ( 33.6 % ) and 526 ( 32.5 % ) were receiving digoxin , respectively . Median ( Q1,Q3 ) digoxin serum concentration on day 7 was 1.1 ( 0.7,1.5 ) ng/mL on dronedarone and 0.7 ( 0.5,1.1 ) ng/mL on placebo ( P<0.001 ) . Among patients on digoxin , there were 15 ( 8.6%/year ) cardiovascular deaths on dronedarone and 2 ( 1.2%/year ) on placebo ( adjusted hazard ratio , 7.31 ; 95 % confidence interval , 1.66–32.20 ; P=0.009 ) . Among patients not on digoxin , there were 6 cardiovascular deaths on dronedarone ( 1.7%/year ) and 8 on placebo ( 2.2%/year ; adjusted hazard ratio , 0.67 ; 95 % confidence interval , 0.23–1.95 ; P=0.46 ; interaction P value 0.01 ) . In patients on digoxin , there were 11 arrhythmic deaths on dronedarone and none on placebo ; and in patients not on digoxin , there were 2 arrhythmic deaths on dronedarone and 4 on placebo ( P value for interaction 0.002 ) . There was no interaction between baseline digoxin use and the adverse effect of dronedarone on heart failure events . Conclusions —In PALLAS , there was a strong effect of concurrent digoxin use on the adverse effect of dronedarone on cardiovascular death , but not on occurrence of heart failure . Clinical Trial Registration —http://www . clinical trials.gov . Unique identifier : NCT01151137 This multicenter , double-blind , placebo-controlled study compares the effects of captopril treatment with those of digoxin treatment during maintenance diuretic therapy in patients with mild to moderate heart failure . Compared with placebo , captopril therapy result ed in significantly improved exercise time ( mean increase , 82 s vs 35 s ) and improved New York Heart Association class ( 41 % vs 22 % ) , but digoxin therapy did not . Digoxin treatment increased ejection fraction ( 4.4 % increase ) compared with captopril therapy ( 1.8 % increase ) and placebo ( 0.9 % increase ) . The number of ventricular premature beats decreased 45 % in the captopril group and increased 4 % in the digoxin group in patients with more than ten ventricular premature beats per hour . Treatment failures , increased requirements for diuretic therapy , and hospitalizations were significantly more frequent in patients receiving placebo compared with those receiving either active drug . Transitory hypotension occurred more frequently with administration of captopril . Captopril treatment is significantly more effective than placebo and is an alternative to digoxin therapy in patients with mild to moderate heart failure who are receiving diuretic maintenance therapy OBJECTIVES To develop and vali date a new risk-of-bias tool for nonr and omized studies ( NRSs ) . STUDY DESIGN AND SETTING We developed the Risk of Bias Assessment Tool for Nonr and omized Studies ( RoBANS ) . A validation process with 39 NRSs examined the reliability ( interrater agreement ) , validity ( the degree of correlation between the overall assessment s of RoBANS and Method ological Index for Nonr and omized Studies [ MINORS ] , obtained by plotting the overall risk of bias relative to effect size and funding source ) , face validity with eight experts , and completion time for the RoBANS approach . RESULTS RoBANS contains six domains : the selection of participants , confounding variables , the measurement of exposure , the blinding of the outcome assessment s , incomplete outcome data , and selective outcome reporting . The interrater agreement of the RoBANS tool except the measurement of exposure and selective outcome reporting domains ranged from fair to substantial . There was a moderate correlation between the overall risks of bias determined using RoBANS and MINORS . The observed differences in effect sizes and funding sources among the assessed studies were not correlated with the overall risk of bias in these studies . The mean time required to complete RoBANS was approximately 10 min . The external experts who were interviewed evaluated RoBANS as a " fair " assessment tool . CONCLUSIONS RoBANS shows moderate reliability , promising feasibility , and validity . The further refinement of this tool and larger validation studies are required Recent studies have led to controversy about whether long-term digoxin therapy after confirmed or suspected myocardial infa rct ion increases mortality . We analyzed the mortality experience in 903 patients enrolled in the Multicenter Investigation of Limitation of Infa rct Size ( MILIS ) . As in previous studies , the decision to treat or not to treat with digoxin was made by the patient 's personal physician on the basis of the usual clinical indications . Cumulative mortality was 28 percent for the 281 digoxin-treated patients as compared with 11 percent for the 622 patients who did not receive digoxin ( P less than 0.001 ; follow-up interval , six days to 36 months ; mean , 25.1 months ) . However , patients treated with digoxin had more base-line characteristics predictive of mortality than did their counterparts . Adjustment for these differences with two separate applications of the Cox method yielded P values of 0.14 and 0.34 for tests of difference in mortality , providing no evidence for a significant excess mortality associated with digoxin . Thus , the findings in the MILIS population do not support the assertion that digoxin therapy is excessively hazardous after infa rct ion , but the existence of an undetected harmful effect can only be excluded with a r and omized study . Until the results of such a study are available , we recommend careful consideration of whether any treatment of ventricular dysfunction is actually needed , consideration of alternatives to digoxin therapy , and restriction of digoxin use to the subgroup of patients ( with severe chronic congestive failure and a dilated left ventricle ) previously shown to have a beneficial clinical response OBJECTIVES The purpose of this study was to investigate the relationship of serum digoxin concentration ( SDC ) and outcomes in women with heart failure ( HF ) . BACKGROUND Controversy continues concerning the clinical utility of digoxin in women with HF . METHODS Our analysis was retrospective with data from the Digitalis Investigation Group ( DIG ) trial . The principal study analysis review ed 4,944 patients with HF due to systolic dysfunction who survived for at least 4 weeks ( all 3,366 patients r and omized to placebo and the 1,578 of 3,372 patients r and omized to digoxin who had serum concentration measured 6 to 30 h [ inclusive ] after the last dose of study drug at 4 weeks ) . RESULTS Continuous multivariable analysis demonstrated a significant linear relationship between SDC and mortality in women ( p = 0.008 ) and men ( p = 0.002 , p = 0.766 for gender interaction ) . Averaging hazard ratios ( HRs ) across serum concentrations from 0.5 to 0.9 ng/ml in women produced a HR for death of 0.8 ( 95 % confidence interval [ CI ] 0.62 to 1.13 , p = 0.245 ) and for death or hospital stay for worsening HF of 0.73 ( 95 % CI 0.58 to 0.93 , p = 0.011 ) . In contrast , SDCs from 1.2 to 2.0 ng/ml were associated with a HR for death for women of 1.33 ( 95 % CI 1.001 to 1.76 , p = 0.049 ) . CONCLUSIONS Retrospective analysis of data from the DIG trial indicates a beneficial effect of digoxin on morbidity and no excess mortality in women at serum concentrations from 0.5 to 0.9 ng/ml , whereas serum concentrations > or = 1.2 ng/ml seem harmful Objective : In heart failure , digitalis increases exercise capacity and reduces morbidity , but has no effect on survival . This raises the suspicion that the inotropic benefits of digitalis may be counteracted by serious adverse effects . Patients with atrial fibrillation ( AF ) were studied to clarify this . Design : In the Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation ( SPORTIF ) III and V studies , 7329 patients with AF at moderate-to-high risk were r and omised to preventive treatment of thromboembolism , either with warfarin or the oral direct thrombin inhibitor ximelagatran . The survival of users and non-users of digitalis was investigated . Results : At baseline , 53.4 % of the study population used digitalis , and these patients had a higher mortality than non-users ( 255/3911 ( 6.5 % ) vs 141/3418 ( 4.1 % ) , p<0.001 ; hazard ratio ( HR ) = 1.58 ( 95 % CI 1.29 to 1.94 ) ) . Digitalis users also had more baseline risk factors . After multivariate risk factor adjustment , the increased mortality persisted ( p<0.001 ; HR = 1.53 ( 95 % CI 1.22 to 1.92 vs 1.23 to 1.92 ) ) . Conclusions : The results suggest that digitalis , like other inotropic drugs , may increase mortality . This may be concealed in heart failure , but be revealed in patients with AF , who need the rate-reducing effect of digitalis , but do not benefit much from an increased inotropy . Cautious interpretation of the data is m and atory since the patients were not r and omised with respect to digitalis use BACKGROUND Heart failure is the leading cause for hospital readmission , the reduction of which is a priority under the Affordable Care Act . Digoxin reduces 30-day all-cause hospital admission in chronic systolic heart failure . Whether digoxin is effective in reducing readmission after hospitalization for acute decompensation remains unknown . METHODS Of the 5153 Medicare beneficiaries hospitalized for acute heart failure and not receiving digoxin , 1054 ( 20 % ) received new discharge prescriptions for digoxin . Propensity scores for digoxin use , estimated for each of the 5153 patients , were used to assemble a matched cohort of 1842 ( 921 pairs ) patients ( mean age , 76 years ; 56 % women ; 25 % African American ) receiving and not receiving digoxin , who were balanced on 55 baseline characteristics . RESULTS Thirty-day all-cause readmission occurred in 17 % and 22 % of matched patients receiving and not receiving digoxin , respectively ( hazard ratio [ HR ] for digoxin , 0.77 ; 95 % confidence interval [ CI ] , 0.63 - 0.95 ) . This beneficial association was observed only in those with ejection fraction < 45 % ( HR 0.63 ; 95 % CI , 0.47 - 0.83 ) , but not in those with ejection fraction ≥ 45 % ( HR 0.91 ; 95 % CI , 0.60 - 1.37 ; P for interaction , .145 ) , a difference that persisted throughout the first 12 months postdischarge ( P for interaction , .019 ) . HRs ( 95 % CIs ) for 12-month heart failure readmission and all-cause mortality were 0.72 ( 0.61 - 0.86 ) and 0.83 ( 0.70 - 0.98 ) , respectively . CONCLUSIONS In Medicare beneficiaries with systolic heart failure , a discharge prescription of digoxin was associated with lower 30-day all-cause hospital readmission , which was maintained at 12 months , and was not at the expense of higher mortality . Future r and omized controlled trials are needed to confirm these findings Background : Digoxin is widely used for rate control of atrial fibrillation . However , recent studies have reported conflicting results on the association of digoxin with mortality when used in patients with atrial fibrillation . Moreover , the relationship of digoxin use to mortality in hypertensive patients with atrial fibrillation has not been examined . Methods and results : All-cause mortality was examined in relation to in-treatment digoxin use in 937 hypertensive patients with ECG left ventricular hypertrophy in atrial fibrillation at baseline ( n = 134 ) or who developed atrial fibrillation during follow-up ( n = 803 ) , r and omly assigned to losartan or atenolol-based treatment , in post-hoc analysis of a sub study of the Losartan Intervention For Endpoint Reduction in hypertension ( LIFE ) trial . During 4.7 ± 1.1 years of mean follow-up , 167 patients died ( 17.8 % ) and 372 ( 39.7 % ) were treated with digoxin . In univariate Cox analyses , in-treatment digoxin use , entered as a time-varying covariate , was associated with a 61 % higher risk of dying ( hazard ratio 1.61 , 95 % confidence interval 1.18–2.19 , P = 0.003 ) . After adjusting for other univariate predictors of death in this population , including age , diabetes , history of ischemic heart disease , stroke , or heart failure , baseline Cornell product , QRS duration , heart rate , serum glucose , creatinine and high-density lipoprotein cholesterol , and a propensity score for digoxin use entered as st and ard covariates , and for in-treatment heart rate , pulse pressure , and Sokolow – Lyon voltage treated as time-varying covariates , digoxin use was no longer a significant predictor of mortality ( hazard ratio 1.04 , 95 % confidence interval 0.73–1.48 , P = 0.839 ) . Conclusion : In hypertensive patients with ECG left ventricular hypertrophy with existing or new atrial fibrillation , digoxin use is not associated with a significantly increased risk of all-cause mortality after adjusting for other independent predictors of death and for the factors associated with the propensity to use digoxin in this population . These findings suggest that factors other than digoxin use may account for the increased mortality found with digoxin use in some studies . Clinical Trials Registration : http:// clinical Previous studies on digoxin use in patients with atrial fibrillation ( AF ) and the risk of all-cause mortality found conflicting results . We conducted a population -based , retrospective , cohort study of patients aged ≥65 years admitted to a hospital with a primary or secondary diagnosis of AF , in Quebec province , Canada , from 1998 to 2012 . The AF cohort was grouped into patients with and without heart failure ( HF ) and into digoxin and no-digoxin users according to the first prescription filled for digoxin within 30 days after AF hospital discharge . We derived propensity score-matched digoxin and no-digoxin treatment groups for the groups of patients with and without HF , respectively , and conducted multivariable Cox proportional hazards regression analyses to determine association between digoxin use and all-cause mortality . The AF propensity score-matched cohorts of patients with and without HF were well balanced on baseline characteristics . In the propensity score-matched HF group , digoxin use was associated with a 14 % greater risk of all-cause mortality ( adjusted hazard ratio 1.14 , 95 % confidence interval 1.10 to 1.17 ) . In the propensity score-matched no-HF group , digoxin use was associated with a 17 % greater risk of all-cause mortality ( adjusted hazard ratio 1.17 , 95 % confidence interval 1.14 to 1.19 ) . In conclusion , our retrospective analyses found that digoxin use was associated with a greater risk for all-cause mortality in patients aged ≥65 years with AF regardless of concomitant HF . Large , multicenter , r and omized controlled trials or prospect i ve cohort studies are required to clarify this issue BACKGROUND Endovascular detachable coil treatment is being increasingly used as an alternative to craniotomy and clipping for some ruptured intracranial aneurysms , although the relative benefits of these two approaches have yet to be established . We undertook a r and omised , multicentre trial to compare the safety and efficacy of endovascular coiling with st and ard neurosurgical clipping for such aneurysms judged to be suitable for both treatments . METHODS We enrolled 2143 patients with ruptured intracranial aneurysms and r and omly assigned them to neurosurgical clipping ( n=1070 ) or endovascular treatment by detachable platinum coils ( n=1073 ) . Clinical outcomes were assessed at 2 months and at 1 year with interim ascertainment of rebleeds and death . The primary outcome was the proportion of patients with a modified Rankin scale score of 3 - 6 ( dependency or death ) at 1 year . Trial recruitment was stopped by the steering committee after a planned interim analysis . Analysis was per protocol . FINDINGS 190 of 801 ( 23.7 % ) patients allocated endovascular treatment were dependent or dead at 1 year compared with 243 of 793 ( 30.6 % ) allocated neurosurgical treatment ( p=0.0019 ) . The relative and absolute risk reductions in dependency or death after allocation to an endovascular versus neurosurgical treatment were 22.6 % ( 95 % CI 8.9 - 34.2 ) and 6.9 % ( 2.5 - 11.3 ) , respectively . The risk of rebleeding from the ruptured aneurysm after 1 year was two per 1276 and zero per 1081 patient-years for patients allocated endovascular and neurosurgical treatment , respectively . INTERPRETATION In patients with a ruptured intracranial aneurysm , for which endovascular coiling and neurosurgical clipping are therapeutic options , the outcome in terms of survival free of disability at 1 year is significantly better with endovascular coiling . The data available to date suggest that the long-term risks of further bleeding from the treated aneurysm are low with either therapy , although somewhat more frequent with endovascular coiling OBJECTIVES This study was conducted to determine the efficacy and safety of long-term treatment with the orally active dopamine agonist ibopamine in patients with mild to moderate chronic congestive heart failure and to compare the results with those of treatment with digoxin and placebo . BACKGROUND Ibopamine and digoxin are drugs that exert hemodynamic and neurohumoral effects . Because there is accumulating evidence that progression of disease in chronic heart failure is related not only to hemodynamic but also to neurohumoral factors , both drugs might be expected to have a favorable long-term effect . METHODS We studied 161 patients with mild to moderate chronic heart failure ( 80 % in New York Heart Association functional class II and 20 % in class III ) , who were treated with ibopamine ( n = 53 ) , digoxin ( n = 55 ) or placebo ( n = 53 ) for 6 months . Background therapy consisted of furosemide ( 0 to 80 mg ) ; all other drugs for heart failure were excluded . Clinical assessment s were made at baseline and after 1 , 3 and 6 months . RESULTS Of the 161 patients , 128 ( 80 % ) completed the study . Compared with placebo , digoxin but not ibopamine significantly increased exercise time after 6 months ( p = 0.008 by intention to treat analysis ) . Ibopamine was only effective in patients with relatively preserved left ventricular function , as it significantly increased exercise time in this subgroup ( for patients with a left ventricular ejection fraction > 0.30 ; p = 0.018 vs. placebo ) . No patient receiving digoxin withdrew from the study because of progression of heart failure , compared with six patients receiving ibopamine and two receiving placebo . At 6 months , plasma norepinephrine was decreased with digoxin and ibopamine therapy ( -106 and -13 pg/ml , respectively ) but increased with placebo administration ( + 62 pg/ml ) ( both p < 0.05 vs. placebo ) . Plasma aldosterone was unaffected , but renin was decreased by both agents after 6 months ( p < 0.05 vs. placebo ) . Total mortality and ambulatory arrhythmias were not significantly affected by the two drugs . CONCLUSIONS Ibopamine and digoxin both inhibit neurohumoral activation in patients with mild to moderate chronic heart failure . However , the clinical effects of these drugs are different and appear to be related to the degree of left ventricular dysfunction BACKGROUND The effects of beta-blockade with different extent of angiotensin-converting enzyme inhibitors ( ACEI ) and digitalization are unknown . To assess the effect of metoprolol succinate controlled release/extended release ( CR/XL ) combined with high versus low doses of ACEI and digitalis , we analyzed data from The Metoprolol CR/XL R and omized Intervention Trial in Chronic Heart Failure ( MERIT-HF ) in which patients with heart failure and left ventricular ejection fraction < or = 40 % were r and omized to metoprolol CR/XL versus placebo . METHODS AND RESULTS Outcome was analyzed separately for those on a low dose ( < or = median ) of the ACEI or digitalis versus high dose ( > median ) . The mean dose of ACEI in the high-dose group ( n = 1457 ) was 3 times higher than that in the low-dose group ( n = 2094 ) . Mortality was reduced to a similar extent in the high- and low-dose ACEI subgroups ( RR = .69 versus .64 , respectively ) . Corresponding figures for combined mortality/all hospitalization and for mortality/hospitalization for heart failure were .85 versus .83 , and .70 versus .68 , respectively . Likewise , reduction in total mortality with metoprolol CR/XL was similar in patients receiving no digitalis ( n = 1447 ; RR = .56 ) , low dose ( n = 1122 ; RR = .71 ) , or high dose ( n = 1421 ; RR = .71 ) . CONCLUSION This analysis of MERIT-HF demonstrates consistent and similar improvement in outcome of patients receiving metoprolol CR/XL when combined with either a high or low dose of an ACEI or digitalis , or no digitalis at all . Thus regardless of ACEI and digitalis dose and whether patients are treated with digitalis or not , it is very important to add a beta-blocker to the existing heart failure therapy . beta-blockers should not be withheld until target doses of ACEI have been achieved BACKGROUND In the main Digitalis Investigation Group ( DIG ) trial , digoxin reduced the risk of 30-day all-cause hospitalization in older systolic heart failure patients . However , this effect has not been studied in older diastolic heart failure patients . METHODS In the ancillary DIG trial , of the 988 patients with chronic heart failure and preserved ( > 45 % ) ejection fraction , 631 were age ≥ 65 years ( mean age 73 years , 45 % women , 12 % non-whites ) , of whom 311 received digoxin . RESULTS All-cause hospitalization 30-day post r and omization occurred in 4 % of patients in the placebo group and 9 % each among those in the digoxin group receiving 0.125 mg and ≥ 0.25 mg a day dosage ( P = .026 ) . Hazard ratios ( HR ) and 95 % confidence intervals ( CI ) for digoxin use overall for 30-day , 3-month , and 12-month all-cause hospitalizations were 2.46 ( 1.25 - 4.83 ) , 1.45 ( 0.96 - 2.20 ) and 1.14 ( 0.89 - 1.46 ) , respectively . There was one 30-day death in the placebo group . Digoxin-associated HRs ( 95 % CIs ) for 30-day hospitalizations due to cardiovascular , heart failure , and unstable angina causes were 2.82 ( 1.18 - 6.69 ) , 0.51 ( 0.09 - 2.79 ) , and 6.21 ( 0.75 - 51.62 ) , respectively . Digoxin had no significant association with 30-day all-cause hospitalization among younger patients ( 6 % vs 7 % for placebo ; HR 0.80 ; 95 % CI , 0.36 - 1.79 ) . CONCLUSIONS In older patients with chronic diastolic heart failure , digoxin increased the risk of 30-day all-cause hospital admission , but not during longer follow-up . Although chance finding due to small sample size is possible , these data suggest that unlike in systolic heart failure , digoxin may not reduce 30-day all-cause hospitalization in older diastolic heart failure patients OBJECTIVES This study sought to analyze the health and economic outcomes of withdrawal of digoxin therapy among U.S. adult patients with stable congestive heart failure . BACKGROUND New information regarding the outcomes of digoxin withdrawal has been provided by the Prospect i ve R and omized Study of Ventricular Failure and Efficacy of Digoxin ( PROVED ) and R and omized Assessment of Digoxin and Inhibitors of Angiotensin-Converting Enzyme ( RADIANCE ) trials . We interpreted and extrapolated the results of these trials to describe implication s on a national level . METHODS We used a decision-analytic model to estimate the outcomes of two alternative strategies to 1 ) continue and 2 ) withdraw digoxin in patients with congestive heart failure with normal sinus rhythm , New York Heart Association functional class II or III and left ventricular ejection fraction < or = 35 % . Epidemiologic assumptions were derived from published reports and expert opinion . Assumptions regarding the effectiveness of digoxin therapy were derived from the RADIANCE and PROVED digoxin withdrawal trials . Hospital and Medicare data were used for economic assumptions . Calculated outcomes included treatment failures , cases of digoxin toxicity and health care costs . RESULTS The continuation of digoxin therapy in these patients with congestive heart failure nationally would avoid an estimated 185,000 clinic visits , 27,000 emergency visits and 137,000 hospital admissions for congestive heart failure . After accounting for an estimated 12,500 cases of digoxin toxicity , the net annual savings would be $ 406 million , with a 90 % range of uncertainty of $ 106 to $ 822 million . One-way sensitivity analysis indicated that digoxin therapy is cost-saving when the assumed annual incidence of digoxin toxicity is < or = 33 % . CONCLUSIONS The continuation of digoxin therapy in patients with stable congestive heart failure should be strongly considered , because this strategy is likely to lead to both lower costs and greater health benefits on the basis of available information In a double‐blind study comparing two active treatments ( digoxin and xamoterol ) and placebo in patients with heart failure , improvements in exercise capacity and quality of life were observed in all three groups , with no significant differences . The substantial benefits seen in the placebo group were probably the result of increased attention from the medical and research staff and suggest the therapeutic value of special heart failure clinics . The relationship between exercise and symptomatic/functional status has been unclear . We developed quantitative measures of quality ‐of‐life variables and examined their relationship with exercise capacity . There were significant relationships between change in exercise duration and changes in breathlessness , tiredness , chest pain , walking difficulty , rate of walking , difficulty with daily tasks , speed of daily tasks , mood , and sleeping . This study confirms the validity of measuring change in exercise capacity and demonstrates that specific measurements of quality of life make an important contribution to the evaluation of the treatment of heart failure Background Recent studies of patients with heart failure and of patients receiving intensive care indicate that digoxin may increase mortality if the patient has atrial fibrillation ( AF ) . Objective To study which patients receive digoxin treatment for AF and what the prognosis is for patients given this treatment . Method 2824 patients with AF were studied prospect ively for a mean of 4.6 years . Information about medication was obtained from the local hospital registry . Information about diagnoses , hospitalisations and deaths was obtained from national registries . Propensity score matching and Cox regression was used to account for confounding . Results Factors associated with digoxin use were permanent AF ( hazard ratio ( HR ) = 3.2 , confidence interval ( CI ) 2.7 to 3.9 ) , absence of pacemaker ( HR = 2.3 , CI 1.6 to 3.2 ) , history of heart failure ( HR = 2.0 , CI 1.7 to 2.5 ) , treatment in an internal medicine ward rather than a cardiology ward ( HR = 1.6 , CI 1.3 to 2.0 ) , female sex ( HR = 1.6 , CI 1.3 to 1.9 ) and age ≥80 years ( HR = 1.4 , CI 1.1 to 1.7 ) . More patients with than without digoxin died ( 51 % vs 31 % , p<0.001 ) . After adjustment for covariates , however , no disadvantages related to digoxin use could be found for all-cause mortality , myocardial infa rct ion , ischaemic stroke , time to readmission to hospital or days at hospital/year at risk . The only end point significantly associated with digoxin use was pacemaker implantations , which were more common in digoxin-treated patients ( HR = 2.0 , CI 1.2 to 3.4 ) . Conclusion Digoxin is mainly given to an elderly and frailer subset of patients with AF and is thus associated with an increased mortality . When differences in patient characteristics are accounted for digoxin use seems to have a neutral effect on mortality and major cardiovascular events in patients with AF 433 patients aged 29 - 80 with mild to moderate heart failure entered a multicentre double-blind r and omised between-patient comparison of xamoterol 200 mg twice daily , digoxin 0.125 mg twice daily , and placebo . Patients were assessed at baseline and after three months . Of 349 who completed the double-blind phase , 300 had valid exercise tests . Compared with placebo , xamoterol significantly increased exercise duration and work done on a bicycle ergometer and improved breathlessness and tiredness during daily life as assessed by visual analogue scale and by Likert scale . Digoxin showed no statistically significant advantage over placebo on any of the measures except the Likert scale . Exercise performance and work done were significantly higher with xamoterol than with digoxin BACKGROUND AND METHODS Aldosterone is important in the pathophysiology of heart failure . In a doubleblind study , we enrolled 1663 patients who had severe heart failure and a left ventricular ejection fraction of no more than 35 percent and who were being treated with an angiotensin-converting-enzyme inhibitor , a loop diuretic , and in most cases digoxin . A total of 822 patients were r and omly assigned to receive 25 mg of spironolactone daily , and 841 to receive placebo . The primary end point was death from all causes . RESULTS The trial was discontinued early , after a mean follow-up period of 24 months , because an interim analysis determined that spironolactone was efficacious . There were 386 deaths in the placebo group ( 46 percent ) and 284 in the spironolactone group ( 35 percent ; relative risk of death , 0.70 ; 95 percent confidence interval , 0.60 to 0.82 ; P<0.001 ) . This 30 percent reduction in the risk of death among patients in the spironolactone group was attributed to a lower risk of both death from progressive heart failure and sudden death from cardiac causes . The frequency of hospitalization for worsening heart failure was 35 percent lower in the spironolactone group than in the placebo group ( relative risk of hospitalization , 0.65 ; 95 percent confidence interval , 0.54 to 0.77 ; P<0.001 ) . In addition , patients who received spironolactone had a significant improvement in the symptoms of heart failure , as assessed on the basis of the New York Heart Association functional class ( P<0.001 ) . Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone , as compared with 1 percent of men in the placebo group ( P<0.001 ) . The incidence of serious hyperkalemia was minimal in both groups of patients . CONCLUSIONS Blockade of aldosterone receptors by spironolactone , in addition to st and ard therapy , substantially reduces the risk of both morbidity and death among patients with severe heart failure BACKGROUND Mineralocorticoid antagonists improve survival among patients with chronic , severe systolic heart failure and heart failure after myocardial infa rct ion . We evaluated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms . METHODS In this r and omized , double-blind trial , we r and omly assigned 2737 patients with New York Heart Association class II heart failure and an ejection fraction of no more than 35 % to receive eplerenone ( up to 50 mg daily ) or placebo , in addition to recommended therapy . The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure . RESULTS The trial was stopped prematurely , according to prespecified rules , after a median follow-up period of 21 months . The primary outcome occurred in 18.3 % of patients in the eplerenone group as compared with 25.9 % in the placebo group ( hazard ratio , 0.63 ; 95 % confidence interval [ CI ] , 0.54 to 0.74 ; P<0.001 ) . A total of 12.5 % of patients receiving eplerenone and 15.5 % of those receiving placebo died ( hazard ratio , 0.76 ; 95 % CI , 0.62 to 0.93 ; P=0.008 ) ; 10.8 % and 13.5 % , respectively , died of cardiovascular causes ( hazard ratio , 0.76 ; 95 % CI , 0.61 to 0.94 ; P=0.01 ) . Hospitalizations for heart failure and for any cause were also reduced with eplerenone . A serum potassium level exceeding 5.5 mmol per liter occurred in 11.8 % of patients in the eplerenone group and 7.2 % of those in the placebo group ( P<0.001 ) . CONCLUSIONS Eplerenone , as compared with placebo , reduced both the risk of death and the risk of hospitalization among patients with systolic heart failure and mild symptoms . ( Funded by Pfizer ; Clinical Trials.gov number , NCT00232180 . ) BACKGROUND Although digoxin has long been used to treat atrial fibrillation ( AF ) and heart failure ( HF ) , its safety remains controversial . OBJECTIVES This study sought to describe digoxin use over time in patients with AF who were stratified by the presence or absence of HF , to characterize the predictors of digoxin use and initiation , and to correlate digoxin use with outcomes . METHODS Longitudinal patterns of digoxin use and its association with a variety of outcomes were assessed in a prospect i ve outpatient registry conducted at 174 U.S. sites with enrollment from June 2010 to August 2011 . RESULTS Among 9,619 patients with AF and serial follow-up every 6 months for up to 3 years , 2,267 ( 23.6 % ) received digoxin at study enrollment , 681 ( 7.1 % ) were initiated on digoxin during follow-up , and 6,671 ( 69.4 % ) were never prescribed digoxin . After adjusting for other medications , heart rate was 72.9 beats/min among digoxin users and 71.5 beats/min among nonusers ( p < 0.0001 ) . Prevalent digoxin use at registry enrollment was not associated with subsequent onset of symptoms , hospitalization , or mortality ( in patients with HF , adjusted hazard ratio [ HR ] for death : 1.04 ; without HF , HR : 1.22 ) . Incident digoxin use during follow-up was not associated with subsequent death in patients with HF ( propensity adjusted HR : 1.05 ) , but was associated with subsequent death in those without HF ( propensity adjusted HR : 1.99 ) . CONCLUSIONS After adjustment for detailed clinical factors , digoxin use in registry patients with AF had a neutral association with outcomes under most circumstances . Because of the multiple conflicting observational reports about digoxin 's safety and possible concerns in specific clinical situations , a large pragmatic trial of digoxin therapy in AF is needed BACKGROUND The role of digoxin in the prognosis of patients with heart failure ( HF ) remains unclear . AIMS To evaluate the relationship of commencing treatment with digoxin ( CTDig ) with the mortality and the morbidity of patients with HF . METHODS Prospect i ve study over 8 years on 4467 patients with HF . Main outcomes were all-cause and cardiovascular mortality , hospitalisations and visits . We analyse the independent relationship of CTDig , with the mortality and the morbidity , stratifying patients for cardiovascular comorbidity , after propensity score-matching for potential confounders ( 1421 patients who CTDig vs. another 1421 patients non-exposed to digoxin ) . RESULTS During a median follow up of 46.1 months , 1872 patients ( 65.9 % ) died , and 2203 ( 77.5 % ) were hospitalised . CTDig was associated with a lower all-cause mortality ( HR = 0.90 [ 95 % CI , 0.84 - 0.97 ] ) , and cardiovascular mortality ( HR = 0.87 [ 0.81 - 0.96 ] ) , hospitalisation ( HR = 0.91 [ 0.86 - 0.97 ] ) , 30-day readmission for HF ( HR = 0.88 [ 0.79 - 0.95 ] ) , and visits ( HR = 0.94 [ 0.90 - 0.98 ] ) ( p < 0.001 in all cases ) , after adjustment for the propensity to take digoxin , other medications , and other potential confounders . These effects of digoxin were independent of gender , or type of HF ( systolic or non-systolic ) . CONCLUSION The data suggest that therapy with digoxin is associated with an improved mortality and morbidity of HF , including women and patients with non-systolic HF |
13,220 | 19,382,860 | Significant improvements were noted in compliance with medicine taking , asthma symptoms , HbA1C , stress levels , smoking quit rates , and self-efficacy .
Process improvements were reported in lower failed appointments , quicker diagnosis and treatment , and improved teaching and training . | Regular care and informational support are helpful in improving disease-related health outcomes .
Communication technologies can help in providing such care and support .
The purpose of this study was to evaluate the empirical evidence related to the role of cell phones and text messaging interventions in improving health outcomes and processes of care . | Objective : To assess the efficacy of an innovative smoking cessation intervention targeted to a multiethnic , economically disadvantaged HIV-positive population . Design : A two-group r and omized clinical trial compared a smoking cessation intervention delivered by cellular telephone with usual care approach . Methods : Current smokers from a large , inner city HIV/AIDS care center were recruited and r and omized to receive either usual care or a cellular telephone intervention . The usual care group received brief physician advice to quit smoking , targeted self-help written material s and nicotine replacement therapy . The cellular telephone intervention received eight counseling sessions delivered via cellular telephone in addition to the usual care components . Smoking-related outcomes were assessed at a 3-month follow-up . Results : The trial had 95 participants and 77 ( 81.0 % ) completed the 3-month follow-up assessment . Analyses indicated biochemically verified point prevalence smoking abstinence rates of 10.3 % for the usual care group and 36.8 % for the cellular telephone group ; participants who received the cellular telephone intervention were 3.6 times ( 95 % confidence interval , 1.3 - 9.9 ) more likely to quit smoking compared with participants who received usual care ( P = 0.0059 ) . Conclusions : These results suggest that individuals living with HIV/AIDS are receptive to , and can be helped by , smoking cessation treatment . In addition , smoking cessation treatment tailored to the special needs of individuals living with HIV/AIDS , such as counseling delivered by cellular telephone , can significantly increase smoking abstinence rates over that achieved by usual care AIMS To assess Sweet Talk , a text-messaging support system design ed to enhance self-efficacy , facilitate uptake of intensive insulin therapy and improve glycaemic control in paediatric patients with Type 1 diabetes . METHODS One hundred and twenty-six patients fulfilled the eligibility criteria ; Type 1 diabetes for > 1 year , on conventional insulin therapy , aged 8 - 18 years . Ninety-two patients were r and omized to conventional insulin therapy ( n = 28 ) , conventional therapy and Sweet Talk ( n = 33 ) or intensive insulin therapy and Sweet Talk ( n = 31 ) . Goal - setting at clinic visits was reinforced by daily text-messages from the Sweet Talk software system , containing personalized goal -specific prompts and messages tailored to patients ' age , sex and insulin regimen . RESULTS HbA(1c ) did not change in patients on conventional therapy without or with Sweet Talk ( 10.3 + /- 1.7 vs. 10.1 + /- 1.7 % ) , but improved in patients r and omized to intensive therapy and Sweet Talk ( 9.2 + /- 2.2 % , 95 % CI -1.9 , -0.5 , P < 0.001 ) . Sweet Talk was associated with improvement in diabetes self-efficacy ( conventional therapy 56.0 + /- 13.7 , conventional therapy plus Sweet Talk 62.1 + /- 6.6 , 95 % CI + 2.6 , + 7.5 , P = 0.003 ) and self-reported adherence ( conventional therapy 70.4 + /- 20.0 , conventional therapy plus Sweet Talk 77.2 + /- 16.1 , 95 % CI + 0.4 , + 17.4 , P = 0.042 ) . When surveyed , 82 % of patients felt that Sweet Talk had improved their diabetes self-management and 90 % wanted to continue receiving messages . CONCLUSIONS Sweet Talk was associated with improved self-efficacy and adherence ; engaging a classically difficult to reach group of young people . While Sweet Talk alone did not improve glycaemic control , it may have had a role in supporting the introduction of intensive insulin therapy . Scheduled , tailored text messaging offers an innovative means of supporting adolescents with diabetes and could be adapted for other health-care setting s and chronic diseases Background The Internet has potential as a medium for health behavior change programs , but no controlled studies have yet evaluated the impact of a fully automated physical activity intervention over several months with real-time objective feedback from a monitor . Objective The aim was to evaluate the impact of a physical activity program based on the Internet and mobile phone technology provided to individuals for 9 weeks . Methods A single-center , r and omized , stratified controlled trial was conducted from September to December 2005 in Bedfordshire , United Kingdom , with 77 healthy adults whose mean age was 40.4 years ( SD = 7.6 ) and mean body mass index was 26.3 ( SD = 3.4 ) . Participants were r and omized to a test group that had access to an Internet and mobile phone – based physical activity program ( n = 47 ) or to a control group ( n = 30 ) that received no support . The test group received tailored solutions for perceived barriers , a schedule to plan weekly exercise sessions with mobile phone and email reminders , a message board to share their experiences with others , and feedback on their level of physical activity . Both groups were issued a wrist-worn accelerometer to monitor their level of physical activity ; only the test group received real-time feedback via the Internet . The main outcome measures were accelerometer data and self-report of physical activity . Results At the end of the study period , the test group reported a significantly greater increase over baseline than did the control group for perceived control ( P < .001 ) and intention/expectation to exercise ( P < .001 ) . Intent-to-treat analyses of both the accelerometer data ( P = .02 ) and leisure time self-report data ( P = .03 ) found a higher level of moderate physical activity in the test group . The average increase ( over the control group ) in accelerometer-measured moderate physical activity was 2 h 18 min per week . The test group also lost more percent body fat than the control group ( test group : −2.18 , SD = 0.59 ; control group : −0.17 , SD = 0.81 ; P = .04 ) . Conclusions A fully automated Internet and mobile phone – based motivation and action support system can significantly increase and maintain the level of physical activity in healthy adults Background : Ethnic minorities or those with low socioeconomic status ( SES ) are at increased risk of cardiovascular disease , type 2 diabetes , and all-cause mortality , compared to higher SES Whites . National surveys also indicate that low-income , ethnic minority women have the highest rates of inactivity in the United States . Purpose : This study ( the Increasing Motivation for Physical ACTivity or IMPACT study ) promoted adoption and maintenance of physical activity ( PA ) in sedentary , low-income women participating in federally funded job training programs . Methods : The study consisted of 2 months of weekly 1-hr classes , then r and om assignment to 10 months of either home-based telephone counseling for PA plus information and feedback via mailed newsletters ( Phone + Mail Counseling condition ) or just the mailed newsletters ( Mail Support condition ) . The IMPACT intervention included behavior change strategies for PA as well as discussion s related to motivational readiness for PA change . Participants completed surveys and physiological assessment s at baseline after the classes ended ( i.e. , at 10 weeks ) and at 6 and 12 months postbaseline . Seventy-three percent of r and omized participants ( n = 72 ) were Latina , with a mean age of 32 ± 10 years . More than half the women had not completed high school , and 73 % had an annual income less than $ 20,000 . Results : After 10 months of a homebased intervention , women in the phone + mail counseling condition had significantly greater increases in estimated total energy expenditure compared to women in the mail support condition ( p < .05 ) . Conclusions : Regular PA counseling delivered via the telephone and through the mail appears effective for encouraging regular PA among low-income women transitioning from welfare or job training to the workforce AIMS To assess the long-term efficacy of a fully automated digital multi-media smoking cessation intervention . DESIGN Two-arm r and omized control trial ( RCT ) . Setting World Wide Web ( WWW ) study based in Norway . PARTICIPANTS Subjects ( n = 396 ) were recruited via internet advertisements and assigned r and omly to conditions . Inclusion criteria were willingness to quit smoking and being aged 18 years or older . INTERVENTION The treatment group received the internet- and cell-phone-based Happy Ending intervention . The intervention programme lasted 54 weeks and consisted of more than 400 contacts by e-mail , web-pages , interactive voice response ( IVR ) and short message service ( SMS ) technology . The control group received a self-help booklet . Additionally , both groups were offered free nicotine replacement therapy ( NRT ) . MEASUREMENTS Abstinence was defined as ' not even a puff of smoke , for the last 7 days ' , and assessed by means of internet surveys or telephone interviews . The main outcome was repeated point abstinence at 1 , 3 , 6 and 12 months following cessation . FINDINGS Participants in the treatment group reported clinical ly and statistically significantly higher repeated point abstinence rates than control participants [ 22.3 % versus 13.1 % ; odds ratio ( OR ) = 1.91 , 95 % confidence interval ( CI ) : 1.12 - 3.26 , P = 0.02 ; intent-to-treat ) . Improved adherence to NRT and a higher level of post-cessation self-efficacy were observed in the treatment group compared with the control group . CONCLUSIONS As the first RCT documenting the long-term treatment effects of such an intervention , this study adds to the promise of digital media in supporting behaviour change Objectives : To determine the effectiveness of a mobile phone text messaging smoking cessation programme . Design : R and omised controlled trial Setting : New Zeal and Participants : 1705 smokers from throughout New Zeal and who wanted to quit , were aged over 15 years , and owned a mobile phone were r and omised to an intervention group that received regular , personalised text messages providing smoking cessation advice , support , and distraction , or to a control group . All participants received a free month of text messaging ; starting for the intervention group on their quit day to assist with quitting , and starting for the control group at six months to encourage follow up . Follow up data were available for 1624 ( 95 % ) at six weeks and 1265 ( 74 % ) at six months . Main outcome measures : The main trial outcome was current non-smoking ( that is , not smoking in the past week ) six weeks after r and omisation . Secondary outcomes included current non-smoking at 12 and 26 weeks . Results : More participants had quit at six weeks in the intervention compared to the control group : 239 ( 28 % ) v 109 ( 13 % ) , relative risk 2.20 ( 95 % confidence interval 1.79 to 2.70 ) , p < 0.0001 . This treatment effect was consistent across subgroups defined by age , sex , income level , or geographic location ( p homogeneity > 0.2 ) . The relative risk estimates were similar in sensitivity analyses adjusting for missing data and salivary cotinine verification tests . Reported quit rates remained high at six months , but there was some uncertainty about between group differences because of incomplete follow up . Conclusions : This programme offers potential for a new way to help young smokers to quit , being affordable , personalised , age appropriate , and not location dependent . Future research should test these findings in different setting s , and provide further assessment of long term quit rates AIMS There is increasing international interest in using emerging technologies to enhance chronic disease management . We aim ed to explore the attitudes of patients and primary care professionals to using mobile technology in order to monitor asthma . METHODS A piloted question naire containing closed and open-ended questions assessing attitudes to using electronic self-monitoring was posted to a r and om sample of general practitioners , asthma nurses , and people with asthma ( 12 years and over ) in Lothian and Kent , UK , with 2 reminders . In addition to descriptive statistics , patient and clinician responses were compared using Chi-squared or independent sample t-tests . Free-text responses were analysed thematically . RESULTS Responses were obtained from 130/300 professionals ( 43 % ) and 202/389 patients ( 52 % ) . Patients rated the technology positively and considered that it may help clinicians to provide care , especially during acute attacks . Although rated similarly , professionals were more sceptical about benefits . Both professionals and patients had concerns about the time and cost implication s. Of the respondents , 28 professionals ( 10 % ) and 62 patients ( 16 % ) returned uncompleted question naires citing lack of perceived relevance . CONCLUSIONS The low completion rate probably reflects the current status of mobile phone-facilitated care as a minority interest for ' early adopters ' of technology . Even for the enthusiastic minority , using mobile phone technology raised questions of clinical benefit , impact on self-management , and concerns about workload and cost , which will need to be addressed prior to wider acceptance AIM To investigate the effectiveness of a nurse short message service ( SMS ) by cellular phone and wire Internet on plasma glucose levels in people with diabetes for six months . BACKGROUND Blood glucose management system using telemedicine approaches may maintain the appropriate blood glucose levels in type-2 diabetic patients . DESIGN A control group pre-test-post-test design was used to assess the effectiveness of nurse 's education . METHODS Twenty-five patients were r and omly assigned to an intervention group and 26 to a control group . The intervention was applied for six months . The goal of the intervention was to keep blood glucose concentrations close to the normal range . Participants were requested to input their blood glucose level , diet and exercise diary everyday in the website by cellular phone or wire Internet . The research er sends optimal recommendations to each patient using SMS by cellular phone and wire Internet weekly . RESULTS Glycosylated hemoglobin ( HbA(1)c ) decreased 1.15 % points at three months and 1.05 % points at six months compared with baseline in the intervention group . Patients in the intervention group had a decrease of two hours post meal glucose ( 2HPMG ) of 85.1 mg/dl at three months and 63.1 mg/dl at six months compared with baseline . CONCLUSION This web-based intervention using SMS of cellular phone improved HbA(1)c and 2HPMG for six months in type-2 diabetic patients . RELEVANCE TO CLINICAL PRACTICE An SMS of cellular phone intervention by a nurse can reduce HbA(1)c and 2HPMG for six months in type-2 diabetic patients BACKGROUND Nurse 's education using telemedicine results in a decrease in blood glucose levels in patients with type 2 diabetes . OBJECTIVE To investigate the effectiveness of an educational intervention that used both the cellular phone and the Internet to provide a short-messaging service ( SMS ) relating to plasma glucose levels . METHODS Twenty-five patients were r and omly assigned to an intervention group and 26 to a control group . The intervention was applied for 12 weeks . The goal of the intervention was to keep blood glucose concentrations close to the normal range . Patients in the intervention group were asked to access a website by using a cellular phone or to wiring the Internet and input their blood glucose levels every day . Participants were sent the optimal recommendations by both cellular phone and the Internet weekly . RESULTS Patients in the intervention group had a mean decrease in glycosylated haemoglobin ( HbA(1)c ) levels of 1.15 % and those in the control group had a mean increase of HbA(1)c levels of 0.07 % ( p=0.005 ) . There was a significant mean change in the 2hrs post-meal glucose ( 2HPMG ) level for the intervention group ( p<0.05 ) , with a mean change of -4.7mmol/l . The mean change in the control group was not significant . CONCLUSION This educational intervention using the Internet and an SMS by cellular phone improved levels of HbA(1)c and 2HPMG Background . Patients cite " forgetting " as a reason for nonadherence to highly active antiretroviral therapy ( HAART ) . We measured the effect of a memory-prompting device on adherence to HAART in memory-intact and memory-impaired human immunodeficiency virus (HIV)-infected subjects . Methods . The study was a prospect i ve , r and omized , controlled trial involving 64 HIV-infected adults . The intervention was the Disease Management Assistance System ( DMAS ) device , combined with monthly adherence counseling . Control subjects received only adherence counseling . The DMAS was programmed with HAART regimen data to provide verbal reminders at dosing times . Adherence was measured for 24 weeks using electronic drug exposure monitor ( eDEM ) caps . Results . A total of 58 subjects completed the 24-week study period ; 28 were HAART naive ( 12 DMAS users and 16 control subjects ) . Mean adherence scores did not differ significantly between DMAS users ( 80 % ) and control subjects ( 65 % ) . Post hoc analysis of 31 memory-impaired subjects ( 14 DMAS users and 17 control subjects ) revealed significantly higher adherence rates among DMAS users ( 77 % ) , compared with control subjects ( 57 % ) ( P=.001 ) . However , analysis of memory-intact subjects showed that adherence was not significantly improved for DMAS users ( 83 % ) , compared with control subjects ( 77 % ) ( P=.25 ) . At week twelve , 38 % of the DMAS users and 14 % of the control subjects had an undetectable plasma HIV RNA load ( P=.014 ) , and at week 24 , the plasma HIV RNA load was undetectable for 34 % of the DMAS users and 38 % of the control subjects ( P=.49 ) . CD4(+ ) cell counts did not differ between the study arms . Virological and immunological responses were not related to DMAS use in memory-impaired subjects . Conclusion . The DMAS prompting device improved adherence for memory-impaired subjects but not for memory-intact subjects OBJECTIVE Investigate the effectiveness of an educational intervention that used both the cellular phone with a short messaging service ( SMS ) and the Internet on the glycemic control of the patients with type 2 diabetes mellitus . METHODS Twenty-five patients were r and omly assigned to an intervention group and twenty-six to a control group . The intervention was applied for 12 months . The goal of the intervention was to keep blood glucose concentrations close to the normal range ( HbA(1)c<7 % ) . Patients in the intervention group were asked to access a website by using a cellular phone or to wiring the Internet and input their blood glucose levels weekly . Participants were sent the optimal recommendations by both cellular phone and the Internet weekly . RESULTS Participants in the intervention group had lower HbA(1)c over 12 months when compared with the control group . At 12 months the change from baseline in HbA(1)c was -1.32 in the intervention group versus + 0.81 in the control group . Two hours post-meal glucose ( 2HPMG ) had a significantly greater decline in the intervention group after 12 months when compared with the control group ( -100.0 versus + 18.1mg/dl ) . CONCLUSION This educational intervention using the Internet and a SMS by cellular phone rapidly improved and stably maintained the glycemic control of the patients with type 2 diabetes mellitus Objective To compare the efficacy of a short messaging service ( SMS ) text messaging and phone reminder to improve attendance rates at a health promotion center . Methods A total of 1 859 participants who had scheduled appointments in the health promotion center of our hospital from April 2007 to May 2007 were enrolled in the study and r and omly assigned into 3 groups : control ( no reminder ) group , SMS text messaging reminder group and telephone reminder group . Attendance rates and costs of interventions were collected . Results A total of 1848 participants were eligible for analysis . Attendance rates of control , SMS and telephone groups were 80.5 % , 87.5 % and 88.3 % , respectively . The attendance rates were significantly higher in SMS and telephone groups than that in the control group , with odds ratio 1.698 , 95 % confidence interval 1.224 to 2.316 , P=0.001 in the SMS group , and odds ratio 1.829 , 95 % confidence interval 1.333 to 2.509 , P<0.001 in the telephone group . However , there was no difference between the SMS group and the telephone group ( P=0.670 ) . The cost effectiveness analysis showed that the cost per attendance for the SMS group ( 0.31 Yuan ) was significantly lower than that for the telephone group ( 0.48 Yuan ) . ConclusionS MS and telephone are effective reminders for improving attendance rate at a health promotion center . SMS reminder may be more cost-effective compared with the telephone reminder BACKGROUND The aim of this study was to retest the hypotheses of Reekie and Devlin ( 1998 ) by conducting a similar r and omized controlled trial in an orthodontic clinic in the Netherl and s. It was hypothesized that a reminder would reduce the failed attendance rate and that the form of the reminder would be irrelevant . METHODS All patients with appointments in the orthodontic clinic at the Academic Centre of Dentistry Amsterdam during a 3-week period were divided into 4 groups . Three groups received a reminder 1 day before the appointment , either by telephone , mail , or short message service ( SMS , a service used to send and receive short text messages to and from cell phones ) . A control group did not receive a reminder . In a follow-up study , r and om sub sample s in each group were interviewed by telephone . Subjects were asked how they felt about receiving a reminder and which reminder they preferred . RESULTS The hypothesis that a reminder would reduce the failed attendance rate was not confirmed . Also , no differences were found between the 4 conditions , indicating that the form of the reminder is irrelevant . However , most of the interviewed participants felt positive or very positive about receiving a reminder . There was a significant preference for a reminder by mail ( 56.3 % ) , followed by a telephone reminder ( 26.0 % ) and a reminder by SMS ( 17.7 % ) . No less than 20 % of the interviewed participants felt negative or very negative about the reminders and considered them to be a waste of time and money . CONCLUSIONS The hypothesis that reminders are useful in the prevention of failed appointments was not confirmed . This study underlines the importance of replication studies . It demonstrates that every research result , whether it is generated by evidence -based or tradition-based research , should be interpreted with care and should be replicated in other studies before the results can be generalized RATIONALE Noncompliance with vaccination schedules undermines the potential benefits of immunization . The purpose of this study was to evaluate whether a reminder of the next vaccine dose sent by the Short Messaging Service ( SMS ) to the vaccinee 's mobile phone increases compliance with hepatitis A + B and hepatitis A vaccination schedule . SUBJECTS AND METHODS In this experimental , controlled study , the study group comprised travelers who went to the Internacional-Clínic Vaccination Centre between the 1st June and 30th September of 2001 for the st and ard immunization schedule against hepatitis A + B and against hepatitis A. Trained health-care workers entered the data into a computer to generate text messages reminding vaccinees of their scheduled doses . Two control groups , one from the same period of the same year including travelers from the third office ( Control 2001 ) and the second , all travelers seen in the same period of the previous year ( Control 2000 ) , were used . RESULTS For the second hepatitis A + B dose , compliance in the study group ( Message Groups ) was 88.4 % ( 83.3 - 92.2 ) ; in the Control 2001 , 80.7 % ( 76.3 - 84.4 , relative risk [ RR ] 1.10 [ 1.02 - 1.17 ] ) ; and in the Control 2000 , 77.2 % ( 73.3 - 80.5 , RR 1.15 [ 1.07 - 1.22 ] ) . For the third hepatitis A + B vaccine dose , results were 47.1 % ( 40.5 - 53.8 ) ; 26.9 % ( 22.8 - 31.7 , RR 1.75 [ 1.41 - 2.17 ] ) ; and 23.6 % ( 20.1 - 27.4 , RR 2.00 [ 1.63 - 2.45 ] ) , respectively . As for the hepatitis A vaccine , compliance rates for the second dose were 27.7 % ( 23.9 - 31.9 ) ; 16.4 % ( 14.4 - 18.6 , RR 1.69 [ 1.40 - 2.04 ] ) ; and 13.2 % ( 11.6 - 14.9 , RR 2.10 [ 1.75 - 2.54 ] ) ; respectively . CONCLUSIONS SMS seems to be an effective tool for increasing compliance with vaccination schedules AIMS To determine whether a smoking cessation service using mobile phone text messaging is as effective for Maori as non-Maori . METHODS A single-blind r and omised controlled trial was undertaken with recruitment targeted to maximise the participation of young Maori . The intervention included regular , personalised text messages providing smoking cessation advice , support , and distraction . Maori text messages related to Maori language , support messages ( in Maori and English ) and information on Maori traditions . Text messaging was free for 1 month . After 6 weeks , the number of messages reduced from 5 per day to 3 per week until the 26-week follow-up . RESULTS Participants included 355 Maori and 1350 non-Maori . Maori in the intervention group were more likely to report quitting ( no smoking in the past week ) at 6 weeks ( 26.1 % ) than those in the control group ( 11.2 % ) RR 2.34 , 95 % CI : 1.44 - 3.79 . There was no significant difference between the RR for Maori and that for non-Maori ( RR : 2.16 , 95%CI : 1.72 - 2.71 ) . CONCLUSIONS A mobile phone-based cessation programme was successful in recruiting young Maori , and was shown to be as effective for Maori as non-Maori at increasing short-term self-reported quit rates . This shows clear potential as a new public health initiative PURPOSE The present study evaluated whether an intervention using the SMS by personal cellular phone and internet would improve the levels of plasma glucose of obese type 2 diabetes at 3 , 6 , 9 , and 12 months . METHODS This is a quasi-experimental design with pre- and follow-up tests . Participants were recruited from the endocrinology outpatient department of tertiary care hospital located in an urban city of South Korea . Eighteen patients were r and omly assigned to an intervention group and 16 to a control group . The goal of the intervention was to decrease body weight and keep blood glucose concentrations close to the normal range . Patients were requested to record their blood glucose level in a weekly diary on the website by personal cellular phones or computer internet . The research er sent optimal recommendations to each patient , by both the cellular phone and the Internet weekly . The intervention was applied for 1 year . RESULTS Glycosylated hemoglobin ( HbA(1)c ) decreased 1.22 percentage points at 3 months , 1.09 percentage points at 6 months , 1.47 percentage points at 9 months , and 1.49 percentage points at 12 months compared with baseline in the intervention group ( all time points , p<0.05 ) . The percentage change in the control group was , however , not significant . Patients in the intervention group had a decrease of 2-h post-pr and ial test ( 2HPPT ) of 120.1mg/dl at 3 months , 58.9 mg/dl at 6 months , 62.0mg/dl at 9 months , and 102.9 mg/dl at 12 months compared with baseline ( all time points , p<0.05 ) . The mean change in the control group was , however , not significant . CONCLUSION This web-based intervention using SMS of personal cellular phone and Internet improved HbA(1)c and 2HPPT at 3 , 6 , 9 , and 12 months in patients with obese type 2 diabetes One of the best strategies for dealing with stress is learning how to relax . However , relaxing is difficult to achieve in typical real world situations . For this study , we developed a specific protocol based on mobile narratives - multimedia narratives experienced on UMTS/3 G phones - to help workers in reducing commuting stress . In a controlled trial 33 commuters were r and omly divided between three conditions : Mobile narratives ( MN ) ; New age music and videos ( NA ) ; no treatment ( CT ) . In two consecutive days the MN and NA sample s experienced during their commute trip 2 x 2 6-minute multimedia experiences on a Motorola A925 3 G phone provided by the " TRE " Italian UMTS carrier : the MN sample experienced a mobile narrative based on the exploration of a desert beach ; the NA sample experienced a commercial new age video with similar visual contents . The trials showed the efficacy of mobile narratives in reducing the level of stress experienced during a commute trip . No effects were found in the other groups . These results suggest that 3 G mobile h and sets may be used as relaxation tool if backed by a specific therapeutic protocol and meaningful narratives Introduction In this paper , we evaluated the feasibility of a telemedical ( TM ) support program and its effect on glycemic control in adolescents with type 1 diabetes mellitus ( T1DM ) . Thirty-six adolescents ( m=20 , median age at the start of the study : 15.3 years ( range : 10.7–19.3 years ) , median age at diagnosis : 9.3 years ( 2.1–13.8 years ) , median duration of disease : 6.4 years ( 1.0–12.8 years ) , HbA1c>8 % , all on intensified insulin therapy ) were r and omized in a crossover trial over 6 months ( 3 months with TM , 3 months with conventional support and paper diary ( PD ) ) . During the TM phase , the patients sent their data ( date , time , blood glucose , carbohydrate intake , insulin dosage ) via mobile phone , at least daily , to our server and diabetologists sent back their advice via short message service ( SMS ) once a week . Results Glycemic control improved during the TM phase , while it deteriorated during the PD phase : TM-PD group HbA1c ( % , median ( range ) ) : 9.05 ( 8–11.3 ) ( at 0 months ) , 8.9 ( 6.9–11.3 ) ( at 3 months ) , and 9.2 ( 7.4–12.6 ) ( at 6 months ) , and PD-TM group : 8.9 ( 8.3–11.6 ) , 9.9 ( 8.1–11 ) , and 8.85 ( 7.3–11.7 ) ( p<0.05 ) . Patients rated the TM support program to be a good idea . Technical problems with General Packet Radio Service ( GPRS ) data transmission led to data loss and decreased patient satisfaction . Conclusion Our telemedical support program , VIE-DIAB , proved to be feasible in adolescents and helped to improve glycemic control AIM Conventional follow-up of type 1 diabetic patients treated with continuous subcutaneous insulin infusion ( CSII ) was compared with intensive coaching using the Web and the cellular phone network for retrospective data transmission and short message service ( SMS ) . METHODS Thirty poorly controlled patients ( HbA1c 7.5 - 10 % ) were enrolled in a bicenter , open-label , r and omized , 12-month , two-period , crossover study . After a 1-month run-in period , 15 patients were r and omly assigned to receive weekly medical support through SMS based upon weekly review of glucose values , while 15 patients continued to download self-monitored blood glucose ( SMBG ) values on a weekly basis without receiving SMS . After 6 months , patients crossed over to the alternate sequence for 6 additional months . Visits at the clinic were maintained every 3 months . RESULTS Patients with long-st and ing inadequately controlled diabetes ( 24 + /- 13 years ) were included . A non-significant trend to reduction in HbA(1c ) ( -0.25+/-0.94 % , P<0.10 ) and mean glucose values ( -9.2+/-25 mg/dl , P=0.06 ) during the 6-month SMS sequence was observed as compared with the no-SMS period . No safety issue ( hypoglycemia , glucose variability ) was reported . Adherence to SMBG was not affected by the trial . Quality of life analysis suggests a significant improvement in DQOL global score , as well as the DQOL satisfaction with life subscale , during the SMS sequence . CONCLUSIONS Long-term telemedical follow-up of insulin pump-treated patients using a cellular phone- , SMS- and Web-based platform is feasible , safe , does not alter quality of life and associated with a trend toward improved metabolic control PURPOSE We sought to evaluate the effect of automated telephone assessment and self-care education calls with nurse follow-up on the management of diabetes . SUBJECTS AND METHODS We enrolled 280 English- or Spanish-speaking adults with diabetes who were using hypoglycemic medications and who were treated in a county health care system . Patients were r and omly assigned to usual care or to receive an intervention that consisted of usual care plus bi-weekly automated assessment and self-care education calls with telephone follow-up by a nurse educator . Outcomes measured at 12 months included survey-reported self-care , perceived glycemic control , and symptoms , as well as glycosylated hemoglobin ( Hb A1c ) and serum glucose levels . RESULTS We collected follow-up data for 89 % of enrollees ( 248 patients ) . Compared with usual care patients , intervention patients reported more frequent glucose monitoring , foot inspection , and weight monitoring , and fewer problems with medication adherence ( all P -0.03 ) . Follow-up Hb A , , levels were 0.3 % lower in the intervention group ( P = 0.1 ) , and about twice as many intervention patients had Hb A1c levels within the normal range ( P = 0.04 ) . Serum glucose levels were 41 mg/dL lower among intervention patients than usual care patients ( P = 0.002 ) . Intervention patients also reported better glycemic control ( P = 0.005 ) and fewer diabetic symptoms ( P < 0.0001 ) , including fewer symptoms of hyperglycemia and hypoglycemia . CONCLUSIONS Automated calls with telephone nurse follow-up may be an effective strategy for improving self-care behavior and glycemic control , and for decreasing symptoms among vulnerable patients with diabetes People with a disability do not have equitable access to the modern telecommunication medium . Many experience difficulty typing , h and ling the phone , dialling or answering calls . For those who are unable to speak , the only option is to type messages using whatever functional control site exists on their body . The provision of accessible mobile phones for people with disabilities can significantly improve their quality of life through an increased range of accessible activities , and can improve their independence , safety , security and self-esteem . This research was aim ed at providing practical ways for people with a disability to participate in the extensive community of home and mobile phone users . The outcomes of ten participants taking part in the evaluation and trial of off-the-shelf telecommunication options are presented . Nine out of ten participants showed high to very high results in terms of their overall performance and satisfaction with the use of the telecommunication equipment provided . With the right policies , processes and support through equipment matching , education , training and delivery , current off-the-shelf solutions can help people with disabilities to effectively communicate with other members of our society and to access the same range of information systems and services enjoyed by able-bodied members of the community Home peak expiratory flow ( PEF ) measurement is recommended by asthma guidelines . In a 16-week r and omized controlled study on 16 subjects with asthma ( 24.6 6.5 years old , asthma duration small ze , Cyrillic 6 months ) , we examined Global System for Mobile Communications ( GSM ) mobile telephone short-message service ( SMS ) as a novel means of telemedicine in PEF monitoring . All subjects received asthma education , self-management plan , and st and ard treatment . All measured PEF three times daily and kept a symptom diary . In the study group , therapy was adjusted weekly by an asthma specialist according to PEF values received daily from the patients . There was no significant difference between the groups in absolute PEF , but PEF variability was significantly smaller in the study group ( 16.12 + /- 6.93 % vs. 27.24 + /- 10.01 % , p = 0.049 ) . forced expiratory flow in 1 second ( FEV1 ; % predicted ) in the study group was slightly but significantly increased ( 81.25 + /- 17.31 vs. 77.63 + /- 14.80 , p = 0.014 ) and in the control group , unchanged ( 78.25 + /- 21.09 vs. 78.88 + /- 22.02 , p = 0.497 ) . Mean FEV1 was similar in the two groups both before and after the study . Controls had significantly higher scores for cough ( 1.85 + /- 0.43 vs. 1.42 + /- 0.28 , p < 0.05 ) and night symptoms ( 1.22 + /- 0.23 vs. 0.85 + /- 0.32 , p < 0.05 ) . There was no significant difference between the groups in daily consumption of inhaled medicine , forced vital capacity , or compliance . Per patient , per week , the additional cost of follow-up by SMS was Euros 1.67 ( equivalent to approximately $ 1.30 per 1 Euro ) , and SMS transmission required 11.5 minutes . Although a study group of 40 patients is needed for the follow-up study to achieve the power of 80 % within the 95 % confidence interval , we conclude that SMS is a convenient , reliable , affordable , and secure means of telemedicine that may improve asthma control when added to a written action plan and st and ard follow-up Practical problems and patients or doctors low compliance has been hampering a wider use of self-management in asthma . Mobile or web technologies for supporting selfmanagement may improve patient – doctor communication and patient self-efficacy ( 1 , 2 ) . Furthermore , recent evidence suggests that interactive Internet-based asthma monitoring improves asthma control ( 3 ) . However , patients may not be willing to use a web asthma diary for more than short periods , possibly because it does not fit into their everyday lives ( 4 ) . The use of mobile phones has been suggested to overcome this problem ( 4 , 5 ) , but , to our knowledge , no data are available on the willingness of patients to use mobile phones , and very few data have been reported on their willingness to use the web for asthma self-management ( 6 ) . In the framework of a running r and omized controlled trial on psycho-educational interventions in asthma , 74 adults with moderate to severe asthma were r and omly allocated to fill a symptoms diary for 1 month . Of these , 37 dropped-out of the trial and the remaining 47 ( 63 % ) completed a self-administered question naire about asthma monitoring . These two groups did not differ significantly regarding age , education , socio-economic status , and asthma severity . Approximately one-third was younger than 31 years and half was older than 40 years ; 84 % were female ; nearly 70 % had low socio-economic background ( class IV and V ) and 44 % had 5 or fewer years of formal education . FEV1 predicted % was below 80 % in 53 % , while 64 % were treated with high-dose inhaled steroids . During the previous year , 56 % had at least one exacerbation requiring oral steroids and one in five was admitted to a hospital because of their asthma . Only 28 % had ever self-monitored asthma before entering the study . However , none of the patients referred unwillingness to monitor their asthma in the future , and 56 % of them were strongly in favor to its use ; furthermore , one-third of patients were happy to monitor their symptoms daily , whereas another third preferred to do it less than once a week . Also , one in five considered it was easy to forget to register symptoms in the paper diary , and all patients considered it to help them better underst and their disease . The proportions of referred willingness to use mobile or web technologies to support self-management are described in Table 1 . There were no significant associations between willingness to use mobile or web technologies and patient ’s sex , age , education level , socio-economic status , tobacco usage , other chronic diseases , and duration and severity of asthma . Caution is needed in the generalization of these results as the patients who were studied were mostly middle-aged women with low education , and low socio-economic background , who had moderate to severe asthma followed at secondary care . Nevertheless , a large majority of patients seem willing and ready to use communication technologies such as mobile phones and the Web to help them manage their asthma . Are the doctors and the health administrators also ready to test the effectiveness of this AL LERGY 2 0 0 6 : 6 1 : 3 8 9 – 3 9 5 • COPYR IGHT a 2006 BLACKWELL MUNKSGAARD • ALL R IGHTS RESERVED • CONTRIBUT IONS TO THIS SECT ION WILL NOT UNDERGO PEER REVIEW , BUT WILL BE REV IEWED BY THE ASSOCIATE EDITORS This study applied a 6-month educational intervention that used the technology of the short message service ( via cellular phones ) and the Internet for obese patients with type 2 diabetes . Eighteen patients were r and omly assigned to an intervention group and 16 were assigned to a control group ( N = 34 ) . Patients in the intervention group were asked to access a web site by using personal cellular phones or computer Internet services to input their blood glucose levels daily . Participants were then sent optimal recommendations via cellular phone and the Internet weekly . After 6 months , the intervention group had a statistically significant decrease in glycosylated hemoglobin , fasting plasma glucose , 2-hour postmeal glucose , and total cholesterol , as compared with the control group |
13,221 | 28,837,665 | CDS was associated with lower antibiotic utilisation , increased compliance with antibiotic guidelines and reductions in antimicrobial resistance .
Conflicting effects of CDS on length of stay , antibiotic costs and system uptake were also noted .
CDS has the potential to improve the adequacy of antibiotic coverage and marginally decrease mortality in hospital-related setting | BACKGROUND Inappropriate antimicrobial use has been shown to be an important determinant of the emergence of antimicrobial resistance ( AMR ) .
Health information technology ( HIT ) in the form of Computerised Decision Support ( CDS ) represents an option for improving antimicrobial prescribing and containing AMR . | OBJECTIVE This study assessed the effect of a h and held computer-based decision support system ( DSS ) on antibiotic use and patient outcomes in a critical care unit . DESIGN A DSS containing four types of evidence ( patient microbiology reports , local antibiotic guidelines , unit-specific antibiotic susceptibility data for common bacterial pathogens , and a clinical pulmonary infection score calculator ) was developed and implemented on a h and held computer for use in the intensive care unit at a tertiary referral hospital . System impact was assessed in a prospect i ve " before/after " cohort trial lasting 12 months . Outcome measures were defined daily doses ( DDDs ) of antibiotics per 1,000 patient-days , patient length of stay , and mortality . RESULTS The number of admissions , APACHE ( Acute Physiology , Age , and Chronic Health Evaluation ) II and SAPS ( Simplified Acute Physiology Score ) II for patients in preintervention , and intervention ( DSS use ) periods were statistically comparable . The mean patient length of stay and the use of antibiotics in the unit during six months of the DSS use decreased from 7.15 to 6.22 bed-days ( p = 0.02 ) and from 1,767 DDD to 1,458 DDD per 1,000 patient-days ( p = 0.04 ) , respectively , with no change in mortality . The DSS was accessed 674 times during 168 days of the trial . Microbiology reports and antibiotic guidelines were the two most commonly used ( 53 % and 22.5 % , respectively ) types of evidence . The greatest reduction was observed in the use of beta-lactamase-resistant penicillins and vancomycin . CONCLUSION H and held computer-based decision support contributed to a significant reduction in patient length of stay and antibiotic prescribing in a critical care unit A prospect i ve quasi-experimental study was undertaken in 218 patients with suspicion of nosocomial infection hospitalized in a polyvalent ICU where a new electronic device ( GERB ) has been design ed for antibiotic prescriptions . Two GERB-based applications were developed to provide local resistance maps ( LRMs ) and preliminary microbiological reports with therapeutic recommendation ( PMRTRs ) . Both applications used the data in the Laboratory Information System of the Microbiology Department to report on the optimal empiric therapeutic option , based on the most likely susceptibility profile of the microorganisms potentially responsible for infection in patients and taking into account the local epidemiology of the hospital department/unit . LRMs were used for antibiotic prescription in 20.2 % of the patients and PMRTRs in 78.2 % , and active antibiotics against the finally identified bacteria were prescribed in 80.0 % of the former group and 82.4 % of the latter . When neither LMRs nor PMRTRs were considered for empiric treatment prescription , only around 40 % of the antibiotics prescribed were active . Hence , the percentage appropriateness of the empiric antibiotic treatments was significantly higher when LRM or PMRTR guidelines were followed rather than other criteria . LRMs and PMRTRs applications are dynamic , highly accessible , and readily interpreted instruments that contribute to the appropriateness of empiric antibiotic treatments OBJECTIVE Computerized medical decision support tools have been shown to improve the quality of care and have been cited by the Institute of Medicine as one method to reduce pharmaceutical errors . We evaluated the impact of an antiinfective decision support tool in a pediatric intensive care unit ( PICU ) . METHODS We enhanced an existing adult antiinfective management tool by adding and changing medical logic to make it appropriate for pediatric patients . Process and outcomes measures were monitored prospect ively during a 6-month control and a 6-month intervention period . M and atory use of the decision support tool was initiated for all antiinfective orders in a 26-bed PICU during the intervention period . Clinician opinions of the decision support tool were surveyed via question naire . RESULTS The rate of pharmacy interventions for erroneous drug doses declined by 59 % . The rate of anti-infective subtherapeutic patient days decreased by 36 % , and the rate of excessive-dose days declined by 28 % . The number of orders placed per antiinfective course decreased 11.5 % , and the robust estimate of the antiinfective costs per patient decreased 9 % . The type of anti-infectives ordered and the number of antiinfective doses per patient remained similar , as did the rates of adverse drug events and antibiotic-bacterial susceptibility mismatches . The surveyed clinicians reported that use of the program improved their antiinfective agent choices as well as their awareness of impairments in renal function and reduced the likelihood of adverse drug events . CONCLUSIONS Use of the pediatric antiinfective decision support tool in a PICU was considered beneficial to patient care by the clinicians and reduced the rates of erroneous drug orders , improved therapeutic dosage targets , and was associated with a decreased robust estimate of antiinfective costs per patient . antiinfective agents , decision support systems , drug therapy , medication errors , child , infant The objective of this prospect i ve clinical usage study was to examine the value of the rule based ' Therapeutic Assistant ' integrated into an existing Patient Data Management System ( PDMS ) in helping to prescribe a initial antibiotic regime in accordance with the requirements of accepted guidelines . A prospect i ve study comparing data before and after the introduction of the ' Therapeutic Assistant ' was carried out . An adequate therapy result ed significantly more often after the introduction of the ' Therapeutic Assistant ' [ p<0.05 ] ; however no difference between the regimes with and without the ' Therapeutic Assistant ' in the period after its introduction could be established . Whether the ' Therapeutic Assistant ' influenced the prescriptions made without it will have to be established in a further study Objective : To evaluate the hospital-wide impact of a st and ardized order set for the management of bacteremic severe sepsis on processes of medical care and patient outcomes . Design : Retrospective , before and after study design . Setting : Barnes-Jewish Hospital , a 1200-bed academic medical center . Patients : Bacteremic patients with severe sepsis ( 200 from the 18-month before period and 200 from the 18-month after period ) . Interventions : Hospital-wide implementation of a st and ardized order set for the management of bacteremic severe sepsis . Measurements and Main Results : A total of 400 patients with bacteremia and severe sepsis were selected at r and om within the specified time periods . Patients in the after group received more intravenous fluids in the first 12 hours after onset of hypotension ( 1627 ± 1862 mL vs. 2054 ± 2237 mL ; p = 0.04 ) and were more likely to receive appropriate initial antibiotic therapy ( 53.0 % vs. 65.5 % , p = 0.01 ) . In-hospital mortality was statistically decreased in the after group ( 55.0 % vs. 39.5 % , p < 0.01 ) , as was the hospital length of stay ( 28.7 ± 30.1 days vs. 22.4 ± 20.9 days ; p = 0.02 ) . Compared with the before group , the after group had reduced occurrence of renal failure ( 49.0 % vs. 36.0 % , p < 0.01 ) , cardiovascular failure ( 70.5 % vs. 57.0 % , p < 0.01 ) , and were less likely to require vasopressors after initial fluid resuscitation ( 68.5 % vs. 52.5 % , p < 0.01 ) . Conclusions : The implementation of a hospital-wide st and ardized order set for the management of bacteremic severe sepsis was associated with greater fluid administration , improved antibiotic therapy , decreased incidence of organ failure , and improved survival OBJECTIVE Antibiotic computerized decision support systems ( CDSSs ) were developed to guide antibiotic decisions , yet prescriptions of CDSS-recommended antibiotics have remained low . Our aim was to identify predictors of patients ' receipt of empiric antibiotic therapies recommended by a CDSS when the prescribing physician had an initial preference for using broad-spectrum antibiotics . METHODS We conducted a prospect i ve cohort study in a 1 500-bed tertiary-care hospital in Singapore . We included all patients admitted from October 1 , 2011 through September 30 , 2012 , who were prescribed piperacillin-tazobactam or carbapenem for empiric therapy and auto-triggered to receive antibiotic recommendations by the in-house antibiotic CDSS . Relevant data on the patient , prescribing and attending physicians were collected via electronic linkages of medical records and administrative data bases . To account for clustering , we used multilevel logistic regression models to explore factors associated with receipt of CDSS-recommended antibiotic therapy . RESULTS One-quarter of the 1 886 patients received CDSS-recommended antibiotics . More patients treated for pneumonia ( 33.2 % ) than sepsis ( 12.1 % ) and urinary tract infections ( 7.1 % ) received CDSS-recommended antibiotic therapies . The prescribing physician - but not the attending physician or clinical specialty - accounted for some ( 13.3 % ) of the variation . Prior hospitalization ( odds ratio [ OR ] 1.32 , 95 % CI , 1.01 - 1.71 ) , presumed pneumonia ( OR 6.77 , 95 % CI , 3.28 - 13.99 ) , intensive care unit ( ICU ) admission ( OR 0.38 , 95 % CI , 0.21 - 0.66 ) , and renal impairment ( OR 0.70 , 95 % CI , 0.52 - 0.93 ) were factors associated with patients ' receipt of CDSS-recommended antibiotic therapies . CONCLUSIONS We observed that ICU admission and renal impairment were negative predictors of patients ' receipt of CDSS-recommended antibiotic therapies . Patients admitted to ICU and those with renal impairment might have more complex clinical conditions that require a physician 's assessment in addition to antibiotic CDSS Electronic clinical decision support systems ( CDSS ) have been hailed for their potential to improve clinical outcomes . Using a pretest/posttest design , an Internet-based CDSS design ed to optimize antimicrobial prescribing was pilot tested for community-acquired pneumonia in 5 rural hospitals in southwestern Idaho . An antimicrobial management team was created in each hospital to address clinicians ’ perception of excessive time required for direct use of the CDSS . In pooled hospital data , agreement with CDSS recommendations improved to a statistically significant level . However , inspection of data at the individual hospital level demonstrated that almost all improvement occurred in a single hospital . Failure in the other hospitals appeared to be primarily a consequence of organizational and cultural barriers . These barriers are discussed to underst and keys for successful future implementation of CDSS in rural hospitals , drawing on experience with cultural barriers from other industries , specifically aviation OBJECTIVES Antibiotic stewardship is important , but the ideal strategy for providing stewardship in a hospital setting is unknown . A practical , sustainable and transferable strategy is needed . This study evaluates the impact of a novel computerized antimicrobial approval system on antibiotic-prescribing behaviour in a hospital . Effects on drug consumption , antibiotic resistance patterns of local bacteria and patient outcomes were monitored . METHODS The study was conducted at a tertiary referral teaching hospital in Melbourne , Australia . The system was deployed in January 2005 and guided the use of 28 restricted antimicrobials . Data were collected over 7 years : 5 years before and 2 years after deployment . Uptake of the system was evaluated using an in-built audit trail . Drug utilization was prospect ively monitored using pharmacy data ( as defined daily doses per 1000 bed-days ) and analysed via time-series analysis with segmental linear regression . Antibiograms of local bacteria were prospect ively evaluated . In-hospital mortality and length of stay for patients with Gram-negative bacteraemia were also reported . RESULTS Between 250 and 300 approvals were registered per month during 2006 . The gradients in the use of third- and fourth-generation cephalosporins ( + 0.52 , -0.05 , -0.39 ; P < 0.01 ) , glycopeptides ( + 0.27 , -0.53 ; P = 0.09 ) , carbapenems ( + 0.12 , -0.24 ; P = 0.21 ) , aminoglycosides ( + 0.15 , -0.27 ; P < 0.01 ) and quinolones ( + 0.76 , + 0.11 ; P = 0.08 ) all fell after deployment , while extended-spectrum penicillin use increased . Trends in increased susceptibility of Staphylococcus aureus to methicillin and improved susceptibility of Pseudomonas spp . to many antibiotics were observed . No increase in adverse outcomes for patients with Gram-negative bacteraemia was observed . CONCLUSIONS The system was successfully adopted and significant changes in antimicrobial usage were demonstrated STUDY OBJECTIVE Despite evidence that guideline adherence improves clinical outcomes , management of pneumonia patients varies in emergency departments ( EDs ) . We study the effect of a real-time , ED , electronic clinical decision support tool that provides clinicians with guideline -recommended decision support for diagnosis , severity assessment , disposition , and antibiotic selection . METHODS This was a prospect i ve , controlled , quasi-experimental trial in 7 Intermountain Healthcare hospital EDs in Utah 's urban corridor . We studied adults with International Classification of Diseases , Ninth Revision codes and radiographic evidence for pneumonia during 2 periods : baseline ( December 2009 through November 2010 ) and post-tool deployment ( December 2011 through November 2012 ) . The tool was deployed at 4 intervention EDs in May 2011 , leaving 3 as usual care controls . We compared 30-day , all-cause mortality adjusted for illness severity , using a mixed-effect , logistic regression model . RESULTS The study population comprised 4,758 ED pneumonia patients ; 14 % had health care-associated pneumonia . Median age was 58 years , 53 % were female patients , and 59 % were admitted to the hospital . Physicians applied the tool for 62.6 % of intervention ED study patients . There was no difference overall in severity-adjusted mortality between intervention and usual care EDs post-tool deployment ( odds ratio [OR]=0.69 ; 95 % confidence interval [ CI ] 0.41 to 1.16 ) . Post hoc analysis showed that patients with community-acquired pneumonia experienced significantly lower mortality ( OR=0.53 ; 95 % CI 0.28 to 0.99 ) , whereas mortality was unchanged among patients with health care-associated pneumonia ( OR=1.12 ; 95 % CI 0.45 to 2.8 ) . Patient disposition from the ED postdeployment adhered more to tool recommendations . CONCLUSION This study demonstrates the feasibility and potential benefit of real-time electronic clinical decision support for ED pneumonia patients BACKGROUND Physicians frequently need to start antibiotic therapy before the results of bacterial cultures and antibiotic susceptibility tests are available . We developed and evaluated a computerized antibiotic consultant to assist physicians in the selection of appropriate empiric antibiotics . METHODS We used a two-stage r and om- selection study to compare antibiotics suggested by the antibiotic consultant with 482 associated antibiotic susceptibility results and the concurrent antibiotics ordered by physicians . The antibiotics ordered by r and omized physicians were then compared between crossover periods of antibiotic consultant use . RESULTS The antibiotic consultant suggested an antibiotic regimen to which all isolated pathogens were shown to be susceptible for 453 ( 94 % ) of 482 culture results , while physicians ordered an antibiotic regimen to which all isolated pathogens were susceptible for 369 culture results ( 77 % ) ( P < .001 ) . The physicians who prescribed antibiotics to which all pathogens were susceptible did so a mean of 21 hours after the culture specimens were collected . Physicians ordered appropriate antibiotics within 12 hours of the culture collection significantly more often when they had use of the antibiotic consultant than during the period before use ( P < .035 ) . Moreover , 88 % of the physicians stated they would recommend the program to other physicians , 85 % said the program improved their antibiotic selection , and 81 % said they felt use of the program improved patient care . CONCLUSIONS Information from computer-based medical records can be used to help improve physicians ' selection of empiric antibiotics for infections OBJECTIVE To implement and evaluate the effect of a computerized decision support tool on antibiotic use in an intensive care unit ( ICU ) . DESIGN Prospect i ve before- and -after cohort study . SETTING Twenty-four bed tertiary hospital adult medical/surgical ICU . PARTICIPANTS All consecutive patients from May 2001 to November 2001 ( N = 524 ) and March 2002 to September 2002 ( N = 536 ) . INTERVENTION A real-time microbiology browser and computerized decision support system for isolate directed antibiotic prescription . MAIN OUTCOME MEASURES Number of courses of antibiotic prescribed , antibiotic utilization ( defined daily doses (DDDs)/100 ICU bed-days ) , antibiotic susceptibility mismatches , and system uptake . RESULTS There was a significant reduction in the proportion of patients prescribed carbapenems [ odds ratio ( OR ) = 0.61 , 95 % confidence interval ( CI ) = 0.39 - 0.97 , P = 0.04 ] , third-generation cephalosporins ( OR = 0.58 , 95 % CI = 0.42 - 0.79 , P = 0.001 ) , and vancomycin ( OR = 0.67 , 95 % CI = 0.45 - 1.00 , P = 0.05 ) after adjustment for risk factors including Apache II score , suspected infection , positive microbiology , intubation , and length of stay . The decision support tool was associated with a 10.5 % reduction in both total antibiotic utilization ( 166 - 149 DDDs/100 ICU bed days ) and the highest volume broad-spectrum antibiotics . There were fewer susceptibility mismatches for initial antibiotic therapy ( OR = 0.63 , 95 % CI = 0.39 - 0.98 , P = 0.02 ) and increased de-escalation to narrower spectrum antibiotics . Uptake of the program was high with 6028 access episodes during the 6-month evaluation period . CONCLUSIONS This tool streamlined collation and clinical use of microbiology results and integrated into the daily ICU workflow . Its introduction was accompanied by a reduction in both total and broad-spectrum antibiotic use and an increase in the number of switches to narrower spectrum antibiotics OBJECTIVES TREAT is a computerized decision support system for antibiotic treatment . In a r and omized controlled trial it improved significantly the percentage of appropriate empirical antibiotic treatment and shortened hospital stay , while the usage of broad-spectrum antibiotics was reduced . The trial was not powered to show significance for the difference in 1 month mortality rate . In the present analysis we looked at 6 month survival in one of the hospitals ( Beilinson Hospital ) that participated in the trial . METHODS We plotted the Kaplan-Meier survival function for all patients [ intention to treat ( ITT ) ] and for patients treated according to the TREAT advice [ per protocol ( PP ) ] . The analysis was repeated for patients with clinical ly or bacteriologically documented bacterial infections . RESULTS At Beilinson Hospital 1683 patients were included in the study , 860 in the intervention arm and 823 in the control arm . In the ITT analysis 180 day survival in control patients was 71 % versus 74 % in the intervention patients ( P = 0.2 ) . In the PP analysis the survival percentages were 71 % and 77 % , respectively ( P = 0.04 ) . In patients with bacterial infections , in the ITT analysis 180 day survival in the control group was 68 % versus 71 % in the intervention patients ( P = 0.1 ) . In the PP analysis the survival percentages were 68 % versus 74 % ( P = 0.04 ) . CONCLUSIONS The present data support an effect of the TREAT decision support system on 6 month survival , mainly because of its benefit in patients with documented bacterial infections OBJECTIVE The aim of this study was to compare the clinical impact of computerized decision support with and without electronic access to clinical guidelines and laboratory data on antibiotic prescribing decisions . DESIGN A crossover trial was conducted of four levels of computerized decision support-no support , antibiotic guidelines , laboratory reports , and laboratory reports plus a decision support system ( DSS ) , r and omly allocated to eight simulated clinical cases accessed by the Web . MEASUREMENTS Rate of intervention adoption was measured by frequency of accessing information support , cost of use was measured by time taken to complete each case , and effectiveness of decision was measured by correctness of and self-reported confidence in individual prescribing decisions . Clinical impact score was measured by adoption rate and decision effectiveness . RESULTS Thirty-one intensive care and infectious disease specialist physicians ( ICPs and IDPs ) participated in the study . Ventilator-associated pneumonia treatment guidelines were used in 24 ( 39 % ) of the 62 case scenarios for which they were available , microbiology reports in 36 ( 58 % ) , and the DSS in 37 ( 60 % ) . The use of all forms of information support did not affect clinicians ' confidence in their decisions . Their use of the DSS plus microbiology report improved the agreement of decisions with those of an expert panel from 65 % to 97 % ( p=0.0002 ) , or to 67 % ( p=0.002 ) when antibiotic guidelines only were accessed . Significantly fewer IDPs than ICPs accessed information support in making treatment decisions . On average , it took 245 seconds to make a decision using the DSS compared with 113 seconds for unaided prescribing ( p<0.001 ) . The DSS plus microbiology reports had the highest clinical impact score ( 0.58 ) , greater than that of electronic guidelines ( 0.26 ) and electronic laboratory reports ( 0.45 ) . CONCLUSION When used , computer-based decision support significantly improved decision quality . In measuring the impact of decision support systems , both their effectiveness in improving decisions and their likely rate of adoption in the clinical environment need to be considered . Clinicians chose to use antibiotic guidelines for one third and microbiology reports or the DSS for about two thirds of cases when they were available to assist their prescribing decisions OBJECTIVES Urinary tract infections ( UTIs ) are one of the leading reasons for antibiotic prescriptions in emergency departments ( EDs ) , with half of these antibiotics being inappropriately prescribed . Our objective was to assess the impact of a computerized decision support system ( CDSS ) on compliance with guidelines on empirical antibiotic prescriptions ( antibiotic and duration ) for UTIs in EDs . METHODS A multicentre prospect i ve before- and -after controlled interventional study was conducted from 19 March to 28 October 2012 . All adults diagnosed with community-acquired UTIs ( cystitis , pyelonephritis or prostatitis ) at three French EDs were included . The antibiotic therapy was considered compliant with guidelines if the antibiotic and the duration prescribed were in accordance with the national guidelines . Data were collected using electronic medical records . Paired tests were used when comparing periods within each ED and global analyses used multivariate logistic mixed models . RESULTS Nine hundred and twelve patients were included during the 30 week study period . The CDSS was used in 59 % of cases ( 182/307 ) . The CDSS intervention improved the compliance of antibiotic prescriptions in only one ED in a bivariate analysis ( absolute increase + 20 % , P = 0.007 ) . The choice of the antibiotic was improved in multivariate analyses but only when the CDSS was used [ OR = 1.94 ( 95 % CI 1.13 - 3.32 ) ] . The CDSS also changed the initial diagnosis in 23 % of cases , in all three EDs . CONCLUSIONS The CDSS only partially improved compliance with guidelines on antibiotic prescriptions in UTIs BACKGROUND Appropriate antibiotic treatment decreases mortality , while superfluous treatment is associated with antibiotic resistance . We built a computerized decision support system for antibiotic treatment ( TREAT ) targeting these outcomes . METHODS Prospect i ve cohort study comparing TREAT 's advice to physician 's treatment followed by a cluster r and omized trial comparing wards using TREAT ( intervention ) versus antibiotic monitoring without TREAT ( control ) . We included patients suspected of harbouring bacterial infections in three hospitals ( Israel , Germany and Italy ) . The primary outcome , appropriate antibiotic treatment , was assessed among patients with microbiologically documented infections ( MDI ) . Length of hospital stay , adverse events , mortality ( interventional trial ) and antibiotic costs ( both studies ) , including costs related to future antibiotic resistance , were compared among all included patients . RESULTS Among 1203 patients included in the cohort study ( 350 with MDI ) , TREAT prescribed appropriate empirical antibiotic treatment significantly more frequently than physicians ( 70 % versus 57 % , P < 0.001 ) using less broad-spectrum antibiotics at half physicians ' antibiotic costs . The r and omized trial included 2326 patients , 570 with MDI . The rate of appropriate empirical antibiotic treatment was higher in intervention versus control wards [ 73 % versus 64 % , odds ratio ( OR ) : 1.48 , 95 % confidence interval ( CI ) : 0.95 - 2.29 , intention to treat , adjusted for location and clustering ] . For patients treated according to TREAT 's advice in intervention wards , the difference with controls was highly significant ( OR : 3.40 , 95 % CI : 2.25 - 5.14 ) . Length of hospital stay , costs related to future resistance and total antibiotic costs were lower in intervention versus control wards . CONCLUSIONS TREAT improved the rate of appropriate empirical antibiotic treatment while reducing antibiotic costs and the use of broad-spectrum antibiotic treatment Objectives Antibiotic resistance has risen dramatically over the past years . For individual patients , adequate initial antibiotic therapy is essential for clinical outcome . Computer-assisted decision support systems ( CDSSs ) are advocated to support implementation of rational anti-infective treatment strategies based on guidelines . The aim of this study was to evaluate long-term effects after implementation of a CDSS . Design This prospect i ve ‘ before/after ’ cohort study was conducted over four observation periods within 5 years . One preinterventional period ( pre ) was compared with three postinterventional periods : directly after intensive implementation efforts ( post1 ) , 2 years ( post2 ) and 3 years ( post3 ) after implementation . Setting Five anaesthesiological-managed intensive care units ( ICU ) ( one cardiosurgical , one neurosurgical , two interdisciplinary and one intermediate care ) at a university hospital . Participants Adult patients with an ICU stay of > 48 h were included in the analysis . 1316 patients were included in the analysis for a total of 12 965 ICU days . Intervention Implementation of a CDSS . Outcome measures The primary end point was percentage of days with guideline adherence during ICU treatment . Secondary end points were antibiotic-free days and all-cause mortality compared for patients with low versus high guideline adherence . Main results Adherence to guidelines increased from 61 % prior to implementation to 92 % in post1 , decreased in post2 to 76 % and remained significantly higher compared with baseline in post3 , with 71 % ( p=0.178 ) . Additionally , antibiotic-free days increased over study periods . At all time periods , mortality for patients with low guideline adherence was higher with 12.3 % versus 8 % ( p=0.014 ) and an adjusted OR of 1.56 ( 95 % CI 1.05 to 2.31 ) . Conclusions Implementation of computerised regional adapted guidelines for antibiotic therapy is paralleled with improved adherence . Even without further measures , adherence stayed high for a longer period and was paralleled by reduced antibiotic exposure . Improved guideline adherence was associated with reduced ICU mortality . Trial registration number IS RCT N54598675 Computer-assisted decision support systems ( CDSS ) are design ed to improve infection management . The aim of this prospect i ve , clinical pre- and post-intervention study was to investigate the influence of CDSS on infection management of severe sepsis and septic shock in intensive care units ( ICUs ) . Data were collected for a total of 180 days during two study periods in 2006 and 2007 . Of the 186 patients with severe sepsis or septic shock , 62 were stratified into a low adherence to infection management st and ards group ( LAG ) and 124 were stratified into a high adherence group ( HAG ) . ICU mortality was significantly increased in LAG versus HAG patients ( Kaplan – Meier analysis ) . Following CDSS implementation , adherence to st and ards increased significantly by 35 % , paralleled with improved diagnostics , more antibiotic-free days and a shortened time until antibiotics were administered . In conclusion , adherence to infection st and ards is beneficial for patients with severe sepsis or septic shock and CDSS is a useful tool to aid adherence OBJECTIVE Develop a clinical decision support tool comprised of an electronic medical record alert and antimicrobial stewardship navigator to facilitate antimicrobial stewardship . DESIGN We analyzed alerts targeting antimicrobial de-escalation to assess the effectiveness of the navigator as a stewardship tool . The alert provides antimicrobial recommendations , then directs providers to the navigator , which includes order management , relevant patient information , evidence -based clinical information , and bidirectional communication capability . SETTING Academic , tertiary care medical center with an electronic medical record . INTERVENTION Alerts containing stewardship recommendations and immediate access to the navigator were created . RESULTS Antibiotic use and response data were collected 1 day before stewardship recommendation via the best practice alert ( BPA ) tool and 1 day after the BPA tool response . A total of 1,285 stewardship BPAs were created . Two hundred and forty-four ( 18.9 % ) of the BPAs were created and acted upon within 72 hours for the purpose of de-escalation : 169 ( 69 % ) were accepted , 30 ( 12 % ) were accepted with modification , and 45 ( 18 % ) were rejected . Statistically significant decreases in total antibiotic use as well as in use of broad-spectrum ( anti-methicillin-resistant Staphylococcus aureus and anti-pseudomonal ) agents occurred when accepted recommendations were compared with rejected recommendations . CONCLUSIONS We describe the successful development of a clinical decision support tool to perform prospect i ve audit and feedback comprised of an alert and navigator system featuring evidence -based recommendations and clinical and educational information . We demonstrate that this tool improves antibiotic use through our example of de-escalation Physicians ' decisions control between 70 % and 80 % of all health care dollars spent [ 1 - 3 ] , and many strategies to influence or control physician decision making have been advocated . These strategies include education , peer review with feedback , administrative interventions , financial incentives and penalties , critical pathways , and , most recently , nationally derived guidelines [ 2 , 4 ] . To date , none of these strategies has been clearly effective [ 4 ] . Berwick [ 5 ] has outlined the inherent flaws in many of these strategies . He concedes that these methods may lead to predictable care but notes that they can not lead to continual improvement of care . Nowhere in health care are these strategies to control or influence physicians more prevalent than in the area of drug use , particularly use of antimicrobial agents [ 6 ] . The hospital-wide use of drugs and the involvement of various health care providers create a system of diffuse responsibility , enormous variation , and escalating costs [ 6 - 9 ] . The United States currently spends $ 40 billion annually on pharmaceuticals ; this is 8 % of the total cost of health care [ 3 , 7 - 9 ] . Prescription drugs now constitute between 5 % and 20 % of an individual hospital 's total budget [ 7 ] . Antimicrobial agents are one of the costliest categories of drug expenditures in hospitals , accounting for approximately 20 % to 50 % of total spending on drugs [ 9 - 14 ] . Investigations in various clinical practice setting s have indicated that as much as 50 % of antibiotic use is inappropriate [ 14 - 17 ] . The consequences of this have been addressed in terms of antimicrobial resistance [ 18 , 19 ] , adverse drug reactions [ 15 , 17 ] , and cost [ 11 - 14 ] . In response to these pressures , professional societies and individual investigators have outlined methods with which to improve antibiotic use [ 20 - 29 ] . Most of these methods ( for example , drug formularies ) use some form of a control mechanism , and , to date , experience with them has been mixed [ 11 , 16 , 25 , 27 , 28 ] . Kassirer [ 30 ] has challenged the health care system to develop strategies that inform rather than enforce or control medical decisions . For more than a decade , we have been developing and investigating clinical management programs that augment and inform clinical decision making , in addition to focusing on continual quality improvement [ 31 , 32 ] , in antibiotic therapy , infection control surveillance , and the safety of drug use . These programs were design ed to provide continuous surveillance and computer-assisted decision support [ 33 , 34 ] to all clinicians responsible for inpatient care in a general hospital . The hallmark of these computer-assisted decision support programs was local clinician-derived consensus practice guidelines [ 5 , 31 , 34 , 35 ] that were programmed into a hospital information system as rules , algorithms , and predictive models . These programs managed antibiotic use at three basic levels : prophylactic use , empiric use , and therapeutic use . We review the clinical and process outcomes and the financial effects of these hospital-wide decision support programs during a 7-year period . Methods LDS Hospital , located in Salt Lake City , Utah , is a 520-bed private , community , acute-care referral hospital that serves as a teaching facility for the University of Utah Schools of Medicine , Nursing , and Pharmacy . The hospital provides most clinical services but not general pediatric care . An integrated , clinical ly oriented hospital information system has been under development at the institution for more than 20 years [ 36 ] . This system routinely collects and stores all patient data from multiple sources throughout the hospital . The system currently serves as the hospital 's clinical computing system , providing clinical information management and establishing computer-based patient records . The computer-based patient record contains both clinical and financial data . The financial data are derived from a st and ard cost-manager microcomputer software system that is linked to the clinical information system [ 37 , 38 ] . The information system also provides online clinical decision support through its expert system capabilities . Infectious diseases surveillance and therapeutics was the first medical domain to use the expert system features of the hospital information system on a widespread clinical basis [ 39 ] . The clinical decision support systems and the implementation methods for this domain were developed , tested , and implemented by clinical investigators in the Division of Infectious Diseases at LDS Hospital [ 37 - 52 ] . The process used to develop the local consensus guidelines for antimicrobial use was similar to the approach described by East and colleagues [ 34 ] . Our approach also included thorough evaluations of published reports , use of national guidelines and local expert opinion , and exhaustive analyses of the LDS Hospital patient data base ; we subsequently developed step-wise logistic regression models [ 48 , 49 ] . Through various committee representations , we also frequently consulted the medical staff of LDS Hospital ; in these consultations , we presented data and interim results . Using the aforementioned formal techniques [ 34 , 35 ] , the staff also helped develop , test , and implement the clinical practice guidelines that were embedded in the decision support programs . The practice guidelines were encoded into the knowledge base of the hospital information system as rules , algorithms , and predictive models . This allowed for decision support at the point of care , with feedback to physicians in real time . Thus , guideline application was patient specific , and recommendations corresponded to actual clinical conditions at a particular point in time . Feedback to physicians was open looped [ 53 ] , and the physicians ultimately decided whether or not to follow the recommendations . Since 1985 , many of these clinical decision support programs and guidelines have been prospect ively developed and tested in the patient population s of LDS Hospital , often in r and omized studies . Decision support programs have been systematic ally exp and ed to include comprehensive , institution-wide antibiotic management programs . These decision support programs were design ed to comprehensively manage all antibiotic agents used in the institution throughout the continuum of hospital care : 1 ) prophylactic [ surgical ] antibiotic use ; 2 ) empiric antibiotic use [ for suspected infection without microbiological data ] ; and 3 ) therapeutic antibiotic use ( for established infection with microbiological data ) . These programs continually track and assist physicians in managing each patient treated with an antibiotic at LDS Hospital and in all aspects of antibiotic use ; no antibiotic can be prescribed at LDS Hospital without being affected by these decision support programs . The methods used in these programs have been described elsewhere [ 37 - 52 ] . These programs are continually up date d as medical knowledge and the health care delivery system change , both locally and nationally . The surgical prophylactic decision support programs were developed with our surgical colleagues and result ed in strategies that ensured appropriate case selection , delivery time , intra-operative dosing , and duration of antibiotic use rather than solely concentrating on the specific antibiotic agent or class of agents for each surgical procedure [ 41 , 42 , 45 ] . The empiric and therapeutic antibiotic decision support programs provide information to the clinician in the form of computer-generated alerts or suggestions on the following : the presence of resistant pathogens ; untreated infections ; an incorrect dose , route , or interval of an antibiotic ; the absence of current renal function data ; the need for serum drug levels ; population -based probabilities of infections in relation to specific patient variables ; and cost-effective alternatives ( for example , oral therapy or narrower-spectrum agents ) [ 43 , 48 , 49 ] . Furthermore , these management programs monitor patients for excessive or suboptimal antibiotic doses , depending on the patients ' current renal function status [ 46 , 47 ] , and they address the prevention , early detection , and archiving of adverse drug events associated with these agents [ 44 , 46 , 50 ] . All but one of the computer-assisted antibiotic decision support programs described were in clinical use throughout the study period ; the exception was the adverse drug event program , which has been used since 1989 . Beginning in 1985 , investigators in the infectious disease division developed data base analysis programs that quantify antibiotic use and expenditures , identify prescriber and diagnosis-related groups for patients receiving antibiotics , track antibiotic resistance patterns , and distinguish therapeutic from prophylactic use of antibiotics . The reports generated by these data base analysis programs summarize antibiotic use by specific agent and place them in the following categories : numbers of patients treated , total milligrams administered , total doses administered , defined daily doses per 100 occupied bed-days [ 12 , 13 , 54 ] , and total amount spent . We used the number of defined daily doses per 100 occupied bed-days because it is a st and ardized technical unit of measurement that estimates drug use . A defined daily dose is based on the average adult maintenance dose ( usually in grams ) for the primary indication of the drug and is adjusted per 100 occupied bed-days . The concept of the defined daily dose per 100 occupied bed-days was established by a joint project of the Nordic Council on Medicines and the World Health Organization Center for Drug Collaboration Statistics [ 12 , 13 , 54 ] . Because the defined daily dose per 100 occupied bed-days is independent of cost ( which eliminates confounding introduced by the buying practice s of group purchasing organizations ) and differences in dose forms , it establishes a st and ardized basis for comparing drug use . The World Health Organization has agreed that the defined daily dose method of analysis can be OBJECTIVES TREAT , a decision support system for antimicrobial therapy , was implemented in an acute medical ward . METHODS Patients admitted on suspicion of infection were included in the study . The evaluation of TREAT was done both retrospectively and prospect ively . Coverage of empirical antimicrobial treatments was compared to recommendations from TREAT and the optimal use of local guidelines . RESULTS Five hundred and eleven patients were included , of whom 162 had a microbiologically documented infection . In the retrospective part of the study , TREAT , physician , and guideline antimicrobial coverage rates were 65 % , 51 % , and 79 % , respectively , and in the prospect i ve part , 68 % , 62 % , and 77 % , respectively . TREAT provided lower coverage than local guidelines ( p<0.001 ) , but was similar to the performance of physicians in a university hospital ( p=0.069 ) . No differences were found in length of hospital stay , or hospital or 30-day mortality . Direct costs were significantly higher for TREAT advice than for local guidelines or the physician prescriptions ( p<0.001 ) , but the ecological costs were lower for TREAT advice than for both local guidelines ( p<0.001 ) and physician prescriptions ( p=0.247 ) . The coverage of TREAT advice for the bacteraemia patients was non-inferior to the physicians ( p=1.00 ) . CONCLUSIONS TREAT can potentially improve the ecological costs of empirical antimicrobial therapy for patients in acute medical wards , but provided lower coverage than local guidelines OBJECTIVES Develop a problem-orientated and data -based decision support system ( DSS ) to improve empirical antibiotic treatment , and compare the performance of the system to that of the physician . DESIGN The DSS was tested in a prospect i ve , noninterventional , comparative cohort study . SETTING University hospital in Israel . SUBJECTS Consecutive patients ( n = 496 ) in four departments of internal medicine suspected of harboring a moderate to severe bacterial infection . INTERVENTIONS None . MAIN OUTCOME MEASURES The percentage of appropriate empirical antibiotic treatments . RESULTS Out of 496 patients included in the study , 219 had positive cultures or serological tests . The physicians prescribed inappropriate empirical antibiotic treatment in 91 of 219 patients ( 42 % ) ; whilst the recommendations of the system were inappropriate in 50 patients ( 23 % ) ( P < 0.05 ) . Superfluous treatment was prescribed in 15 % of patients by the physician , and in 11 % by the system . Out of the 91 patients given inappropriate treatment by the physician , the DSS advised treatment to which the pathogens were susceptible in 61 patients . The advantage of the DSS over the physician was most evident in multiresistant gram-negative isolates , enterococci and Staphylococcus aureus . Out of the 277 patients with negative cultures , the DSS advised narrower-spectrum antibiotic treatment than prescribed by the physicians in 27 % of patients , and broader-spectrum in 13 % . CONCLUSION A problem-orientated , data -based DSS outperformed physicians in the choice of appropriate empirical antibiotic treatment , and recommended less broad-spectrum antibiotics We studied the effect of a bayesian pharmacokinetic dosing program on the outcome of aminoglycoside therapy in patients with clinical infections . Patients were r and omized to a control ( dosing based on physician choice ; n = 75 ) or experimental group ( dosing based on the bayesian program ; n = 72 ) . Both groups used serum aminoglycoside concentration data when making dosing decisions . Improved response rates were seen in the experimental ( 60 % ; 42/68 ) compared with the control group ( 48 % ; 36/68 ) . A higher , but not statistically significant , incidence of toxicity was found in the control ( 7/75 ; 9.7 % ) versus the experimental group ( 4/72 ; 5.1 % ) . Mean length of total hospital stay was significantly longer for patients in the control group ( 20.3 days ) compared with the experimental group ( 16.0 days ) ( p = 0.028 ) . The variables from multivariate analysis with a significant impact on length of stay were patient group and length of aminoglycoside therapy . On the basis of a reduced length of stay , a potential cost savings of $ 1311 per patient can be achieved PURPOSE The implementation of a penicillin allergy screening tool to optimize the use of aztreonam is described . METHODS This study was conducted at a 528-bed tertiary referral community teaching facility and compared the use of aztreonam in patients before and after the implementation of a multipronged intervention consisting of a penicillin allergy screening tool ( PAST ) , education , order set decision support , and prospect i ve review of aztreonam orders by the antimicrobial stewardship team and clinical pharmacists . Patients for whom aztreonam was prescribed at any time during their presentation to the hospital January 1-June 30 , 2013 ( preintervention period ) , and September 1 , 2013-February 28 , 2014 ( postintervention period ) were eligible for inclusion . Primary outcomes included total and inappropriate aztreonam usage . Secondary outcomes included cost avoidance and safety . RESULTS A total of 496 aztreonam orders were review ed . The total number of days of therapy ( DOT ) with aztreonam significantly decreased from 9.5 per 1,000 patient-days in the preintervention group to 4.4 per 1,000 patient-days in the postintervention group ( p < 0.0001 ) . The number of inappropriate aztreonam DOT decreased from 4.0 per 1,000 patient days to 0.8 per 1,000 patient-days ( p < 0.0001 ) . The median number of inappropriate aztreonam doses decreased significantly in the postintervention period , as did inappropriate aztreonam DOT ( p < 0.0001 for both comparisons ) . An estimated cost avoidance of $ 60,000-$100,000 was realized , depending on the alternative antibiotic selected . CONCLUSION Implementation of the PAST and provider and pharmacist education reduced the use of aztreonam by promoting the first-line use of β-lactam alternatives OBJECTIVES Emergence of multiresistant Gram-negative organisms in intensive care units ( ICUs ) throughout the world is a concerning problem . Therefore we undertook a study to follow the resistance patterns of the most common clinical ly isolated Gram-negative organisms within our ICU following an antibiotic stewardship intervention to evaluate whether a reduction in broad-spectrum antibiotics improves local antibiotic resistance patterns . METHODS This prospect i ve study was conducted over a 7 year period within an ICU at a tertiary teaching hospital in Melbourne , Australia . All clinical ly isolated Gram-negative organisms were identified and extracted from the hospital pathology system . Three monthly antibiograms were created . The pre-interventional period occurred between January 2000 and June 2002 ( 10 quarters ) and the post-interventional period was defined from July 2002 to December 2006 ( 18 quarters ) . Segmented linear regression was used to analyse for a difference in the rates of change in susceptibility . RESULTS A total of 2838 Gram-negative organisms were isolated from clinical sites from ICU patients during the study period . There was significant improvement in susceptibility of Pseudomonas to imipenem 18.3%/year [ 95 % confidence interval ( CI ) : 4.9 - 31.6 ; P = 0.009 ] and gentamicin 11.6%/year ( 95 % CI : 1.8 - 21.5 ; P = 0.02 ) compared with the pre-intervention trend . Significant changes in the rates of gentamicin and ciprofloxacin susceptibility were also observed in the inducible Enterobacteriaceae group although these were less clinical ly significant . CONCLUSIONS This study demonstrates improved antibiotic susceptibility of ICU Gram-negative isolates including Pseudomonas following an intervention aim ed at reducing broad-spectrum antibiotics BACKGROUND Gentamicin is an aminoglycoside antibiotic that is highly effective in treating Gram-negative infections , but inappropriate use leads to toxicity . In 2010 , the Australian Therapeutic Guidelines ( Antibiotic ) were revised to recommend the use of computerised methods to individualise dosing of gentamicin and optimise therapy , rather than traditional nomogram approaches . AIM To determine whether gentamicin prescribing was compliant with the Australian Therapeutic Guidelines , version 14 ( 2010 ) in a setting where computerised dose recommendation re sources and computerised decision support were available , and to determine why the re sources were effective or ineffective in achieving compliance to guidelines . METHODS During phase 1 , a retrospective audit of gentamicin prescribing from 1 January 2012 to 31 December 2012 ( n = 826 ) at a 320-bed teaching hospital in Sydney was undertaken . In phase 2 , 12 doctors from specialties with high-volume prescribing of gentamicin were interviewed . RESULTS Intravenous gentamicin was used in 545 cases , 81 % of which were for short-term therapy ( ≤48 h ) . Doctors feared inducing toxicity in patients , but limited the dose rather than altering the dosing interval according to renal function . Of the ' continued ' dosing cases , 55 % went unmonitored and the computerised dose recommendation service was rarely used . Doctors were unaware of its availability despite electronic alerts accompanying prescriptions of gentamicin . CONCLUSIONS In comparison with the national guidelines , there was significant under-dosing and monitoring practice s were haphazard . Computerised electronic alerts were ineffective in informing users . To improve prescribing practice s , we recommend exploring alternative computerised decision support approaches ( e.g. pre-written orders ) and more pervasive and persuasive implementation strategies We developed a decision support tool to assist physicians anticipating the need for antibiotic therapy . The initial screen alerts physicians of pertinent patient information , provides direct access to other essential medical information , and stimulates clinical judgment by suggesting an antibiotic regimen . The decision support tool also suggests the dose and interval for any ordered antibiotics selected by the physicians . During a 7-month pilot study , all antibiotics for patients admitted to the Shock/Trauma/Respiratory Intensive Care Unit ( STRICU ) were ordered using the decision support tool . Clinical data from the study period and a 12-month control period ( the previous year ) were collected and compared . The decision support tool was used to order antibiotics 588 times during the study period and the suggested antibiotics were used 218 ( 37 % ) times . The computer suggested dosages were used over 90 % of the time . The mean cost of antibiotics was $ 87.00 ( p < 0.04 ) less per patient during the study period as compared to the control period . Prospect i ve assessment revealed only 3 antibiotic adverse drug events ( ADEs ) ( 0.9 % ) among 336 study patients as compared to 15 ADEs ( 2.4 % ) among 626 control patients ( p = 0.164 ) BACKGROUND AND METHODS Optimal decisions about the use of antibiotics and other antiinfective agents in critically ill patients require access to a large amount of complex information . We have developed a computerized decision-support program linked to computer-based patient records that can assist physicians in the use of antiinfective agents and improve the quality of care . This program presents epidemiologic information , along with detailed recommendations and warnings . The program recommends antiinfective regimens and courses of therapy for particular patients and provides immediate feedback . We prospect ively studied the use of the computerized antiinfectives-management program for one year in a 12-bed intensive care unit . RESULTS During the intervention period , all 545 patients admitted were cared for with the aid of the antiinfectives-management program . Measures of processes and outcomes were compared with those for the 1136 patients admitted to the same unit during the two years before the intervention period . The use of the program led to significant reductions in orders for drugs to which the patients had reported allergies ( 35 , vs. 146 during the preintervention period ; P<0.01 ) , excess drug dosages ( 87 vs. 405 , P<0.01 ) , and antibiotic-susceptibility mismatches ( 12 vs. 206 , P<0.01 ) . There were also marked reductions in the mean number of days of excessive drug dosage ( 2.7 vs. 5.9 , P<0.002 ) and in adverse events caused by antiinfective agents ( 4 vs. 28 , P<0.02 ) . In analyses of patients who received antiinfective agents , those treated during the intervention period who always received the regimens recommended by the computer program ( n=203 ) had significant reductions , as compared with those who did not always receive the recommended regimens ( n= 195 ) and those in the preintervention cohort ( n = 766 ) , in the cost of antiinfective agents ( adjusted mean , $ 102 vs. $ 427 and $ 340 , respectively ; P<0.001 ) , in total hospital costs ( adjusted mean , $ 26,315 vs. $ 44,865 and $ 35,283 ; P<0.001 ) , and in the length of the hospital stay days ( adjusted mean , 10.0 vs. 16.7 and 12.9 ; P<0.001 ) . CONCLUSIONS ; A computerized antiinfectives-management program can improve the quality of patient care and reduce costs OBJECTIVE To determine whether antimicrobial ( AM ) courses ordered with an antimicrobial computer decision support system ( CDSS ) were more likely to be appropriate than courses ordered without the CDSS . DESIGN Retrospective cohort study . Blinded expert review ers judged whether AM courses were appropriate , considering drug selection , route , dose , and duration . SETTING A 279-bed university-affiliated Department of Veterans Affairs ( VA ) hospital . PATIENTS A 500-patient r and om sample of in patients who received a therapeutic AM course between October 2007 and September 2008 . Intervention . An optional CDSS , available at the point of order entry in the VA computerized patient record system . RESULTS CDSS courses were significantly more likely to be appropriate ( 111/254 , 44 % ) compared with non-CDSS courses ( 81/246 , 33 % , P = .013 ) . Courses were more likely to be appropriate when the initial provider diagnosis of the condition being treated was correct ( 168/273 , 62 % ) than when it was incorrect , uncertain , or a sign or symptom rather than a disease ( 24/227 , 11 % , P < .001 . In multivariable analysis , CDSS-ordered courses were more likely to be appropriate than non-CDSS-ordered courses ( odds ratio [ OR ] , 1.83 ; 95 % confidence interval [ CI ] , 1.13 - 2.98 ) . Courses were also more likely to be judged appropriate when the initial provider diagnosis of the condition being treated was correct than when it was incorrect , uncertain , or a sign or symptom rather than a disease ( OR , 3.56 ; 95 % CI , 1.4 - 9.0 ) . CONCLUSIONS Use of the CDSS was associated with more appropriate AM use . To achieve greater improvements , strategies are needed to improve provider diagnoses of syndromes that are infectious or possibly infectious |
13,222 | 20,187,106 | Current evidence suggests that peginterferon alpha-2a is associated with higher SVR than peginterferon alfa-2b .
However , the paucity of evidence on adverse events curbs the decision to definitively recommend one peginterferon over the other , because any potential benefit must outweigh the risk of harm | UNLABELLED A combination of weekly pegylated interferon ( peginterferon ) alpha and daily ribavirin represents the st and ard of care for the treatment of chronic hepatitis C according to current guidelines .
It is not established which of the two licensed products ( peginterferon alpha-2a or peginterferon alfa-2b ) is most effective .
We performed a systematic review of head-to-head r and omized trials to assess the benefits and harms of the two treatments . | CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs UNLABELLED Although two pegylated interferons ( Peg-IFN ) are available to treat chronic hepatitis C virus ( HCV ) infection , no head-to-head comparative studies have been published . We aim to compare the efficacy and safety of PEG IFN alfa-2b ( PEG 2b ) versus PEG IFN alfa-2a ( PEG 2a ) , plus ribavirin ( RBV ) . A prospect i ve , r and omized , multi-center , open-label clinical trial including 182 human immunodeficiency virus (HIV)-hepatitis C virus ( HCV ) patients naïve for HCV therapy was performed . Patients were assigned to PEG 2b ( 80 - 150 mug/week ; n = 96 ) or PEG 2a ( 180 mug/week ; n = 86 ) , plus RBV ( 800 - 1200 mg/day ) for 48 weeks . The primary endpoint was sustained virological response ( SVR : negative HCV-RNA 24 weeks after completion of treatment ) . At baseline , both groups were well balanced : 73 % male ; 63 % HCV genotype 1 or [ corrected ] 4 ; 29 % had fibrosis index of 3 or greater . The overall SVR was 44 % ( 42 % PEG 2b versus 46 % PEG 2a , P = 0.65 ) . Among genotypes 1 or [ corrected ] 4 , SVRs were 28 % versus 32 % ( P = 0.67 ) and 62 % versus 71 % ( P = 0.6 ) in genotypes 2 or [ corrected ] 3 for PEG 2b and PEG 2a , respectively . Early virological response ( EVR ; > or=2 log reduction from baseline or negative HCV-RNA at week 12 ) was 70 % in the PEG 2b group and 80 % in the PEG 2a group ( P = 0.13 ) , reaching a positive predictive value of SVR of 64 % and a negative predictive value of 100 % in both arms . Side effects were present in 96 % of patients but led to treatment discontinuation in 10 % of patients ( 8 % on PEG 2b and 13 % on PEG 2a , P = 0.47 ) . CONCLUSION In patients with HIV , HCV therapy with PEG 2b or PEG 2a plus RBV had no significant differences in efficacy and safety BACKGROUND / AIMS To compare the pharmacokinetics , pharmacodynamics , and antiviral activity of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C virus genotype 1 . METHODS Thirty-six patients were r and omised to peginterferon alfa-2b ( 1.5 microg/kg/week ) or peginterferon alfa-2a ( 180 microg/week ) for 4 weeks , then in combination with ribavirin ( 13 mg/kg/day ) for a further 4 weeks . The pharmacokinetic profile of both peginterferons , mRNA expression of a selected group of interferon-induced gene transcripts , and serum HCV-RNA levels were assessed . RESULTS Patients receiving peginterferon alfa-2b had significantly greater up-regulation of interferon-alfa response genes compared with those receiving peginterferon alfa-2a . Correspondingly , patients treated with peginterferon alfa-2b also had a significantly greater log10 maximum and log10 time-weighted average decrease in serum HCV-RNA . A greater proportion of peginterferon alfa-2b patients achieved a > or = 2.0 log10 reduction in serum HCV-RNA levels by week 8 ( 72 % vs 44 % of peginterferon alfa-2a patients , P = 0.09 ) . There was an approximately 16-fold greater exposure to peginterferon in the serum of patients treated with peginterferon alfa-2a . CONCLUSIONS These findings suggest that the biological activity , measured by early interferon-induced gene transcripts and early antiviral responsiveness , may have been greater in patients treated with peginterferon alfa-2b despite their lower exposure to the drug compared with patients treated with peginterferon alfa-2a CONTEXT Controversy and uncertainty ensue when the results of clinical research on the effectiveness of interventions are subsequently contradicted . Controversies are most prominent when high-impact research is involved . OBJECTIVES To underst and how frequently highly cited studies are contradicted or find effects that are stronger than in other similar studies and to discern whether specific characteristics are associated with such refutation over time . DESIGN All original clinical research studies published in 3 major general clinical journals or high-impact-factor specialty journals in 1990 - 2003 and cited more than 1000 times in the literature were examined . MAIN OUTCOME MEASURE The results of highly cited articles were compared against subsequent studies of comparable or larger sample size and similar or better controlled design s. The same analysis was also performed comparatively for matched studies that were not so highly cited . RESULTS Of 49 highly cited original clinical research studies , 45 cl aim ed that the intervention was effective . Of these , 7 ( 16 % ) were contradicted by subsequent studies , 7 others ( 16 % ) had found effects that were stronger than those of subsequent studies , 20 ( 44 % ) were replicated , and 11 ( 24 % ) remained largely unchallenged . Five of 6 highly-cited nonr and omized studies had been contradicted or had found stronger effects vs 9 of 39 r and omized controlled trials ( P = .008 ) . Among r and omized trials , studies with contradicted or stronger effects were smaller ( P = .009 ) than replicated or unchallenged studies although there was no statistically significant difference in their early or overall citation impact . Matched control studies did not have a significantly different share of refuted results than highly cited studies , but they included more studies with " negative " results . CONCLUSIONS Contradiction and initially stronger effects are not unusual in highly cited research of clinical interventions and their outcomes . The extent to which high citations may provoke contradictions and vice versa needs more study . Controversies are most common with highly cited nonr and omized studies , but even the most highly cited r and omized trials may be challenged and refuted over time , especially small ones BACKGROUND The efficacy and tolerability of Peg-Interferon alpha-2a ( Peg-IFNalpha-2a ) versus Peg-Interferon alpha-2b ( Peg-IFNalpha-2b ) were compared in a patient cohort with hepatitis C virus (HCV)-related active chronic hepatitis , unresponsive to previous antiviral treatment with st and ard IFN ( 6 MU three times/week ) plus ribavirin ( 10.6 mg/kg/day ) for a period of at least 3 months . PATIENTS AND METHODS A total of 143 patients were enrolled and r and omized into two treatment groups ( A-B ) . Group A ( 71 patients ) received one vial of Peg-IFNalpha-2a weekly ( 180 microg ) subcutaneously whereas Group B ( 72 patients ) received 1.5 microg/kg of Peg-IFNalpha-2b weekly subcutaneously . Interferon was combined with ribavirin ( 15 mg/kg/day ) in both groups and all patients who demonstrated nondetectable HCV-RNA or a > or=2(log ) reduction in viral load at week 12 , were treated for 48 weeks , with a 24-week follow up . RESULTS Group A ( 10/71 ) and Group B ( 8/72 ) patients discontinued treatment due to severe side effects . At the end of therapy , HCV-RNA was undetectable in 17/71 ( 23.9 % ) Group A and in 19/72 ( 26.4 % ) of Group B patients . When terminating follow up , a sustained virological response was observed in 14/71 in Group A ( 19.7 % ) and 13/72 in Group B ( 18.0 % ) . CONCLUSIONS Within the limits of the relatively small sample size , Peg-IFNalpha-2a and Peg-IFNalpha-2b demonstrated nonstatistically significant differences in effectiveness in patients nonresponsive to previous antiviral treatment UNLABELLED The overall mortality of patients infected with hepatitis C virus ( HCV ) has not been fully eluci date d. This study analyzed mortality in subjects positive for antibody to HCV ( anti-HCV ) in a community-based , prospect i ve cohort study conducted in an HCV hyperendemic area of Japan . During a 10-year period beginning in 1995 , 1125 anti-HCV-seropositive residents of Town C were enrolled into the study and were followed for mortality through 2005 . Cause of death was assessed by death certificates . Subjects with detectable HCV core antigen ( HCVcAg ) or HCV RNA were considered as having hepatitis C viremia and were classified as HCV carriers ; subjects who were negative for both HCVcAg and HCV RNA ( i.e. , viremia-negative ) were considered as having had a prior HCV infection and were classified as HCV noncarriers . Among the anti-HCV-positive subjects included in the analysis , 758 ( 67.4 % ) were HCV carriers , and 367 were noncarriers . A total of 231 deaths occurred in these subjects over a mean follow-up of 8.2 years : 176 deaths in the HCV carrier group and 55 in the noncarrier group . The overall mortality rate was higher in HCV carriers than in noncarriers , adjusted for age and sex ( hazard ratio , 1.53 ; 95 % confidence interval , 1.13 - 2.07 ) . Although liver-related deaths occurred more frequently among the HCV carriers ( hazard ratio , 5.94 ; 95 % confidence interval , 2.58 - 13.7 ) , the rates of other causes of death did not differ between HCV carriers and noncarriers . Among HCV carriers , a higher level of HCVcAg ( > or=100 pg/mL ) and persistently elevated alanine aminotransferase levels were important predictors of liver-related mortality . CONCLUSION The presence of viremia increases the rate of mortality , primarily due to liver-related death , among anti-HCV-seropositive persons in Japan Patients infected with hepatitis C virus ( HCV ) genotype 1 and with serum HCV RNA concentrations over 800 000 IU/mL have relatively low rates of virologic response to pegylated interferons . The 2 forms of pegylated interferon have different pharmacokinetic profiles , and pilot studies comparing them have yielded varying results . We compared the virologic response to 12 weeks of treatment with peginterferon alpha-2a plus ribavirin vs peginterferon alpha-2b plus ribavirin in 380 patients who were infected with HCV genotype 1 and had high viral loads . We observed no between-group differences in viral load reduction over time and no differences in the percentage of patients treated with peginterferon alpha-2a or peginterferon alpha-2b plus ribavirin who achieved early virologic response ( EVR ) , defined as > /=2-log reduction in HCV RNA concentration or undetectable HCV RNA at 12 weeks ( 66%vs 63 % ) . Serum levels of interferon were more frequently below the level of quantitation in patients treated with peginterferon alpha-2b plus ribavirin ( 58 - 68 % ) than in those treated with peginterferon alpha-2a plus ribavirin ( 1 - 2 % ) . Patients treated with peginterferon alpha-2b plus ribavirin had higher rates of discontinuation for safety reasons ( 6%vs 1 % ) . In conclusion , a substantial percentage of patients infected with HCV genotype 1 and high viral load can achieve EVR when treated with peginterferon and ribavirin . The 2 pegylated interferons showed comparable anti-HCV activity during the first 12 weeks of treatment when combined with the same doses of ribavirin ( 1000 - 1200 mg/day ) , but discontinuations for safety reasons were higher in the patients treated with peginterferon alpha-2b plus ribavirin The two available pegylated interferon formulations , peginterferon alpha-2a and peginterferon alpha-2b , have different pharmacokinetic profiles ; as a result they may have differing abilities to suppress the hepatitis C virus . A recently reported study by Formann and colleagues assessing early viral kinetics among 20 patients receiving peginterferon alpha-2b either once or twice weekly suggests that once-weekly administration of peginterferon alpha-2b is not sufficient for continuous exposure to interferon over 160 h. Twice-weekly administration is recommended to avoid increases in viral load as interferon levels decline prior to the end of the one-week dosing period . The objective of this study was to compare viral dynamics and pharmacokinetics between peginterferon alpha-2a and peginterferon alpha-2b in interferon-naive chronic hepatitis C patients . Patients were r and omized to receive peginterferon alpha-2a 180 microg ( n=10 ) or peginterferon alpha-2b 1.0 microg/kg ( n=12 ) once weekly . Serum peginterferon concentrations were measured at baseline , 24 , 48 , 120 and 168h . Hepatitis C virus ( HCV ) RNA was measured at baseline , 24 , 48 , 120 and 168 h during week 1 and then at 4 and 12 weeks . Peginterferon alpha-2b achieved maximal serum levels at 24 h , and then decreased rapidly . Of the 12 patients who received peginterferon alpha-2b , no drug was detectable in seven ( 58 % ) patients at 120 h and in 11 ( 92 % ) at 168 h. In contrast , peginterferon alpha-2a concentrations increased continuously over time , reaching maximal serum levels from 48 to 168 h. Drug was detectable in all 10 patients at 168 h. At weeks 1 and 4 no significant difference was observed in mean HCV RNA between the groups . However , at week 12 , mean HCV RNA was significantly lower in the peginterferon alpha-2a group versus the peginterferon alpha-2b group ( 2.8126 vs 3.8726 ; P<0.01 ) . The differences in mean HCV RNA values at 12 weeks may be related to the different absorption and distribution profiles of the two drugs . In conclusion , once-weekly administration of peginterferon alpha-2b ( 1.0 microg/kg/wk ) may be insufficient for continuous interferon exposure ; twice-weekly administration may help avoid increases in viral replication as interferon levels decline . Larger-scale studies assessing both viral kinetics and sustained virological responses are needed to confirm these observations BACKGROUND Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus ( HCV ) infection . However , these regimens have not been adequately compared . METHODS At 118 sites , patients who had HCV genotype 1 infection and who had not previously been treated were r and omly assigned to undergo 48 weeks of treatment with one of three regimens : peginterferon alfa-2b at a st and ard dose of 1.5 microg per kilogram of body weight per week or a low dose of 1.0 microg per kilogram per week , plus ribavirin at a dose of 800 to 1400 mg per day , or peginterferon alfa-2a at a dose of 180 microg per week plus ribavirin at a dose of 1000 to 1200 mg per day . We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the st and ard-dose peginterferon alfa-2b regimen and the peginterferon alfa-2a regimen . RESULTS Among 3070 patients , rates of sustained virologic response were similar among the regimens : 39.8 % with st and ard-dose peginterferon alfa-2b , 38.0 % with low-dose peginterferon alfa-2b , and 40.9 % with peginterferon alfa-2a ( P=0.20 for st and ard-dose vs. low-dose peginterferon alfa-2b ; P=0.57 for st and ard-dose peginterferon alfa-2b vs. peginterferon alfa-2a ) . Estimated differences in response rates were 1.8 % ( 95 % confidence interval [ CI ] , -2.3 to 6.0 ) between st and ard-dose and low-dose peginterferon alfa-2b and -1.1 % ( 95 % CI , -5.3 to 3.0 ) between st and ard-dose peginterferon alfa-2b and peginterferon alfa-2a . Relapse rates were 23.5 % ( 95 % CI , 19.9 to 27.2 ) for st and ard-dose peginterferon alfa-2b , 20.0 % ( 95 % CI , 16.4 to 23.6 ) for low-dose peginterferon alfa-2b , and 31.5 % ( 95 % CI , 27.9 to 35.2 ) for peginterferon alfa-2a . The safety profile was similar among the three groups ; serious adverse events were observed in 8.6 to 11.7 % of patients . Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12 , a sustained virologic response was achieved in 86.2 % and 78.7 % , respectively . CONCLUSIONS In patients infected with HCV genotype 1 , the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon-ribavirin regimens or between the two doses of peginterferon alfa-2b . ( Clinical Trials.gov number , NCT00081770 . BACKGROUND & AIMS Patients with chronic hepatitis C virus ( HCV ) infection are frequently treated with a combination of pegylated interferon ( peginterferon ) and ribavirin . This study compared the efficacy and safety of peginterferon alfa-2a and peginterferon alfa-2b , each in combination with ribavirin . METHODS A total of 320 consecutive , treatment-naive , HCV RNA-positive patients with chronic hepatitis were r and omly assigned to once-weekly peginterferon alfa-2a ( 180 microg , group A ) or peginterferon alfa-2b ( 1.5 microg/kg , group B ) plus ribavirin 1000 mg/day ( body weight < 75 kg ) or 1200 mg/day ( body weight > or=75 kg ) for 48 weeks ( genotype 1 or 4 ) or 24 weeks ( genotype 2 or 3 ) . The primary end point was sustained virological response ( SVR ) by intention-to-treat . RESULTS More patients in group A than group B achieved an SVR ( 110/160 [ 68.8 % ] vs 87/160 [ 54.4 % ] ; P = .008 ) . Higher SVR rates were obtained in group A than group B among patients with genotype 1/4 ( 51/93 [ 54.8 % ] vs 37/93 [ 39.8 % ] ; P = .04 ) , with genotype 2/3 ( 59/67 [ 88.1 % ] vs 50/67 [ 74.6 % ] ; P = .046 ) , without cirrhosis ( 96/127 [ 75.6 % ] vs 75/134 [ 55.9 % ] ; P = .005 ) , and with baseline levels HCV RNA > 500,000 IU/mL ( 58/84 [ 69 % ] vs 43/93 [ 46.2 % ] ; P = .002 ) . SVR rates in groups A and B were not statistically different among patients with baseline HCV RNA < or=500,000 IU/mL ( 52/76 [ 68.4 % ] vs 44/67 [ 65.7 % ] ; P = .727 ) or in patients with cirrhosis ( 14/33 [ 42.4 % ] vs 12/26 [ 46.1 % ] ; P = .774 ) . CONCLUSIONS In patients with chronic HCV infection , peginterferon alfa-2a plus ribavirin produced a significantly higher SVR rate than peginterferon alfa-2b plus ribavirin BACKGROUND There is good evidence of selective outcome reporting in published reports of r and omized trials . METHODS We examined reporting practice s for trials of gabapentin funded by Pfizer and Warner-Lambert 's subsidiary , Parke-Davis ( hereafter referred to as Pfizer and Parke-Davis ) for off-label indications ( prophylaxis against migraine and treatment of bipolar disorders , neuropathic pain , and nociceptive pain ) , comparing internal company documents with published reports . RESULTS We identified 20 clinical trials for which internal documents were available from Pfizer and Parke-Davis ; of these trials , 12 were reported in publications . For 8 of the 12 reported trials , the primary outcome defined in the published report differed from that described in the protocol . Sources of disagreement included the introduction of a new primary outcome ( in the case of 6 trials ) , failure to distinguish between primary and secondary outcomes ( 2 trials ) , relegation of primary outcomes to secondary outcomes ( 2 trials ) , and failure to report one or more protocol -defined primary outcomes ( 5 trials ) . Trials that presented findings that were not significant ( P > or = 0.05 ) for the protocol -defined primary outcome in the internal documents either were not reported in full or were reported with a changed primary outcome . The primary outcome was changed in the case of 5 of 8 published trials for which statistically significant differences favoring gabapentin were reported . Of the 21 primary outcomes described in the protocol s of the published trials , 6 were not reported at all and 4 were reported as secondary outcomes . Of 28 primary outcomes described in the published reports , 12 were newly introduced . CONCLUSIONS We identified selective outcome reporting for trials of off-label use of gabapentin . This practice threatens the validity of evidence for the effectiveness of off-label interventions |
13,223 | 26,123,476 | We found mixed outcomes across both patient and HCP groups , with approximately half of the review s showing positive changes with record access .
Patients believe that record access increases their perception of control ; however , outcome measures thought to create psychological concerns ( such as patient anxiety as a result of seeing their medical record ) are still unanswered .
Nurses are more likely than physicians to gain time efficiencies by using a PAEHR system with the main concern from physicians being the security of the PAEHRs .
CONCLUSIONS This review implements a novel scoring system , which shows there is a lack of rigorous empirical testing that separates the effect of record access from other existing disease management programs .
Current research is too targeted within certain clinical groups ' needs , and although there are positive signs for the adoption of PAEHRs , there is currently insufficient evidence about the effect of PAEHRs on health outcomes for patients or HCPs | BACKGROUND Patient accessible electronic health records ( PAEHRs ) enable patients to access and manage personal clinical information that is made available to them by their health care providers ( HCPs ) .
It is thought that the shared management nature of medical record access improves patient outcomes and improves patient satisfaction .
However , recent review s have found that this is not the case .
Furthermore , little research has focused on PAEHRs from the HCP viewpoint .
HCPs include physicians , nurses , and service providers .
OBJECTIVE We provide a systematic review of review s of the impact of giving patients record access from both a patient and HCP point of view .
The review covers a broad range of outcome measures , including patient safety , patient satisfaction , privacy and security , self-efficacy , and health outcome . | Abstract Objective . Nowadays , registration of patient data on paper is gradually being replaced by registration using an intensive care information system ( ICIS ) . The aim of this study was to evaluate the effect of the use of an ICIS on nursing activity . Design . R and omized controlled trial with a crossover design . Setting . An 18-bed medical-surgical ICU in a teaching hospital . Patients , nurses and interventions . During a 6week period 145 consecutive adult patients admitted to the ICU after uncomplicated cardiothoracic surgery were r and omized into two groups : for one group the documentation was carried out using a paper-based registration ( Paper ) , in the second group an ICIS was used for documentation . Measurements and results . The nursing activities for these patients were studied during two separate periods : the admission period and the registration phase ( the period directly following the admission procedure ) . The duration of the admission procedure was measured by time-motion analysis and the nursing activities in the registration phase were studied by work sampling methodology . All nursing activities during the registration phase were grouped in four main categories : patient care , documentation , unit-related and personal time . The duration of the admission procedure was longer in the ICIS group ( 18.1±4.1 versus 16.8±3.1 min , p<0.05 ) . In the registration phase , a 30 % reduction in documentation time ( Paper 20.5 % of total nursing time versus ICIS 14.4 % , p<0.001 ) , corresponding to 29 min ( per 8h nursing shift ) was achieved . This time was completely re-allocated to patient care . Conclusions . The use of the present ICIS in patients after cardiothoracic surgery alters nursing activity ; it reduces the time for documentation and increases the time devoted to patient care . Electronic Supplementary Material is available if you access this article at http://dx.org/10.1007/s00134-002-1542-9 . On that page ( frame on the left side ) , a link takes you directly to the supplementary material Objective To determine the percentage of time that intensive care unit ( ICU ) nurses spend on documentation and other nursing activities before and after installation of a third-generation ICU information system . Design Prospect i ve data collection using real-time time-motion analysis , before and after installation of the ICU information system . Setting A ten-bed surgical ICU at a Veterans Affairs medical center . SubjectsICU nurses . Interventions Installation of a third-generation ICU information system . Measurements and Main Results Ten ICU nurses were studied before and after installation of the ICU information system . Each ICU nurse ’s activities and tasks , during 4-hr observation periods , were categorized in real-time by a nurse observer and recorded in a laptop computer . Each recorded task was automatically time-stamped and logged into a data file . The percentage of time spent on documentation decreased from 35.1 ± 8.3 % to 24.2 ± 7.6 % ( p = .025 ) after the ICU information system was installed . The percentage of time providing direct patient care increased from 31.3 ± 9.2 % to 40.1 ± 11.7 % ( p = .085 ) . The percentage of time doing patient assessment , a direct patient care task , increased from 4.0 ± 4.7 % to 9.4 ± 4.4 % ( p = .001 ) . Conclusions Installation of a third-generation ICU information system decreased the percentage of time ICU nurses spent on documentation by > 30 % . Almost half of the time saved on documentation was spent on patient assessment , a direct patient care task Computerized physician order entry ( CPOE ) has been shown to improve quality , and to reduce re source utilization , but most available data suggest that it takes longer to enter orders using CPOE . We had previously implemented a CPOE system , and elected to evaluate its impact on physician time in the new setting . To do this , we performed a prospect i ve study using r and om reminder methodology . Key findings were that interns spent 9.0 % of their time ordering with CPOE , compared to 2.1 % before , although CPOE saved them an additional 2 % of time , so that the net difference was 5 % of their total time . However , this is counterbalanced by decreased time for other personnel such as nursing and pharmacy , and by the quality and efficiency changes . We conclude that while CPOE has many benefits , it represents a major process change , and organizations must factor this in when they implement it This article describes a comparative study that examined the frequencies of nursing activities , when using a clinical information system ( CIS ) and a paper-based documentation system in an Australian intensive care unit . The study unit had half the beds equipped with a CIS , and the remaining beds used paper documentation . Work sampling methodology was used to observe nurses working with both systems . Though there were differences for all activities between the environments and the directions of the differences were logical , none were statistically significant using a chi-square test ( P = .11 - 0.65 ) , probably because of the small sample size . This study established that work sampling methodology using a r and om timer is a valid and relatively easy method to capture work activity in the clinical area . Although this article does not provide definitive information regarding the benefits of a CIS over manual documentation , a number of important method ological issues are discussed , including the study design , procedure , use of dedicated observers , and the distinction between basic versus fully optioned systems . Future research should evaluate the efficiency , impact on patient outcomes and nursing practice , and cost effectiveness of fully optioned systems OBJECTIVE To measure the impact on nursing activity of introducing computerized medical records into intensive care units ( ICUs ) . DESIGN Prospect i ve data collection monitoring the activity of ICU nurses before and after installation of a computerized charting system . SETTING A six-bed coronary care unit and an eight-bed medical ICU at the Minneapolis VA Medical Center . SUBJECTS Registered nurses providing intensive care services . INTERVENTIONS Installation of a Clinical Information System that computerized the ICU medical records . MEASUREMENTS AND MAIN RESULTS Before computer installation , nurses spent 24 % of their time manipulating data ( 7 % gathering and 17 % charting ) . After installation , charting time decreased to 10 % , and data gathering time decreased to 4 % , while 10 % of time was spent at computer terminals entering or review ing data . The total time manipulating data post-installation was thus 24 % ( i.e. , unchanged from previous ) . Computerized charting did not alter time spent in patients ' rooms ( 43 % pre- and 43 % postinstallation ) compared with time spent at the central station ( 37 % pre- and 36 % post-installation ) or elsewhere ( 20 % pre- and 21 % postinstallation ) . Relative time spent at various tasks varied between units and from shift to shift , but the net effect of computerized charting was that nurses had more time available at the central station for monitoring , and that the computer terminals were used primarily in the patient rooms . CONCLUSIONS Computerized charting will not necessarily provide ICU nurses with a net excess of time for tasks unrelated to manipulating data OBJECTIVE To study the effect of an Internet-based personal health record on the empowerment of patients undergoing IVF . DESIGN R and omized clinical trial . SETTING Patients undergoing IVF and intracytoplasmic sperm injection ( ICSI ) in an academic research environment . PATIENT(S ) We selected patients who were undergoing an IVF or ICSI treatment , have an Internet connection , and speak fluent Dutch . INTERVENTION(S ) An Internet-based personal health record that provides patients with general and personal information concerning their given treatment and that also provides facilities for communication with fellow patients and physicians . MAIN OUTCOME MEASURE(S ) Patient empowerment ( measured as a multidimensional concept consisting of self-efficacy , actual and perceived knowledge , and involvement in the decision process ) , patient satisfaction , meaning of infertility problems , social support , anxiety , and depression . RESULT ( S ) A total of 91 female and 89 male participants were suitable for analysis . No significant differences were observed in per person change in patient empowerment . We did not find any significant differences regarding per person change in patient satisfaction , the meaning of infertility problems , social support , anxiety , and depression . CONCLUSION ( S ) Usage of the personal health record did not have any effects on patient empowerment , but , at the same time , the study did not find that the personal health record had any significant adverse effects either The purpose of this project was to study the applicability of pen-based computer technology to home health care through the development of a pen-based computer system for a Hospital/Community-Patient Review Instrument ( H/C-PRI ) used for nursing home placement . The sample included nurses ( n = 12 ) from the four regional Visiting Nurse Service of New York offices , as well as all patients on whom a H/C-PRI was completed during the pre-period ( n = 238 ) and patients on whom a H/C-PRI was completed during the post-period ( n = 238 ) . The quality of documentation was higher for patients whose H/C-PRI was performed using the pen-based computer ( 0 % calculation errors ) than for those patients whose H/C-PRI was documented in the usual manner ( 11 % calculation errors ) BACKGROUND To determine whether a Web-based diabetes case management program based in an electronic medical record can improve glycemic control ( primary outcome ) and diabetes-specific self-efficacy ( secondary outcome ) in adults with type 1 diabetes , a pilot r and omized controlled trial was conducted . METHODS A 12-month r and omized trial tested a Web-based case management program in a diabetes specialty clinic . Patients 21 - 49 years old with type 1 diabetes receiving multiple daily injections with insulin glargine and rapid-acting analogs who had a recent A1C > 7.0 % were eligible for inclusion . Participants were r and omized to receive either ( 1 ) usual care plus the nurse-practitioner-aided Web-based case management program ( intervention ) or ( 2 ) usual clinic care alone ( control ) . We compared patients in the two study arms for changes in A1C and self-efficacy measured with the Diabetes Empowerment Scale . RESULTS A total of 77 patients were recruited from the diabetes clinic and enrolled in the trial . The mean baseline A1C among study participants was 8.0 % . We observed a nonsignificant decrease in average A1C ( -0.48 ; 95 % confidence interval -1.22 to 0.27 ; P = 0.160 ) in the intervention group compared to the usual care group . The intervention group had a significant increase in diabetes-related self-efficacy compared to usual care ( group difference of 0.30 ; 95 % confidence interval 0.01 to 0.59 ; P = 0.04 ) . CONCLUSIONS Use of a Web-based case management program was associated with a beneficial treatment effect on self-efficacy , but change in glycemic control did not reach statistical significance in this trial of patients with moderately poorly controlled type 1 diabetes . Larger studies may be necessary to further clarify the intervention 's impact on health outcomes |
13,224 | 25,045,166 | Compared with anticoagulation , aspirin may be associated with higher risk of DVT following hip fracture repair , although bleeding rates were substantially lower .
Aspirin was similarly effective after lower extremity arthroplasty and may be associated with lower bleeding risk . | BACKGROUND Hip fracture surgery and lower extremity arthroplasty are associated with increased risk of both venous thromboembolism and bleeding .
The best pharmacologic strategy for reducing these opposing risks is uncertain .
PURPOSE To compare venous thromboembolism ( VTE ) and bleeding rates in adult patients receiving aspirin versus anticoagulants after major lower extremity orthopedic surgery . | A prospect i ve study involving 120 consecutive patients undergoing total hip replacement was performed to compare the effectiveness of aspirin ( high and low dose ) or a combination of heparin plus dihydroergotamine ( heparin-DHE ) in preventing isotopic and phlebographic deep vein thrombosis ( DVT ) , and to evaluate their effect on postoperative platelet changes . Phlebographic DVT was demonstrated in 9 cases ( 30 % ) in control group , in 1 ( 3.3 % ) in aspirin ( high-dose ) group ( p less than 0.01 ) , in 1 ( 3.3 % ) in aspirin ( low-dose ) group ( p less than 0.01 ) and in 5 ( 16.6 % ) in heparin-DHE group ( p = NS ) . Aspirin was able to reduce the postoperative increase in circulating platelet aggregates , platelet factor 4 and beta-thromboglobulin observed in control group . This study shows that aspirin is effective in the prevention of DVT for patients undergoing total hip replacement . Small aspirin dose ( 250 mg/day ) represents an effective form of prophylaxis in these patients A r and omized trial was carried out with 194 patients to compare the effectiveness of sodium warfarin or aspirin with that of placebo in the prevention of venous thromboembolism after surgery for fractured hip . Prophylaxis was commenced postoperatively and continued for 21 days or until patient discharge , whichever was earlier . All patients underwent surveillance with iodine 125-fibrinogen leg scanning and impedance plethysmography , with subsequent venography . Venous thromboembolism occurred in 13 patients ( 20.0 % ) in the warfarin group , 27 patients ( 40.9 % ) in the aspirin group , and 29 patients ( 46.0 % ) in the placebo group . Proximal vein thrombosis or pulmonary embolism occurred in 6 patients ( 9.2 % ) in the warfarin group , 7 patients ( 10.6 % ) in the aspirin group , and 19 patients ( 30.2 % ) in the placebo group . The results of this study show that sodium warfarin therapy is safe and effective in preventing thromboembolic complications in patients undergoing surgery for fractured hip , and that aspirin therapy is an equally safe and effective method for preventing proximal vein thrombosis or pulmonary embolism Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more This study compares the benefits of aspirin and warfarin prophylactic agents for patients with thromboembolic disease after total joint arthroplasty . It is a prospect i ve r and omized study of 388 patients having total hip or total knee surgery . All consecutive patients having total hip or total knee surgery were entered into this study and evaluated with preoperative and postoperative ventilation perfusion scans and a postoperative venogram . The aspirin and warfarin treatment groups were compared by size and location of venographically revealed clots and changes in ventilation perfusion scans . The results showed that there was no difference in the size or location of deep venous thrombosis in the aspirin or warfarin treatment groups . The venogram was negative in 44.5 % of patients ; 28.8 % had small calf clots , 16 % had large calf clots , 3.9 % had popliteal clots , and 6.7 % had femoral clots . Patients with total knee replacement had a 2.6 times greater incidence of calf deep venous thrombosis than patients with total hip replacement . There was no difference between the aspirin and warfarin groups in the incidence of changes in ventilation perfusion scans ( 18.9 % ) . There was no difference between the 2 groups in bleeding complications . The results suggest that aspirin and warfarin are equivalent in prophylaxis against thromboembolic disease , as determined by prevention of venographic changes or changes in ventilation perfusion scans We have evaluated the quality of life and functional outcome after unilateral primary total hip replacement ( THR ) . Between 5 January 1998 and 31 July 2000 , we recruited a consecutive series of 627 patients undergoing this procedure and investigated them prospect ively . Each was assessed before operation and review ed after six months , 18 months , three years and five years . The Short Form-36 Health Survey ( SF-36 ) and Harris Hip scores were evaluated at each appointment . All dimensions of the SF-36 except for mental health and general health perception , improved significantly after operation and this was maintained throughout the follow-up . The greatest improvement was seen at the six-month assessment . On average , women reported lower SF-36 scores pre-operatively , but the gender difference did not continue post-operatively . The Harris Hip scores improved significantly after operation , reaching a plateau after 18 months . The improved quality of life was sustained five years after THR OBJECTIVE To compare the health-related quality of life of people with osteoarthritis before and after primary total hip and knee replacement surgery with that of the general Australian population . DESIGN A prospect i ve cohort study . SETTING Three Sydney hospitals , public and private . PARTICIPANTS Patients with osteoarthritis undergoing primary total hip ( n = 59 ) and knee ( n = 92 ) joint replacement surgery . MAIN OUTCOME MEASURE Medical Outcomes Study Short Form ( SF-36 ) scores before and 12 months after joint replacement surgery ( compared with population norms ) . RESULTS Patients in each age group showed a significant improvement in health-related quality of life after joint replacement surgery in most scales of the SF-36 , particularly physical function , role physical and bodily pain . SF-36 scores for the 42 hip-replacement patients aged 55 - 74 years improved to equal or exceed the population norm on all scales . SF-36 scores of the 52 knee replacement patients aged 55 - 74 years improved , but physical function and bodily pain scores remained significantly worse than the population norm . SF-36 scores for both hip ( n = 17 ) and knee ( n = 40 ) replacement patients aged 75 years and over improved significantly , becoming similar to population norms for this age group . CONCLUSIONS Total hip or knee replacement for osteoarthritis significantly improves patient health and well-being at 12 months after surgery . Age alone should not be a barrier to surgery Aspirin has been demonstrated to be an effective prophylactic agent against postoperative venous thromboembolic disease , but the optimum dosage is unknown . We compared the efficacy of daily doses of 3.6 grams of aspirin ( high dose ) with that of 1.2 grams ( low dose ) in 182 patients . All patients were more than forty years old and all underwent a total hip replacement . This r and omized , prospect i ve , double-blind study was done using only objective dta for diagnosis . Twenty-three ( 44 per cent ) of fifty-two women who were treated with the low dose had thrombi , compared with eighteen ( 34 per cent ) of fifty-three women who were given the high dose . Thrombi developed in thirteen ( 32 per cent ) and in eighteen ( 49 per cent ) of thirty-seven men who were given the high dose . There were no statistically significant differences among the four groups , nor was there a significant difference among the subgroups that were determined according to prior history of venous thromboembolic disease . Therefore , the higher dose of aspirin was neither more nor less effective than the lower dose . Our data continue to support the use of 1.2 grams in men In a prospect i ve and controlled study , we compared the prophylactic effect of high-dose acetylsalicylic acid ( ASA ) and dihydroergotamine-heparin ( DHEH ) in 82 patients over 50 years of age undergoing total hip replacement . The patients were screened by pulmonary scan and 125I fibrinogen uptake . Phlebography was done if the 125 I fibrinogen test was positive . According to our criteria , thromboembolism developed in 9 of 40 receiving ASA and in 5 of 42 patients receiving DHEH . The effect of ASA was limited to men ; in 16 men on this therapy , none had thromboembolism versus 9 of 24 women . Twenty-two patients showed wound hematomas , but none needed surgical intervention A prospect i ve , r and omized study of the effectiveness of intraoperative and postoperative use of intermittent pneumatic compression , alone or in combination with oral administration of either aspirin or low-dose warfarin , was done of a consecutive series of patients who had a total hip replacement and were more than thirty-nine years old . All patients began walking by the third postoperative day . One hundred and ninety-six patients who had 217 total hip arthroplasties were included . Twenty-eight per cent of the procedures were revisions of a previous total hip replacement or of an endoprosthesis , and the remainder were primary arthroplasties . Patients were r and omized as to the type of prophylaxis that they received : intermittent pneumatic compression alone , seventy-six hips ; intermittent pneumatic compression and aspirin , seventy-two hips ; or intermittent pneumatic compression and low-dose warfarin , sixty-nine hips . Before discharge from the hospital , and at an average of seven days after the operation , all patients were evaluated for the presence of proximal deep-vein thrombosis with either venography on the side of the operation or with bilateral venous ultrasonography . The relative frequency with which thrombosis occurred in a proximal vein was not significantly different in the three groups ; the over-all relative frequency was 10 per cent . Intermittent compression during and after the operation effectively reduces the rate of proximal-vein thrombosis after total hip replacement . With the number of patients in our study , the effectiveness of this technique could not be shown to be augmented by oral administration of either aspirin or low-dose warfarin Two hundred seventy-five patients undergoing unilateral total knee arthroplasty were prospect ively r and omized to receive spinal epidural anesthesia ( SEA ) , a VenaFlow calf compression device , and enoxaparin ( group A ) or SEA , VenaFlow , and aspirin ( group B ) . Aspirin was started on the day of surgery , whereas enoxaparin was started 48 hours after surgery . Anticoagulants were continued for 4 weeks after surgery . All patients had an in-hospital ultrasound screening test on postoperative days 3 to 5 and a second follow-up ultrasound 4 to 6 weeks after surgery . The overall deep venous thrombosis rates in groups A and B were 14.1 % and 17.8 % ( P = not significant ) , respectively . When used in combination with pneumatic compression devices and SEA , enoxaparin was not superior to aspirin in preventing deep venous thrombosis after total knee arthroplasty BACKGROUND The study objective was to determine the relative efficacy and safety of a low-molecular-weight heparinoid ( Orgaran ) compared with aspirin for the prevention of postoperative venous thromboembolism in patients undergoing surgery for fractured hips . A double-blind , r and omized , controlled trial was used to study 251 consecutive eligible and consenting patients undergoing surgery for hip fracture in seven participating hospitals . METHODS AND RESULTS Patients received either fixed-dose Orgaran by subcutaneous injection every 12 hours in a dose of 750 anti-Factor Xa units or aspirin 100 mg orally twice daily ; both regimens were started 12 to 24 hours after surgery and continued for 14 days or until discharge , if sooner . All patients had postoperative 125I-fibrinogen leg scanning and impedance plethysmography . If the results of one or both tests were positive , then venography was performed . Otherwise , venography was done at day 14 , or sooner if the patient was ready for discharge . Pulmonary embolism in symptomatic patients was diagnosed on the basis of a high probability perfusion/ventilation lung scan , a positive angiogram , or a clinical ly significant embolism detected at autopsy . Evaluable venograms were obtained in 90 of the 125 patients r and omly assigned to receive Orgaran and in 87 of the 126 patients assigned to receive aspirin . Venous thromboembolism was detected in 25 ( 27.8 % ) patients in the Orgaran group and in 39 ( 44.3 % ) patients in the aspirin group . Thus , there was a relative risk reduction of 37 % with Orgaran ( P=.028 ; 95 % confidence interval , 3.7 % to 59.7 % ) . Six ( 6.8 % ) of 88 patients in the Orgaran group and 12 ( 14.3 % ) of 84 patients in the aspirin group developed proximal deep vein thrombosis or pulmonary embolism , a relative risk reduction of 52 % with Orgaran ( P=.137 ; 95 % confidence interval , -30.7 % to 84.6 % ) . Hemorrhagic complications occurred in 2 ( 1.6 % ) patients given Orgaran and 8 ( 6.4 % ) patients given aspirin ( P=.10 ) . There was one major bleed in the Orgaran group compared with four in the aspirin group . CONCLUSIONS This study demonstrates that Orgaran is significantly more efficacious than aspirin in preventing postoperative venous thromboembolism in patients undergoing surgery for fractured hips , with no evidence of any increase in hemorrhagic complications BACKGROUND The role of aspirin in thromboprophylaxis after total hip arthroplasty ( THA ) is controversial . OBJECTIVE To compare extended prophylaxis with aspirin and dalteparin for prevention of symptomatic venous thromboembolism ( VTE ) after THA . DESIGN Multicenter r and omized , controlled trial with a noninferiority design based on a minimal clinical ly important difference of 2.0 % . R and omization was electronically generated ; patients were assigned to a treatment group through a Web-based program . Patients , physicians , study coordinators , health care team members , outcome adjudicators , and data analysts were blinded to interventions . ( Current Controlled Trials : IS RCT N11902170 ) . SETTING 12 tertiary care orthopedic referral centers in Canada . PATIENTS 778 patients who had elective unilateral THA between 2007 and 2010 . INTERVENTION After an initial 10 days of dalteparin prophylaxis after elective THA , patients were r and omly assigned to 28 days of dalteparin ( n = 400 ) or aspirin ( n = 386 ) . MEASUREMENTS Symptomatic VTE confirmed by objective testing ( primary efficacy outcome ) and bleeding . RESULTS Five of 398 patients ( 1.3 % ) r and omly assigned to dalteparin and 1 of 380 ( 0.3 % ) r and omly assigned to aspirin had VTE ( absolute difference , 1.0 percentage point [ 95 % CI , -0.5 to 2.5 percentage points ] ) . Aspirin was noninferior ( P < 0.001 ) but not superior ( P = 0.22 ) to dalteparin . Clinical ly significant bleeding occurred in 5 patients ( 1.3 % ) receiving dalteparin and 2 ( 0.5 % ) receiving aspirin . The absolute between-group difference in a composite of all VTE and clinical ly significant bleeding events was 1.7 percentage points ( CI , -0.3 to 3.8 percentage points ; P = 0.091 ) in favor of aspirin . LIMITATION The study was halted prematurely because of difficulty with patient recruitment . CONCLUSION Extended prophylaxis for 28 days with aspirin was noninferior to and as safe as dalteparin for the prevention of VTE after THA in patients who initially received dalteparin for 10 days . Given its low cost and greater convenience , aspirin may be considered a reasonable alternative for extended thromboprophylaxis after THA . PRIMARY FUNDING SOURCE Canadian Institutes of Health Research |
13,225 | 23,076,892 | Urinary incontinence may be improved with the use of local oestrogen treatment .
Conversely , systemic hormone replacement therapy using conjugated equine oestrogen may worsen incontinence .
There were too few data to reliably address other aspects of oestrogen therapy , such as oestrogen type and dose , and no direct evidence comparing routes of administration .
The risk of endometrial and breast cancer after long-term use of systemic oestrogen suggests that treatment should be for limited periods , especially in those women with an intact uterus | BACKGROUND It is possible that oestrogen deficiency may be an aetiological factor in the development of urinary incontinence in women .
This is an up date of a Cochrane review first published in 2003 and subsequently up date d in 2009 .
OBJECTIVES To assess the effects of local and systemic oestrogens used for the treatment of urinary incontinence . | The effect of oral oestriol ( 3 mg/day for 4 weeks followed by 2 mg/day for a further 6 weeks ) on the vaginal bacterial flora , vaginal cytology and urogenital symptoms was assessed in a double-blind , placebo-controlled study in 35 women with symptoms of the urogenital oestrogen deficiency syndrome . No significant differences were observed with regard to the occurrence or severity of urogenital symptoms , vaginal pH , karyopyknotic index ( KPI ) or the baseline results of vaginal bacterial cultures in the 18 patients ( mean age 71.6 + /- 1.0 years ) treated with oestriol and the 17 women ( mean age 72.6 + /- 1.4 years ) who received placebo tablets . A decrease in both vaginal pH ( P less than 0.001 ) and the proportion of faecal-type bacteria ( P less than 0.05 ) , and an increase in the KPI ( P less than 0.01 ) and the proportion of lactobacilli ( P less than 0.001 ) were recorded after 10 weeks of treatment with oral oestriol . At the end of the following 10 medication-free weeks all of these parameters except vaginal pH had returned to values that were not significantly altered from the corresponding baseline levels . In the patients treated with placebo no significant changes occurred in vaginal pH , KPI or the proportion of lactobacilli in vaginal cultures during the course of this study . Urogenital symptoms improved in both groups after medication ( and even after the medication-free period ) in relation to the baseline assessment , which reflects the latter 's subjective nature BACKGROUND In postmenopausal women , raloxifene hydrochloride has favorable effects on bone and lipid metabolism and does not stimulate reproductive tissues . The studies reported herein evaluated the long-term ( 3-year ) effects of raloxifene treatment on bone mineral density ( BMD ) , serum lipid levels , and drug tolerability in healthy postmenopausal women . METHODS A total of 1145 healthy European and North American postmenopausal women aged 45 through 60 years were enrolled in 2 parallel , double-blind , r and omized , placebo-controlled trials of identical design and r and omly assigned to receive raloxifene hydrochloride , 30 , 60 , or 150 mg , or placebo daily ; all groups received 400 to 600 mg of elemental calcium . Assessment s included measurements for BMD by dual-energy x-ray absorptiometry , markers of bone turnover , and serum lipid levels . RESULTS Lumbar spine BMD changed from baseline to 36 months as follows : placebo ( mean percentage change + SE ) , -1 . 32 % + 0.22 % ; raloxifene , 30 mg , 0.71 % + 0.23 % ; raloxifene , 60 mg , 1 . 28 % + 0.23 % ; and raloxifene , 150 mg , 1.20 % + 0.24 % . Comparable BMD changes were observed in the hip and total body . Biochemical markers of bone turnover were suppressed by raloxifene to normal premenopausal ranges through 3 years . Serum low-density lipoprotein cholesterol was reduced 7 % to 12 % below baseline through 3 years . Study withdrawals due to any reason ( 37 % ) and withdrawals due to adverse events ( 14 % ) were not different among groups . The only significant adverse effect of therapy was hot flashes ( 25 % in the 60-mg raloxifene group vs 18 % in the placebo group ) ; hot flashes were typically reported as mild and were not associated with study withdrawal ( 1.7 % for 60-mg raloxifene vs 2.4 % for placebo ) . CONCLUSIONS Raloxifene preserves BMD at important skeletal sites , lowers serum low-density lipoprotein cholesterol levels , and has a tolerability profile comparable to placebo . These results indicate a favorable benefit-risk profile of raloxifene for long-term use in healthy postmenopausal women . Arch Intern Med . 2000;160:3444 - 3450 Twenty-nine postmenopausal women with slight to severe stress urinary incontinence and estrogen deficiency symptoms in the urogenital tract were treated with estriol , p.o . 4 mg once daily , and either phenylpropanolamine ( PPA ) , p.o . 50 mg twice daily , or placebo for periods of 6 weeks according to a r and omized double-blind crossover schedule . At urodynamic recordings the maximum urethral closure pressure increased by 22 % with combined treatment ( p less than 0.001 ) and an additional effect of PPA to estriol was shown ( p = 0.022 ) . The pressure transmission ratio increased , by about 15 % , with both treatments ( p less than 0.07 ) . The number of leakage episodes was reduced by 28 % with combined treatment ( p = 0.007 ) , but not with estriol alone ( p = 0.08 ) . Both combined treatment and estriol alone reduced significantly ( p less than 0.01 ) the urinary incontinence complaints . Twelve women ( 43 % ) preferred combined treatment , while 7 ( 25 % ) preferred estriol alone . In women with initially slight to very severe urine loss , combined treatment reduced also ( p = 0.02 ) the amount of urine loss , measured at a st and ardized physical stress test . Signs of estrogen deficiency in vulva , vagina and urethra were reduced , 75 % ( p less than 0.001 ) or 65 % ( p = 0.001 ) with estriol given in combination with PPA or alone . Maturation index of both urethral and vaginal epithelium displayed significant changes . It is concluded that the combined treatment , PPA + estriol , by affecting both the muscular and mucosal factor of the urethra , is more effective than estriol alone for treatment of female stress urinary incontinence in the postmenopausal ages A r and omized open comparative cross-over trial was carried out in 20 postmenopausal women , mean age 69 years , suffering from urinary incontinence due to urethral sphincteric insufficiency . They were treated with phenylpropanolamine ( PPA ) 50 mg p.o . twice daily or estriol vaginal suppositories 1 mg daily separately and in combination for periods of 4 weeks . Urodynamic investigations were carried out before and after each period of treatment . Both PPA and estriol increased the maximal urethral closure pressure and the continence area significantly compared to the initial values , but combined treatment was substantially more effective . The functional urethral length increased significantly while on estriol . No significant change was registered in the bladder pressure or in the pressure transmission ratio . PPA was clinical ly more effective than estriol , but not sufficient to obtain complete continence . With combined treatment 8 patients became completely continent , 9 were considerably improved and only 1 patient remained unchanged . 2 patients dropped out of the study because of side effects . Combined treatment with PPA and estriol represents a recommendable treatment to postmenopausal women with urinary incontinence due to urethral sphincteric insufficiency The objective of the study was to assess the effects of low-dose vaginal treatment with oestradiol before vaginal operation . In a double-blind r and omized study including 43 postmenopausal women scheduled for vaginal repair operation for genital descensus , it was found that 7 patients suffered from concomitant urinary stress incontinence . Vagifem ( 25 micrograms oestradiol ) or placebo was administered as vaginal pessaries daily , 3 weeks prior to surgery and the clinical effects evaluated . One month postoperatively the prevalence of bacteriuria ( > 100,000 CFU/ml urine ) was significantly lower when using oestradiol than in the placebo group . At follow-up 3 years later 40 women ( 93 % ) answered the question naires . None received hormone replacement therapy . Nineteen percent in the preoperative oestradiol group and 11 % in the preoperative placebo group had had more than two episodes of cystitis treated with antibiotics . This difference is not statistically significant ( p > 0.05 ) . Recurrent cystitis was not correlated to bacteriuria postoperatively . Seventy-nine percent of the women with genital prolapse but only 29 % of the women with concomitant urinary stress incontinence were cured ( p < 0.05 ) . Neither preoperative oestradiol treatment nor body weight had any influence on relapse . Preoperative low-dose vaginal oestradiol treatment may reduce the incidence of bacteriuria in the immediate postoperative period but no long-lasting effects on recurrent cystitis or relapse were seen . Longer-lasting hormone replacement therapy may be necessary to achieve lasting effects CONTEXT AND OBJECTIVE Estriol is an estrogen with considerably weaker stimulatory effects on endometrial proliferation than estradiol . A study was conducted to determine the level of estrogen receptors ( ERs ) and progesterone receptors ( PRs ) in women who received 14-day vaginal estriol therapy , compared with those who did not receive this therapy . ER and PR gene expression was analyzed in the endometrium , myometrium and vagina of postmenopausal women treated with estriol . DESIGN AND SETTING Analytical cross-sectional study , at the Research Institute of the Polish Mothers ' Memorial Hospital , Lodz , Pol and . METHODS Twenty-seven postmenopausal women ( 57 - 74 years of age ) were included in the study . All of them were waiting for per vaginam hysterectomy or plastic surgery on the vagina and perineum because of uterine prolapse . ER and PR gene expression was determined by means of the technique of reverse transcription polymerase chain reaction ( RT-PCR ) . RESULTS In the estriol-treated patients , in comparison with the control group , a significant increase in ER gene expression was observed in the endometrium and vagina , while enhanced PR gene expression was found in the endometrium . However , under histological examination of the endometrium , estrogen stimulation of low and medium degree was diagnosed for 21.4 % and 14.3 % of the estriol-treated women , respectively . CONCLUSION The results obtained suggest that the women who received 14 days of treatment with vaginal estriol had higher ER and PR mRNA levels . No difference between these groups regarding endometrial proliferation was observed BACKGROUND No authors have investigated whether the administration of local oestrogens in addition to antimuscarinics could have a synergistic effect in the therapy of overactive bladder ( OAB ) . OBJECTIVES To compare the efficacy of antimuscarinics alone versus antimuscarinics in combination with local oestrogens for OAB ; to verify whether risk factors for lower antimuscarinic efficacy can be overcome by the concomitant use of local oestrogens . DESIGN , SETTING , AND PARTICIPANTS Some 229 postmenopausal women with symptomatic urodynamically proven detrusor overactivity were prospect ively enrolled at a tertiary level urogynaecology centre and divided into two groups . INTERVENTION Women in group 1 ( n=129 ) were prescribed tolterodine extended release ( ER ) 4 mg once daily ; women in group 2 ( n=100 ) were prescribed both tolterodine ER 4 mg and concomitant oestriol cream application once daily . MEASUREMENTS All women underwent clinical evaluation and urodynamics in accordance with the Good Urodynamic Practice s Guidelines . After 12 wk of treatment the two groups were compared in terms of subjective efficacy for OAB symptom improvement using a three-point scale . Nonresponders were compared to the patients who improved or were cured in order to identify risk factors for resistance to therapy . RESULTS AND LIMITATIONS There was no significant difference between the two groups in terms of efficacy of therapy : 80.6 % in group 1 versus 82 % in group 2 ( p=0.86 ) . Patients with urodynamically proven detrusor overactivity ( DO ) occurring during provocative manoeuvres and patients with coital incontinence during orgasm reported a higher failure rate both in the overall study population and in group 2 . A possible limitation of the study is the nonr and omised design . CONCLUSIONS No synergistic effect of local oestrogens and antimuscarinics in the treatment of OAB was found . Antimuscarinic treatment has lower cure rates in women with symptomatic DO complaining of incontinence at orgasm or in patients with DO following provocative manoeuvres . The association of local oestrogens does not influence the role of the two mentioned risk factors Objective To assess the efficacy and safety of intravaginal estriol administration on urinary incontinence , urogenital atrophy , and recurrent urinary tract infections in postmenopausal women . Design Eighty-eight postmenopausal women with urogenital aging symptoms were enrolled in this prospect i ve , r and omized , placebo-controlled study . Participants were r and omly divided into two groups , with each group consisting of 44 women . Women in the treatment group received intravaginal estriol ovules : 1 ovule ( 1 mg ) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy . Women in the control group received inert placebo vaginal suppositories in a similar regimen . We evaluated urogenital symptomatology , urine cultures , colposcopic findings , urethral cytologic findings , urethral pressure profiles , and urethrocystometry before as well as after 6 months of treatment . Results After therapy , the symptoms and signs of urogenital atrophy significantly improved in the treatment group in comparison with the control group . Thirty ( 68 % ) of the treated participants , and only seven ( 16 % ) of the control participants registered a subjective improvement of their incontinence . In the treated participants , we observed significant improvements of colposcopic findings , and there were statistically significant increases in mean maximum urethral pressure , in mean urethral closure pressure as well as in the abdominal pressure transmission ratio to the proximal urethra . Urethrocystometry showed positive but not statistically significant modifications . Conclusions Our results show that intravaginal administration of estriol may represent a satisfactory therapeutic choice for those postmenopausal women with urogenital tract disturbances who have contraindications or refuse to undergo st and ard hormone therapy Objective To determine whether postmenopausal hormone therapy improves the severity of urinary incontinence . Methods We included measures of incontinence and voiding frequency in the Heart and Estrogen/Progestin Replacement Study , a r and omized , blinded trial of the effect of hormone therapy among 2763 postmenopausal women younger than 80 years with coronary disease and intact uteri . This report includes 1525 participants who reported at least one episode of incontinence per week at baseline . Participants were r and omly assigned to 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate in one tablet daily ( n = 768 ) or placebo ( n = 757 ) and were followed for a mean of 4.1 years . Severity of incontinence was classified as improved ( decrease of at least two episodes per week ) , unchanged ( change of at most one episode per week ) , or worsened ( increase of at least two episodes per week ) . Results Incontinence improved in 26 % of the women assigned to placebo compared with 21 % assigned to hormones , while 27 % of the placebo group worsened compared with 39 % of the hormone group ( P = .001 ) . This difference was evident by 4 months of treatment and was observed for both urge and stress incontinence . The number of incontinent episodes per week increased an average of 0.7 in the hormone group and decreased by 0.1 in the placebo group ( P < .001 ) . Conclusion Daily oral estrogen plus progestin therapy was associated with worsening urinary incontinence in older postmenopausal women with weekly incontinence . We do not recommend this therapy for the treatment of incontinence CONTEXT Menopausal hormone therapy has long been credited with many benefits beyond the indications of relieving hot flashes , night sweats , and vaginal dryness , and it is often prescribed to treat urinary incontinence ( UI ) . OBJECTIVE To assess the effects of menopausal hormone therapy on the incidence and severity of symptoms of stress , urge , and mixed UI in healthy postmenopausal women . DESIGN , SETTING , AND PARTICIPANTS Women 's Health Initiative multicenter double-blind , placebo-controlled , r and omized clinical trials of menopausal hormone therapy in 27,347 postmenopausal women aged 50 to 79 years enrolled between 1993 and 1998 , for whom UI symptoms were known in 23,296 participants at baseline and 1 year . INTERVENTIONS Women were r and omized based on hysterectomy status to active treatment or placebo in either the estrogen plus progestin ( E + P ) or estrogen alone trials . The E + P hormones were 0.625 mg/d of conjugated equine estrogen plus 2.5 mg/d of medroxyprogesterone acetate ( CEE + MPA ) ; estrogen alone consisted of 0.625 mg/d of conjugated equine estrogen ( CEE ) . There were 8506 participants who received CEE + MPA ( 8102 who received placebo ) and 5310 who received CEE alone ( 5429 who received placebo ) . MAIN OUTCOME MEASURES Incident UI at 1 year among women without UI at baseline and severity of UI at 1 year among women who had UI at baseline . RESULTS Menopausal hormone therapy increased the incidence of all types of UI at 1 year among women who were continent at baseline . The risk was highest for stress UI ( CEE + MPA : relative risk [ RR ] , 1.87 [ 95 % confidence interval { CI } , 1.61 - 2.18 ] ; CEE alone : RR , 2.15 [ 95 % CI , 1.77 - 2.62 ] ) , followed by mixed UI ( CEE + MPA : RR , 1.49 [ 95 % CI , 1.10 - 2.01 ] ; CEE alone : RR , 1.79 [ 95 % CI , 1.26 - 2.53 ] ) . The combination of CEE + MPA had no significant effect on developing urge UI ( RR , 1.15 ; 95 % CI , 0.99 - 1.34 ) , but CEE alone increased the risk ( RR , 1.32 ; 95 % CI , 1.10 - 1.58 ) . Among women experiencing UI at baseline , frequency worsened in both trials ( CEE + MPA : RR , 1.38 [ 95 % CI , 1.28 - 1.49 ] ; CEE alone : RR , 1.47 [ 95 % CI , 1.35 - 1.61 ] ) . Amount of UI worsened at 1 year in both trials ( CEE + MPA : RR , 1.20 [ 95 % CI , 1.06 - 1.36 ] ; CEE alone : RR , 1.59 [ 95 % CI , 1.39 - 1.82 ] ) . Women receiving menopausal hormone therapy were more likely to report that UI limited their daily activities ( CEE + MPA : RR , 1.18 [ 95 % CI , 1.06 - 1.32 ] ; CEE alone : RR , 1.29 [ 95 % CI , 1.15 - 1.45 ] ) and bothered or disturbed them ( CEE + MPA : RR , 1.22 [ 95 % CI , 1.13 - 1.32 ] ; CEE alone : RR , 1.50 [ 95 % CI , 1.37 - 1.65 ] ) at 1 year . CONCLUSIONS Conjugated equine estrogen alone and CEE + MPA increased the risk of UI among continent women and worsened the characteristics of UI among symptomatic women after 1 year . Conjugated equine estrogen with or without progestin should not be prescribed for the prevention or relief of UI An intervention trial using oral oestriol to treat urinary incontinence was performed in a number of patients taken from a representative sample of 562 women aged 75 yr . The clinical series consisted of 34 patients who took part in a double-blind crossover study of the possible effects of oestriol , given in a single daily dose of 3 mg , and of a placebo over a period of 3 mth . The clinical examinations included bacteriological cultures and an assessment of the degree of atrophy of the surface membranes in the vagina . In most patients , oestriol was effective in reversing the atrophy . The clinical effect was excellent in urgency and mixed incontinence , but not in stress incontinence OBJECTIVE To assess the efficacy , tolerability , and acceptance of a vaginal ring delivering the equivalent of 50 or 100 microg per day of estradiol ( E2 ) , compared with placebo , for relief of moderate to severe vasomotor symptoms and urogenital symptoms in postmenopausal women . METHODS Women with moderate to severe vasomotor symptoms ( seven or more per day or 56 per week average ) received 13 weeks of treatment with a vaginal ring delivering 50 microg per day E2 ( n = 113 ) or 100 microg per day E2 ( n = 112 ) , or a placebo vaginal ring ( n = 108 ) . Severity of vasomotor symptoms was assessed by a daily diary card and the Greene Climacteric Scale . Urogenital signs and symptoms were evaluated via patient and physician assessment and vaginal cytology . Participant satisfaction with the vaginal ring was evaluated via question naire . RESULTS Vasomotor symptoms significantly improved in both treatment groups , compared with placebo ( P < .05 ) . There was a trend toward greater improvement in patient assessment of urogenital signs with active rings compared with placebo . For women with vaginal atrophy at baseline ( n = 60 ) , the maturation index improved significantly in both treatment groups compared with placebo . Total Greene Climacteric Scale scores significantly improved for both E2 vaginal ring groups ( P < .05 ) compared with placebo . The vaginal rings were well tolerated . Most adverse events were mild or moderate and consistent with estrogen therapy . CONCLUSION A novel vaginal ring delivering the equivalent of 50 or 100 microg per day of E2 significantly reduced the number and severity of vasomotor symptoms and improved urogenital symptoms , compared with placebo . The E2 vaginal ring was well tolerated Objectives To assess the efficacy of an oestradiol‐releasing vaginal ring and oestriol pessaries in the alleviation of lower urinary tract symptoms occurring after the menopause In a double-blind , placebo-controlled study , 109 patients suffering from local and vasomotor postmenopausal complaints were r and omly assigned to treatment with either depot vaginal suppositories containing 3.5 mg oestriol ( E3 ) or a placebo . The treatment schedule comprised one vaginal suppository twice weekly for 3 weeks initially , followed by maintenance therapy with one vaginal suppository weekly for the 6-month study period . The effectiveness of the therapy was assessed on the basis of question naires ( Kupperman index for vasomotor complaints and an original urogenital index for local complaints ) and gynaecological examinations which included assessment s of vaginal cytology , vaginal pH and Döderlein bacilli . To rule out induced endometrial proliferation , endometrial biopsies were performed in 50 women before and after the study . The vaginal depot ( E3 ) formulation showed highly significant superiority over the placebo with respect to therapeutic effect on local urogenital complaints and alleviation of vasomotor complaints , including hot flushes . Analysis of the endometrial biopsies indicated that the monotherapy used caused no endometrial stimulation . Taking into account the minimal rate of adverse effects , the 3.5 mg E3 depot formulation studied represents a useful variant in the range of preparations available for the treatment of post-menopausal complaints A prospect i ve r and omised double-blind placebo-controlled trial of 17-beta oestradiol 25-mg vaginal tablets or placebo daily for 12 weeks was undertaken in 110 postmenopausal women with urinary frequency , urgency and /or urge incontinence recruited from a tertiary referral urogynaecology clinic . After 3 months the only statistically significant difference was a greater reduction in urinary urgency in those women with sensory urgency treated with 17-beta oestradiol compared to placebo . This may be due to the effective treatment of local vaginal atrophy by low-dose oestrogen rather than any effect on the lower urinary tract CONTEXT Raloxifene hydrochloride , a selective estrogen receptor modulator , prevents bone loss in postmenopausal women , but whether it reduces fracture risk in these women is not known . OBJECTIVE To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures . DESIGN The Multiple Outcomes of Raloxifene Evaluation ( MORE ) study , a multicenter , r and omized , blinded , placebo-controlled trial . SETTING AND PARTICIPANTS A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis . The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events . INTERVENTIONS Participants were r and omized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills ; in addition , all women received supplemental calcium and cholecalciferol . MAIN OUTCOME MEASURES Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits . Nonvertebral fracture was ascertained by interview at 6-month-interim visits . Bone mineral density was determined annually by dual-energy x-ray absorptiometry . RESULTS At 36 months of the evaluable radiographs in 6828 women , 503 ( 7.4 % ) had at least 1 new vertebral fracture , including 10.1 % of women receiving placebo , 6.6 % of those receiving 60 mg/d of raloxifene , and 5.4 % of those receiving 120 mg/d of raloxifene . Risk of vertebral fracture was reduced in both study groups receiving raloxifene ( for 60-mg/d group : relative risk [ RR ] , 0.7 ; 95 % confidence interval [ CI ] , 0.5 - 0.8 ; for 120-mg/d group : RR , 0.5 ; 95 % CI , 0.4 - 0.7 ) . Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture . Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly ( RR , 0.9 ; 95 % CI , 0.8 - 1.1 for both raloxifene groups combined ) . Compared with placebo , raloxifene increased bone mineral density in the femoral neck by 2.1 % ( 60 mg ) and 2.4 % ( 120 mg ) and in the spine by 2.6 % ( 60 mg ) and 2.7 % ( 120 mg ) P<0.001 for all comparisons ) . Women receiving raloxifene had increased risk of venous thromboembolus vs placebo ( RR , 3.1 ; 95 % CI , 1.5 - 6.2 ) . Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer . CONCLUSIONS In postmenopausal women with osteoporosis , raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture CONTEXT The timing of initiation of hormone therapy may influence its effect on cardiovascular disease . OBJECTIVE To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began . DESIGN , SETTING , AND PARTICIPANTS Secondary analysis of the Women 's Health Initiative ( WHI ) r and omized controlled trials of hormone therapy in which 10,739 postmenopausal women who had undergone a hysterectomy were r and omized to conjugated equine estrogens ( CEE ) or placebo and 16,608 postmenopausal women who had not had a hysterectomy were r and omized to CEE plus medroxyprogesterone acetate ( CEE + MPA ) or placebo . Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998 . MAIN OUTCOME MEASURES Statistical test for trend of the effect of hormone therapy on coronary heart disease ( CHD ) and stroke across categories of age and years since menopause in the combined trials . RESULTS In the combined trials , there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 370 [ corrected ] cases of CHD and 239 cases of stroke in the placebo group . For women with less than 10 years since menopause began , the hazard ratio ( HR ) for CHD was 0.76 ( 95 % confidence interval [ CI ] , 0.50 - 1.16 ) ; 10 to 19 years , 1.10 ( 95 % CI , 0.84 - 1.45 ) ; and 20 or more years , 1.28 ( 95 % CI , 1.03 - 1.58 ) ( P for trend = .02 ) . The estimated absolute excess risk for CHD for women within 10 years of menopause was -6 per 10,000 person-years ; for women 10 to 19 years since menopause began , 4 per 10,000 person-years ; and for women 20 or more years from menopause onset , 17 per 10,000 person-years . For the age group of 50 to 59 years , the HR for CHD was 0.93 ( 95 % CI , 0.65 - 1.33 ) and the absolute excess risk was -2 per 10,000 person-years ; 60 to 69 years , 0.98 ( 95 % CI , 0.79 - 1.21 ) and -1 per 10,000 person-years ; and 70 to 79 years , 1.26 ( 95 % CI , 1.00 - 1.59 ) and 19 per 10,000 person-years ( P for trend = .16 ) . Hormone therapy increased the risk of stroke ( HR , 1.32 ; 95 % CI , 1.12 - 1.56 ) . Risk did not vary significantly by age or time since menopause . There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women ( HR of 0.70 for 50 - 59 years ; 1.05 for 60 - 69 years , and 1.14 for 70 - 79 years ; P for trend = .06 ) . CONCLUSIONS Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause , but this trend test did not meet our criterion for statistical significance . A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause . These data should be considered in regard to the short-term treatment of menopausal symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00000611 To determine whether the combined contraceptive pill used intravaginally was as effective as the st and ard conjugated estrogen cream for the treatment of urogenital symptoms in postmenopausal Thai women AIMS This is the first study design ed to describe the natural history of stress urinary incontinence ( SUI ) and overactive bladder ( OAB ) , using vali date d symptom syndrome severity scores developed for the purpose . METHODS Two separate but related studies were involved , ( i ) a clinic sample ( N = 2,052 ) from a r and omised controlled trial ( RCT ) and ( ii ) a prospect i ve cohort study ( N = 12,750 ) with 3-year follow-up . Subjects in both studies were women aged 40 or more living in the community , approached using similar postal question naires . Severity scores using st and ardised urinary symptoms were derived for SUI and OAB from weightings obtained from logistic regression models of symptoms in relation to urodynamic diagnosis . Symptom severity scores were plotted for baseline and 3 years of follow-up to demonstrate the natural history of the main categories of SUI and OAB . RESULTS Overactive bladder and SUI syndrome severity scores showed good criterion validity in relation to relevant clinical measures and good test-retest reliability . OAB severity increased progressively with age including a period of accelerated increase in the 60s . In contrast , SUI severity showed two age-related peaks around age 60 and again at age 80 . SUI severity also showed a more fluctuating pattern from year to year compared to OAB . CONCLUSIONS Contrasting patterns of natural history for OAB and SUI syndromes were identified consistent with differences in the patterns of related co-morbidities . Further studies are needed to confirm these findings Purpose To assess the effects of the combination of pelvic floor rehabilitation and intravaginal estriol administration on stress urinary incontinence ( SUI ) , urogenital atrophy and recurrent urinary tract infections in postmenopausal women . Methods Two-hundred-six postmenopausal women with urogenital aging symptoms were enrolled in this prospect i ve r and omized controlled study . Patients were r and omly divided into two groups and each group consisted of 103 women . Subjects in the treatment group received intravaginal estriol ovules , such as 1 ovule ( 1 mg ) once daily for 2 weeks and then 2 ovules once weekly for a total of 6 months as maintenance therapy plus pelvic floor rehabilitation . Subjects in the control group received only intravaginal estriol in a similar regimen . We evaluated urogenital symptomatology , urine cultures , colposcopic findings , urethral cytologic findings , urethral pressure profiles and urethrocystometry before , as well as after 6 months of treatment . Results After therapy , the symptoms and signs of urogenital atrophy significantly improved in both groups . 61/83 ( 73.49 % ) of the treated patients , and only 10/103 ( 9.71 % ) of the control patients referred a subjective improvement of their incontinence . In the patients treated by combination therapy with estriol plus pelvic floor rehabilitation , we observed significant improvements of colposcopic findings , and there were statistically significant increases in mean maximum urethral pressure ( MUP ) , in mean urethral closure pressure ( MUCP ) , as well as in the abdominal pressure transmission ratio to the proximal urethra ( PTR ) . Conclusions Our results showed that combination therapy with estriol plus pelvic floor rehabilitation was effective and should be considered as a first-line treatment for symptoms of urogenital aging in postmenopausal women OBJECTIVES To investigate the efficacy and tolerability of a continuously applied 7-day-Estradiol patch ( Fem7 , Merck KGaA , Germany ) delivering 50 microg estradiol per day in the treatment of hysterectomized women with postmenopausal complaints compared with placebo . DESIGN A multicentre , r and omized , double-blind study with an initial screening phase ( phase I ) , a 3-month double-blind placebo-controlled phase ( phase II ) and a 3-month open follow-up phase ( phase III ) . METHODS 186 patients were r and omized for a 3-cycle placebo-controlled study followed by a 3-cycle open follow-up ( total duration ; 6 months ) . The changes in Kupperman Index ( primary efficacy variable ) , hot flushes and urogenital symptom score were studied from baseline to the end of the study . In addition , skin tolerability was assessed and patients were also asked to grade the subjective acceptance of therapy . RESULTS A reduction in Kupperman Index was observed in both groups , and at each cycle of the placebo-controlled treatment phase the 7-day-Estradiol patch was superior compared with placebo ( last value vs. baseline P = 0.0006 ) . From the second treatment week onwards a distinct difference was noted in the reduction of hot flushes from baseline between the 7-day-Estradiol patch group and the placebo group . The difference between the groups was statistically significant for each cycle and at the end of the controlled treatment phase ( mean weekly hot flush reduction at the end of the placebo-controlled treatment phase : -32.5 for the 7-day-Estradiol patch vs. -22.0 for placebo , P = 0.0025 ) . The efficacy of the 7-day-Estradiol patch within the application period did not show any difference between days 1 - 3 and 4 - 7 . Subjective acceptance of the 7-day-Estradiol patch was good and 72.4 % of patients who took active medication throughout the study were willing to consider continuing its use . CONCLUSIONS The 7-day-Estradiol patch is well tolerated and provides effective relief of moderate to severe vasomotor symptoms in hysterectomized women , with a rapid onset of action and 7-day duration of therapeutic effect . Although a placebo effect was observed , the 7-day-Estradiol patch significantly reduced hot flushes and other menopausal symptoms throughout the application period BACKGROUND Recurrent urinary tract infections are a problem for many postmenopausal women . Estrogen replacement restores atrophic mucosa , lowers vaginal pH , and may prevent urinary tract infections . METHODS We enrolled 93 postmenopausal women with a history of recurrent urinary tract infections in a r and omized , double-blind , placebo-controlled trial of a topically applied intravaginal estriol cream . Midstream urine cultures were obtained at enrollment , monthly for eight months , and whenever urinary symptoms occurred . Vaginal cultures and pH measurements were obtained at entry and after one and eight months . The women were assigned to receive either estriol ( n = 50 ) or placebo ( n = 43 ) , both administered intravaginally ; 36 and 24 , respectively , completed the eight months of follow-up . RESULTS The incidence of urinary tract infection in the group given estriol was significantly reduced as compared with that in the group given placebo ( 0.5 vs. 5.9 episodes per patient-year , P < 0.001 ) . Survival analysis showed that more of the women in the estriol group than in the placebo group remained free of urinary tract infection ( P < 0.001 ) . Lactobacilli were absent in all vaginal cultures before treatment and reappeared after one month in 22 of 36 estriol-treated women ( 61 percent ) but in none of the 24 placebo recipients ( P < 0.001 ) . With estriol the mean vaginal pH declined from 5.5 to 3.8 ( P < 0.001 ) , whereas there was no significant change with placebo . The rate of vaginal colonization with Enterobacteriaceae fell from 67 percent to 31 percent in estriol recipients but was virtually unchanged ( from 67 to 63 percent ) in the placebo recipients ( P < 0.005 ) . Side effects were minor , but caused 10 estriol recipients ( 28 percent ) and 4 placebo recipients ( 17 percent ) to discontinue treatment . CONCLUSIONS The intravaginal administration of estriol prevents recurrent urinary tract infection in postmenopausal women , probably by modifying the vaginal flora Objective To investigate the effect of hormone replacement therapy on post‐menopausal urinary stress incontinence Objective : The aim of this study was to compare the efficacy of the ultralow-dose estradiol vaginal ring with that of oral oxybutynin in the treatment of overactive bladder in postmenopausal women . Methods : Postmenopausal women with an overactive bladder were recruited from the general gynecology clinic . Participants were r and omized to receive either the ultralow-dose estradiol vaginal ring or oral oxybutynin for 12 weeks . The primary outcome was a decrease in the number of voids in 24 hours . The secondary outcomes were quality -of-life question naires , vaginal pH levels , and vaginal maturation index . Results : Fifty-nine women were enrolled . Thirty-one were r and omized to receive oxybutynin , whereas 28 received the estradiol vaginal ring . Women who received oxybutynin had a mean decrease of 3.0 voids per day , and women who received the vaginal ring had a mean decrease of 4.5 voids per day , with no significant difference between the groups . There was a significant improvement in Urogenital Distress Inventory and Incontinence Impact Question naire scores in both groups , with no significant difference in improvement between the two groups . Conclusions : Ultralow-dose estradiol-releasing vaginal ring and oral oxybutynin seem to be similarly effective in decreasing the number of daily voids in postmenopausal women with overactive bladder OBJECTIVE : To estimate the effect of 3 years of treatment with raloxifene on urinary incontinence in postmenopausal women . METHODS : We used measures of urinary incontinence severity , frequency , and type in the Multiple Outcomes of Raloxifene trial , a multicenter r and omized , controlled trial of women who were at least 2 years postmenopausal with osteoporosis . At 10 U.S. sites of this trial , 963 women r and omly assigned to raloxifene or placebo completed question naires about incontinence at baseline and 3 years later . We analyzed the odds of worsening severity and frequency of incontinence and type of incontinence after 3 years of treatment with raloxifene . RESULTS : The mean age of our subjects was 68.3 ± 7 years . After 3 years of treatment , there was no significant difference between raloxifene and placebo groups in urinary incontinence severity ( multivariable odds ratio [ OR ] 1.02 ; 95 % [ CI ] 0.78 , 1.34 ) . The majority of the women ( 60 % ) had no change in urinary incontinence episodes from baseline to year 3 . The odds of worsening urinary incontinence severity after 3 years of raloxifene treatment were 1.05 ( 95 % CI 0.75 , 1.48 ) . Similarly , the odds of developing new onset incontinence were 0.95 ( 95 % CI 0.59 , 1.52 ) . Finally , raloxifene did not effect the odds of having stress ( OR 1.01 ; 95 % CI 0.71 , 1.43 ) or urge ( OR 1.20 ; 95 % CI 0.86 , 1.68 ) incontinence after 3 years of use . CONCLUSION : In postmenopausal women with osteoporosis , 3 years of treatment with raloxifene had no effect on urinary incontinence . LEVEL OF EVIDENCE : AIM Previous clinical studies suggest hormone replacement therapy ( HRT ) alleviates menopausal symptoms and may improve health-related quality of life ( HRQL ) . Most studies on HRT and HRQL were limited in duration ( 12 months or less ) and scope ( few and non-st and ard HRQL measures ) . The aim of this paper is to assess HRQL in the Estrogen Replacement and Atherosclerosis ( ERA ) trial . METHODS A subset of women within a r and omized , blinded , placebo-controlled secondary prevention trial has been studied in outpatient and community setting s at 5 US sites . A total of 246 postmenopausal women with angiographically documented heart disease ( mean age 66 years , 83 % Caucasian ) were enrolled in the ERA trial . Participants received either 0.625 mg/day conjugated equine estrogen only , estrogen plus 2.5 mg/day medroxyprogesterone acetate , or placebo . HRQL was assessed using vali date d question naire instruments at baseline and follow-up ( mean 3.2 years of trial ) . Physical and mental functioning , life satisfaction , depressive symptoms , urinary incontinence , sleep disturbance , and frequency and intensity of physical symptoms were evaluated . RESULTS In this group of women with established coronary disease , active therapy was not significantly associated with more favorable outcomes for any HRQL . The estrogen-only group reported more urinary incontinence than the placebo group ( p<0.05 ) . Analyses restricted to adherent women ( those who took > or = 80 % of pills ) showed a similar pattern of results , showing that the estrogen only group reported significantly higher urinary incontinence compared to placebo ( p<0.01 ) . CONCLUSION The hormone replacement regimens in the ERA trial did not improve HRQL of postmenopausal women with heart disease The Heart and Estrogen/progestin Replacement Study ( HERS ) is a r and omized , double-blind , placebo-controlled trial design ed to test the efficacy and safety of estrogen plus progestin therapy for prevention of recurrent coronary heart disease ( CHD ) events in women . The participants are postmenopausal women with a uterus and with CHD as evidence d by prior myocardial infa rct ion , coronary artery bypass graft surgery , percutaneous transluminal coronary angioplasty , or other mechanical revascularization or at least 50 % occlusion of a major coronary artery . Between February 1993 and September 1994 , 20 HERS centers recruited and r and omized 2763 women . Participants ranged in age from 44 to 79 years , with a mean age of 66.7 ( SD 6.7 ) years . Most participants were white ( 89 % ) , married ( 57 % ) , and had completed high school or some college ( 80 % ) . As expected , the prevalence of coronary risk factors was high : 62 % were past or current smokers , 59 % had hypertension , 90 % had serum LDL-cholesterol of 100 mg/dL or higher , and 23 % had diabetes . Each woman was r and omly assigned to receive one tablet containing 0.625 mg conjugated estrogens plus 2.5 mg medroxyprogesterone acetate daily or an identical placebo . Participants will be evaluated every 4 months for an average of 4.2 years for the occurrence of CHD events ( CHD death and nonfatal myocardial infa rct ion ) . We will also assess other major CHD endpoints , including revascularization and hospitalization for unstable angina . The primary analysis will compare the rate of CHD events in women assigned to active treatment with the rate in those assigned to placebo . The trial was design ed to have power greater than 90 % to detect a 35 % reduction in the incidence of CHD events , assuming a 50 % lag in effect for 2 years and a 5 % annual event rate in the placebo group . The design , analysis , and conduct of the study are controlled by the Steering Committee of Principal Investigators and coordinated at the University of California , San Francisco . HERS is the largest trial of any intervention to reduce the risk of recurrent CHD events in women with heart disease and is the first controlled trial to seek evidence of the efficacy and safety of postmenopausal hormone therapy to prevent recurrent CHD events Objective : Determine the effect of raloxifene or estrogen , as compared with placebo , on the reporting of urinary incontinence in postmenopausal women participating in an osteoporosis prevention trial . Design : The current analysis is based on adverse event data that were collected as part of a double-blind , r and omized , placebo-controlled trial design ed to assess the efficacy and safety of raloxifene for osteoporosis prevention in postmenopausal women . Women were 40 to 60 years of age at study entry and had a prior hysterectomy . A total of 619 women were r and omized to placebo , raloxifene 60 or 150 mg/d , or conjugated equine estrogen 0.625 mg/d and followed for up to 3 years . Urinary incontinence was self-reported and rated by participants as " mild , " " moderate , " or " severe . " Results : The prevalence of urinary incontinence as reported by patients at baseline was similar across treatment groups ( 3 % to 6 % , P = 0.46 ) . During 3 years of follow-up , new or worsening urinary incontinence was reported with the following frequency : placebo ( 1.3 % ) , raloxifene 60 mg/d ( 0.7 % ) , raloxifene 150 mg/d ( 0.6 % ) , and conjugated equine estrogen ( 7.0 % ) . The percentage of estrogen subjects reporting urinary incontinence was significantly greater than that for placebo and both doses of raloxifene ( P ≤ 0.02 ) . Conclusion : During 3 years of follow-up , conjugated equine estrogen was associated with an increased incidence of reports of urinary incontinence in women with a prior hysterectomy and this was significantly greater than both placebo and raloxifene Objective We evaluated the relationship between annually measured serum endogenous estradiol and the development or worsening of stress and urge incontinence symptoms during a period of 8 years in women transitioning through menopause . Methods This is a longitudinal analysis of women with incontinence in the Study of Women ’s Health Across the Nation , a multicenter , multiracial/ethnic prospect i ve cohort study of community-dwelling women transitioning through menopause . At baseline and at each of the eight annual visits , the Study of Women ’s Health Across the Nation elicited the frequency and type of incontinence using a self-administered question naire and drew a blood sample on days 2 to 5 of the menstrual cycle . All endocrine assays were performed using a double-antibody chemiluminescent immunoassay . We analyzed the data using discrete Cox survival models and generalized estimating equations with time-dependent covariates . Results Estradiol levels drawn at either the annual visit concurrent with or previous to the first report of incontinence were not associated with the development of any ( hazard ratio , 0.99 ; 95 % CI , 0.99 - 1.01 ) , stress , or urge incontinence in previously continent women . Similarly , estradiol levels were not associated with the worsening of any ( odds ratio , 1.00 ; 95 % CI , 0.99 - 1.01 ) , stress , or urge incontinence in incontinent women . The change in estradiol levels from one year to the next was also not associated with the development ( hazard ratio , 0.98 ; 95 % CI , 0.97 - 1.00 ) or worsening ( odds ratio , 1.03 ; 95 % CI , 0.99 - 1.05 ) of incontinence . Conclusions We found that annually measured values and year-to-year changes in endogenous estradiol levels had no effect on the development or worsening of incontinence in women transitioning through menopause The use of oestrogens in the treatment of genuine stress incontinence was assessed by a double‐blind prospect i ve trial in 36 postmenopausal women with genuine stress incontinence who received 3 months of cyclical treatment with either piperazine oestrone sulphate or a matching placebo . Patients were assessed subjectively and objective ly before and after treatment by 7‐day bladder charts , urethral pressure profiles ( UPP ) , the Urilos nappy test , vaginal cytology and hormone assays ( plasma oestrogens and gonadotrophins ) . There was no statistical difference in the subjective response to treatment between the two groups . After 6 weeks of treatment there was a greater reduction in the number of pad changes/24 h in the oestrogen‐treated patients that approached statistical significance but , because of a marked response in the placebo group , this difference was not significant after 3 months of treatment . There were also no significant differences between the two groups with respect to the UPP or Urilos measurements but the vaginal cytology and hormone profiles were significantly affected by oestrogens . In view of the possible risks of oestrogen therapy its use in genuine stress incontinence is limited OBJECTIVE To examine the effects of oral estrogen/progestin on incontinence and related lower urinary tract conditions among female nursing home ( NH ) residents . DESIGN R and omized placebo-controlled trial . SETTING Five NHs . PARTICIPANTS Thirty-two incontinent female residents of average age 88 . MEASUREMENTS Subjects were r and omized to receive either oral estrogen ( 0.625 mg ) combined with progesterone ( 2.5 mg ) or placebo , daily for 6 months . Measures of incontinence severity , the clinical appearance of the vagina , vaginal and urethral cytology , and urine and vaginal cultures were made at baseline , 3 months , and 6 months . In addition to active drug or placebo , all subjects received regular toileting assistance ( prompted voiding ) by trained research aides during 3-day data - collection periods to compensate for mobility and cognitive impairments . RESULTS At 3 and 6 months there were no significant differences between the groups in the severity of incontinence , the prevalence of bacteriuria , or the results of vaginal cultures . Several clinical findings associated with atrophic vaginitis improved more in the active than the placebo group and vaginal pH and vaginal and urethral cytology exhibited a partial estrogenic effect . CONCLUSIONS Our results must be interpreted with caution because of the size and the select nature of our subject sample . Up to 6 months of oral estrogen had only a partial estrogenic effect on vaginal and urethral epithelium and no clinical effects in this patient population . We believe that future studies of estrogen for urinary incontinence in frail NH residents should utilize a topical preparation and consider targeting urinary tract infection as an additional outcome measure OBJECTIVE To investigate whether patients who were treated with TVT-O procedure for urodynamic stress incontinence had a significant improvement in their urodynamic findings and their post-operative symptoms ( frequency , urgency , nocturia ) if they were treated post-operatively with vaginal oestradiol for 6 months compared to the non-treated group . METHODS Prospect i ve r and omised study . 190 patients were asked to participate in our study . Finally , a total of 92 patients in group 1 and 91 patients in group 2 completed the study . In group 1 , which was the treatment group , patients having the TVT-O procedure for urodynamic stress incontinence were instructed to use post-operatively oestradiol tablets , 25 micrograms ( Vagifem , Novo Nordisk ) vaginally , once daily , nocte , for 2 weeks and then twice weekly for 6 months . The patients in group 2 ( control group ) had the TVT-O procedure only . All patients were review ed in 2 months and again in 6 months time . RESULTS There was no statistically significant difference between the two groups concerning pre-operative and post-operative haemoglobin , operative time , hospital stay or return to work . The within group analysis did not show significant differences between pre-operative and post-operative urodynamic data in both groups . Patients treated with vaginal estradiol post-operatively showed a statistically significant reduction in relation to the symptoms of urgency and frequency but not in relation to nocturia and urge incontinence compared to the non-treated group . There is no difference in relation to the efficacy of TVT-O procedure between the groups at 6 months follow-up . CONCLUSION It appears that vaginal oestradiol treatment could be offered to postmenopausal patients after a TVT-O procedure having the symptoms of frequency and urgency provided they are aware of the lack of evidence regarding long term benefit BACKGROUND Although many studies have assessed the effects of estrogen and raloxifene hydrochloride on bone mineral density and serum lipid concentrations , there are few direct comparative data . METHODS R and omized placebo-controlled trial for 3 years , intention-to-treat analysis . Six hundred nineteen postmenopausal women with prior hysterectomy ( mean age , 53.0 years ) were studied in 38 centers in Europe , North America , Australasia , and South Africa . They were r and omized to 60 mg/d or 150 mg/d of raloxifene , 0.625 mg/d of conjugated equine estrogen ( CEE ) , or placebo . Bone density of the lumbar spine and proximal femur , biochemical markers of bone turnover , and fasting serum lipid concentrations were assessed for 3 years . RESULTS Compared with baseline , bone density in the lumbar spine progressively declined by 2.0 % in the placebo group ( P < .05 ) , was stable in the 2 raloxifene groups , and increased 4.6 % in the subjects receiving CEE ( P < .001 ) . Effects in both raloxifene groups were different from those observed in the CEE and placebo groups ( P < .001 ) . Bone density in the total hip showed similar results . Conjugated equine estrogen produced significantly greater depression of serum osteocalcin , bone-specific alkaline phosphatase , and urine C-telopeptide , compared with raloxifene . Each of the active treatments caused comparable depression of low-density lipoprotein cholesterol below placebo levels ( P < .001 at most time points ) . Raloxifene did not affect high-density lipoprotein cholesterol , whereas CEE increased it by 13.4 % compared with placebo at 3 years ( P < .001 ) . Triglyceride concentrations increased 24.6 % in the CEE group at 3 years ( P < .003 ) , a significantly greater change than in the raloxifene groups , which were 4.9 % and 8.0 % above baseline ( P < or = .002 ) but not different from placebo . Urinary incontinence was reported in 11 women receiving CEE , but in only 1 or 2 in each of the other groups ( P < or = .01 compared with the other groups ) . Hernias occurred less frequently in those receiving 150 mg/d of raloxifene or CEE ( P = .03 vs placebo ) . CONCLUSIONS Raloxifene and CEE have beneficial effects on bone density and bone turnover , although effects of CEE are more marked . Raloxifene and CEE produce different patterns of lipid responses and have distinct adverse effect profiles OBJECTIVE : To estimate the effect of hormone therapy on risk of stress and urge urinary incontinence . METHODS : The Heart Estrogen/progestin Replacement Study was a r and omized , placebo-controlled , double-blinded trial to evaluate daily oral conjugated estrogen ( 0.625 mg ) plus medroxyprogesterone acetate ( 2.5 mg ) therapy for the prevention of heart disease events in women with established heart disease . The 1,208 participants in Heart Estrogen/progestin Replacement Study who reported no loss of urine in the previous 7 days at baseline are included in this analysis . RESULTS : During 4.2 years of treatment , 64 % of women r and omly assigned to hormone therapy compared with 49 % of those assigned to placebo reported weekly incontinence ( P < .001 ) . The higher risk of incontinence in the hormone group was evident at 4 months , persisted throughout the treatment period , and was independent of the age of the women . The odds ratios for weekly incontinence among women on hormone therapy compared with placebo were 1.5 for urge incontinence ( 95 % confidence interval [ CI ] 1.2–1.8 ; P < .001 ) and 1.7 for stress incontinence ( 95 % CI 1.5–2.1 ; P < .001 ) . Four years of treatment with hormone therapy caused an excess risk of 12 % for weekly urge incontinence and 16 % for weekly stress incontinence ; the corresponding numbers needed to harm were 8.6 ( 95 % CI 5.8–16.6 ) and 6.2 ( 95 % CI 4.6–9.4 ) . CONCLUSION : Estrogen plus progestin therapy increases risk of urge and stress incontinence within 4 months of beginning treatment . LEVEL OF EVIDENCE : Aims The major aims of the study were to compare the safety of a continuous low-dose estradiol-releasing vaginal ring ( ESTring ) to that of a vaginal estradiol tablet ( Vagifem ® ) on the endometrium and the relief of subjective symptoms and signs of urogenital estrogen deficiency . Quality of life and acceptability of treatment delivery were also assessed . Study design A prospect i ve , r and omized study in which women were assigned in a 2 : 1 ratio to ESTring and Vagifem and followed for 12 months . The primary endpoint was endometrial safety , based on the results of ultrasound measurement of endometrial thickness and a progestogen challenge test at baseline and week 48 . Efficacy was determined by subjective assessment of urogenital estrogen deficiency symptoms at baseline and weeks 3 , 12 , 24 , 36 and 48 and assessment of signs of vaginal epithelial atrophy by the clinician at baseline , 12 and 48 weeks . In addition , pelvic floor strength , vaginal cytological evaluation and pH , bacteruria and patient acceptability were assessed . Quality of life was assessed using a menopause-specific quality -of-life question naire and a 2-day bladder diary at baseline and 12 and 48 weeks . The comparability of the two groups was assessed using ANOVA , χ2 or Fisher 's exact tests . Results A total of 126 women were r and omized to ESTring and 59 to Vagifem . There was no statistical difference between the groups in the alleviation of symptoms and signs of urogenital estrogen deficiency . Maturation indices increased in both groups , from generally atrophic at baseline to proliferative or highly proliferative at 48 weeks . After 48 weeks of treatment , there was no statistically significant difference in endometrial thickness between the two groups . A statistically smaller proportion of bleeding/spotting occurred in the ESTring group ( n = 0 ) compared to the Vagifem users ( n = 4 ) . Estradiol and total estrone serum levels increased during treatment in both groups but remained within the normal postmenopausal range . General health status in both groups was unchanged but the urogenital component of health burden was significantly improved in both groups . Bladder diary variables showed no differences between treatment groups . Conclusion Equivalent endometrial safety and efficacy in the relief of the symptoms and signs of urogenital estrogen deficiency were demonstrated for the 12 months ' use of a low-dose estradiol-releasing vaginal ring and a vaginal estradiol tablet Objective : To test the usefulness of urodynamic examination in female urinary incontinence . Material and Methods : As part of a population -based , r and omized , controlled treatment study in general practice , the control group was offered urodynamic examination before and after delayed treatment starting 6 months after inclusion in the study , i.e. after the first outcome evaluation comparing the initially treated group with the control group . The intervention group was offered urodynamic examination only after the final outcome evaluation at 12 months . Eighty-seven women , aged 50 - 74 , from three Norwegian municipalities participated . Results : There was no difference in treatment outcome whether the patients had urodynamic examination or not . Eleven patients ( 26 % of 42 control patients ) had their diagnosis revised after urodynamic examination , ten of them with a subsequent change in treatment . The outcome for this group was no different than for the other patients . As a subgroup , the 11 patients had more severe leakage ( p = 0.048 ) and more previous gynecological operations ( p = 0.038 ) than the other control group patients . Conclusions : Our study supports the idea that in general practice , or in rather unselected patients , women with urinary incontinence may be classified and treated without urodynamic examination . If there is little or no improvement during the first few months referral should be considered , and this should be done sooner for patients with severe incontinence or prior gynecological operations than for other patients OBJECTIVE To assess the effect of vulvovaginal estrogen on mucocutaneous sensory threshold and circumvaginal motor strength . METHODS Thirty-nine postmenopausal , hypoestrogenic women with mixed lower-genitourinary-tract complaints were placed in four masked treatment arms by permuted-block r and omization for 6 weeks . One group received topical estradiol ( E2 ) cream and pelvic muscle biofeedback training , the second received topical E2 cream and sham biofeedback , the third received placebo cream and pelvic muscle biofeedback training , and the fourth received placebo cream and sham biofeedback . Circumvaginal muscle strength was measured by averaging maximum intravaginal pressure ( mmHg ) generated over a set of four pelvic muscle contractions . Absolute changes in von Frey threshold ( mN ) and maximum intravaginal pressure ( mmHg ) over 4 and 6 weeks were reported as summary measures . Of 39 subjects , 30 completed the study . RESULTS Topical estradiol cream significantly improved mechanical sensitivity of the vulvar vestibule to von Frey hairs , a -1.2-mN threshold decrease at 4 weeks ( F = 10.29 ; P = .004 ) , and a -1.6-mN threshold decrease at 6 weeks ( F = 8.24 ; P = .009 ) compared with placebo cream . Stratification by age showed significantly greater improvement in mechanical sensitivity in the older ( 70 - 79 years ) age group r and omized to estrogen cream and a -5.49-mN threshold reduction ( F = 17.65 ; P = .002 ) . Maximum intravaginal pressures during circumvaginal muscle contraction did not differ between estrogen and placebo cream users ( F = 0.00 ; P = .99 ) . CONCLUSION Improved sensation to mechanical stimuli can result from a rapidly acting , direct effect of topical E2 cream on the vulvar vestibule OBJECTIVE To assess the effects of hormone therapy on urinary tract infection frequency and to examine potential risk factors . METHODS We used data from the Heart and Estrogen/ Progestin Replacement Study , a r and omized , blinded trial of the effects of hormone therapy on coronary heart disease events among 2763 postmenopausal women aged 44–79 with established coronary heart disease . Participants were r and omly assigned to 0.625 mg of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate or placebo and followed for a mean of 4.1 years . History of physician‐diagnosed urinary tract infections and risk factors were assessed by self‐report at baseline and each annual visit . RESULTS Urinary tract infection frequency was higher in the group r and omized to hormone treatment , although the difference was not statistically significant ( odds ratio [ OR ] 1.16 , 95 % confidence interval [ CI ] 0.99 , 1.37 ) . Statistically significant risk factors for urinary tract infections in multivariable analysis included : women with diabetes on treatment ( insulin OR 1.81 , 95 % CI 1.40 , 2.34 ) , oral medications OR 1.44 , 95 % CI 1.09 , 1.90 ) , poor health ( OR 1.34 , 95 % CI 1.14 , 1.57 ) , childbirth ( OR 1.38 , 95 % CI 1.00 , 1.90 ) , vaginal itching ( OR 1.63 , 95 % CI 1.07 , 2.50 ) , vaginal dryness ( OR 1.30 , 95 % CI 1.04 , 1.67 ) , and urge incontinence ( OR 1.51 , 95 % CI 1.30 , 1.75 ) . Urinary tract infections in the previous year were strongly associated with a single urinary tract infection ( OR 7.00 , 95 % CI 5.91 , 8.29 ) as well as multiple urinary tract infections ( OR 18.51 , 95 % CI 14.27 , 24.02 ) . CONCLUSIONS Oral hormone therapy did not reduce frequency of urinary tract infections . Potentially modifiable risk factors in postmenopausal women are different from those in younger women , and include diabetes , vaginal symptoms , and urge incontinence Objective . Our study was aim ed at evaluating the efficacy of therapy with promestriene , a synthetic diethyl-ether of estradiol with no distal hormonal effects , in patients undergoing surgical correction for stress urinary incontinence ( SUI ) . Material s and methods . Ninety-eight healthy , postmenopausal women , non-users of hormone replacement therapy , with a diagnosis of SUI and vulvovaginal dystrophy , were recruited and openly r and omized into two main groups . Group I ( 48 patients ) received promestriene 10 mg daily , by vaginal capsule , for 21 days before the operation . Group II ( 50 patients ) underwent the surgical procedure with TVT ( Tension-free Vaginal Tape ) directly , without pharmacological preparation . The results were collected and analyzed using SAS software ( version 8) . Results . The two groups were homogeneous in terms of age , parity and body mass index . There were no significant differences between the two groups with respect to the time required to accomplish the TVT , blood loss , length of hospital stay , blood component measurements and postoperative subjective symptoms . There were slight differences postoperatively in problems during intercourse and the appearance of new genital symptoms , but again they were not shown to be statistically significant . Conclusions . Our results , although preliminary and subjective , confirm the efficacy of remedial surgical treatment of SUI with TVT . Preoperative administration of promestriene seems to favor trophism and vascularization of the whole muscular and fascial support of the pelvic floor and facilitates performance of the operation , but is not supported statistically OBJECTIVES To study the effects of hormonal replacement on hot flushes , other symptoms linked to menopause , and blood pressure . METHODS The study included 1006 early postmenopausal women aged 45 - 58 years , participating in the Danish Osteoporosis Prevention Study ( DOPS ) r and omised to Hormonal replacement therapy ( HRT ) ( n=502 ) or no HRT ( n=504 ) in an open label trial . Symptom scores were recorded at baseline , after 6 month , 1 , 2 , and 5 years on a modified Greene scale ( range 0 - 4 with 0 equalling no symptoms , and 4 maximal symptoms ) . RESULTS HRT efficiently alleviated hot flushes ( mean+/-S.E.M. score 0.48+/-0.04 in HRT vs. 0.83+/-0.05 in no HRT after 5 years , P<0.01 by repeated measures ANOVA ) , sleeping difficulties associated with hot flushes ( 0.21+/-0.60 vs. 0.37+/-0.86 , P<0.01 ) , vaginal dryness ( 0.45+/-0.04 vs. 0.73+/-0.05 , P<0.01 ) , dyspareunia ( 0.27+/-0.04 vs. 0.39+/-0.04 , P<0.01 ) , and libido ( 0.48+/-0.05 vs. 0.59+/-0.05 , P=0.08 ) . In the untreated group the occurrence of mood swings ( from 0.77+/-0.05 at baseline to 0.45+/-0.04 after 5 years , 2P<0.01 ) and oedemas ( from 0.59+/-0.04 to 0.43+/-0.04 , 2P=0.02 ) decreased with age while the occurrence of incontinence increased ( from 0.43+/-0.03 to 0.52+/-0.04 , 2P<0.01 ) . These changes were not influenced by HRT . Furthermore , HRT had no influence on presence of headache ( 0.54+/-0.05 vs. 0.58+/-0.05 after 5 years ) , voiding pattern ( 0.49+/-0.04 vs. 0.53+/-0.04 ) , or blood pressure ( mean systolic pressure 123+/-18 vs. 123+/-19 , diastolic pressure 77+/-10 vs. 77+/-11 ) . CONCLUSIONS HRT is efficient in controlling hot flushes and vaginal dryness , and symptoms related to these conditions . However , no effect on blood pressure or other menopause symptoms was recorded Objective : To evaluate whether the frequency of overactive bladder ( OAB ) symptoms increases in menopause patients after a tension-free vaginal tape ( TVT ) procedure , and to determine if topical estrogen therapy can help prevent these symptoms . Design : After undergoing a preoperative assessment , enrolled patients were r and omly allocated to receive TVT plus postoperative vaginal estrogen therapy ( ET group ) or TVT without adjunctive medical treatment ( No ET group ) . The pre- and postoperative assessment s included : acquisition of a urogynecologic history with st and ardized questions regarding urinary function ( including a 10- grade visual analogue scale score ) , urogynecologic clinical examination , and urodynamic assessment . Follow-up assessment s were performed at 1 , 3 , and 6 months after surgery . Results : Fifty-six of 59 patients were evaluable ; 28 received topic vaginal estrogen after surgery ( ET group ) and 28 did not receive adjunctive medical treatment ( No ET group ) . The overall OAB syndrome rate in menopause patients ( No ET group ) was 7 % ( 2 of 28 patients ) at baseline and 32 % ( 9 of 28 patients ) 6 months after surgery ( P = 0.04 ) . At the 6-month follow-up assessment , the incidence of urinary urgency was 4 % ( 1 of 28 patients ) and 29 % ( 8 of 28 patients ) in the ET and No ET groups , respectively ( P = 0.01 ) . Differences in frequency and nocturia were not statistically significant . Analysis of the visual analogue scale scores revealed that at the 6-month follow-up assessment , urgency significantly improved in the ET group compared with the No ET group ( 0.23 ± 1.0 vs 2.30 ± 3.7 , respectively ; P = 0.02 ) . Conclusions : The TVT procedure seems to increase the frequency of OAB syndrome in menopause patients . Vaginal estriol therapy significantly reduces symptoms of urinary urgency , has a high rate of patient satisfaction , and can be used to treat postmenopausal women for at least 6 months after a TVT procedure The present investigation was performed to study the urodynamic effects of hormones on the lower urinary tract in women . Twenty‐four stress incontinent and 6 continent women were r and omly given E2 and E3 orally in doses of 4–8 mg per day for 3 weeks . Another group of 8 women were given a single i.m . injection of 1000 mg gestagen OBJECTIVE To investigate the effects of the combination of pelvic floor muscle exercise ( PFME ) and estriol on postmenopausal stress incontinence ( SI ) . STUDY DESIGN Sixty-six patients with postmenopausal SI were r and omized to a group treated with a combination of estriol ( 1 mg/d ) and PFME ( group A , n = 32 ) and a group treated with PFME alone ( group B , n = 34 ) . Efficacy was evaluated every three months based on stress scores obtained from a urinary incontinence ( UI ) question naire . RESULTS A significant decrease in stress score was observed in mild and moderate UI patients in both groups three months after the commencement of therapy ( A and B , P < .0001 ) . The therapeutic effect in group A was more prominent for up to 18 months in mild UI and for up to 12 months in moderate UI ( A vs. B , P < .05 ) . Kaplan-Meier analysis showed that the cumulative morbidity rate in mild SI patients was significantly lower in group A ( 0 % ) than in group B ( 12 % , P < .005 ) . CONCLUSION Combination therapy with estriol plus PFME was effective and is capable of serving as first-line treatment for mild SI Objective To assess the efficacy of cyclic postmenopausal hormone replacement in treating urinary incontinence in hypoestrogenic women . Methods Eighty-three hypoestrogenic women complaining of urinary incontinence were included . All patients were community-dwelling , age 45 years or older , with involuntary loss of urine occurring at least once a week and urodynamic evidence of genuine stress incontinence and /or detrusor instability . Evaluation consisted of a comprehensive clinical and urodynamic research protocol . The hypoestrogenic entry criterion was a plasma estradiol level of 30 pg/mL or less . Parabasal cells on vaginal smears were also monitored . The primary outcome was the number of incontinent episodes per week , as documented on a st and ardized urinary diary . Secondary outcomes were the quantity of fluid loss , voluntary diurnal and nocturnal micturition frequency , generic and condition-specific health-related quality of life measurements , and patient satisfaction . A r and omized , placebo-controlled , double-blind design was used . Subjects in the treatment group were given conjugated equine estrogens ( 0.625 mg ) and medroxyprogesterone ( 10 mg ) cyclically for 3 months . Controls received placebo tablets . Results ( All results are presented as mean ± st and ard deviation . ) Subjects were 67 ± 9 years old . The menopause duration was 18 ± 11 years . The duration of incontinence was 9 ± 9 years . Estradiol level at baseline was 9 ± 9 pg/mL , and the parabasal cell count was 42 ± 44 % . The number of incontinent episodes at baseline was 13 ± 10 for the treatment group and 16 ± 4 for controls . No significant changes occurred in the number of incontinent episodes after treatment : 10 ± 10 for the treatment group , and 13 ± 14 for the controls ( P = .7 ) . Also , fluid loss was not changed : 176 ± 106 g for the treatment group and 64 ± 88 g for the control group at baseline , and 101 ± 150 and 51 ± 69 g after treatment , respectively ( P = .7 ) . There were no significant differences for either diurnal or nocturnal voluntary micturition , quality of life measures , or patient 's perception of improvement . Conclusion Three-month cyclic hormone replacement therapy did not affect either clinical or quality of life variables of incontinent , hypoestrogenic women . Long-term effects are unlikely to be substantially different . The use of estrogen supplementation as preventive or adjuvant therapy was not evaluated in this study BACKGROUND To assess the effect of estriol treatment per vaginam before Burch culposuspension in postmenopausal women with stress urinary incontinence ( IUS ) . METHODS DESIGN prospect i ve r and omised study . SETTING Department of Gynaecology , Obstetrics and Physiopathology of Human Reproduction-Medical School-University of Naples Federico II . PATIENTS twenty women in postmenopause at least from five years with a urogenital symptomatology due to IUS . INTERVENTIONS women were r and omised into one of two groups ( treated or control ) and they were su bmi tted to an evaluation of vulva and vagina trophism . All the women were su bmi tted to a urodynamic examination and to a transvaginal ultrasonography with evaluation of pubis-bladder neck distance , bladder and proximal urethra position , before treatment , one week before the operation and after six months from the same operation . EVALUATIONS subjective symptomatology and urodynamic parameters between treated and control groups before and after operation . RESULTS After 12 weeks of treatment , a significant improvement of subjective symptomatology and a not significant improvement of all the urodynamic parameters in the treated group in comparison with the control group have been demonstrated , while any anatomic alteration compared with the basal hasn t been observed . After six months from the operation in all the women a significant reduction of subjective quantity of urine lost after a strain has been demonstrated and significant variations of urodynamic parameters without significant differences between treated group and control group were also observed . CONCLUSIONS The estriol treatment per vaginam is not so effective on the result of Burch culposuspension in postmenopausal women with IUS BACKGROUND Phenylpropanolamine is commonly found in appetite suppressants and cough or cold remedies . Case reports have linked the use of products containing phenylpropanolamine to hemorrhagic stroke , often after the first use of these products . To study the association , we design ed a case-control study . METHODS Men and women 18 to 49 years of age were recruited from 43 U.S. hospitals . Eligibility criteria included the occurrence of a subarachnoid or intracerebral hemorrhage within 30 days before enrollment and the absence of a previously diagnosed brain lesion . R and om-digit dialing identified two matched control subjects per patient . RESULTS There were 702 patients and 1376 control subjects . For women , the adjusted odds ratio was 16.58 ( 95 percent confidence interval , 1.51 to 182.21 ; P=0.02 ) for the association between the use of appetite suppressants containing phenylpropanolamine and the risk of a hemorrhagic stroke and 3.13 ( 95 percent confidence interval , 0.86 to 11.46 ; P=0.08 ) for the association with the first use of a product containing phenylpropanolamine . All first uses of phenylpropanolamine involved cough or cold remedies . For men and women combined , the adjusted odds ratio was 1.49 ( 95 percent confidence interval , 0.84 to 2.64 ; P=0.17 ) for the association between the use of a product containing phenylpropanolamine and the risk of a hemorrhagic stroke , 1.23 ( 95 percent confidence interval , 0.68 to 2.24 ; P=0.49 ) for the association with the use of cough or cold remedies that contained phenylpropanolamine , and 15.92 ( 95 percent confidence interval , 1.38 to 184.13 ; P=0.03 ) for the association with the use of appetite suppressants that contained phenylpropanolamine . An analysis in men showed no increased risk of a hemorrhagic stroke in association with the use of cough or cold remedies containing phenylpropanolamine . No men reported the use of appetite suppressants . CONCLUSIONS The results suggest that phenylpropanolamine in appetite suppressants , and possibly in cough and cold remedies , is an independent risk factor for hemorrhagic stroke in women Estrogen deficient women are prone to problems such as vaginal dryness , dyspareunia and a predilection to recurrent urinary tract infections and urinary incontinence . A preliminary double-blinded study in 67 symptomatic postmenopausal women confirmed : ( 1 ) that atrophic vaginitis is associated with an increase in the lateral wall vaginal pH ; ( 2 ) this is paralleled by similar changes in pH in the urethra ; ( 3 ) locally applied vaginal conjugated estrogen cream normalizes the pH in the vagina and urethra . Thus , the testing of the vaginal pH serves both as a surrogate for evaluating urethral pH and as a monitor of compliance with treatment Thirty-six postmenopausal women with objective ly verified stress incontinence were treated with oral estriol ( Triovex , 2 mg x 1 ) and phenylpropanolamine ( Kontexin , 50 mg x 2 ) alone and in combination . After an initial four-week single-blind period with phenylpropanolamine ( PPA ) , either estriol or estriol and PPA were given r and omly in four-week periods , in a crossover design . PPA and estriol in combination as well as PPA alone , raised the intraurethral pressure and significantly reduced the urinary loss by 35 per cent in a st and ardized physical strain test . In women with an initial low urethral pressure estriol also induced pressure increase . The leakage episodes and the assessed leakage amounts were significantly reduced by both estriol and PPA given separately as single treatment ( 28 % ) or when given as combined therapy ( 40 % ) . Most of the women preferred the combined treatment to either drug alone . Additive but no synergistic effects are indicated Objectives : The primary objective of the Selective estrogen Menopause And Response to Therapy 3 ( SMART-3 ) trial was to compare the efficacy and safety of two doses of bazedoxifene (BZA)/conjugated estrogens ( CE ) versus placebo for the treatment of moderate to severe vulvar/vaginal atrophy ( VVA ) associated with menopause . Methods : This was a phase 3 , multicenter , double-blind , r and omized , placebo-controlled , and active comparator-controlled study . Healthy postmenopausal women ( n = 664 ; aged 40 - 65 y ) were r and omized to BZA 20 mg/CE 0.625 mg , BZA 20 mg/CE 0.45 mg , BZA 20 mg , or placebo once daily for 12 weeks . Changes in vaginal maturation , vaginal pH , and severity of the most bothersome symptom of VVA from baseline were assessed at screening and at weeks 4 and 12 . Adverse events were recorded throughout the study . Results : BZA 20 mg/CE 0.625 or CE 0.45 mg significantly ( P < 0.01 ) increased superficial cells and decreased parabasal cells compared with placebo . Vaginal pH and most bothersome symptom significantly improved with BZA 20 mg/CE 0.625 mg compared with placebo ( P < 0.05 ) . Improvements in vaginal dryness were also observed with both BZA/CE doses ( P < 0.05 ) . The incidence of treatment-related adverse events were similar across treatment groups . Conclusions : BZA/CE is effective in treating moderate to severe VVA and vaginal symptoms . These data further support the use of a tissue-selective estrogen complex containing BZA/CE as a new menopausal therapy for postmenopausal women Abstract . One thous and two hundred women , aged 61 , r and omly selected from a defined geographical area in South Sweden , were interviewed by an anonymous question naire about their urogenital symptoms . Seventy‐five percent cooperated , of whom 29.2 % admitted to some degree of urinary incontinence and 48.8 % some degree of lower genital tract disorder . Stress incontinence symptoms were reported by 11.8 % of the women , urge incontinence by 7.9 % and both types combined—“mixed ” by 9.5 % . Four percent of all women ( 18 % of stress incontinence ) experienced a loss sufficient to necessitate the wearing of a sanitary napkin or change of under clothing several times a day . Thirteen percent had repeated urinary tract infections . Itch , discharge and smarting pain was reported by 15 % . Thirty‐eight percent had vaginal dryness and dyspareunia . Only 4 % of the women were undergoing estrogen therapy OBJECTIVE The purpose of this study was to assess the urogenital effects of raloxifene , tamoxifen , conjugated equine estrogen , and placebo in healthy postmenopausal women . STUDY DESIGN This r and omized , double-blind , placebo-controlled study compared the urogenital effects of 0.625 mg of conjugated equine estrogen ( n = 15 women ) , 20 mg of tamoxifen ( n = 14 women ) , 60 mg of raloxifene , ( n = 15 women ) , and placebo ( n = 13 women ) . Evaluations at baseline and evaluations after 20 weeks receiving the drug included a pelvic examination with cytologic evaluation of vagina and urethra , pelvic organ prolapse quantitation , and urethral axis deflection by cotton swab test ( only in patients with incontinence [ 33 % ] ) . RESULTS Conjugated equine estrogen increased the maturation value of both urethral and vaginal cytologic condition ( P = .002 , P = .032 , respectively ) . There was a decrease in vaginal maturation value in the raloxifene group ( not significant ) . Two of 8 women in the conjugated equine estrogen group showed evidence of worsening prolapse by pelvic organ prolapse quantitation ; the condition of 2 of 8 women improved . In the raloxifene , tamoxifen , and placebo groups 8 of 12 women , 4 of 13 women , and 2 of 11 women had worsening in prolapse scores , respectively , whereas none of the women had improvement . Increased cotton swab deflection was found in 3 of 5 women in the raloxifene group , in 5 of 8 women in the tamoxifen group , in 0 of 4 women in the placebo group , and in 0 of 2 women in the conjugated equine estrogen group . Seventy-five percent of the patients who received raloxifene and 60 % of the patients who received tamoxifen had increases in prolapse by any measure ( ie , pelvic organ prolapse quantitation or cotton swab or clinical assessment ) compared with 18 % of the patients in the placebo group and 22 % of the patients in the conjugated equine estrogen group ( P = .015 ) , although symptoms did not differ among groups . CONCLUSION Neither raloxifene nor tamoxifen improve cytohormonal effects in the vagina or urethra , whereas conjugated equine estrogen does . Raloxifene and tamoxifen appear to show worsening prolapse compared with conjugated equine estrogen and placebo . The clinical relevance of these effects is unknown and requires investigation UNLABELLED Oestrogen deficiency in postmenopausal women is thought to be important in the genesis of lower urinary tract symptoms , in particular the ' urge syndrome ' . Evidence to support the use of oestrogen therapy in symptomatic postmenopausal women is , however , limited . Oestriol is a weak , naturally occurring oestrogen that may be beneficial to the urogenital tissues without stimulating the endometrium . We have investigated the use of oestriol in the treatment of postmenopausal sensory and motor urge incontinence . MATERIAL S AND METHODS A double-blind , placebo-controlled , r and omised , multicentre study of 3 mg oral oestriol/day for 3 months in the treatment of women with urge incontinence was undertaken . RESULTS AND CONCLUSIONS Sixty-four women were recruited into the study . Although oestriol produced both subjective and objective improvement in lower urinary tract function , it was not significantly better than placebo . Some of the difficulties of running a multicentre study were encountered |
13,226 | 29,945,924 | Results There is considerable inter- and intra-individual variation in the absorption and metabolism of COCs .
This risk increases in typical users whenever the CFI is prolonged : late restarts are a common reason for pill omissions .
Shortening or eliminating the CFI improves contraceptive efficacy using the lowest doses available , without evidence to date of compromised safety .
Conclusions There is no scientific evidence to support a 7-day CFI and it should be replaced either by a continuous flexible regimen , or extended regimens with a shortened CFI , prescribed first-line .
In women preferring a monthly ‘ bleed ’ , a 4-day CFI similarly provides a greater safety margin when pills are omitted | Aim This review summarises the available data on the disadvantages of the 7-day contraceptive-free interval ( CFI ) of combined oral contraceptives ( COCs ) , in contrast to shorter CFIs or continuous use – including flexible regimens – and provides recommendations for practice .
Even with perfect use , the loss of endocrine suppression during the st and ard 7-day CFI allows follicular development with the risk of escape ovulation in a vulnerable minority . | BACKGROUND This study was conducted to compare ovarian activity of an oral contraceptive containing drospirenone ( drsp ) 3 mg plus ethinylestradiol ( EE ) 20 mcg administered in 24/4 regimen compared with the conventional 21/7 regimen , during intended use and following predefined dosing errors . STUDY DESIGN Women aged 18 - 35 years who ovulated or had a follicular diameter of > or=15 mm on or before Day 23 during a pretreatment cycle were admitted into this double-blind , r and omized study . Participants underwent 3 treatment cycles with drsp 3 mg/EE 20 mcg in a 24/4 ( n=52 ) or a 21/7 ( n=52 ) regimen . In the third treatment cycle , the initial three pills in both groups were replaced with placebos . Ovarian activity was classified using the Hoogl and scale during pretreatment and during Cycles 2 and 3 . RESULTS Suppression of ovarian activity was more pronounced with the 24/4 regimen -- the odds ratio for a lower Hoogl and score ( i.e. , greater ovarian suppression ) with the 24/4 regimen compared with the conventional 21/7 regimen were 6.01 ( 95 % CI : 2.29 - 17.94 ) and 3.06 ( 95 % CI : 1.44 - 6.65 ) for Cycles 2 and 3 , respectively . More women in the 24/4 regimen group had no ovarian activity 87.8 % vs. 56.0 % during Cycle 2 and 55.1 % vs. 30.0 % during Cycle 3 . The 24/4 regimen was associated with a more consistent suppression ( less fluctuation ) of endogenous estradiol . CONCLUSION The drsp 3 mg/EE 20 mcg oral contraceptive in a 24/4 regimen was associated with greater ovarian suppression ( despite intentional dosing error ) , which results in decreased hormonal fluctuations , and may increase contraceptive efficacy with the low-dose formulation OBJECTIVE : To estimate whether women receiving daily text-message reminders have increased oral contraceptive pill adherence compared with women not receiving reminders . METHODS : This r and omized controlled trial estimated whether there was an effect of daily text-message reminders on oral contraceptive pill adherence of new oral contraceptive pill users . Pill-taking was tracked for 3 months by an electronic monitoring device with wireless data collection . During the study period , participants assigned the intervention received a daily reminder text message . Eighty-two women were assigned r and omly to detect a 1.6±2.0 pill difference ( 90 % power , 5 % & agr ; , 15 % dropout ) . RESULTS : Participants were 79 % white , non-Hispanic , 99 % high school graduates , and 99 % nulliparous with a mean age of 22 years . Most reported condom use with past coital activity , and more than half reported prior emergency contraception use . The mean number of missed pills per cycle did not differ significantly between the groups : 4.9±3.0 for the text-message group and 4.6±3.5 for the control group ( P=.60 ) . The number of missed pills per cycle increased over the course of the study , but this pattern did not increase differentially between the groups . Adherence recorded by the electronic monitoring device indicated much poorer adherence than that recorded by patient diaries . Despite poor pill-taking , there were no pregnancies . CONCLUSION : Daily text-message reminders did not improve oral contraceptive pill adherence . Although the lack of benefit may be attributed to the frequent use of alternative reminder systems in the control group , the rate of missed pills when measured objective ly was still very high in both groups . CLINICAL TRIAL REGISTRATION : Clinical trials.gov , www . clinical trials.gov , NCT00733707 . LEVEL OF EVIDENCE : OBJECTIVE To compare ovulation inhibition and ovarian activity with 21-day and 24-day regimens of a low-dose combined oral contraceptive ( COC ) containing 60 microg of gestodene and 15 microg of ethinyl estradiol . DESIGN Interventional observational study . SETTING Reproductive medicine unit . PATIENT(S ) Fifty-eight healthy volunteers aged 18 - 35 years . INTERVENTION(S ) Ovarian activity was monitored every other day with the use of ultrasound to measure the diameters of follicle-like structures and blood sample s to measure serum concentrations of 17beta-E2 and progesterone . Subjects were observed for five cycles : pretreatment and posttreatment control cycles and three cycles in which the COC was administered for either 21 or 24 days of each cycle . MAIN OUTCOME MEASURE(S ) Occurrence of ovulation and evidence of ovarian activity . RESULT ( S ) The study was completed by 27 ( 90 % ) of the 30 subjects who received the 24-day regimen and by 24 ( 79 % ) of the 28 subjects who received the 21-day regimen . Ovulation was inhibited in all cycles in the 24-day group and in 74 of 75 cycles in the 21-day group . Luteinized unruptured follicles were seen in no cycles with the 24-day regimen and in 6 ( 8 % ) of 75 cycles with the 21-day regimen . Mean ovarian follicular development and serum 17beta-E2 and progesterone levels were lower in the 24-day group . CONCLUSION ( S ) The 24-day regimen is an innovative strategy for maintaining effective ovulation inhibition at ultra-low doses of contraceptive steroids Objectives The primary objective of this analysis was to characterise the steady-state pharmacokinetics ( PK ) of ethinylestradiol ( EE ) and drospirenone ( DRSP ) in a r and omised Phase III study that investigated the contraceptive efficacy and safety of three different regimens of EE 20 µg/DRSP 3 mg . Methods Non-linear mixed-effects modelling was used to develop population PK models for EE and DRSP . EE and DRSP serum concentrations were determined in blood sample s obtained from approximately 1100 healthy young women on two occasions during the first cycle ( Week 3 ) and after 6 months ( Week 27 ) of EE 20 µg/DRSP 3 mg use . EE 20 µg/DRSP 3 mg was administered as a flexible extended regimen [ 24–120 days ’ active hormonal intake followed by 4 days with no tablet intake ( tablet-free interval ) ] , a conventional 28-day cyclic regimen ( 24 days ’ active hormonal intake followed by 4 days of placebo tablets ) or a fixed extended regimen ( 120 days ’ uninterrupted active hormonal intake followed by a 4-day tablet-free interval ) over 1 year . Results The population PK of EE and DRSP in this population were successfully described using the developed population models . All three regimens led to similar steady-state drug exposure during long-term treatment . Only minor changes ( ≤8 % ) in the steady-state PK of EE and DRSP were observed between Week 3 and Week 27 of an extended regimen . Body weight ( BW ) and age had a small , statistically significant impact on the PK of EE and DRSP ( BW only ) in a covariate analysis , however , these changes were not considered to be clinical ly relevant . Conclusions Extending the established 24/4-day regimen of EE 20 µg/DRSP 3 mg does not change the known steady-state PK of EE and DRSP , suggesting that the clinical efficacy is also similar . This is in line with the published clinical results from this study We have examined the pharmacokinetic parameters derived from the analysis of plasma ethinyl estradiol ( EE ) and norethindrone levels after administration of a single dose of three bioequivalent norethindrone-1mg/mestranol (ME)-50 micrograms formulations ( Ortho-NovumR 1/50 , NorinylR 1/50 and Norcept-MR 1/50 ) and three norethindrone-1mg/ethinyl estradiol-35 micrograms formulations ( Ortho-Novum 1/35R , NorinylR 1/35 , Norcept-ER 1/35 ) in a r and omized crossover design involving 24 women for the 35 micrograms and 27 women for the 50 micrograms agents . Differences between the AUC-EE of pairs from the same manufacturer ( 1 + 35 and 1 + 50 ) were not significantly different , indicating that 50 micrograms of mestranol was equivalent to 35 micrograms ethinyl estradiol with respect to this pharmacokinetic parameter . The Cmax values were also similar . Inter-individual coefficients of variation ( C.V. ) for the AUC-EE were 47 % and 57 % for the 1 + 35 and 1 + 50 agents , respectively . Intra-individual C.V.s were 41 % and 42 % , respectively . For norethindrone , the AUC was larger with the 1 + 50 formulations than with the 1 + 35 group ( 87.9 vs. 72.8 pg hr/ml ) . Additionally , the Cmax values were larger for the 1/50 group ( 17.7 vs. 14.0 ) . Since the amount of norethindrone in the two dosage groups was the same , this difference in the pharmacokinetics between the 35 micrograms EE and the 50 micrograms ME formulations remains unexplained . The inter-individual C.V. averaged 56 % for both dosage groups . The intra-individual C.V.s were 17 % and 46 % for the 1 + 35 and 1 + 50 groups , respectively . The large variation in blood levels of ethinyl estradiol and norethindrone between and within individuals may overshadow clinical differences attributable to differences in dosage BACKGROUND Unscheduled bleeding may affect satisfaction and compliance with extended oral contraceptive ( OC ) regimens . The bleeding patterns of two variants of a flexible dosing regimen design ed to manage intracyclic bleeding problems during extended cycles were compared with that of a conventional OC regimen . STUDY DESIGN This was a 1-year , open-label , active-controlled , Phase 3 study conducted in the USA . Healthy women ( 18 - 45 years ) received an ethinylestradiol ( EE ) 20 mcg/drospirenone 3 mg OC in two flexible extended regimens or in a conventional 24/4 ( i.e. , 28-day ) regimen . The primary regimen [ management of intracyclic bleeding ( flexible(MIB ) ) regimen ] was an extended dosing regimen that required subjects to initiate 4-day tablet-free intervals after 3 days of breakthrough bleeding/spotting . An alternative extended regimen [ active period control ( flexible(APC ) ) regimen ] allowed subjects to initiate a 4-day tablet-free interval irrespective of the occurrence of bleeding . Bleeding profiles were compared between treatments . Efficacy and safety outcomes were also assessed . RESULTS The full analysis set comprised 1864 women ( flexible(MIB ) , N=1406 ; flexible(APC ) , N=232 ; conventional 24/4 , N=226 ) . Over 1 year , subjects in the flexible(MIB ) group experienced significantly fewer ( mean±SD , 40±30 ) bleeding/spotting days than those in the conventional 24/4 group ( 52±35 ) . The corresponding value in the flexible(APC ) group was 47±33 days . The pregnancy rate in the flexible(MIB ) group was 1.65 per 100 woman-years ( 95 % confidence interval , 0.96 - 2.65 ) . All three regimens were well tolerated . CONCLUSION A flexible(MIB ) dosing regimen of EE 20 mcg/drospirenone 3 mg is associated with good contraceptive efficacy and fewer bleeding/spotting days than the conventional 24/4 regimen BACKGROUND The study was conducted to evaluate follicular development and hormone patterns with three oral contraceptive ( OC ) regimens before , during and after the 7-day hormone-free interval ( HFI ) or 7-day ethinyl estradiol (EE)-supplemented interval . STUDY DESIGN The study is a single-center , open-label , prospect i ve , r and omized trial to evaluate pituitary-ovarian suppression with three OC regimens containing identical hormones : 30 mcg of EE and 150 mcg of levonorgestrel ( LNG ) . METHODS After a st and ard 21/7 OC baseline cycle , subjects were r and omized to one of three treatment groups : ( 1 ) three 21/7-day cycles of 150 mcg LNG/30 mcg EE for 21 days followed by 7 days of placebo ( n=10 ) ; ( 2 ) one 84/7-day cycle of 150 mcg LNG/30 mcg EE for 84 days followed by 7 days of placebo ( n=12 ) and ( 3 ) one 84/7EE-day cycle of 150 mcg LNG/30 mcg EE for 84 days followed by 7 days of 10 mcg EE ( n=11 ) . Estradiol ; follicle-stimulating hormone ( FSH ) ; luteinizing hormone and inhibin-B levels , ovarian follicles and daily symptom diaries were collected . RESULTS Compared to subjects receiving placebo during the 7-day HFI , those receiving EE demonstrated reductions ( p<.05 ) in both FSH and estradiol . Number of developing follicles was less after the 7-day EE interval compared to that after 7-day HFI . Subjects on the 84/7 and 84/7EE regimens reported less ( p=.03 ) daily menstrual flow than those on the 21/7-day regimen . A trend ( p=.06 ) toward reduced headaches during the 7-day EE-supplemented interval was noted . CONCLUSIONS Supplementation of the st and ard 7-day HFI with 10 mcg EE after 84 days of an extended OC decreased FSH levels and decreased the number of developing follicles OBJECTIVES The purpose of this study was to characterize ovarian follicular and endometrial development during conventional vs. continuous oral contraceptive ( OC ) dosing regimens , to explore follicular development during the hormone-free interval ( HFI ) and to examine follicular development following OC discontinuation . STUDY METHODS A r and omized clinical trial involving 36 clinical ly normal healthy women between the ages of 18 and 35 years ( 24.4 + /- 3.9 , SEM ) . Transvaginal ultrasonography and blood sampling were done to ascertain ovarian function . RESULTS Fewer follicles > 4 mm developed during continuous vs. conventional OC use ( p = .006 ) . No dominant follicles developed during continuous OC use vs. eight dominant follicles ( 16.1 + /- 3.3 mm ) during the conventional OC regimen . Two of eight ( 25 % ) dominant follicles ovulated . All dominant follicles began development during the HFI . Following discontinuation of OC use , ovulation took approximately 5 days longer when compared to natural cycles . CONCLUSION Continuous OC regimens more effectively prevent dominant follicle development and breakthrough ovulation . The slight delay in time to ovulation following OC discontinuation and natural cycles could be attributed to suppression of follicle wave activity BACKGROUND There is growing interest from women and clinicians in extended or tailored use of the combined oral contraceptive ( COC ) pill . Potential advantages include less bleeding , greater contraceptive efficacy and user satisfaction . We examined the effect of a tailored pill regimen , compared with the st and ard regimen , on continuation and satisfaction rates at 1 year and associated bleeding patterns . STUDY DESIGN This was a r and omized controlled trial with 503 women aged 18 - 45 years . Women were r and omized to either the st and ard regimen ( 21 daily pills followed by a 7-day pill-free interval ) or tailored regimen ( daily pills until three consecutive days bleeding triggers a 3-day pill-free interval ) of Microgynon 30 ® ( ethinyl oestradiol 30 mcg , levonorgestrel 150 mcg ) . Primary outcome was COC continuation at 12 months ; secondary outcomes included satisfaction with pill regimen regarding contraception and bleeding pattern . Daily electronic diaries were used to record women 's pill use , switching to other contraceptive methods , menstrual bleeding patterns and satisfaction levels . RESULTS Eighty-three percent of women were already taking the COC at recruitment , 13 % were restarting the COC and 4 % were first time COC users . Seventy-one percent of all women were followed up at 12 months . Continuation rates at 1 year were 82 % in the tailored arm versus 80 % in the st and ard arm [ odds ratio (OR)=1.13 ; 95 % confidence interval (CI)=0.67 - 1.91 ] . Satisfaction with contraceptive regimen was 86 % ( tailored ) versus 94 % ( st and ard ) ( OR=0.37 ; 95 % CI=0.17 - 0.79 ) , and satisfaction with bleeding pattern was 79 % versus 87 % , respectively ( OR=0.53 ; 95 % CI=0.30 - 0.93 ) . Median number of bleeding days per month was 2.4 ( tailored ) and 4.9 ( st and ard ) . Incidence , duration and intensity of bleeding episodes were significantly lower in the tailored arm . CONCLUSIONS In women familiar with st and ard use of the COC , switching to tailored COC use or continuing with st and ard use were both associated with high COC continuation rates and high satisfaction with contraceptive regimen and bleeding pattern . While significant differences tended to favor the st and ard group , tailored COC use was associated with significantly less bleeding , suited some women very well and can provide a suitable alternative to st and ard use Abstract Objective : To analyze adherence to an oral contraceptive ( OC ) regimen and correlate results to participants ’ socio-demographic and behavioral characteristics . Methods : Women were prospect ively enrolled and followed for 6 months . At enrollment , subjects were given a card for recording daily pill intake ; its completion was checked at 6 months when women completed a self-administered question naire . Results : Out of 755 eligible subjects , 704 agreed to participate ; 402 women completed 6 months of recording of use of an OC and properly filled the question naire . Good adherence was reported by 64 % of participants ; 20.9 % missed one pill and 14.9 % missed more than one pill . Mean number of missed pills per subject was 0.59 and mean number of pills delayed for less than 24 h was 1.18 . Best adherence to a COC regimen was associated with evening time intake ( p = 0.0019 ) . No statistically significant associations of adherence with socio-demographic characteristics were found . Age was only marginally associated with having missed at least one pill . Conclusion : In the present study , a lower number of missed pills were observed than previously reported , but the proportion of missed pills was similar . No association with specific subject characteristics that could serve as markers of increased risk of nonadherence was found OBJECTIVE : To estimate real-life effectiveness of oral contraceptive pills by progestogen , length of pill-free interval , and body mass index while focusing on the effect of progestogens with a long half-life and on 24-day oral contraceptive pills regimens . METHODS : Outcome data from 52,218 U.S. participants in the International Active Surveillance of Women Taking Oral Contraceptives — a large , prospect i ve , controlled , noninterventional , long-term cohort study with active surveillance of the study participants —were used to analyze contraceptive failure in association with oral contraceptive pills use . Low loss to follow-up is ensured by a comprehensive follow-up procedure . Contraceptive failure rates are described by Pearl Index and life-table analysis . Inferential statistics for contraceptive failure are based on Cox regression models . RESULTS : Analyses are based on 1,634 unintended pregnancies during 73,269 woman-years of oral contraceptive pills exposure . Life-table estimates of contraceptive failure for a 24-day regimen of drospirenone and ethinyl estradiol and 21-day regimens of other progestogens were 2.1 % and 3.5 % after the first study year , and 4.7 % and 6.7 % after the third year . The adjusted hazard ratio was 0.7 ( 95 % confidence interval 0.6–0.8 ) . Direct comparisons of the 24-day and 21-day regimens of drospirenone and norethisterone , respectively , showed also lower contraceptive failure rates for 24-day regimens . Contraceptive failure rates adjusted for age , parity and educational level showed a slight increase with higher body mass index . CONCLUSION : The 24-day oral contraceptive regimens containing a progestogen with a long half-life show higher contraceptive effectiveness under routine medical conditions compared with conventional 21-day regimens . Obesity seems to be associated with a slight reduction of contraceptive effectiveness . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00335257 . LEVEL OF EVIDENCE : This study was design ed to evaluate follicular activity in women taking oral contraceptives with imposed imperfect compliance . After completing a 28-day cycle of either triphasic norgestimate/EE ( NGM/EE ) ( Ortho Tri-Cyclen , Ortho-McNeil Pharmaceutical , Raritan , NJ ) or monophasic levonorgestrel/EE ( LNG/EE ) ( Alesse , Wyeth-Ayerst Laboratories , Philadelphia , PA ) , women were instructed to intentionally " miss " the first two active pills of the next pack . The first two tablets in the second treatment cycle were deliberately omitted , thereby extending the pill-free interval from 7 days to 9 days . Subjects were r and omized to take NGM/EE ( n = 40 ) or LNG/EE ( n = 39 ) for two consecutive cycles . The mean maximum follicular diameter was significantly greater in women taking LNG/EE than in those taking NGM/EE ( 16.4 + /- 7.1 mm vs. 12.6 + /- 8.3 mm , p = 0.047 ) . The LNG/EE group had significantly higher median serum estradiol concentrations compared to women taking NGM/EE on pill Days 10 [ 29.5 pg/mL ( range : 10.0 - 540.0 pg/mL ) vs. 2.5 pg/mL ( range : 2.0 - 6.0 pg/mL ) , p < 0.001 ] and 14 [ 11.0 pg/mL ( range : 2.0 - 416.0 pg/mL ) vs. 2.0 pg/mL ( range : 2.0 - 3.0 pg/mL ) , p = 0.001 ] . Two women in the NGM/EE group and three women in the LNG/EE group had at least one progesterone level > or =3 ng/mL ; none of these women demonstrated a maximum follicular diameter > 13 mm . Significantly greater follicular activity was observed after an extended pill-free interval in women taking LNG/EE compared to those taking triphasic NGM/EE . The clinical implication s of these findings require further study The objective of the study was to determine the suppressive effect on ovarian activity of 20 micrograms ethinylestradiol plus 75 micrograms gestodene administered for 21 or 23 days . The study was design ed as a double-blind , r and omized , multicenter trial in 60 women . A pre-treatment cycle , three treatment cycles and a post-treatment period were monitored by ovarian ultrasound and by LH , FSH , 17 beta-estradiol and progesterone measurements every other day . No ovulation and no luteinized , unruptured follicle were observed . Suppression of ovarian activity was more pronounced by the 23-day regimen . 17 beta-Estradiol serum levels during the last six days of a cycle and during the first six days of the next cycle were significantly less ( p < 0.05 ) in the 23-day regimen . The superiority of the 23-day regimen in comparison to the 21-day regimen with regard to the suppression of ovarian activity was shown in this study . The observed differences in the 17 beta-estradiol levels and follicular development between a 21-day and 23-day preparation combine to suggest that shortening the pill-free interval in combined oral contraceptives may increase the contraceptive safety margin in women on low-dose formulations OBJECTIVE Our purpose was to test the hypothesis that omitting the first three pills of the contraceptive cycle leads to ovulation . STUDY DESIGN Ninety-nine women , r and omly assigned to 1 of 3 treatments of combined oral contraceptives , completed the study . Treatments contained ethinyl estradiol and either monophasic gestodene , triphasic gestodene , or monophasic desogestrel . Pituitary-ovarian activity was monitored by ultrasonography of the ovaries and assay of serum concentrations of estradiol , progesterone , and follicle-stimulating hormone over 1 normal cycle ( study period 1 ) and 1 cycle after an extended pill-free interval of 10 days ( study period 2 ) . RESULTS None of the women experienced normal ovulation as evaluated by ultrasonography and serum progesterone concentrations . However , follicle-stimulating hormone reached a maximal serum concentration in most women during the first 7 pill-free days , indicating complete pituitary recovery , and increases in serum estradiol concentrations were seen in each woman although with marked interindividual variation . During study period 2 we found follicles of > 18 mm in 24 % , 24 % , and 40 % of the monophasic gestodene , triphasic gestodene , and monophasic desogestrel groups , respectively . CONCLUSIONS Follicular growth up to preovulatory size is common in women missing the first one to three pills of their contraceptive cycle . Although this creates the prerequisite for ovulation , normal ovulation did not occur when pill omissions were limited to only 3 days OBJECTIVE This investigation tests the hypothesis that triphasic oral contraceptives are associated with the development of large , persistent ovarian cysts . STUDY DESIGN Weekly vaginal ultrasonography was used in a r and omized , double-blind , placebo-controlled , parallel-group , single-center study that compared the incidence , risk , size , and time to resolution of ovarian follicles in healthy women who took Estrostep or Loestrin oral contraceptives ( manufactured by Parke-Davis ) or a placebo during three consecutive menstrual cycles . RESULTS Sixty-three percent of placebo-treated subjects developed follicles greater than 18 mm , compared with 39 % and 23 % in the Estrostep and Loestrin groups . The risks for each group of developing a large follicle during a single cycle were not different . No dominant follicle persisted for greater than 2 weeks for any subject . CONCLUSION These results demonstrate that follicular development continues during treatment with oral contraceptives . In addition , the findings fail to support the hypothesis that triphasic oral contraceptives result in persistent ovarian cysts OBJECTIVE : To estimate whether progestin type or estrogen dose influences bleeding patterns , adverse effects , or satisfaction with combined oral contraceptives dosed continuously . METHODS : This was a r and omized , double blind , 4-arm active treatment study . Subjects received either 100 & mgr;g levonorgestrel/20 & mgr;g ethinyl estradiol ( E2 ) ( 20LNG group ) , 100 & mgr;g levonorgestrel/30 & mgr;g ethinyl E2 ( 30LNG group ) , 1,000 & mgr;g norethindrone acetate/20 & mgr;g ethinyl E2 ( 20NETA group ) , or 1,000 & mgr;g norethindrone acetate/30 & mgr;g ethinyl E2 ( 30NETA group ) for 180 days . Subjects logged bleeding events and adverse effects on a daily menstrual calendar . An exit survey measured satisfaction with bleeding patterns . RESULTS : One hundred thirty-nine women were enrolled . Patients in the 20NETA and 30NETA arms had significantly more days of amenorrhea than the 30LNG arm in the second 90 days ( P < .008 ) . The 30LNG group reported more spotting days than the 20NETA group over the entire study period ( P < .008 ) and the 30NETA group for the second 90 days ( P < .008 ) . Only a small number of bleeding days were reported with no differences between groups . No differences in adverse effects between groups were found . Women in the 30LNG arm reported lower levels of satisfaction with their bleeding patterns than the other groups ( 30LNG compared with 20NETA , P = .01 ; 30LNG compared with 30NETA , P = .001 ) . CONCLUSION : The addition of 10 & mgr;g of ethinyl E2 to a 20 & mgr;g ethinyl E2 pill containing levonorgestrel or norethindrone acetate did not improve bleeding patterns . During continuous dosing , the use of oral contraceptives containing 1,000 & mgr;g norethindrone acetate result ed in more days of amenorrhea and fewer days of spotting than preparations containing 100 & mgr;g levonorgestrel . LEVEL OF EVIDENCE : A study to determine the pharmacokinetics of single doses of ethynylestradiol ( EE ) of 35 - 100 ug administered to a total of 98 women in the United States , Thail and , Nigeria , Sri Lanka , and Singapore . After EE ingestion , plasma sample s were collected at various intervals with 65 % of U.S. patients exhibiting peak plasma EE levels between 60 - 90 minutes , and 2/3 showed detectable EE levels at 24 hours using 50 - 80 ug doses . To assess within-subject variation and range of variation between individuals , subjects in Palo Alto using 35 ug doses were tested twice showing a variation within subjects of 51.8 % and between subjects was 119 % . In Tucson , subjects using 100 ug EE doses showed a within-subject variation of 13.5 % and between subjects was 37 % . Absorption phase half-life ranged from 14 - 22 minutes , distribution phase varied from 1 - 3 hours , and the elimination half life ranged from 6 - 14 hours . Nigeria indicated the lowest plasma EE levels while Thail and had the highest levels even when body surface differences were accounted for . Dietary differences may cause differences in drug absorption ; in addition , differences in relative muscle/fat ratios could effect storage and metabolism BACKGROUND Oral contraceptives ( OCs ) are the most widely used method of reversible contraception . Recent alterations of the st and ard 28-day regimen have included shortening the traditional hormone-free interval ( HFI ) , supplementing the HFI with low-dose estrogen , or increasing the number of active pills administered , thus extending the time between withdrawal bleeding episodes by a variable number of months . In light of these changes in regimens , clinicians may be seeking evidence that the new regimens are safe and will not result in unexpected adverse events . METHODS We initiated a long-term extension trial to evaluate the safety of a 91-day extended-regimen OC containing 150 mcg levonorgestrel/30 mcg ethinyl estradiol ( EE ) for 84 days , followed by 7 days of 10 mcg EE . After participation in a 1-year , open-label , phase 3 contraceptive program , 320 women qualified for enrollment in a multicenter , nonr and omized study of 91-day extended-regimen OCs for up to 3 additional consecutive years ; 116 completed the study . We evaluated incidence of reported adverse events ( AEs ) , rates of study discontinuation , and reported bleeding patterns . RESULTS Total exposure was equivalent to 8292 28-day cycles . Participants reported no thromboembolic events . Thirty-one ( 9.7 % ) women discontinued treatment due to AEs . Unscheduled bleeding and spotting diminished during the course of the trial . Overall rates of study discontinuation and incidence of AEs were consistent with those observed in the phase 3 clinical program . CONCLUSION This study demonstrated that the AE profile of the 91-day extended-regimen OC over 4 years was similar to that seen in the 1-year clinical trials , with no unexpected adverse events A multicenter , international , r and omized , comparative trial was conducted to assess the acceptability , efficacy and safety of two different schedules of a contraceptive pill , containing 250 micrograms levonorgestrel and 50 micrograms ethinyl estradiol , administered by the vaginal route . One schedule of daily administration for 21 days with a seven-day interruption to allow withdrawal bleeding was compared to daily administration without interruption for bleeding . A total of 900 women were recruited in three countries , Brazil , Egypt and China ; 7,090 women-months of vaginal pill use were recorded ( 3,364 using the pills intermittently and 3,726 continuously ) . Four undesired pregnancies occurred , one in Egypt and three in China , all four in women using the pills intermittently . There was a statistically significant difference ( p = 0.486 ) in pregnancy rate between the two groups . There were no other significant differences in discontinuation rates despite marked differences in bleeding patterns , amenorrhea predominating in the continuous use group . Hemoglobin levels increased significantly in the two groups but hematocrit was significantly higher in the continuous use group This prospect i ve , r and omized comparative clinical study involving 416 women investigated follicle development over a period of 12 oral contraceptive treatment cycles . Women were allocated to two groups , one group ( n = 207 ) received a preparation containing 30 micrograms ethinylestradiol and 75 micrograms gestodene daily , and the other group ( n = 209 ) received 20 micrograms ethinylestradiol and 150 micrograms desogestrel , daily . Follicular development was monitored by transvaginal ultrasonography of the ovaries , during days 18 - 21 in the pretreatment cycle and in treatment cycles 1 , 3 , 6 , 9 and 12 . Follicular development was found to be twice as frequent in the group receiving 20 micrograms ethinylestradiol/desogestrel as in the group receiving 30 micrograms ethinylestradiol/gestodene . For all cycles , follicles of 10 - 30 mm were found in 18 % of women in the desogestrel group , compared with 9.7 % in the gestodene group , whilst follicles with a diameter of > 30 mm were present in 5 % of the desogestrel group compared with 1.9 % of the gestodene group . The difference between the treatment groups with respect to follicle diameters of 10 - 30 mm and > 30 mm was statistically significant ( p < 0.05 and p < 0.001 , respectively ) . No ruptured follicles were observed in either group throughout the study , suggesting that there was no escape ovulation , however , there was one pregnancy in the desogestrel group that could not be explained either by drug interactions or missed pills . It can be concluded that the ethinylestradiol dose in an oral contraceptive has a significant effect on follicular ovarian activity , and that reducing the dose to 20 micrograms is associated with a significant increase in follicle size OBJECTIVE To assess the efficacy and safety of Seasonale , 91-day extended cycle oral contraceptive ( OC ) . METHODS A parallel , r and omized , multicenter open-label , 1-year study of the OC Seasonale [ 30 microg ethinyl estradiol (EE)/150 microg levonorgestrel ( LNG ) , and Nordette-28 ( 30 microg EE/150 microg LNG ) ] in sexually active , adult women ( 18 - 40 years ) of childbearing potential . Patients received either four 91-day cycles of extended cycle regimen OC , or 13 cycles of the conventional 28-day OC with daily monitoring of compliance and bleeding via electronic diaries . RESULTS When taken daily for 84 days followed by 7 days of placebo , the extended cycle regimen was effective in preventing pregnancy and had a safety profile that was comparable to that observed with the 28-day OC regimen that served as the control . While unscheduled ( breakthrough ) bleeding was reported among patients treated with the extended cycle regimen , it decreased with each successive cycle of therapy and was comparable to that reported by patients who received the conventional OC regimen by the fourth extended cycle . CONCLUSION This study demonstrated that Seasonale , 91-day extended cycle OC containing 84 days of 30 microg EE/150 microg LNG followed by 7 days of placebo , was effective , safe and well tolerated Objectives This follow-up study was planned to establish the frequency with which women miss their contraceptive pill , and to observe their behavior when they forget it . In those women who changed from a continuous cycle to an interrupted type of cycle , or vice versa , the study also aim ed to evaluate the impact of this change on the pattern of omission of pills . Methods The longitudinal , prospect i ve cohort study included healthy women of child-bearing age for whom a change of pill was being prescribed by their gynecologist . Data were recorded during the 6 months preceding inclusion in the study , and for the 6 months of follow-up ; the women were asked to complete a diary in which they recorded the number and exact times of pill omission , and their behavior at each omission . Results A total of 617 gynecologists included 3316 women into the study ; of these , a group of 2418 ( 73 % ) revisited the same gynecologist at follow-up . The groups who either visited the same or a different gynecologist were similar with respect to age , oral contraception type , omission type and frequency . A large non-compliance rate and women 's difficulties in maintaining safe contraception after missing a pill were observed in the group with follow-up . Women were never risk-free when they missed a pill ; they turned to numerous sources for discordant or conflicting information ; 15 % of ' not-forgetting ' women at the pre- inclusion cycle recorded at least one omission at the last cycle of the 6-month follow-up period . Omission fluctuations during the observational period make it difficult to design ate ' forgetful ' or ' non-forgetful ' classes of women . Administration of the pill in a continuous cycle , and probably ' study ' and ' auto- question naire ' effects , contributed to an improvement in compliance . In the group taking the continuous cycle pill , the omission number slightly decreased , particularly on the first day and week of the cycle , irrespective of the initial cycle type . Conclusions The importance of the phenomenon of non-compliance rate is confirmed as well as women 's difficulties in knowing how to maintain contraceptive safety . The continuous cycle regimen is likely to improve women 's compliance during the critical period of the cycle OBJECTIVE This study describes ovarian activity suppression of a 21/7-active low-dose combined oral contraceptive ( COC ) regimen that included only ethinyl estradiol ( EE ) during the traditional hormone-free interval ( HFI ) and two commercially available 28-day regimens , a 24/4 and a 21/7 regimen . STUDY DESIGN The r and omized , open-label , parallel-group descriptive study was conducted at two US sites . Healthy , reproductive-aged women ( n=146 ) were r and omized to one of three groups for three consecutive 28-day cycles , as follows : treatment 1 ( n=39 completed ) : 21/7-active COC [ 21 days of 150 mcg desogestrel (DSG)/20 mcg EE , followed by 7 days of 10 mcg EE ( DSG/EE+7 days EE ) ] , treatment 2 ( n=39 completed ) : 24 days of 3 mg drospirenone (DRSP)/20 mcg EE , followed by 4 placebo (PBO)-pill days ( DRSP/EE+4 days PBO ) and treatment 3 ( n=42 completed ) : 21 days of 100 mcg levonorgestrel (LNG)/20 mcg EE , followed by 7 PBO-pill days ( LNG/EE+7 days PBO ) . The primary outcome was ovarian activity suppression assessed by transvaginal ultrasound and serum hormone concentrations and classified using the Hoogl and and Skouby ( H/S ) method . RESULTS Ovarian activity rate ( H/S grade 4 or 5 ) was low for all three treatments : 0 % [ 95 % confidence interval ( CI ) 0 - 2.8 ] for DSG/EE+7 days EE , 1 % ( 95 % CI 0.2 - 5.2 ) for DRSP/EE+4days PBO and 1 % ( 95 % CI 0 - 3.9 ) for LNG/EE+7 days PBO . All three treatments showed similar suppression of serum progesterone , 17β-estradiol , follicle-stimulating hormone and luteinizing hormone levels . CONCLUSIONS The 21/7-active low-dose COC regimen ( DSG/EE+7 days EE ) showed ovarian activity suppression that was similar to the 24/4 ( DRSP/EE+4 days PBO ) and 21/7 ( LNG/EE+7days PBO ) regimens . IMPLICATION S The 21/7-active low-dose COC regimen ( DSG/EE+7 days EE ) that included only EE during the traditional HFI showed suppression of ovarian follicular activity that was similar to the 24/4 ( DRSP/EE+4days PBO ) and the 21/7 ( LNG/EE+7 days PBO ) comparator regimens CONTEXT Continuous oral contraception may better suppress the ovary and endometrium , lending itself to the treatment of other medical conditions . OBJECTIVE Our objective was to determine the effects of continuous vs. cyclical oral contraception . DESIGN This was a r and omized double-blind trial . SETTING This trial was performed at an academic medical center in Pennsylvania . PATIENTS A total of 62 healthy women with regular menses were included in the study . INTERVENTION Cyclical oral contraception ( 21-d active/7-d placebo given for six consecutive 28-d cycles ) vs. continuous ( 168-d active pill ) therapy using a monophasic pill ( 20 microg ethinyl estradiol and 1 mg norethindrone acetate ) was examined . MAIN OUTCOME MEASURES The primary outcome was vaginal bleeding , and secondary outcomes included hormonal , pelvic ultrasound , quality of life , and safety measures . RESULTS There was no statistically significant difference in the number of total bleeding days between groups , but moderate/heavy bleeding was significantly greater with the cyclical regimen [ mean 11.0 d ( sd 8.5 ) vs. continuous 5.2 d ( sd 6.8 ) ; P = 0.005 ] , with both groups decreasing over time . Endogenous serum and urinary estrogens measured over six cycles were significantly lower ( P = 0.02 and 0.04 , respectively ) in the continuous group than the cyclical group . Women in the continuous group also had a smaller ovarian volume and lead follicle size over the course of the trial by serial ultrasound examinations . The Moos Menstrual Distress Question naire showed that women on continuous therapy had less associated menstrual pain ( P = 0.01 ) and favorable improvements in behavior ( P = 0.04 ) during the premenstrual period . CONCLUSIONS Continuous oral contraception does not result in a reduction of bleeding days over a 168-d period of observation but provides greater suppression of the ovary and endometrium . These effects are associated with improved patient symptomatology BACKGROUND Migraine headaches are a significant problem for American women with many of them suffering from headaches around the time of their menstrual cycle . Women taking oral contraceptives in the st and ard 21/7 cycle regimen often suffer from headaches around the time of the hormone free intervals ( HFIs ) as well . Extended oral contraceptive regimens have been shown to decrease the frequency , but not eliminate these headaches . This study is a double-blind , r and omized , placebo-controlled pilot study of participants with menstrual-related migraines ( MRMs ) who were initiated on extended combined oral contraceptives and given frovatriptan prophylactically during HFIs . METHODS Participants having spontaneous menstrual cycles or taking daily combined oral contraceptives in a 21/7 regimen with MRMs were placed on a contraceptive containing levonorgestrel and ethinyl estradiol . Analyses compared headache scores during pre- study baseline cycles to those in a 168-day extended regimen with placebo versus frovatriptan treatments during HFIs . RESULTS Daily headache scores decreased ( p=0.034 ) from 1.29 ± 0.10 during pre- study cycles to 1.10 ± 0.14 during extended combined oral contraceptive use . Frovatriptan blocked the increase in headache score over the placebo during HFIs . However , following the withdrawal of frovatriptan , headache scores increased ( p>0.01 ) despite resuming combined oral contraceptive use . CONCLUSIONS Extended combined oral contraceptive regimen reduces MRM severity . Frovatriptan prevents headaches during HFIs , but is associated with new headache symptoms when withdrawn |
13,227 | 30,018,779 | Limited evidence exists as to the effect of exercise training on emerging biomarkers | Background Biomarkers are important in the diagnosis , risk stratification and management of patients with heart failure ( HF ) .
The established biomarkers of myocardial stretch , brain natriuretic peptide ( BNP ) and amino ( N ) portion of BNP ( NT-proBNP ) have been extensively studied , and early analyses have demonstrated response to exercise training .
Several other biomarkers have been identified over the last decade and may provide valuable and complementary information which may guide treatment strategies , including exercise therapy . | Background —The determinants of prognosis in patients with heart failure and preserved ejection fraction ( HF-PEF ) are poorly documented . Methods and Results —We evaluated data from 4128 patients in the I-PRESERVE trial ( Irbesartan in Heart Failure with Preserved Ejection Fraction Study ) . Multivariable Cox regression models were developed using 58 baseline demographic , clinical , and biological variables to model the primary outcome of all-cause mortality or cardiovascular hospitalization ( 1505 events ) , all-cause mortality ( 881 events ) , and HF death or hospitalization ( 716 events ) . Log N-terminal pro – B-type natriuretic peptide , age , diabetes mellitus , and previous hospitalization for HF were the most powerful factors associated with the primary outcome and with the HF composite . For all-cause mortality , log N-terminal pro – B-type natriuretic peptide , age , diabetes mellitus , and left ventricular EF were the strongest independent factors . Other independent factors associated with poor outcome included quality of life , a history of chronic obstructive lung disease , log neutrophil count , heart rate , and estimated glomerular filtration rate . The models accurately stratified the actual 3-year rate of outcomes from 8.1 % to 59.9 % ( primary outcome ) 2.7 % to 36.5 % ( all-cause mortality ) , and 2.1 % to 38.9 % ( HF composite ) for the lowest to highest septiles of predicted risks . Conclusions —In a large sample of elderly patients with HF and preserved EF enrolled in I-Preserve , simple clinical , demographic , and biological variables were associated with outcome and identified subgroups at very high and very low risk of events . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00095238 Background —Exercise intolerance is the primary symptom in older patients with heart failure and preserved ejection fraction ( HFPEF ) ; however , little is known regarding its mechanisms and therapy . Methods and Results —Seventy-one stable elderly ( 70±1 years ) patients ( 80 % women ) with compensated HFPEF and controlled blood pressure were r and omized into a 12-month follow-up double-blind trial of enalapril 20 mg/d versus placebo . Assessment s were peak exercise oxygen consumption ; 6-minute walk test ; Minnesota Living with HF Question naire ; MRI ; Doppler echocardiography ; and vascular ultrasound . Compliance by pill count was excellent ( 94 % ) . Twenty-five patients in the enalapril group versus 34 in the placebo group completed the 12-month follow-up . During follow-up , there was no difference in the primary outcome of peak exercise oxygen consumption ( enalapril , 14.5±3.2 mL/kg/min ; placebo , 14.3±3.4 mL/kg/min ; P=0.99 ) , or in 6-minute walk distance , aortic distensibility ( the primary mechanistic outcome ) , left ventricle mass , or neurohormonal profile . The effect size of enalapril on peak exercise oxygen consumption was small ( 0.7 % ; 95 % CI , 4.2 % to 5.6 % ) . There was a trend toward improved Minnesota Living with HF Question naire total score ( P=0.07 ) , a modest reduction in systolic blood pressure at peak exercise ( P=0.02 ) , and a marginal improvement in carotid arterial distensibility ( P=0.04 ) . Conclusions —In stable , older patients with compensated HFPEF and controlled blood pressure , 12 months of enalapril did not improve exercise capacity or aortic distensibility . These data , combined with those from large clinical event trials , suggest that angiotensin inhibition does not substantially improve key long-term clinical outcomes in this group of patients . This finding contrasts sharply with observations in HF with reduced EF and highlights our incomplete underst and ing of this important and common disorder BACKGROUND Preliminary evidence suggests that meditative exercise may have benefits for patients with chronic systolic heart failure ( HF ) ; this has not been rigorously tested in a large clinical sample . We sought to investigate whether tai chi , as an adjunct to st and ard care , improves functional capacity and quality of life in patients with HF . METHODS A single-blind , multisite , parallel-group , r and omized controlled trial evaluated 100 out patients with systolic HF ( New York Heart Association class I-III , left ventricular ejection fraction ≤40 % ) who were recruited between May 1 , 2005 , and September 30 , 2008 . A group-based 12-week tai chi exercise program ( n = 50 ) or time-matched education ( n = 50 , control group ) was conducted . Outcome measures included exercise capacity ( 6- minute walk test and peak oxygen uptake ) and disease-specific quality of life ( Minnesota Living With Heart Failure Question naire ) . RESULTS Mean ( SD ) age of patients was 67 ( 11 ) years ; baseline values were left ventricular ejection fraction , 29 % ( 8 % ) and peak oxygen uptake , 13.5 mL/kg/min ; the median New York Heart Association class of HF was class II . At completion of the study , there were no significant differences in change in 6-minute walk distance and peak oxygen uptake ( median change [ first quartile , third quartile ] , 35 [ -2 , 51 ] vs 2 [ -7 , 54 ] meters , P = .95 ; and 1.1 [ -1.1 , 1.5 ] vs -0.5 [ -1.2 , 1.8 ] mL/kg/min , P = .81 ) when comparing tai chi and control groups ; however , patients in the tai chi group had greater improvements in quality of life ( Minnesota Living With Heart Failure Question naire , -19 [ -23 , -3 ] vs 1 [ -16 , 3 ] , P = .02 ) . Improvements with tai chi were also seen in exercise self-efficacy ( Cardiac Exercise Self-efficacy Instrument , 0.1 [ 0.1 , 0.6 ] vs -0.3 [ -0.5 , 0.2 ] , P < .001 ) and mood ( Profile of Mood States total mood disturbance , -6 [ -17 , 1 ] vs -1 [ -13 , 10 ] , P = .01 ) . CONCLUSION Tai chi exercise may improve quality of life , mood , and exercise self-efficacy in patients with HF . Trial Registration clinical trials.gov Identifier : NCT00110227 Background — Exercise training reduces the symptoms of chronic heart failure . Which exercise intensity yields maximal beneficial adaptations is controversial . Furthermore , the incidence of chronic heart failure increases with advanced age ; it has been reported that 88 % and 49 % of patients with a first diagnosis of chronic heart failure are > 65 and > 80 years old , respectively . Despite this , most previous studies have excluded patients with an age > 70 years . Our objective was to compare training programs with moderate versus high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with postinfa rct ion heart failure . Methods and Results — Twenty-seven patients with stable postinfa rct ion heart failure who were undergoing optimal medical treatment , including & bgr;-blockers and angiotensin-converting enzyme inhibitors ( aged 75.5±11.1 years ; left ventricular [ LV ] ejection fraction 29 % ; & OV0312;o2peak 13 mL · kg−1 · min−1 ) were r and omized to either moderate continuous training ( 70 % of highest measured heart rate , ie , peak heart rate ) or aerobic interval training ( 95 % of peak heart rate ) 3 times per week for 12 weeks or to a control group that received st and ard advice regarding physical activity . & OV0312;o2peak increased more with aerobic interval training than moderate continuous training ( 46 % versus 14 % , P<0.001 ) and was associated with reverse LV remodeling . LV end-diastolic and end-systolic volumes declined with aerobic interval training only , by 18 % and 25 % , respectively ; LV ejection fraction increased 35 % , and pro-brain natriuretic peptide decreased 40 % . Improvement in brachial artery flow-mediated dilation ( endothelial function ) was greater with aerobic interval training , and mitochondrial function in lateral vastus muscle increased with aerobic interval training only . The MacNew global score for quality of life in cardiovascular disease increased in both exercise groups . No changes occurred in the control group . Conclusions — Exercise intensity was an important factor for reversing LV remodeling and improving aerobic capacity , endothelial function , and quality of life in patients with postinfa rct ion heart failure . These findings may have important implication s for exercise training in rehabilitation programs and future studies AIMS Diastolic dysfunction ( DD ) was identified as a predictor of adverse prognosis in heart failure with reduced ejection fraction ( HFREF ) . It is , however , unknown if DD is improved by exercise training , which is known to induce reverse remodelling , and if the training effect is attenuated in elderly HFREF patients . We therefore assessed DD in a cohort of referent controls ( RCs ) and HFREF patients and studied the response of DD to endurance exercise in two age groups ( ≤55 years and ≥65 years ) . METHODS AND RESULTS Sixty RC ( 30 ≤ 55 years , mean age 50 ± 5 years ; 30 ≥ 65 years , 72 ± 4 years ) and 60 HFREF patients ( 30 ≤ 55 years , 46 ± 5 years ; 30 ≥ 65 years , 72 ± 5 years , EF 28 ± 5 % ) were r and omized to 4 weeks of supervised endurance training or to a control group . Exercise training was effective in reducing LV isovolumetric relaxation time by 29 % in young and by 26 % in old HFREF patients ( P < 0.05 for both ) . As assessed by tissue Doppler , septal E ' increased by 37 % in young and by 39 % among old HFREF patients ( P < 0.005 for both ) result ing in a significant decrease in the E/E ' ratio from 13 ± 1 to 10 ± 1 in young and 14 ± 1 to 11 ± 1 in old HFREF patients ( P < 0.05 for both ) . Serum levels of N-terminal pro brain natriuretic peptide were significantly reduced after endurance training in HFREF patients of all ages . CONCLUSION In HFREF , diastolic function is significantly impaired in all age groups . Endurance training is highly effective in improving left ventricular diastolic function in HFREF patients regardless of age . This study is registered at Clinical Trials.gov ( number : NCT00176319 ) AIMS The purpose of this study was to evaluate whether yoga training in addition to st and ard medical therapy can improve cardiac function and reduce N terminal pro B-type natriuretic peptide ( NT pro BNP ) in heart failure ( HF ) . METHODS 130 patients were recruited and r and omized into two groups : Control Group ( CG ) ( n = 65 ) , Yoga Group ( YG ) . In YG , 44 patients and in CG , 48 patients completed the study . Cardiac function using left ventricular ejection fraction ( LVEF ) , myocardial performance index ( Tei index ) , and NT pro BNP , a biomarker of HF , was assessed at baseline and after 12 weeks . RESULT Improvement in LVEF , Tei index , and NT pro BNP were statistically significant in both the groups . Furthermore , when the changes in before and after 12 weeks were in percentage , LVEF increased 36.88 % in the YG and 16.9 % in the CG , Tei index was reduced 27.87 % in the YG and 2.79 % in the CG , NT pro BNP was reduced 63.75 % in the YG and 10.77 % in the CG . The between group comparisons from pre to post 12 weeks were significant for YG improvements ( LVEF , P < 0.01 , Tei index , P < 0.01 , NT pro BNP , P < 0.01 ) . CONCLUSION These results indicate that the addition of yoga therapy to st and ard medical therapy for HF patients has a markedly better effect on cardiac function and reduced myocardial stress measured using NT pro BNP in patients with stable HF Purpose Most training studies in patients with chronic heart failure ( CHF ) do not consider CHF aetiology in the interpretation of the results . About 60 % of the patients in those studies have ischemic CHF ( IHF ) and 40 % non-ischemic CHF ( NHF ) . Recently , we conducted a r and omized controlled trial to study three different training modalities in 60 patients with severe CHF , with a similar distribution of IHF and NHF patients . In the present post hoc analysis we compared the differences in training results between ischemic and non-ischemic patients . Methods Left ventricular ejection fraction ( EF ) , end diastolic volume ( EDV ) , end systolic volume ( ESV ) , measured with radionuclide ventriculography ( RNV ) and echocardiography , NT-pro BNP , peak oxygen uptake ( peak $ $ V_{{{\rm O}_{2 } } } $ $ ) , working capacity and muscular volume were analyzed before and after training in 45 patients training for 40 sessions , 3 times per week . Fifteen patients served as control group . The outcome was analyzed considering the aetiology of CHF , either ischemic or non-ischemic . Results There were no significant differences in improvements of peak $ $ V_{{{\rm O}_{2 } } } $ $ , working capacity and muscular volume between IHF and NHF patients . In NHF patients , EF increased while EDV and ESV decreased after training . These parameters remained unchanged in IHF patients after training . NT-pro BNP decreased significantly in NHF patients and increased in IHF patients after training . In the control group , patients showed a mild improvement of EF and a decrease of NT-pro BNP . Conclusion This post hoc analysis shows that training intervention is associated with significant reverse remodelling in NHF , but not in IHF patients , whereas $ $ V_{{{\rm O}_{2 } } } $ $ peak and muscle volume improve regardless of CHF aetiology . Future prospect i ve studies are needed to confirm our findings Background In patients with heart failure , inflammation has been associated with worse functional capacity , but it is uncertain whether it could affect their response to exercise training . We evaluated whether inflammatory biomarkers are related to differential effect of exercise on the peak oxygen uptake ( V˙O2 ) among patients with heart failure . Design Open , parallel group , r and omized controlled trial . Methods Patients with heart failure and ejection fraction ≤0.4 were r and omized into exercise training or control for 12 weeks . Patients were classified according to : 1 ) inflammatory biomarkers blood levels , defined as ‘ low ’ if both interleukin-6 and tumor necrosis factor-alpha blood levels were below median , and ‘ high ’ otherwise ; and 2 ) galectin-3 blood levels , which also reflect pro-fibrotic processes . Results Forty-four participants ( 50 ± 7 years old , 55 % men , 25 % ischemic ) were allocated to exercise training ( n = 28 ) or control ( n = 16 ) . Exercise significantly improved peak V˙O2 among participants with ‘ low ’ inflammatory biomarkers ( 3.5 ± 0.9 vs. −0.7 ± 1.1 ml/kg per min , p = 0.006 ) , as compared with control , but not among those with ‘ high ’ inflammatory biomarkers ( 0.4 ± 0.6 vs. −0.2 ± 0.7 ml/kg per min , p = 0.54 , p for interaction = 0.009 ) . Similarly , exercise improved peak V˙O2 among participants with below median ( 2.4 ± 0.8 vs. −0.3 ± 0.9 ml/kg per min , p = 0.032 ) , but not among those with above median galectin-3 blood levels ( 0.3 ± 0.7 vs. −0.7 ± 1.0 ml/kg per min , p = 0.41 , p for interaction = 0.053 ) . Conclusion In patients with heart failure , levels of biomarkers that reflect pro-inflammatory and pro-fibrotic processes were associated with differential effect of exercise on functional capacity . Further studies should evaluate whether exercise training can improve clinical outcomes in patients with heart failure and low levels of these biomarkers Background Cardiac rehabilitation ( CR ) improves the symptoms , exercise capacity and quality of life of chronic heart failure ( CHF ) patients . Its effects on new plasma biomarkers of prognostic importance are unknown . The present study aim ed at analysing the effects of a structured CR programme on plasma cardiac biomarkers in a large population of patients with CHF and reduced left ventricular ejection fraction ( LVEF ) . Methods We enrolled 107 consecutive CHF patients with LVEF ≤ 45 % in an ambulatory CR programme . Peak VO2 and plasma levels of Galectin-3 , mid-regional proANP ( MR-proADM ) , soluble suppressor of tumorigenicity 2 ( sST2 ) and mid-regional pro-adrenomedullin ( MR-proANP ) were assessed at inclusion and at the end of CR . Twenty-four unenrolled patients were managed with st and ard medical care and evaluated over the same period ( no-CR group ) . Results Galectin-3 , sST2 , MR-proADM and MR-proANP plasma levels decreased after CR , with respective median reductions of 6.3 % for Galectin 3 ( p < 0.001 ) , 7.4 % for sST2 ( p = 0.036 ) , 6.4 % for MR-proADM ( p = 0.001 ) and 16 % for MR-proANP ( p < 0.001 ) . MR-proADM was negatively correlated with peak VO2 ( ρ = −0.529 , 95 % confidence interval [ CI ] −0.654 to −0.375 , p < 0.001 ) , and so were their relative variations along the course of CR ( ρ = −0.357 , 95 % CI –0.518 to −0.172 , p < 0.001 ) . No change occurred in terms of biomarkers in the no-CR group . Conclusions Plasma cardiac biomarkers such as Galectin-3 , MR-proADM , sST2 and MR-proANP all decreased after CR in CHF patients , suggesting an overall improvement in the neuro-hormonal profile AIMS This study was design ed to evaluate the effects of combined endurance/resistance training on NT-proBNP levels in patients with chronic heart failure ( CHF ) . The safety of resistive weight training for patients with CHF is question ed . Possible detrimental effects include an increase in ventricular diastolic pressure and secondary unfavourable remodelling . Circulating levels of the N-terminal fragment of brain natriuretic peptide ( NT-proBNP ) reflect left ventricular diastolic wall stress and are strongly related to mortality and treatment success in CHF . METHODS AND RESULTS In this study , 27 consecutive patients with stable CHF and left ventricular ejection fraction ( LVEF ) < 35 % were enrolled in a 4 months non-r and omized combined endurance/resistance training programme . Blood sampling for measurement of NT-proBNP , functional assessment , cardiopulmonary exercise testing , echocardiography and radionuclide angiography were performed at entry and after 4 months . After 4 months , exercise training caused a significant reduction in circulating concentrations of NT-proBNP ( 2124+/-397 pg/ml before , 1635+/-304 pg/ml after training , p=0.046 , interaction ) , whereas no changes were observed in an untrained heart failure control group . NYHA functional class ( p=0.02 , interaction ) , maximal ( peak VO2 : p=0.035 , interaction ; maximal workload : p<0.00001 , interaction ) and submaximal ( workload at anaerobic threshold : p=0.001 , interaction ; rate-pressure product at anaerobic threshold : p=0.001 , interaction ) exercise parameters as well as work efficiency ( Wattmax/VO2peak : p=0.0001 , interaction ) were significantly improved . In addition , a decrease in left ventricular end-systolic diameter was observed in the trained heart failure group ( p=0.016 ) . CONCLUSION Four months of combined endurance/resistance training significantly reduced circulating levels of NT-proBNP in patients with CHF , without evidence of adverse remodelling . Exercise training might offer additional non-pharmacological modulation of the activated neurohormonal pathways in the setting of CHF Introduction : Several established tools are available to assess study quality and reporting of r and omized controlled trials ; however , these tools were design ed with clinical intervention trials in mind . In exercise training intervention trials some of the traditional study quality criteria , such as participant or research er blinding , are extremely difficult to implement . Methods : We developed the Tool for the assEssment of Study qualiTy and reporting in EXercise ( TESTEX ) – a study quality and reporting assessment tool , design ed specifically for use in exercise training studies . Our tool is a 15-point scale ( 5 points for study quality and 10 points for reporting ) and addresses previously unmentioned quality assessment criteria specific to exercise training studies . Results : There were no systematic differences between the summated TESTEX scores of each observer [ H(2 ) = 0.392 , P = 0.822 ] . There was a significant association between the summated TESTEX scores of the three observers , with almost perfect agreement between observers 1 and 2 [ intra-class correlation coefficient ( ICC ) = 0.93 , 95 % confidence interval ( CI ) 0.82–0.97 , P < 0.001 ] , observers 1 and 3 ( ICC = 0.96 , 95 % CI 0.89–0.98 , P < 0.001 ) and observers 2 and 3 ( ICC = 0.91 , 95 % CI 0.75–0.96 , P < 0.001 ) . Conclusions : The TESTEX scale is a new , reliable tool , specific to exercise scientists , that facilitates a comprehensive review of exercise training trials Background Heart failure with preserved ejection fraction ( HFpEF ) is remarkably common in elderly people with highly prevalent comorbid conditions . Despite its increasing in prevalence , there is no evidence -based effective therapy for HFpEF . We sought to evaluate whether inspiratory muscle training ( IMT ) improves exercise capacity , as well as left ventricular diastolic function , biomarker profile and quality of life ( QoL ) in patients with advanced HFpEF and nonreduced maximal inspiratory pressure ( MIP ) . Design and methods A total of 26 patients with HFpEF ( median ( interquartile range ) age , peak exercise oxygen uptake ( peak VO2 ) and left ventricular ejection fraction of 73 years ( 66–76 ) , 10 ml/min/kg ( 7.6–10.5 ) and 72 % ( 65–77 ) , respectively ) were r and omized to receive a 12-week programme of IMT plus st and ard care vs. st and ard care alone . The primary endpoint of the study was evaluated by positive changes in cardiopulmonary exercise parameters and distance walked in 6 minutes ( 6MWT ) . Secondary endpoints were changes in QoL , echocardiogram parameters of diastolic function , and prognostic biomarkers . Results The IMT group improved significantly their MIP ( p < 0.001 ) , peak VO2 ( p < 0.001 ) , exercise oxygen uptake at anaerobic threshold ( p = 0.001 ) , ventilatory efficiency ( p = 0.007 ) , metabolic equivalents ( p < 0,001 ) , 6MWT ( p < 0.001 ) , and QoL ( p = 0.037 ) as compared to the control group . No changes on diastolic function parameters or biomarkers levels were observed between both groups . Conclusions In HFpEF patients with low aerobic capacity and non-reduced MIP , IMT was associated with marked improvement in exercise capacity and OBJECTIVE Functional electrical stimulation ( FES ) improves exercise capacity and endothelial function in chronic heart failure ( CHF ) patients . This study evaluates the impact of FES on quality of life and emotional stress in patients with moderate to severe CHF . METHODS Thirty patients with stable CHF ( 24 men ; NYHA class II-III ; left ventricular ejection fraction < 35 % ) were r and omly assigned ( 2:1 ) to a 6-week FES training program ( n=20 ) or placebo ( n=10 ) . Question naires addressing quality of life [ Kansas City Cardiomyopathy Question naire ( KCCQ ) , functional and overall ] , and emotional stress [ Zung self-rating depression scale ( SDS ) , Beck Depression Inventory ( BDI ) ] , as well as plasma B-type natriuretic peptide ( BNP ) and 6-min walking distance test ( 6MWT ) were assessed at baseline and after completion of training protocol . RESULTS A significant improvement in KCCQ functional ( F=76.666 , p<0.001 ) , KCCQ overall ( F = 41.508 , p<0.001 ) , BDI ( F = 17.768 , p<0.001 ) and Zung SDS ( F = 27.098 , p<0.001 ) was observed in the FES group compared to placebo . Patients in the FES group had also a significant increase in 6MWT ( F = 19.413 , p<0.001 ) and a trend towards reduction in plasma BNP ( F = 4.252 , p=0.053 ) compared to placebo . CONCLUSION FES seems to have a beneficial effect on quality of life , exercise capacity and emotional stress in patients with moderate to severe CHF OBJECTIVES We sought to determine whether structured exercise training ( ET ) improves maximal exercise capacity , left ventricular diastolic function , and quality of life ( QoL ) in patients with heart failure with preserved ejection fraction ( HFpEF ) . BACKGROUND Nearly one-half of patients with heart failure experience HFpEF , but effective therapeutic strategies are sparse . METHODS A total of 64 patients ( age 65 ± 7 years , 56 % female ) with HFpEF were prospect ively r and omized ( 2:1 ) to supervised endurance/resistance training in addition to usual care ( ET , n = 44 ) or to usual care alone ( UC ) ( n = 20 ) . The primary endpoint was the change in peak Vo(2 ) after 3 months . Secondary endpoints included effects on cardiac structure , diastolic function , and QoL. RESULTS Peak Vo(2 ) increased ( 16.1 ± 4.9 ml/min/kg to 18.7 ± 5.4 ml/min/kg ; p < 0.001 ) with ET and remained unchanged ( 16.7 ± 4.7 ml/min/kg to 16.0 ± 6.0 ml/min/kg ; p = NS ) with UC . The mean benefit of ET was 3.3 ml/min/kg ( 95 % confidence interval [ CI ] : 1.8 to 4.8 , p < 0.001 ) . E/e ' ( mean difference of changes : -3.2 , 95 % CI : -4.3 to -2.1 , p < 0.001 ) and left atrial volume index ( milliliters per square meter ) decreased with ET and remained unchanged with UC ( -4.0 , 95 % CI : -5.9 to -2.2 , p < 0.001 ) . The physical functioning score ( 36-Item Short-Form Health Survey ) improved with ET and remained unchanged with UC ( 15 , 95 % CI : 7 to 24 , p < 0.001 ) . The ET-induced decrease of E/e ' was associated with 38 % gain in peak Vo(2 ) and 50 % of the improvement in physical functioning score . CONCLUSIONS Exercise training improves exercise capacity and physical dimensions of QoL in HFpEF . This benefit is associated with atrial reverse remodeling and improved left ventricular diastolic function . ( Exercise Training in Diastolic Heart Failure-Pilot Study : A Prospect i ve , R and omised , Controlled Study to Determine the Effects of Physical Training on Exercise Capacity and Quality of Life [ Ex-DHF-P ] ; IS RCT N42524037 ) Background : Small studies have suggested that high-intensity interval training ( HIIT ) is superior to moderate continuous training ( MCT ) in reversing cardiac remodeling and increasing aerobic capacity in patients with heart failure with reduced ejection fraction . The present multicenter trial compared 12 weeks of supervised interventions of HIIT , MCT , or a recommendation of regular exercise ( RRE ) . Methods : Two hundred sixty-one patients with left ventricular ejection fraction ⩽35 % and New York Heart Association class II to III were r and omly assigned to HIIT at 90 % to 95 % of maximal heart rate , MCT at 60 % to 70 % of maximal heart rate , or RRE . Thereafter , patients were encouraged to continue exercising on their own . Clinical assessment s were performed at baseline , after the intervention , and at follow-up after 52 weeks . Primary end point was a between-group comparison of change in left ventricular end-diastolic diameter from baseline to 12 weeks . Results : Groups did not differ in age ( median , 60 years ) , sex ( 19 % women ) , ischemic pathogenesis ( 59 % ) , or medication . Change in left ventricular end-diastolic diameter from baseline to 12 weeks was not different between HIIT and MCT ( P=0.45 ) ; left ventricular end-diastolic diameter changes compared with RRE were −2.8 mm ( −5.2 to −0.4 mm ; P=0.02 ) in HIIT and −1.2 mm ( −3.6 to 1.2 mm ; P=0.34 ) in MCT . There was also no difference between HIIT and MCT in peak oxygen uptake ( P=0.70 ) , but both were superior to RRE . However , none of these changes was maintained at follow-up after 52 weeks . Serious adverse events were not statistically different during supervised intervention or at follow-up at 52 weeks ( HIIT , 39 % ; MCT , 25 % ; RRE , 34 % ; P=0.16 ) . Training records showed that 51 % of patients exercised below prescribed target during supervised HIIT and 80 % above target in MCT . Conclusions : HIIT was not superior to MCT in changing left ventricular remodeling or aerobic capacity , and its feasibility remains unresolved in patients with heart failure . Clinical Trial Registration : URL : http://www . clinical trials.gov . Unique identifier : NCT00917046 In einer Querschnittsuntersuchung konnte kürzlich eine mäßiggradige Korrelation zwischen Serum-BNP ( brain natriuretic peptide ) und der ergometrischen Leistungsfähigkeit chronisch herzinsuffizienter Patienten gezeigt werden ( Krüger et al. , 2002 ) . Ob BNP , das auf erhöhte myokardiale W and spannung reagiert , i m klinischen Follow-up eine ausreichende Sensitivität für Veränderungen der körperlichen Leistungsfähigkeit aufweist , ist jedoch ungeklärt . Daher wurden 42 chronisch herzinsuffiziente Patienten in Trainings- ( T ; 58 ± 10 Jahre ; n = 14 NYHA II ; n = 5 NYHA III ) und Kontrollgruppe ( KO ; 54 ± 9 , n = 17 NYHA II ; n = 6 NYHA III ) r and omisiert . T absolvierte ein 12-wöchiges fahrradergometrisches Ausdauertraining ( 4X/Wo , 45 min ) . Eine venöse Blutentnahme und eine Fahrrad-Spiroergometrie f and en vor und nach der Experimentalphase statt . Aus Gründen der Messstabilität wurde statt BNP das in äquimolaren Mengen sezernierte und diagnostisch äquivalente NT-proBNP bestimmt . In beiden Gruppen sank das durchschnittliche NT-proBNP geringfügig ( T : von 1092 ± 980 auf 805 ± 724 pg × ml–1 ; KO : von 1075 ± 1068 auf 857 ± 1138 pg × ml–1 ; Gruppendifferenz T vs. KO : p = 0,65 ) . Die anaerobe Schwelle ( AT ) als Maß der Ausdauerleistungsfähigkeit stieg in T ( von 0,96 ± 0,17 auf 1,10 ± 0,22 l × min–1 ) und blieb in KO nahezu konstant ( von 1,02 ± 0,27 auf 1,00 ± 0,27 l × min–1 ; T vs. KO : p < 0,001 ) . Es best and keine Korrelation zwischen den trainingsinduzierten Veränderungen der AT und den Effekten auf NT-proBNP ( r = 0,02 ; p = 0,89 ) , auch nicht bei ausschließlicher Berücksichtigung von T ( r = 0,09 , p = 0,72 ) . Eine durch Ausdauertraining verbesserte körperliche Leistungsfähigkeit herzinsuffizienter Patienten zeigt sich somit nicht i m Verhalten des Serum-NT-proBNP . Die Empfindlichkeit dieses Parameters ist für die Verlaufskontrolle solcher Maßnahmen nicht hinreichend . Möglicherweise sind therapeutische Interventionen , die primär am Myokard angreifen , eher in der Lage , über Spontanschwankungen hinausgehende NT-proBNP-Veränderungen auszulösen . Eine ergometrische Testung der körperlichen Leistungsfähigkeit kann in der Verlaufsbeurteilung chronisch herzinsuffizienter Patienten nicht durch Bestimmungen von NT-proBNP ersetzt werden . Recently , in a cross-sectional study ( Krüger et al. , 2002 ) a correlation of moderate degree was documented between serum BNP ( brain natriuretic peptide ) and exercise capacity in patients with chronic heart failure ( CHF ) . However , it remains unknown if BNP , which increases in response to high myocardial wall stress , is sufficiently sensitive for changes in exercise capacity during clinical follow-up . To eluci date this , 42 CHF patients were recruited and r and omized into a training ( T ; 58 ± 10 years ; n = 14 NYHA II ; n = 5 NYHA III ) and a control group ( CO ; 54 ± 9 , n = 17 NYHA II ; n = 6 NYHA III ) . T carried out 12 weeks of endurance training on a cycle ergometer ( 4 sessions per week , 45 min duration ) . Venous blood sampling and cycle ergometry with simultaneous gas exchange measurements were carried out prior to and after the experimental phase . Due to its superior stability during laboratory procedures , NTproBNP was determined instead of BNP . Both proteins are secreted in equimolar amounts and share an identical diagnostic meaning . In both groups , NT-proBNP decreased slightly ( T : from 1092 ± 980 to 805 ± 724 pg × ml–1 ; CO : from 1075 ± 1068 to 857 ± 1138 pg × ml–1 ; T vs CO : p = 0.65 ) . Anaerobic threshold ( AT ) as a measure of exercise capacity went up in T ( from 0.96 ± 0.17 to 1.10 ± 0.22 l × min–1 ) but remained almost constant in CO ( pre : 1.02 ± 0.27 ; post : 1.00 ± 0.27 l × min–1 ; T vs CO : p < 0.001 ) . The correlation between changes in NT-proBNP and changes in AT remained insignificant ( r = 0.02 , p = 0.89)—even if only T was considered ( r = 0.09 , p = 0.72 ) . Improved exercise capacity in CHF patients due to 3 months of endurance training is not reflected in the course of NT-proBNP . These findings are inconsistent with a sufficient sensitivity of this parameter to detect changes in exercise capacity during clinical follow-up . Changes in NT-proBNP beyond its spontaneous variability are more likely to be detected following therapeutical interventions which aim more clearly at the myocardium . In determining alterations of functional capacity ergometric testing can not be replaced by serial determinations of NT-proBNP Background More than 60 % of patients decline participation in cardiac rehabilitation after a myocardial infa rct ion . Options to improve physical activity ( PA ) and other risk factors in these high‐risk individuals are limited . We conducted a phase 2 r and omized controlled trial to determine feasibility , safety , acceptability , and estimates of effect of tai chi on PA , fitness , weight , and quality of life . Methods and Results Patients with coronary heart disease declining cardiac rehabilitation enrollment were r and omized to a “ LITE ” ( 2 sessions/week for 12 weeks ) or to a “ PLUS ” ( 3 sessions/week for 12 weeks , then maintenance classes for 12 additional weeks ) condition . PA ( accelerometry ) , weight , and quality of life ( Health Survey Short Form ) were measured at baseline and 3 , 6 , and 9 months after baseline ; aerobic fitness ( stress test ) was measured at 3 months . Twenty‐nine participants ( 13 PLUS and 16 LITE ) were enrolled . Retention at 9 months was 90 % ( LITE ) and 88 % ( PLUS ) . No serious tai chi – related adverse events occurred . Significant mean between group differences in favor of the PLUS group were observed at 3 and 6 months for moderate‐to‐vigorous PA ( 100.33 min/week [ 95 % confidence interval , 15.70–184.95 min/week ] and 111.62 min/week ; [ 95 % confidence interval , 26.17–197.07 min/week ] , respectively , with a trend toward significance at 9 months ) , percentage change in weight , and quality of life . No changes in aerobic fitness were observed within and between groups . Conclusions In this community sample of patients with coronary heart disease declining enrollment in cardiac rehabilitation , a 6‐month tai chi program was safe and improved PA , weight , and quality of life compared with a 3‐month intervention . Tai chi could be an effective option to improve PA in this high‐risk population . Clinical Trial Registration URL : http://www . clinical trials.gov . Unique identifier : NCT02165254 Purpose : The purpose of this study was to compare an Exercise Training Group ( EX ) with an Attention‐Control Group ( AT‐C ) to more specifically assess the impact of exercise training on individuals with heart failure ( HF ) . Methods : Forty‐two individuals with HF were r and omized to AT‐C or EX that met with the same frequency and format of investigator interaction . Baseline , 12‐ and 24‐week measurements of B‐type naturetic peptide ( BNP ) , 6‐minute walk test ( 6‐MWT ) , and the Kansas City Cardiomyopathy Question naire ( KCCQ ) were obtained . Results : BNP tended to increase in the AT‐C while remaining stable in the EX over time . A clinical ly significant increase in 6‐MWT was demonstrated by the EX but not the AT‐C. The EX achieved a clinical ly significant change on the KCCQ at 12 weeks , with further improvement by 24 weeks , while the AT‐C demonstrated a clinical ly significant change at 24 weeks . Conclusions : Attention alone was inadequate to positively impact BNP levels or 6‐MWT distances , but did have a positive impact on quality of life after 24 weeks . Although exercise offers enhanced benefits , individuals with HF unable to participate in an exercise program may still gain quality of life benefits from participation in a peersupport group that discusses topics pertinent to HF PURPOSE To examine the effects of a 12-week tai chi program on quality of life and exercise capacity in patients with heart failure . METHODS Thirty patients with chronic stable heart failure and left ventricular ejection fraction < or = 40 % ( mean [ + /- SD ] age , 64 + /- 13 years ; mean baseline ejection fraction , 23 % + /- 7 % ; median New York Heart Association class , 2 [ range , 1 to 4 ] ) were r and omly assigned to receive usual care ( n = 15 ) , which included pharmacologic therapy and dietary and exercise counseling , or 12 weeks of tai chi training ( n = 15 ) in addition to usual care . Tai chi training consisted of a 1-hour class held twice weekly . Primary outcomes included quality of life and exercise capacity . Secondary outcomes included serum B-type natriuretic peptide and plasma catecholamine levels . For 3 control patients with missing data items at 12 weeks , previous values were carried forward . RESULTS At 12 weeks , patients in the tai chi group showed improved quality -of-life scores ( mean between-group difference in change , -25 points , P = 0.001 ) , increased distance walked in 6 minutes ( 135 meters , P = 0.001 ) , and decreased serum B-type natriuretic peptide levels ( -138 pg/mL , P = 0.03 ) compared with patients in the control group . A trend towards improvement was seen in peak oxygen uptake . No differences were detected in catecholamine levels . CONCLUSION Tai chi may be a beneficial adjunctive treatment that enhances quality of life and functional capacity in patients with chronic heart failure who are already receiving st and ard medical therapy Patients with chronic heart failure ( CHF ) experience progressive deterioration of functional capacity and quality of life ( QoL ) . This prospect i ve , r and omized , controlled trial assesses the effect of exercise training ( ET ) protocol on functional capacity , rehospitalization , and QoL in CHF patients older than 70 years compared with a control group . A total of 343 elderly patients with stable CHF ( age , 76.90±5.67 , men , 195 , 56.9 % ) were r and omized to ET ( TCG , n=170 ) or usual care ( UCG , n=173 ) . The ET protocol involved supervised training sessions for 3 months in the hospital followed by home-telemonitored sessions for 3 months . Assessment s , performed at baseline and at 3 and 6 months , included : ECG , resting echocardiography , NT-proBNP , 6-minute walk test ( 6MWT ) , Minnesota Living with Heart Failure Question naire , and comprehensive geriatric assessment with the InterRAI-HC instrument . As compared to UCG , ET patients at 6 months showed : i ) significantly increased 6MWT distance ( 450±83 vs. 290±97 m , p<0.001 ) ; ii ) increased ADL scores ( 5.00±2.49 vs. 6.94±5.66 , p=0.037 ) ; iii ) 40 % reduced risk of rehospitalisation ( hazard ratio=0.558 , 95%CI , 0.326 - 0.954 , p=0.033 ) ; and iv ) significantly improved perceived QoL ( 28.6±12.3 vs. 44.5±12.3 , p<0.001 ) . In hospital and home-based telemonitored exercise confer significant benefits on the oldest CHF patients , improving functional capacity and subjective QoL and reducing risk of rehospitalisation Purpose . To assess if Tai Chi added to endurance training ( ET ) is more effective than ET alone in improving exercise tolerance and quality of life ( QOL ) of elderly patients with chronic heart failure ( CHF ) . Design . Sixty CHF patients , age 73.8 ± 6 years , M/F 51/9 , were enlisted . Thirty pts were r and omized to combined training ( CT ) performing Tai Chi + ET and 30 patients to ET ( ET only ) . Methods . At baseline and after 12 weeks all patients underwent 6-minute walking test ( 6MWT ) , assessment of amino terminal probrain natriuretic peptide ( NT-pro BNP ) , quadriceps maximal voluntary contraction ( MVC ) and peak torque ( PT ) , QOL question naire ( MacNewQLMI ) , blood pressure ( BP ) , and heart rate ( HR ) . All patients performed 4 sessions of exercise/week . Results . Distance at 6mwt improved in both groups with significant between-groups differences ( P = .031 ) . Systolic BP and NT-proBNP decreased significant in the CT group compared to ET ( P = .025 ) and P = .015 ) , resp . ) . CT group had a greater significant improvement in physical perception ( P = .026 ) and a significant increase of PT compared to ET group . Conclusions . The association of Tai Chi and ET improves exercise tolerance and QOL of patients with CHF more efficiently than ET Abstract Background Over 50 % of patients with symptomatic heart failure ( HF ) experience HF with preserved ejection fraction ( HFpEF ) . Exercise training ( ET ) is effective in improving cardiorespiratory fitness and dimensions of quality of life in patients with HFpEF . A systemic pro‐inflammatory state induced by comorbidities as the cause of myocardial structural and functional alterations has been proposed in HFpEF . ET modifies myocardial structure and has been related to inflammatory state . We investigated Ghrelin , related adipokines , markers of inflammation , and neuro‐hormonal activation in patients undergoing a structured ET vs. usual care are with HFpEF . Methods and results Ex‐DHF‐P was a prospect i ve , controlled , r and omized multi‐centre trial on structured and supervised ET in patients with HFpEF . We performed a post hoc analysis in 62 patients from Ex‐DHF‐P. Ghrelin , adiponectin , leptin , IL‐1ß , IL‐6 , IL‐10 , tumour necrosis factor‐alpha , MR‐proANP , MR‐proADM , CT‐proET1 , and CT‐proAVP were assessed to seize the impact of ET on these markers in patients with HFpEF . Thirty‐six ( 58 % ) patients were female , mean age was 64 years , and median ghrelin was 928 pg/mL ( interquartile range 755–1156 ) . When stratified for high versus low ghrelin , groups significantly differed at baseline in presence obesity , waist circumference , and adiponectin levels ( P < 0.05 , respectively ) . Overall , ghrelin levels rose significantly to 1013 pg/mL ( interquartile range 813–1182 ) ( P < 0.001 ) . Analysis of covariance modelling for change in ghrelin identified ET ( P = 0.013 ) and higher baseline adiponectin levels ( P = 0.035 ) as influencing factors . Conclusions Exercise training tended to increase ghrelin levels in Ex‐DHF‐P. This increase was especially pronounced in patients with higher baseline adiponectin levels . Future trials are needed to investigate the effect of ET on endogenous ghrelin levels in regard to interactions with cardiac structure and clinical ly meaningful surrogate parameters BACKGROUND Exercise training is recommended for chronic heart failure ( HF ) patients to improve functional status and reduce risk of adverse outcomes . Elevated plasma levels of amino-terminal pro-brain natriuretic peptide ( NT-proBNP ) , high-sensitivity C-reactive protein ( hs-CRP ) , and cardiac troponin T ( cTnT ) are associated with increased risk of adverse outcomes in this patient population . Whether exercise training leads to improvements in biomarkers and how such improvements relate to clinical outcomes are unclear . METHODS AND RESULTS Amino-terminal pro-brain natriuretic peptide , hs-CRP , and cTnT levels were assessed at baseline and 3 months in a cohort of 928 subjects from the HF-ACTION study , a r and omized clinical trial of exercise training versus usual care in chronic HF patients with reduced left ventricular ejection fraction ( < 35 % ) . Linear and logistic regressions were used to assess 3-month biomarker levels as a function of baseline value , treatment assignment ( exercise training vs usual care ) , and volume of exercise . Linear regression and Cox proportional hazard modeling were used to evaluate the relations between changes in biomarker levels and clinical outcomes of interest that included change in peak oxygen consumption ( peak VO2 ) , hospitalizations , and mortality . Exercise training was not associated with significant changes in levels of NT-proBNP ( P = .10 ) , hs-CRP ( P = .80 ) , or detectable cTnT levels ( P = .83 ) at 3 months . Controlling for baseline biomarker levels or volume of exercise did not alter these findings . Decreases in plasma concentrations of NT-proBNP , but not hs-CRP or cTnT , were associated with increases in peak VO2 ( P < .001 ) at 3 months and decreased risk of hospitalizations or mortality ( P ≤ .04 ) , even after adjustment for a comprehensive set of known predictors . CONCLUSIONS Exercise training did not lead to meaningful changes in biomarkers of myocardial stress , inflammation , or necrosis in patients with chronic HF . Only improvements in NT-proBNP translated to reductions in peak VO2 and reduced risk of clinical events OBJECTIVES To assess the effects of a home-based aerobic and resistance training program on the physical function of adults with New York Heart Association ( NYHA ) class II and III patients and systolic heart failure ( HF ) . DESIGN R and omized controlled trial . SETTING Home based . PARTICIPANTS Stable patients ( N=24 ; mean age , 60 ± 10 y ; left ventricular ejection fraction , 25 % ± 9 % ; 50 % white ; 50 % women ) with New York Heart Association ( NYHA ) classes II and III ( NYHA class III , 58 % ) systolic heart failure ( HF ) . INTERVENTION A 12-week progressive home-based program of moderate-intensity aerobic and resistance exercise . Attention control wait list participants performed light stretching and flexibility exercises . MAIN OUTCOME MEASURES A 10-item performance-based physical function measure , the Continuous Scale Physical Functional Performance test ( CS-PFP10 ) , was the major outcome variable and included specific physical activities measured in time to complete a task , weight carried during a task , and distance walked . Other measures included muscle strength , HRQOL ( Minnesota Living With Heart Failure Question naire , Epworth Sleepiness Scale ) , functional capacity ( Duke Activity Status Index ) , and disease severity ( brain natriuretic peptide ) levels . RESULTS After the exercise intervention , 9 of 10 specific task activities were performed more rapidly , with increased weight carried by exercise participants compared with the attention control wait list group . Exercise participants also showed significant improvements in CS-PFP10 total score ( P<.025 ) , upper and lower muscle strength , and HRQOL ( P<.001 ) compared with the attention control wait list group . Adherence rates were 83 % and 99 % for the aerobic and resistance training , respectively . CONCLUSIONS Patients with stable HF who participate in a moderate-intensity combined aerobic and resistance exercise program may improve performance of routine physical activities of daily living by using a home-based exercise approach . Performance-based measures such as the CS-PFP10 may provide additional insights into physical function in patients with HF that more commonly used exercise tests may not identify . Early detection of subtle changes that may signal declining physical function that are amenable to intervention potentially may slow further loss of function in this patient population BACKGROUND C-type natriuretic peptide ( CNP ) is structurally related to cardiac natriuretic peptides and is currently considered as an endothelium-derived hyperpolarizing factor . Endothelial dysfunction , commonly observed in chronic heart failure ( HF ) patients is positively affected by physical training . METHODS To evaluate the effect of aerobic physical training on the expression of CNP , 90 HF patients on optimal pharmacological treatment ( age 62+/-2 years , mean+/-SEM ) , r and omly assigned in a 3 : 1 ratio to either control group ( C , 19 patients ) or home-based aerobic exercise-training program group ( T , 71 patients ) , completed the protocol . Plasma assay of CNP , brain natriuretic peptide or B-type natriuretic peptide ( BNP ) , and norepinephrine ; echocardiogram ; and cardiopulmonary-stress test were performed in all patients at enrollment and after 9 months . RESULTS At baseline , in both groups , CNP plasma level was significantly related to BNP ( R=0.50 ) , ejection fraction ( R=0.43 ) , and peak oxygen uptake ( VO2 , R=0.43 , all P<0.001 ) . After 9 months , trained patients showed an improvement in peak VO2 ( P<0.001 ) and ejection fraction ( P<0.05 ) , whereas norepinephrine ( P<0.05 ) , BNP ( P<0.001 ) , and CNP ( P<0.001 ) decreased . No changes occurred in group C. In group T , the decrease in CNP was significantly related to the increase in peak VO2 ( R=0.31 , P<0.01 ) , and the relation between CNP and BNP was preserved at the end of the program ( R=0.41 , P<0.001 ) . CONCLUSION Clinical and functional improvement after physical training in HF patients is associated with a decrease in adrenergic activation and in both CNP and BNP concentration . Changes in CNP plasma concentration after physical training might reflect an improvement in endothelial function BACKGROUND Regular exercise is recommended to improve outcomes in patients with heart failure . Exercise is known to decrease inflammation and thought to decrease myocardial stress ; however , studies of exercise in heart failure have had mixed results on levels of N-terminal pro-B-type natriuretic peptide ( NT-proBNP ) and high-sensitivity C-reactive protein ( hsCRP ) . A multimarker analysis may help to identify distinct subgroups of patients who respond to exercise . Our primary study objective was to identify common and distinct patterns of change in hsCRP and NT-proBNP and to quantify the influence of exercise therapy on the observed patterns of change . METHODS AND RESULTS NT-proBNP and hsCRP were assessed in a r and om sample of 320 participants from the biomarker sub study of HF-ACTION , a r and omized clinical trial of exercise training versus usual care in patients with stable and chronic heart failure . Growth mixture modeling was used to identify unique biomarker patterns over 12 months . Three statistically independent and clinical ly meaningful biomarker patterns of NT-proBNP and hsCRP were identified . Two patterns were combined and compared with the " low/stable " pattern , which was characterized by the lowest levels of NT-proBNP and hsCRP over time . Participants who were taking a loop diuretic and had hypertension or ischemic etiology were ∼2 times as likely to be in the " elevated/worsening " biomarker pattern . Participants r and omized to the exercise intervention were less likely to be in the elevated/worsening pattern of NT-proBNP and hsCRP ( relative risk ratio 0.56 , 95 % confidence interval 0.32 - 0.98 ; P = .04 ) . CONCLUSIONS Exercise therapy was protective for reducing the frequency of membership in the elevated/worsening biomarker pattern , indicating that exercise may be helpful in delaying the progression of heart failure BACKGROUND B-Type natriuretic peptides ( BNP ) and cardiac troponin T ( cTnT ) predict cardiovascular events in heart failure ( HF ) patients , but additional refinement in risk stratification may be possible by targeting pathways leading to fibrosis . We aim ed to assess the value of serial measurements of soluble suppression of tumorigenicity 2 ( sST2 ) and galectin-3 to identify risk for adverse pathophysiologic processes . METHODS New York Heart Association ( NYHA ) functional class III-IV HF patients ( n = 180 ; LVEF ≤40 % ) were prospect ively evaluated with biomarkers collected every 3 months over 2 years and analyzed regarding a primary end point of death/cardiac transplantation and a secondary end point of HF-related hospitalization or death/transplantation . RESULTS Time-dependent univariate analyses demonstrated that elevations of sST2 ( ≥49.3 ng/mL male , ≥33.5 ng/mL female ) and galectin-3 ( ≥22.1 ng/mL ) were predictive of the primary and secondary end points . In multivariate models adjusted for BNP , cTnT , and clinical variables , sST2 but not galectin-3 remained an independent predictor ( hazard ratio 3.22 , 95 % confidence interval 1.76 - 5.89 ; P < .001 ) . With serial measurements , only sST2 demonstrated incremental value in reclassifying patients to higher risk . CONCLUSIONS Serial monitoring of sST2 ( indicating myocardial fibrosis and remodeling ) and cTnT ( reflecting myocardial injury ) identifies highest-risk HF out patients and may be valuable to guide patient tailored therapy during follow-up evaluations . Serial galectin-3 monitoring in ambulatory HF patients may not be of benefit PURPOSE : Chronic heart failure ( CHF ) patients often present with (pre)diabetes , which negatively influences prognosis . Unlike the proven effect of exercise on glucose regulation in the general population , its effect in CHF is unclear . Therefore , this study aim ed at investigating the effect of exercise training on glucose regulation in stable CHF patients . METHODS : Twenty-two CHF patients were r and omized into training ( EX , n = 15 ) and control ( CON , n = 7 ) groups . Before and after a 12-week training intervention involving endurance and resistance training , glucose tolerance ( 2-hour oral glucose tolerance test ) , exercise tolerance ( cardiopulmonary exercise test ) , muscle strength ( isokinetic dynamometer ) , heart function ( echocardiography ) , glycated hemoglobin , body composition ( dual-energy x-ray absorptiometry ) , and quality of life ( EQ5D ) were assessed . RESULTS : At baseline , glucose levels 2 hours after glucose intake were elevated in both groups . Whereas area under the glucose curve did not change , area under the insulin curve decreased following training ( EX , −13 ± 23 % vs CON , + 22 ± 33 % ; P < .05 ) . Changes in the ratio of mitral peak velocity of early filling/early diastolic mitral annular velocity and waist-to-hip fat mass ratio were related to changes in the insulin curve . Exercise training result ed in improved oxygen uptake at the second ventilatory threshold ( EX , + 10 ± 5 % vs CON , −8 ± 5 % ; P < .05 ) and isokinetic strength endurance of the upper leg ( EX , + 25 ± 9 % vs CON , −6 ± 5 % ; P < 0.05 ) . Lean body tissue was increased by 2.2 ± 0.5 % in EX versus 0.2 ± 0.6 % in CON ( P < .05 ) . CONCLUSION : Our data suggest that exercise training attenuates worsening of glucose regulation typically seen in a stable CHF population BACKGROUND It remains unclear whether patients with chronic heart failure ( CHF ) and advanced left ventricular ( LV ) dysfunction on β-blocker therapy benefit from exercise training ( ET ) . METHODS AND RESULTS We studied 45 CHF patients with advanced LV dysfunction [ ejection fraction ( LVEF ) < 25 % ] and impaired exercise tolerance [ normalized peak oxygen uptake ( PVO₂ ) < 70 % ] receiving a β-blocker : 33 patients participated in a cardiac rehabilitation program with ET ( ET group ) and 12 did not ( inactive control group ) . Exercise capacity , LV dimension and plasma B-type natriuretic peptide ( BNP ) were assessed before and after a 3-month study period . At baseline , both groups had markedly reduced LVEF ( ET group 18 ± 4 % vs. Control group 18 ± 5 % , NS ) and impaired exercise capacity ( normalized PVO₂ 51 ± 10 % vs. 55 ± 9 % , NS ) . Although one patient in the ET group withdrew from the program due to worsening CHF , no serious cardiac events occurred during the ET sessions . After 3 months , the ET group ( n = 24 ) had significantly improved PVO₂ by 16 ± 15 % ( 1,005 ± 295 to 1,167 ± 397ml/min , P < 0.001 ) , while the PVO₂ of the control group was unchanged . LV end-diastolic dimension decreased in both groups to a similar extent , but plasma BNP was significantly decreased only in the ET group ( 432 to 214 pg/ml , P < 0.05 ) . CONCLUSIONS The data indicate that in CHF patients with advanced LV dysfunction on β-blocker therapy , ET successfully improves exercise capacity and BNP without adversely affecting LV remodeling or causing serious cardiac complications Background Inspiratory and peripheral muscle training improves muscle strength , exercise tolerance , and quality of life in patients with chronic heart failure ( HF ) . However , studies investigating different workloads for these exercise modalities are still lacking . Objective To examine the effects of low and moderate intensities on muscle strength , functional capacity , and quality of life . Design A r and omized controlled trial . Methods Thirty-five patients with stable HF ( aged > 18 years , NYHA II/III , LVEF < 40 % ) were r and omized to : non-exercise control group ( n = 9 ) , low-intensity training group ( LIPRT , n = 13 , 15 % maximal inspiratory workload , and 0.5 kg of peripheral muscle workload ) or moderate-intensity training group ( MIPRT , n = 13 , 30 % maximal inspiratory workload and 50 % of one maximum repetition of peripheral muscle workload ) . The outcomes were : respiratory and peripheral muscle strength , pulmonary function , exercise tolerance by the 6-minute walk test , symptoms based on the NYHA functional class , and quality of life using the Minnesota Living with Heart Failure Question naire . Results All groups showed similar quality -of-life improvements . Low and moderate intensities training programs improved inspiratory muscle strength , peripheral muscle strength , and walking distance . However , only moderate intensity improved expiratory muscle strength and NYHA functional class in HF patients . Conclusions The low-intensity inspiratory and peripheral resistance muscle training improved inspiratory and peripheral muscle strength and walking distance , demonstrating that LIPRT is an efficient rehabilitation method for debilitated HF patients . In addition , the moderate-intensity resistance training also improved expiratory muscle strength and NYHA functional class in HF patients OBJECTIVES We sought to evaluate the effect of physical training on neurohormonal activation in patients with heart failure ( HF ) . BACKGROUND Patients with HF benefit from physical training . Chronic neurohormonal activation has detrimental effects on ventricular remodeling and prognosis of patients with HF . METHODS A total of 95 patients with HF were assigned r and omly into two groups : 47 patients ( group T ) underwent a nine-month training program at 60 % of the maximal oxygen uptake ( VO2 ) , whereas 48 patients did not ( group C ) . The exercise load was adjusted during follow-up to achieve a progressive training effect . Plasma assay of B-type natriuretic peptide ( BNP ) , amino-terminal pro-brain natriuretic peptide ( NT-proBNP ) , norepinephrine , plasma renin activity , and aldosterone ; quality -of-life question naire ; echocardiogram ; and cardiopulmonary stress test were performed upon enrollment and at the third and ninth month . RESULTS A total of 85 patients completed the protocol ( 44 in group T , left ventricular ejection fraction [ EF ] 35 + /- 2 % , mean + /- SEM ; and 41 in group C , EF 32 + /- 2 % , p = NS ) . At the ninth month , patients who underwent training showed an improvement in workload ( + 14 % , p < 0.001 ) , peak VO2 ( + 13 % , p < 0.001 ) , systolic function ( EF + 9 % , p < 0.01 ) , and quality of life . We noted that BNP , NT-proBNP , and norepinephrine values decreased after training ( -34 % , p < 0.01 ; -32 % , p < 0.05 ; -26 % , p < 0.01 , respectively ) . Increase in peak VO2 with training correlated significantly with the decrease in both BNP/NT-proBNP level ( p < 0.001 and p < 0.01 , respectively ) . Patients who did not undergo training showed no changes . CONCLUSIONS Clinical benefits after physical training in patients with HF are associated with blunting of adrenergic overactivity and of natriuretic peptide overexpression The present study investigates whether lower-limb dominant exercise training in patients with chronic heart failure ( CHF ) improves endothelial function primarily in the trained lower extremities or equally in the upper and lower extremities . Twenty-eight patients with CHF were r and omized to the exercise or control group . The exercise group underwent cycle ergometer training for 3 months while controls continued an inactive sedentary lifestyle . Exercise capacity ( 6-min walk test ) and flow-mediated vasodilation in the brachial and posterior tibial arteries were evaluated . After 3 months , walking performance increased only in the exercise group ( 488+/-16 to 501+/-14 m [ control ] ; 497+/-23 to 567+/-39 m [ exercise , p<0.05 ] ) . The flow-mediated vasodilation in the brachial arteries did not change in either group ( 4.2+/-0.5 to 4.5+/-0.4 % [ control ] ; 4.3+/-0.5 to 4.6+/-0.4 % [ exercise ] ) , but that in the posterior tibial arteries increased only in the exercise group ( 4.1+/-0.5 to 4.1+/-0.3 % [ control ] ; 3.6+/-0.3 to 6.4+/-0.6 % [ exercise , p<0.01 ] ) . Cycle ergometer training improved flow-mediated vasodilation in the trained lower limbs , but not in the untrained upper limbs . Exercise training appears to correct endothelial dysfunction predominantly by a local effect in the trained extremities Objective Abnormal expression of cellular adhesion molecules may be related to endothelial dysfunction , a key feature in chronic heart failure . This study compares the effects of 10-wk supervised moderate-intensity continuous aerobic exercise ( CAE ) and intermittent aerobic exercise ( IAE ) programs on markers of endothelial damage , disease severity , functional and metabolic status , and quality -of-life in chronic heart failure patients . Design Fifty-seven patients between 41 and 81 yrs with New York Heart Association class II – III chronic heart failure and with a left ventricular ejection fraction of 35%–55 % were r and omized into three groups : nonexercising control , CAE , and IAE , which exercised three times a week for 10 wks . Endothelial damage was assessed by serum markers of vascular cell adhesion molecule-1 , serum intercellular adhesion molecule-1 , and nitric oxide ; disease severity was measured by left ventricular ejection fraction and N-terminal probrain natriuretic peptide ; metabolic status was evaluated by body composition analysis and lipid profile levels ; functional status was evaluated by cardiorespiratory exercise stress test and 6-min walking distance ; quality -of-life was assessed with Left Ventricular Dysfunction-36 and Short-Form 36 question naires at the baseline and at the end of the 10th week . Results Significant decreases in serum vascular cell adhesion molecule-1 or serum intercellular adhesion molecule-1 in IAE and CAE groups after training were found , respectively . Resting systolic and diastolic blood pressure , peak systolic and diastolic blood pressure , 6-min walking distance , and the mental health and vitality components of Short-Form 36 improved in the CAE group , whereas left ventricular ejection fraction and 6-min walking distance improved in the IAE group compared with the control group . Conclusions Both moderate-intensity CAE and IAE programs significantly reduced serum markers of adhesion molecules and prevented the change in VO2 in patients with chronic heart failure BACKGROUND Diastolic dysfunction in long-term heart failure is accompanied by abnormal neurohormonal control and ventricular stiffness . The diastolic phase is determined by a balance between pressure gradients and intrinsic ventricular wall properties : according to a mathematical model , the latter ( ie , left ventricular [ LV ] elastance , K(LV ) ) may be calculated by the formula : K(LV ) = (70/[DT-20])(2 ) mm Hg/mL , where DT is the transmitral Doppler deceleration time . METHODS AND RESULTS In 54 patients with chronic systolic heart failure ( 39 men , 15 women ; age 65 + /- 10 years ; New York Heart Association [ NYHA ] , 2.3 + /- 0.9 ; ejection fraction [ EF ] , 32 % + /- 5 % ) , we analyzed the relationship between K(LV ) and an index of neurohormonal derangement ( levels of brain natriuretic peptide [ BNP ] ) , and investigated whether 3 months of physical training could modulate diastolic operating stiffness . Patients were r and omized to physical training ( n = 27 ) or to a control group ( n = 27 ) . Before and after training , patients underwent Doppler echocardiogram and cardiopulmonary stress test . At baseline , ventricular stiffness was related to BNP levels ( P < .01 ) . Training improved NYHA class , exercise performance , and estimated pulmonary pressure . BNP was reduced . Ventricular volumes , mean blood pressure , and EF remained unchanged . A 27 % reduction of elastance was observed ( K(LV ) , 0.111 + /- 0.044 from 0.195 + /- 0.089 mm Hg/mL ; P < .01 ) , whose magnitude was related to changes in BNP ( P < .05 ) and to K(LV ) at baseline ( P < .01 ) . No changes in K(LV ) were observed in controls after 3 months ( 0.192 + /- 0.115 from 0.195 + /- 0.121 mm Hg/mL ) . CONCLUSIONS In heart failure , left ventricular diastolic stiffness is related to neurohormonal derangement and is modified by physical training . This improvement in LV compliance could result from a combination of hemodynamic improvement and regression of the fibrotic process OBJECTIVES To test the hypothesis that exercise training ( ET ) improves exercise capacity and other clinical outcomes in older persons with heart failure with reduced ejection fraction ( HfrEF ) . DESIGN R and omized , controlled , single-blind trial . SETTING Outpatient cardiac rehabilitation program . PARTICIPANTS Fifty-nine patients aged 60 and older with HFrEF recruited from hospital records and referring physicians were r and omly assigned to a 16-week supervised ET program ( n=30 ) or an attention-control , nonexercise , usual care control group ( n=29 ) . INTERVENTION Sixteen-week supervised ET program of endurance exercise ( walking and stationary cycling ) three times per week for 30 to 40 minutes at moderate intensity regulated according to heart rate and perceived exertion . MEASUREMENTS Individuals blinded to group assignment assessed four domains pivotal to HFrEF pathophysiology : exercise performance , left ventricular ( LV ) function , neuroendocrine activation , and health-related quality of life ( QOL ) . RESULTS At follow-up , the ET group had significantly greater exercise time and workload than the control group , but there were no significant differences between the groups for the primary outcomes : peak exercise oxygen consumption ( VO(2 ) peak ) , ventilatory anaerobic threshold ( VAT ) , 6-minute walk distance , QOL , LV volumes , EF , or diastolic filling . Other than serum aldosterone , there were no significant differences after ET in other neuroendocrine measurements . Despite a lack of a group " training " effect , a subset ( 26 % ) of individuals increased VO(2 ) peak by 10 % or more and improved other clinical variables as well . CONCLUSION In older patients with HFrEF , ET failed to produce consistent benefits in any of the four pivotal domains of HF that were examined , although the heterogeneous response of older patients with HFrEF to ET requires further investigation to better determine which patients with HFrEF will respond favorably to ET BACKGROUND Abnormal ventilatory/hemodynamic responses to exercise contribute to functional impairment in patients with heart failure ( HF ) . This study investigates how interval and continuous exercise regimens influence functional capacity by modulating ventilatory efficiency and hemodynamic function in HF patients . METHODS Forty-five HF patients were r and omized to perform either aerobic interval training ( AIT ; 3-minute intervals at 40 % and 80 % VO(2peak ) ) or moderate continuous training ( MCT ; sustained 60 % VO()for 30 min/day , 3 days/week for 12 weeks , or to a control group that received general healthcare ( GHC ) . A noninvasive bio-reactance device was adopted to measure cardiac hemodynamics , whereas a near-infrared spectroscopy was employed to assess perfusion/O2 extraction in frontal cerebral lobe ( ∆[THb]FC/∆[HHb]FC ) and vastus lateralis ( ∆[THb]VL/∆[HHb]VL ) , respectively . RESULTS Following the 12-week intervention , the AIT group exhibited higher oxygen uptake efficiency slope ( OUES ) and lower VE-VCO2 slope than the MCT and GHC groups . Furthermore , AIT , but not MCT , boosted cardiac output ( CO ) and increased ∆[THb]FC , ∆[THb]VL , and ∆[HHb]VL during exercise . In multivariate analyses , CO was the dominant predictor of VO(2peak ) . ∆[THb]FC and ∆[THb]VL , which modulated the correlation between CO and OUES , were significantly correlated with OUES . Simultaneously , ∆[THb]VL was the only factor significantly associated with VE-VCO2 slope . Additionally , AIT reduced plasma brain natriuretic peptide , myeloperoxidase , and interleukin-6 levels and increased the Short Form-36 physical/mental component scores and decreased the Minnesota Living with Heart Failure question naire score . CONCLUSIONS AIT effectively improves oxygen uptake efficiency by enhancing cerebral/muscular hemodynamics and suppresses oxidative stress/inflammation associated with cardiac dysfunction , and also promotes generic/disease-specific qualities of life in patients with HF BACKGROUND Supervised cardiac rehabilitation programs have been offered to patients following myocardial infa rct ( MI ) , coronary artery bypass graft surgery ( CABG ) and percutaneous coronary intervention ( PCI ) for many years . However , limited information is available on the usefulness of rehabilitation programs in chronic heart failure ( CHF ) . The aim of our study was to evaluate the outcome of supervised physical training on CHF patients by measuring both central and peripheral factors . METHODS This was a prospect i ve r and omized study , including 43 patients with CHF , New York Heart Association ( NYHA ) class II or III , mean age 68 years . After initial measurements of VO2 peak , 6 min walk distance , muscle strength , plasma levels of atrial natriuretic peptide ( ANP ) and brain natriuretic peptide ( BNP ) , echocardiogram , measurements of pulmonary function and quality of life question naire , patients were r and omized to either a training group ( n = 21 ) or a control group ( n = 22 ) . The training group had supervised aerobic and resistance training program twice a week for five months . After the training program was completed , all measurements were repeated in both groups . RESULTS No training related adverse events were reported . Significant improvement was found between groups in the six minute walk test ( + 37.1 m vs. + 5.3 m , p = 0.01 ) , work load on the bicycle exercise test ( + 6.1 W vs. + 2.1 W , p = 0.03 ) , time on the bicycle exercise test ( + 41 s vs. + 0 s , p = 0.02 ) and quadriceps muscle strength test ( + 2.8 kg . vs. + 0.2 kg . , p = 0.003 ) . Quality of life factors that reflect exercise tolerance and general health , improved significantly in the training group compared to the control group . No other significant changes were found between the two groups . CONCLUSION Supervised physical training as used in this study appears safe for CHF patients in NYHA class II or III . The improvement in functional capacity observed in the training group seems to be related to peripheral factors rather than in central cardiovascular performance BACKGROUND Functional electrical stimulation ( FES ) improves exercise capacity , quality of life , emotional stress , and endothelial function in chronic heart failure with impaired systolic function . We sought to investigate the effects of FES on the above parameters in patients with preserved ejection fraction ( HFpEF ) . METHODS Thirty HFpEF patients , 18 female and 12 male , aged 69 ± 8 years , in New York Heart Association class II or III and with mean ejection fraction 63 % ± 6 % , were r and omly ( 1:1 ) assigned to a 6-week FES program or placebo . Assessment was performed at baseline and after completion of training protocol and included 6-minute walked distance , quality of life ( Kansas City Cardiomyopathy Question naire and Minnesota Living with Heart Failure Question naire ) , depressive symptoms ( Beck Depression Inventory and Zung self-rated depression scores ) , B-type natriuretic peptide , endothelial function ( flow-mediated dilatation ) , and left ventricular diastolic function . RESULTS A significant improvement in 6-minute walked distance ( F = 21.61 , P = .001 ) , Kansas City Cardiomyopathy Question naire summary ( F = 8.68 , P = .006 ) , Minnesota Living with Heart Failure Question naire ( F = 6.43 , P = .017 ) , Beck Depression Inventory ( F = 6.66 , P = .015 ) , Zung ( F = 6.25 , P = .019 ) , and flow-mediated dilatation diameter ( F = 11.98 , P = .002 ) was observed in the FES group compared with placebo group ; B-type natriuretic peptide also declined but not significantly ( F = 0.249 , P = .622 ) , and there was a tendency toward lower mitral E/e ' wave ratio ( F = 3.066 , P = .091 ) . CONCLUSION As in heart failure and reduced left ventricular ejection fraction , FES also improves exercise capacity , quality of life , emotional status , and endothelial function in HFpEF . Given the lack of effective evidence -based therapies in these patients , FES warrants further investigation OBJECTIVES The aim of this study was to determine whether biomarkers of myocardial stress and fibrosis improve prediction of the mode of death in patients with chronic heart failure . BACKGROUND The 2 most common modes of death in patients with chronic heart failure are pump failure and sudden cardiac death . Prediction of the mode of death may facilitate treatment decisions . The relationship between amino-terminal pro-brain natriuretic peptide ( NT-proBNP ) , galectin-3 , and ST2 , biomarkers that reflect different pathogenic pathways in heart failure ( myocardial stress and fibrosis ) , and mode of death is unknown . METHODS HF-ACTION ( Heart Failure : A Controlled Trial Investigating Outcomes of Exercise Training ) was a r and omized controlled trial of exercise training versus usual care in patients with chronic heart failure due to left ventricular systolic dysfunction ( left ventricular ejection fraction ≤35 % ) . An independent clinical events committee prospect ively adjudicated mode of death . NT-proBNP , galectin-3 , and ST2 levels were assessed at baseline in 813 subjects . Associations between biomarkers and mode of death were assessed using cause-specific Cox proportional hazards modeling , and interaction testing was used to measure differential associations between biomarkers and pump failure versus sudden cardiac death . Discrimination and risk reclassification metrics were used to assess the added value of galectin-3 and ST2 in predicting mode of death risk beyond a clinical model that included NT-proBNP . RESULTS After a median follow-up period of 2.5 years , there were 155 deaths : 49 from pump failure , 42 from sudden cardiac death , and 64 from other causes . Elevations in all biomarkers were associated with increased risk for both pump failure and sudden cardiac death in both adjusted and unadjusted analyses . In each case , increases in the biomarker had a stronger association with pump failure than sudden cardiac death , but this relationship was attenuated after adjustment for clinical risk factors . Clinical variables along with NT-proBNP levels were stronger predictors of pump failure ( C statistic : 0.87 ) than sudden cardiac death ( C statistic : 0.73 ) . Addition of ST2 and galectin-3 led to improved net risk classification of 11 % for sudden cardiac death , but not pump failure . CONCLUSIONS Clinical predictors along with NT-proBNP levels were strong predictors of pump failure risk , with insignificant incremental contributions of ST2 and galectin-3 . Predictability of sudden cardiac death risk was less robust and enhanced by information provided by novel biomarkers AIMS The purpose of this study was to evaluate the effectiveness , feasibility , and safety of a 4-week high-intensity inspiratory muscle training ( hi-IMT ) in patients with chronic heart failure ( CHF ) . METHODS AND RESULTS A double-blind r and omized clinical trial was carried out in 22 patients with CHF . Participants were assigned to the hi-IMT or sham-IMT group . The trainer device was a prototype of the Orygen-Dual Valve . The training workloads were adjusted weekly at the inspiratory pressure which allowed the performance of 10 consecutive maximal repetitions ( 10RM ) . Main outcomes were strength and endurance of the respiratory muscles assessed by maximal respiratory pressures ( PImax and PEmax ) and a 10RM manoeuvre , respectively . Twenty-one patients presented impairment in respiratory muscle strength and endurance . Patients in the hi-IMT group showed a significant improvement in both strength and endurance : inspiratory muscle strength in the intervention group increased 57.2 % compared with 25.9 % in the control group ( P = 0.001 ) . The percentage change in endurance was 72.7 % for the hi-IMT group compared with 18.2 % in the sham-IMT group ( P < 0.001 ) . No adverse effects occurred during the intervention . CONCLUSION A 4-week hi-IMT with the use of the Orygen-Dual Valve is shown to be an effective , feasible , and safe tool to improve weakness and fatigue of the inspiratory muscles . The key point of this study is to discuss immediate practical implication s in terms of respiratory muscle dysfunction postulated as a potential prognostic factor and as an additional therapeutic target . TRIALS REGISTRATION NCT01606553 Background Decreased exercise capacity is the main factor restricting the daily life of patients with chronic heart failure . N-terminal pro-brain natriuretic peptide ( NT pro-BNP ) is strongly related to the severity of and is an independent predictor of outcome in chronic heart failure . Design The study aim ed to evaluate the effect of exercise training on functional capacity and on changes in NT pro-BNP levels and to assess the effect of exercise training on quality of life . Material s and methods Sixty patients ( 45 men/15 women , mean age 52.7 years ; ±5.3 SD ) , with stable heart failure ( 45 ischaemic/hypertensive and 15 idiopathic patients ) , in New York Heart Association ( NYHA ) functional class II ( n = 35 ) to III ( n = 25 ) , with an ejection fraction less than 40 % , were r and omly assigned to a training ( n = 30 ) and a control group ( n = 30 ) . The training group ( 30 patients ) performed 3 months of supervised physical training programme using a bicycle ergometer for 30 min three times a week at a load corresponding to 60–70 % of their oxygen consumption ( Vo2 ) peak . The control group did not change their previous physical activity . A grade d maximal exercise test with respiratory gas analysis and an endurance test with constant workload corresponding to 85 % of the peak oxygen load at the baseline and after 3 months were performed , and at the same times NT pro-BNP levels were measured . Results The exercise capacity increased from 15.8 ( ±2.3 SD ) to 29.9 ( ±2.1 SD ) min ( P<0.0001 ) and the peak Vo2 tended to improve from 14.5 ( ±1.4 SD ) to 17.7 ( ±2.6 SD ) ml/kg per min ( P<0.0001 ) during the supervised training period . Vo2 at the anaerobic threshold increased from 12.9 ( ±1.0 SD ) to 15.5 ( ±1.7 SD ) ml/kg per min ( P<0.0001 ) . NT pro-BNP levels decreased from 3376 ( ±3133 SD ) to 1434 ( ±1673 SD ) pg/ml ( P=0.043 ) . The positive training effects were associated with an improvement in the NYHA functional class . Conclusion Physical training of moderate intensity significantly improves the exercise capacity and neurohormonal modulation in patients with chronic heart failure . This is associated with an alleviation of symptoms and improvement in quality of life Background Both endurance training ( ET ) and cardiac resynchronization therapy ( CRT ) improve quality of life ( QOL ) and exercise tolerance in patients with advanced chronic heart failure ( CHF ) . Design A r and omized intervention trial to study the effect on exercise capacity of ET in addition to CRT in patients with CHF and dyssynchrony . Methods Seventeen patients ( eight men , aged 59 ± 9 years ) with CHF and dyssynchrony were r and omized to CRT with ( n = 8) or without ( n = 9 ) ET and compared with two matched control CHF groups ( st and ard care with ET : n = 9 , st and ard care only : n = 10 ) . At baseline and after 5 months , exercise tolerance , left ventricular ( LV ) remodelling , QOL and NT-pro brain natriuretic peptide ( NT-proBNP ) levels were assessed . Results Peak oxygen consumption ( VO2peak ) , maximal workload ( Wattmax ) , circulatory power , LV ejection fraction , dyssynchrony and QOL improved in both CRT groups . However , the increase in VO2peak ( + 40 % versus + 16 % , P = 0.005 ) , Wattmax ( + 43 % versus + 13 % , P = 0.0005 ) , and circulatory power ( + 74 % versus + 32 % , P = 0.01 ) , was significantly greater in the trained versus the untrained CRT patients . Comparison of the four patient groups confirmed the cumulative effects of CRT plus ET . Conclusions ET in resynchronized CHF patients is feasible and further enhances exercise tolerance . Patients with severe CHF should be prescribed an exercise training programme after implantation in order to maximize the expected benefit . Eur J Cardiovasc Prev Rehabil 14 : 99 - 106 © 2007 The European Society of IMPORTANCE More than 80 % of patients with heart failure with preserved ejection fraction ( HFPEF ) , the most common form of heart failure among older persons , are overweight or obese . Exercise intolerance is the primary symptom of chronic HFPEF and a major determinant of reduced quality of life ( QOL ) . OBJECTIVE To determine whether caloric restriction ( diet ) or aerobic exercise training ( exercise ) improves exercise capacity and QOL in obese older patients with HFPEF . DESIGN , SETTING , AND PARTICIPANTS R and omized , attention-controlled , 2 × 2 factorial trial conducted from February 2009 through November 2014 in an urban academic medical center . Of 577 initially screened participants , 100 older obese participants ( mean [ SD ] : age , 67 years [ 5 ] ; body mass index , 39.3 [ 5.6 ] ) with chronic , stable HFPEF were enrolled ( 366 excluded by inclusion and exclusion criteria , 31 for other reasons , and 80 declined participation ) . INTERVENTIONS Twenty weeks of diet , exercise , or both ; attention control consisted of telephone calls every 2 weeks . MAIN OUTCOMES AND MEASURES Exercise capacity measured as peak oxygen consumption ( V̇O2 , mL/kg/min ; co- primary outcome ) and QOL measured by the Minnesota Living with Heart Failure ( MLHF ) Question naire ( score range : 0 - 105 , higher scores indicate worse heart failure-related QOL ; co- primary outcome ) . RESULTS Of the 100 enrolled participants , 26 participants were r and omized to exercise ; 24 to diet ; 25 to exercise + diet ; 25 to control . Of these , 92 participants completed the trial . Exercise attendance was 84 % ( SD , 14 % ) and diet adherence was 99 % ( SD , 1 % ) . By main effects analysis , peak V̇O2 was increased significantly by both interventions : exercise , 1.2 mL/kg body mass/min ( 95 % CI , 0.7 to 1.7 ) , P < .001 ; diet , 1.3 mL/kg body mass/min ( 95 % CI , 0.8 to 1.8 ) , P < .001 . The combination of exercise + diet was additive ( complementary ) for peak V̇O2 ( joint effect , 2.5 mL/kg/min ) . There was no statistically significant change in MLHF total score with exercise and with diet ( main effect : exercise , -1 unit [ 95 % CI , -8 to 5 ] , P = .70 ; diet , -6 units [ 95 % CI , -12 to 1 ] , P = .08 ) . The change in peak V̇O2 was positively correlated with the change in percent lean body mass ( r = 0.32 ; P = .003 ) and the change in thigh muscle : intermuscular fat ratio ( r = 0.27 ; P = .02 ) . There were no study -related serious adverse events . Body weight decreased by 7 % ( 7 kg [ SD , 1 ] ) in the diet group , 3 % ( 4 kg [ SD , 1 ] ) in the exercise group , 10 % ( 11 kg [ SD , 1 ] in the exercise + diet group , and 1 % ( 1 kg [ SD , 1 ] ) in the control group . CONCLUSIONS AND RELEVANCE Among obese older patients with clinical ly stable HFPEF , caloric restriction or aerobic exercise training increased peak V̇O2 , and the effects may be additive . Neither intervention had a significant effect on quality of life as measured by the MLHF Question naire . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00959660 AIMS Vent-HeFT is a multicentre r and omized trial design ed to investigate the potential additive benefits of inspiratory muscle training ( IMT ) on aerobic training ( AT ) in patients with chronic heart failure ( CHF ) . METHODS AND RESULTS Forty-three CHF patients with a mean age of 58 ± 12 years , peak oxygen consumption ( peak VO2 ) 17.9 ± 5 mL/kg/min , and LVEF 29.5 ± 5 % were r and omized to an AT/IMT group ( n = 21 ) or to an AT/SHAM group ( n = 22 ) in a 12-week exercise programme . AT involved 45 min of ergometer training at 70 - 80 % of maximum heart rate , three times a week for both groups . In the AT/IMT group , IMT was performed at 60 % of sustained maximal inspiratory pressure ( SPImax ) while in the AT/SHAM group it was performed at 10 % of SPImax , using a computer biofeedback trainer for 30 min , three times a week . At baseline and at 3 months , patients were evaluated for exercise capacity , lung function , inspiratory muscle strength ( PImax ) and work capacity ( SPImax ) , quality of life ( QoL ) , LVEF and LV diameter , dyspnoea , C-reactive protein ( CRP ) , and NT-proBNP . IMT result ed in a significantly higher benefit in SPImax ( P = 0.02 ) , QoL ( P = 0.002 ) , dyspnoea ( P = 0.004 ) , CRP ( P = 0.03 ) , and NT-proBNP ( P = 0.004 ) . In both AT/IMT and AT/SHAM groups PImax ( P < 0.001 , P = 0.02 ) , peak VO2 ( P = 0.008 , P = 0.04 ) , and LVEF ( P = 0.005 , P = 0.002 ) improved significantly ; however , without an additional benefit for either of the groups . CONCLUSION This r and omized multicentre study demonstrates that IMT combined with aerobic training provides additional benefits in functional and serum biomarkers in patients with moderate CHF . These findings advocate for application of IMT in cardiac rehabilitation programmes Abstract Objectives . Exercise training might improve cardiac function as well as functional capacity in patients with chronic heart failure ( CHF ) . N-terminal pro-B-type natriuretic peptide ( NT pro-BNP ) , is associated with the severity of the disease , and has been reported to be an independent predictor of outcome in CHF . We evaluated the effect of a four months group-based aerobic interval training program on circulating levels of NT pro-BNP in patients with CHF . We have previously reported improved functional capacity in 80 patients after exercise in this exercise program . Methods . Seventy-eight patients with stable CHF ( 21 % women ; 70±8 years ; left ventricular ejection fraction 30±8.6 % ) on optimal medical treatment were r and omized either to interval training ( n=39 ) , or to a control group ( n=39 ) . Circulating levels of NT pro-BNP , a six minute walk test ( 6MWT ) and cycle ergometer test were evaluated at baseline , post exercise , and further after 12 months . Results . There were no significant differences in NT pro-BNP levels from baseline to either post exercise or long-term follow-up between or within the groups . Inverse correlations were observed between NT pro-BNP and 6MWT ( r=−0.24 , p=0.035 ) and cycle exercise time ( r=−0.48 , p<0.001 ) at baseline . But no significant correlations were observed between change in NT pro-BNP and change in functional capacity ( 6MWT ; r=0.12 , p=0.33 , cycle exercise time ; r=0.04 , p=0.72 ) . Conclusion . No significant changes in NT pro-BNP levels were observed after interval training , despite significant improvement of functional capacity |
13,228 | 30,068,234 | Conclusion Anaemia in heart failure is overwhelmingly characterized by impaired erythropoietin production , which is exacerbated with age , female sex , left ventricular ejection fraction , inflammation and disease severity | Background Despite multiple factors correlating with the high prevalence of anaemia in heart failure , the prevailing mechanisms have yet to be established .
The purpose of this study is to systematic ally review the literature and determine whether low circulating haemoglobin is primarily underlain by erythropoietin resistance or defective production in heart failure . | BACKGROUND Considerable morbidity and mortality are still associated with congestive heart failure ( CHF ) syndromes , despite improvement in therapy . Activation of neurohormonal , inflammatory , and oxidative mechanisms has been shown to contribute to the significant morbidity and mortality . Erythropoietin ( EPO ) is a cytokine known to regulate erythroid proliferation , attenuate apoptosis and oxidative stress , and promote angiogenesis . We prospect ively evaluated the predictive value of baseline EPO , N-terminal pro-B-type natriuretic peptide , and C-reactive protein levels in patients with clinical ly controlled chronic CHF . METHODS One hundred eighty-eight out patients from a CHF clinic had baseline assessment of EPO , N-terminal pro-B-type natriuretic peptide , and C-reactive protein levels and a complete clinical data profile . These patients were followed up for 24 months for any hospitalization due to CHF or mortality . RESULTS Circulating EPO levels were higher in CHF patients and increased in subjects with higher New York Heart Association scores . Levels of EPO ( at a cutoff of 23 mU/mL ) and N-terminal pro-B-type natriuretic peptide ( cutoff at the median of 1556 pg/mL ) were found to be strong predictors of mortality and CHF hospitalization , whereas C-reactive protein levels ( cutoff of 10 mg/L ) predicted CHF hospitalizations but not mortality . Left ventricular ejection fraction was found to be a predictor of mortality but not of CHF hospitalizations . Serum levels of EPO were significantly correlated with N-terminal pro-B-type natriuretic peptide and C-reactive protein levels but not with left ventricular ejection fraction . CONCLUSION If confirmed in large-scale clinical studies , determination of circulating EPO levels may aid in predicting morbidity and mortality in patients with clinical ly controlled congestive CHF BACKGROUND Hyporesponders to erythropoietin-stimulating agents ( ESAs ) have been associated with an increased subsequent risk of death or cardiovascular events . We hypothesized that subjects who are hyporesponsive to erythropoietin alfa would have higher plasma volumes and lower red cell deficits than subjects who are responsive to therapy . METHODS As part of a prospect i ve , single blind , r and omized , placebo-controlled study comparing erythropoietin alfa with placebo in older adults ( n = 56 ) with heart failure and a preserved ejection fraction ( HFPEF ) , we performed blood volume analysis with the use of an indicator dilution technique with (131)iodine-labeled albumin . We evaluated differences in plasma volumes and red cell volumes in hyporesponders ( eg , < 1 g/dL increase in hemoglobin within the first 4 weeks of treatment with erythropoetin alfa ) compared with subjects who were responders and controls . RESULTS Nine of 28 subjects ( 32 % ) assigned to ESA were hyporesponders . Hyporesponders did not differ from responders nor control subjects by any baseline demographic , clinical , or laboratory parameter , including hemoglobin . Hyporesponders had a greater total blood volume expansion ( 1,264.7 ± 387 vs 229 ± 206 mL ; P = .02 ) but less of a red cell deficit ( -96.2 ± 126 vs -402.5 ± 80.6 mL ; P = .04 ) and a greater plasma volume expansion ( + 1,360.8 ± 264.5 vs + 601.1 ± 165.5 mL ; P = .01 ) . Among responders , the increase in hemoglobin with erythropoietin alfa was associated primarily with increases in red cell volume ( r = 0.91 ; P < .0001 ) as well as a decline in plasma volume ( r = -0.55 ; P = .06 ) . CONCLUSIONS Among older adults with HFPEF and anemia , hyporesponders to erythropoietin alfa had a hemodilutional basis of their anemia , suggesting that blood volume analysis can identify a cohort likely to respond to therapy BACKGROUND Iron deficiency may impair aerobic performance . This study aim ed to determine whether treatment with intravenous iron ( ferric carboxymaltose ) would improve symptoms in patients who had heart failure , reduced left ventricular ejection fraction , and iron deficiency , either with or without anemia . METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association ( NYHA ) functional class II or III , a left ventricular ejection fraction of 40 % or less ( for patients with NYHA class II ) or 45 % or less ( for NYHA class III ) , iron deficiency ( ferritin level < 100 microg per liter or between 100 and 299 microg per liter , if the transferrin saturation was < 20 % ) , and a hemoglobin level of 95 to 135 g per liter . Patients were r and omly assigned , in a 2:1 ratio , to receive 200 mg of intravenous iron ( ferric carboxymaltose ) or saline ( placebo ) . The primary end points were the self-reported Patient Global Assessment and NYHA functional class , both at week 24 . Secondary end points included the distance walked in 6 minutes and the health-related quality of life . RESULTS Among the patients receiving ferric carboxymaltose , 50 % reported being much or moderately improved , as compared with 28 % of patients receiving placebo , according to the Patient Global Assessment ( odds ratio for improvement , 2.51 ; 95 % confidence interval [ CI ] , 1.75 to 3.61 ) . Among the patients assigned to ferric carboxymaltose , 47 % had an NYHA functional class I or II at week 24 , as compared with 30 % of patients assigned to placebo ( odds ratio for improvement by one class , 2.40 ; 95 % CI , 1.55 to 3.71 ) . Results were similar in patients with anemia and those without anemia . Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality -of-life assessment s. The rates of death , adverse events , and serious adverse events were similar in the two study groups . CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency , with or without anemia , improves symptoms , functional capacity , and quality of life ; the side-effect profile is acceptable . ( Clinical Trials.gov number , NCT00520780 ) BACKGROUND A number of animal studies and our own clinical trials point towards a possible influence of the renin-angiotensin-system ( RAS ) on erythropoietin ( EPO ) production . In this study we investigated the role of angiotensin II in the regulation of EPO production in humans . METHODS After a hemorrhage of 750 ml as a basic physiological stimulus 72 healthy male volunteers received in a parallel design either placebo ( physiologic electrolyte solution ) for 6 h , angiotensin II i.v . for 6 h ( 1 - 3 microgram min-1 , sufficient to increase systolic blood pressure by 20 mmHg ) , the selective AT1-receptor antagonist losartan , the ACE-inhibitor captopril , angiotensin II + losartan , or angiotensin II + captopril . RESULTS Administration of angiotensin II alone and in combination with captopril result ed in a significantly higher Cmax EPO ( 67 % higher vs. placebo , P < 0.05 ) and AUCEPO ( 0 - 24h ) ( 40 % higher vs. placebo , P < 0.05 ) . In the groups receiving losartan or captopril alone or the combination of angiotensin II + losartan no significant difference of Cmax EPO and AUCEPO(0 - 24h ) compared to placebo could be detected . CONCLUSIONS This study shows in a model of controlled , basic physiological stimulation of renal EPO production that angiotensin II is able to increase EPO levels in humans . This effect of angiotensin II can be blocked by the specific AT1-receptor antagonist losartan but not by the ACE-inhibitor captopril . The result may be interpreted as a hint that one signal for the control of EPO production in humans may be mediated by angiotensin II (AT1)-receptors Background Anaemia and iron deficiency are frequent following major surgery . The present study aims to identify the iron deficiency patterns in cardiac surgery patients at their admission to a cardiac rehabilitation programme , and to determine which perioperative risk factor(s ) may be associated with functional and absolute iron deficiency . Design This was a retrospective study on prospect ively collected data . Methods The patient population included 339 patients . Functional iron deficiency was defined in the presence of transferrin saturation < 20 % and serum ferritin ≥100 µg/l . Absolute iron deficiency was defined in the presence of serum ferritin values < 100 µg/l . Results Functional iron deficiency was found in 62.9 % of patients and absolute iron deficiency in 10 % of the patients . At a multivariable analysis , absolute iron deficiency was significantly ( p = 0.001 ) associated with mechanical prosthesis mitral valve replacement ( odds ratio 5.4 , 95 % confidence interval 1.9–15 ) and tissue valve aortic valve replacement ( odds ratio 4.5 , 95 % confidence interval 1.9–11 ) . In mitral valve surgery , mitral repair carried a significant ( p = 0.013 ) lower risk of absolute iron deficiency ( 4.4 % ) than mitral valve replacement with tissue valves ( 8.3 % ) or mechanical prostheses ( 22.5 % ) . Postoperative outcome did not differ between patients with functional iron deficiency and patients without iron deficiency ; patients with absolute iron deficiency had a significantly ( p = 0.017 ) longer postoperative hospital stay ( median 11 days ) than patients without iron deficiency ( median nine days ) or with functional iron deficiency ( median eight days ) . Conclusions Absolute iron deficiency following cardiac surgery is more frequent in heart valve surgery and is associated with a prolonged hospital stay . Routine screening for iron deficiency at admission in the cardiac rehabilitation unit is suggested BACKGROUND Erythropoietin ( Epo ) , a growth factor produced by the kidney , is important in heart failure patients to promote oxygen delivery to tissues . Seventy-two chronic heart failure ( CHF ) patients at our outpatient clinic were subjected to morning serum Epo-level measurements and classified according to NYHA criteria . RESULTS Forty-eight patients of classes III and IV had a significantly elevated serum Epo-level of 42.9+/-40.3 mIU/ml ( mean+/-1 S.D. ) when compared to the mean level of 24 patients of classes I and II who had a normal range mean value of 13.4+/-6.2 mIU/ml ( P<0.05 ) . Patients on angiotensin-converting enzyme ( ACE ) inhibitors showed a trend towards lower serum Epo-levels compared to patients treated with angiotensin-II type-1 receptor antagonists ( AT(1 ) antagonists ) ( levels : 33.3+/-35.6 mIU/ml and 43.6+/-38.1 mIU/ml ) . This trend did not , however , reach statistical significance ( P=0.36 ) . CONCLUSION We suggest that a desirable Epo increase in class III and IV CHF patients could be achieved by either recombinant human Epo administration or , possibly , by appropriate selection of the concomitant medical therapy . A large prospect i ve study shall investigate the possible advantage of AT(1 ) antagonists over ACE-inhibitors with regard to Epo effect Background : Recombinant erythropoietin has become a routine component of care of patients with chronic kidney disease reducing the need for blood transfusions but raising the risks for cardiovascular events . We undertook this secondary analysis of subjects enrolled in the Correction of Hemoglobin and Outcomes in Renal Insufficiency ( CHOIR ) trial to examine the interrelationships between epoetin-alfa maintenance doses utilized and achieved hemoglobin ( Hb ) irrespective of treatment target and r and omized allocation . Methods : We performed a post hoc analysis from the CHOIR trial . Inclusion criteria were Hb < 11.0 g/dl and estimated glomerular filtration rates of 15 - 50 ml/min/1.73 m2 . To be included in the present analysis , subjects needed to be free of the composite event at 4 months , receive epoetin-alfa , and have ≥1 postbaseline Hb measurement . The mean weekly dose of epoetin-alfa received up to the time of first event or censure was the main exposure variable , while the achieved Hb at month 4 was the confounder representing the subject 's underlying response to treatment . The primary outcome was the composite of death , heart failure hospitalization , stroke , or myocardial infa rct ion . A Cox proportional hazard regression model was used in time-to-event analysis . Results : Among 1,244 subjects with complete data , the average weekly dose of epoetin-alfa ranged 143.3-fold from 133 to 19,106 units/week at the time of first event or censure . Cox proportional hazard analysis found that those in the middle tertile of Hb achieved ( > 11.5 to < 12.7 g/dl ) and the lowest tertile of epoetin-alfa dose exposure level ( < 5,164 units/week ) had the lowest risk . Irrespective of Hb achieved , the relative risk in the highest tertile ( > 10,095 units/week ) of epoetin-alfa dose exposure level was significantly escalated ( hazard ratios ranged from 2.536 to 3.572 , p < 0.05 , when compared to the group of middle Hb tertile and lowered dose tertile ) . In a multivariable model that adjusted for achieved Hb , albumin , cholesterol , age , prior heart failure , prior stroke , prior deep venous thrombosis , atrial fibrillation or malignancy , the average weekly dose had a significant ( p = 0.005 ) relative risk of 1.067 per 1,000 units of epoetin-alfa for the primary end point . Conclusions : In the CHOIR trial , average epoetin-alfa doses > 10,095 units/week were associated with increased risks for cardiovascular events irrespective of the Hb achieved within the first 4 months of treatment . These data suggest the weekly epoetin-alfa dose and not the Hb achieved was a principal determinant in the primary outcome observed implicating a cardiovascular toxicity of this erythrocyte-stimulating agent Aims Anaemia in heart failure ( HF ) is associated with a poor prognosis . Although inflammation is assumed to be an important cause of anaemia , the association between anaemia and inflammatory markers in patients with HF has not been well established . Methods Data from a multicentre r and omised clinical trial , in which patients were eligible if they were > 18 years of age and admitted for HF ( New York Heart Association II – IV ) , were used . In a subset of 326 patients , haemoglobin ( Hb ) , haematocrit , high sensitivity C-reactive protein ( hsCRP ) , interleukin-(IL ) 6 , soluble tumour necrosis factor receptor (sTNFR)-1 and erythropoietin ( Epo ) were measured at discharge and the primary endpoint was all-cause mortality . Follow-up was 18 months . Results Anaemia ( Hb < 13 g/dl ( men ) and < 12 g/dl ( women ) ) was present in 40 % ( 130/326 ) of the study population . Median levels of IL-6 , hsCRP and sTNFR-1 were significantly higher in anaemic patients than in non-anaemic patients . Logistic regression demonstrated that each increase in hsCRP values ( OR 1.58 per SD log hsCRP ; 95 % CI 1.09 to 2.29 ; p=0.016 ) and each increase in sTNFR-1 values ( OR 1.62 per SD log sTNFR-1 ; 95 % CI 1.24 to 2.11 ; p<0.001 ) were independently associated with anaemia . Epo ( HR 1.31 per log Epo ; 95 % CI 1.01 to 1.69 ; p=0.041 ) and sTNFR-1 ( HR 1.47 per log sTNFR-1 ; 95 % CI 1.16 to 1.86 ; p=0.001 ) levels were independently associated with outcome . Conclusion Anaemia is present in 40 % of patients hospitalised for HF and is independently associated with inflammation Background — Patients with chronic heart failure ( CHF ) are frequently anemic . An increase in hemoglobin could enhance exercise performance by increasing oxygen delivery . We investigated the effect of erythropoietin ( EPO ) on exercise performance in anemic patients with CHF . Methods and Results —Twenty-six anemic patients aged 57±11 years were r and omized to receive EPO ( 15 000 to 30 000 IU per week ) or placebo for 3 months . Parameters measured at baseline and end therapy included blood parameters ( hemoglobin , hematocrit , plasma volume ) , exercise parameters ( peak oxygen consumption [ & OV0312;o2 ] , exercise duration , 6-minute walk ) , muscle aerobic metabolism ( half-time of & OV0312;o2 and near infrared recovery ) , and forearm vasodilatory function . EPO was well tolerated by all patients . Twelve patients in the EPO group felt improvement versus 1 in the placebo group ( P < 0.05 ) . There were significant increases in hemoglobin ( 11.0±0.5 to 14.3±1.0 g/dL , P < 0.05 ) , peak & OV0312;o2 ( 11.0±1.8 to 12.7±2.8 mL · min−1 · kg−1 , P < 0.05 ) and exercise duration ( 590±107 to 657±119 s , P < 0.004 ) in the EPO group but no significant changes in the control group . Resting and hyperemic forearm vascular resistance and indices of the rate of muscle oxidative capacity were unchanged in both groups . Conclusion —EPO significantly enhances exercise capacity in patients with CHF . One mechanism of improvement in & OV0312;o2 is increased oxygen delivery from increased hemoglobin concentration BACKGROUND Angiotensin-converting enzyme inhibitors ( ACEIs ) have been shown to lower hematocrit and erythropoietin ( EPO ) , but a direct link between angiotensin II ( Ang II ) and EPO in humans has not been shown . METHODS Placebo or Ang II was infused for six hours in nine healthy male volunteers with and without blockade of the Ang II subtype 1 receptor ( AT1R ) . EPO concentrations were measured 3 , 6 , 12 , and 24 hours after the start of the infusion . RESULTS Ang II raised the mean arterial pressure by about 20 mm Hg . Consistent with the known diurnal variation , EPO levels rose significantly ( P < or = 0.02 ) during the day in all groups . During Ang II infusion , EPO levels rose to significantly higher levels after 6 and 12 hours compared with placebo [ 9.9 + /- 3.5 vs. 7.2 + /- 3.1 mU/mL ( 3 h , P = NS ) ; 16.9 + /- 4.5 vs. 8.8 + /- 3.7 mU/mL ( 6 h , P = 0.01 ) ; 17.0 + /- 8.6 vs. 11.1 + /- 4.7 mU/mL ( 12 h , P = 0.01 ) ] and returned to baseline after 24 hours ( 7.9 + /- 3.8 vs. 10.6 + /- 8.6 mU/mL , P = NS ) . With AT1R blockade , blood pressure remained normal during Ang II infusion , and EPO levels were never significantly different from placebo [ 6.8 + /- 4.8 , 10.5 + /- 5.6 , 13.1 + /- 9.0 , and 12.4 + /- 10.1 mU/mL at 3 , 6 , 12 , and 24 h after infusion , respectively , P = NS ] . CONCLUSIONS Ang II increases EPO levels in humans . This increase requires the participation of AT1R OBJECTIVES We prospect ively investigated the causes of anemia in patients with advanced congestive heart failure ( CHF ) . BACKGROUND Anemia is common in patients with advanced CHF , and its etiology is generally considered to be multifactorial . However , despite its importance , precise information is lacking regarding the prevalence of putative etiologic factors . METHODS Patients who were hospitalized for decompensated advanced CHF and who were stabilized after their initial treatment underwent evaluation of " clinical ly significant " anemia , defined as a hemoglobin content < 12 g/dl for men and < 11.5 g/dl for women . Patients with a serum creatinine concentration > 3 mg/dl or patients with concurrent diseases that are known to cause anemia were not included . The initial evaluation included measurements of vitamin B(12 ) , folic acid , thyroid-stimulating hormone , erythropoietin , lactate dehydrogenase , Coombs test , multiple fecal occult tests , and bone marrow aspiration . Patients without diagnosis by these methods underwent red cell mass measurement with (51)Cr assay . RESULTS The mean age of the 37 patients was 57.9 + /- 10.9 years and mean left ventricular ejection fraction 22.5 + /- 5.9 % . Iron deficiency anemia was confirmed by bone marrow aspiration in 27 patients ( 73 % ) , 2 patients ( 5.4 % ) had dilutional anemia , and 1 patient ( 2.7 % ) had drug-induced anemia . No specific cause was identified in 7 patients ( 18.9 % ) who were considered to have " anemia of chronic disease . " Serum ferritin for the iron-deficient patients was not a reliable marker of iron deficiency in this population . CONCLUSIONS In this group of patients , iron deficiency was the most common cause of anemia . The iron status of patients with end-stage chronic CHF should be thoroughly evaluated and corrected before considering other therapeutic interventions The mechanism of cortisol-induced hypertension remains unknown . We investigated a possible role of erythropoietin ( EPO ) as a mediator of hypertension in healthy male subjects treated with cortisol . In Study 1 , blood pressure ( BP ) and serum EPO concentrations were measured on alternate days in nine subjects treated with 80 mg of cortisol per day for 5 days . In Study 2 the same parameters were measured in eight subjects r and omised to cortisol ( 80 mg/day ) or placebo and 10 subjects r and omised to cortisol ( 200 mg/day ) or placebo for 5 days . In Study 1 , cortisol caused a significant increase in systolic BP ( SBP ) ( 115 ± 2 vs 126 ± 2 mm Hg , control vs day 5 , P < 0.001 ) and serum epo concentrations ( 14.5 ± 2.7 vs24.3 ± 2.7 mU/mL , P < 0.001 ) . in study 2 both doses of cortisol increased sbp ( 118 ± 2 vs 113 ± 2 mm Hg , 80 mg cortisol vs placebo , P < 0.05 and 129 ± 3 vs 113 ± 2 mm Hg , 200 mg cortisol vs placebo , P < 0.001 ) . serum epo concentrations were significantly increased at 200 mg cortisol ( 25.2 ± 11.9 vs 15.9 ± 3.5 mU/mL , P < 0.01 ) but not 80 mg cortisol ( 21.3 ± 2.9 vs14.9 ± 3.1 mU/mL ) . In the 200 mg group there was a positive correlation between the change in SBP and the change in serum EPO concentration ( r2 = 0.43 , P < 0.05 ) . these results point to a possible role for epo as the mediator of cortisol-induced hypertension The aim of this study was to analyze the time course of erythropoietin ( EPO ) during Earth-bound microgravity simulations such as bed rest , isolation and confinement ( IC ) , head-down tilt ( HDT ; -6 degrees ) , and immersion to evaluate which factors could contribute to alterations in EPO under real microgravity conditions during and after short- ( < 10 days ) and long-term ( > 6 mo ) spaceflights . During bed rest ( 24h ) , no significant changes in EPO could be observed . Subjects confined in a diving chamber facility for 60 days showed a decrease in EPO . In the recovery period a slight increase was observed , but EPO concentrations did not reach the pre-IC control level . In the control period before HDT , subjects showed normal resting values for EPO , but on day 2 of HDT the EPO concentrations were decreased ( P < 0.01 ) . Later the EPO levels remained below the control value and were increased after HDT ( P < 0.05 ) . After immersion ( 24 h ) increased EPO concentrations could be determined ( P < 0.05 ) . During a short-term spaceflight the astronauts showed in-flight ( day 4 ) decreased and unchanged EPO concentrations . During a long-term spaceflight , 24 h after recovery , the cosmonaut showed slightly elevated EPO concentration , which increased markedly during the following days . It is concluded that 1 ) HDT ( -6 degrees ) causes a rapid decrease in EPO in humans , 2 ) IC per se leads to diminished EPO concentrations , 3 ) EPO regulation in humans during short- and long-term spaceflights might be different , 4 ) changes in central blood volume , i.e. , central venous pressure , seem to be involved in the modulation of EPO production and release under simulated and real microgravity conditions , and 5 ) the HDT ( -6 degrees ) Earth-bound simulation reflects mostly the changes in EPO production and release observed under real microgravity conditions in humans Current evidence suggests that angiotensin II may be involved in the regulation of renal erythropoietin ( EPO ) production . The present study assessed the role of angiotensin II ( A II ) in different doses in the control of EPO production in humans . In a parallel , r and omized , placebo-controlled open design , 60 healthy male volunteers received a 6-h intravenous infusion of : placebo ( placebo , electrolyte solution ) , a pressor dose of A II ( 1–3 µg/min ; A II press ) , a combination of a pressor dose of A II and the selective AT1-receptor blocker losartan , 50 mg ( A II press + L ) , a subpressor dose of A II ( 0.0375–0.15 µg/min ; A II subpress ) and a combination of a subpressor dose of A II and losartan ( A II subpress + L ) . A II press treatment result ed in a significant increase of the maximum EPO concentration ( CmaxEPO , 41 % higher versus placebo ) and the amount of EPO produced in 24 h ( AUCEPO(0–24 h ) , 61 % larger versus placebo ) , A II subpress treatment increased CmaxEPO ( 35 % higher versus placebo ) and AUCEPO(0–24 h ) ( 34 % larger versus placebo ) . A II press + L and A II subpress + L treatments did not significantly increase CmaxEPO and AUCEPO(0–24 h ) compared to placebo . A II affects EPO production in a dose-dependent manner . The signal seems to be mediated via AT1-receptors . A II appears to be one modulator EPO production in humans OBJECTIVES Our objective was to evaluate in a double-blind , r and omized , placebo-controlled study possible modifications in NT-pro-brain natriuretic peptide ( NT-proBNP ) and C-reactive protein ( CRP ) levels together with clinical and functional parameters , in a group of anemic patients with chronic heart failure ( CHF ) and chronic renal failure ( CRF ) receiving intravenous iron therapy , without recombinant human erythropoietin ( rhEPO ) , versus placebo . BACKGROUND Chronic heart failure and CRF associated with absolute or relative iron deficiency anemia is a common problem . This situation is linked with a variable inflammatory status . Both NT-proBNP and CRP are recognized markers for left ventricular dysfunction and inflammatory status , respectively . In this double-blind , r and omized , placebo-controlled study , modifications in NT-proBNP and CRP level and clinical and functional parameters , in anemic patients with CHF and CRF receiving intravenous iron therapy , without rhEPO , versus placebo were evaluated . METHODS Forty patients with hemoglobin ( Hb ) < 12.5 g/dl , transferrin saturation < 20 % , ferritin < 100 ng/ml , creatinine clearance ( CrCl ) < 90 ml/min , and left ventricular ejection fraction ( LVEF ) < or = 35 % were r and omized into 2 groups ( n = 20 for each ) . For 5 weeks , group A received isotonic saline solution and group B received iron sucrose complex , 200 mg weekly . Minnesota Living with Heart Failure Question naire ( MLHFQ ) and 6-min walk ( 6MW ) test were performed . NT-pro brain natriuretic peptide and CRP were evaluated throughout the study . No patients received erythroprotein any time . RESULTS After 6 months follow-up , group B showed better hematology values and CrCl ( p < 0.01 ) and lower NT-proBNP ( 117.5 + /- 87.4 pg/ml vs. 450.9 + /- 248.8 pg/ml , p < 0.01 ) and CRP ( 2.3 + /- 0.8 mg/l vs. 6.5 + /- 3.7 mg/l , p < 0.01 ) . There was a correlation initially ( p < 0.01 ) between Hb and NT-proBNP ( group A : r = -0.94 and group B : r = -0.81 ) and after 6 months only in group A : r = -0.80 . Similar correlations were observed with Hb and CRP . Left ventricular ejection fraction percentage ( 35.7 + /- 4.7 vs. 28.8 + /- 2.4 ) , MLHFQ score , and 6MW test were all improved in group B ( p < 0.01 ) . Additionally , group B had fewer hospitalizations : 0 of 20 versus group A , 5 of 20 ( p < 0.01 ; relative risk = 2.33 ) . CONCLUSIONS Intravenous iron therapy without rhEPO substantially reduced NT-proBNP and inflammatory status in anemic patients with CHF and moderate CRF . This situation was associated with an improvement in LVEF , NYHA functional class , exercise capacity , renal function , and better quality of life AIMS Erythropoietin ( EPO ) resistance , an important cause of anaemia in patients with heart and renal failure , is associated with increased mortality . The hypothesis of the present study was that exogenous EPO decreases hepcidin levels and that the decrease in hepcidin levels upon EPO treatment is related to the bone marrow response . METHODS AND RESULTS In the EPOCARES trial , patients with renal failure ( glomerular filtration rate 20 - 70 mL/min ) , heart failure , and anaemia were r and omized to receive 50 IU/kg/week EPO ( n = 20 ) or not ( n = 13 ) . Haemoglobin ( Hb ) , hepcidin-25 , ferritin , reticulocytes , serum transferrin receptor ( sTfR ) , IL-6 , and high-sensitivity C-reactive protein were measured at baseline and during treatment . Hepcidin-25 was measured by weak cation exchange chromatography/matrix assisted laser desorption ionization time-of-flight mass spectrometry . Baseline hepcidin levels were increased compared with a healthy reference population and were inversely correlated with Hb ( r(2 ) = 0.18 , P = 0.02 ) , and positively with ferritin ( r(2 ) = 0.51 , P < 0.001 ) , but not with renal function , high-sensitivity C-reactive protein or IL-6 . Erythropoietin treatment increased reticulocytes ( P < 0.001 ) and sTfR ( P < 0.001 ) , and decreased hepcidin ( P < 0.001 ) . Baseline hepcidin levels and the magnitude of the decrease in hepcidin correlated with the increase in reticulocytes ( r(2 ) = 0.23 , P = 0.03 ) and sTfR ( r(2 ) = 0.23 , P = 0.03 ) and also with the Hb response after 6 months ( r(2 ) = 0.49 , P = 0.001 ) . CONCLUSION In this group of patients with combined heart and renal failure and anaemia , increased hepcidin levels were associated with markers of iron load and not with markers of inflammation . The ( change in ) hepcidin levels predicted early and long-term bone marrow response to exogenous EPO . In our group hepcidin seems to reflect iron load and response to EPO rather than inflammation and EPO resistance BACKGROUND Patients with systolic heart failure and anemia have worse symptoms , functional capacity , and outcomes than those without anemia . We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia . METHODS In this r and omized , double-blind trial , we assigned 2278 patients with systolic heart failure and mild-to-moderate anemia ( hemoglobin level , 9.0 to 12.0 g per deciliter ) to receive either darbepoetin alfa ( to achieve a hemoglobin target of 13 g per deciliter ) or placebo . The primary outcome was a composite of death from any cause or hospitalization for worsening heart failure . RESULTS The primary outcome occurred in 576 of 1136 patients ( 50.7 % ) in the darbepoetin alfa group and 565 of 1142 patients ( 49.5 % ) in the placebo group ( hazard ratio in the darbepoetin alfa group , 1.01 ; 95 % confidence interval , 0.90 to 1.13 ; P=0.87 ) . There was no significant between-group difference in any of the secondary outcomes . The neutral effect of darbepoetin alfa was consistent across all prespecified subgroups . Fatal or nonfatal stroke occurred in 42 patients ( 3.7 % ) in the darbepoetin alfa group and 31 patients ( 2.7 % ) in the placebo group ( P=0.23 ) . Thromboembolic adverse events were reported in 153 patients ( 13.5 % ) in the darbepoetin alfa group and 114 patients ( 10.0 % ) in the placebo group ( P=0.01 ) . Cancer-related adverse events were similar in the two study groups . CONCLUSIONS Treatment with darbepoetin alfa did not improve clinical outcomes in patients with systolic heart failure and mild-to-moderate anemia . Our findings do not support the use of darbepoetin alfa in these patients . ( Funded by Amgen ; RED-HF Clinical Trials.gov number , NCT00358215 . ) |
13,229 | 30,233,362 | Conclusions : Chinese medicine may provide an efficiently alternative choice for the treatment of RA in terms of the bone-protecting efficiency . | Background : Rheumatoid Arthritis ( RA ) is a systemic autoimmune disease leading to joint destruction .
The prevention of bone and cartilage destruction has received increased attention in recent years .
Objective : To evaluate the current evidence s regarding the bone-protecting efficacy of Chinese medicine or the combination of Chinese medicine and Western medicine for RA . | Objective To investigate the effects of Qingre Huoxue Decoction 清热活血方 , clearing heat and promoting blood flow ; QRHXD ) , on the radiographic progression in patients with rheumatoid arthritis ( RA ) by X-ray imaging . Methods Eighty-six patients with active RA diagnosed as damp-heat and blood stasis syndrome were r and omized into a QRHXD group and a QRHXD plus methotrexate ( MTX ) group , with 43 cases in each group . After one-year of treatment , 21 cases in each group ( 42 in total ) were evaluated . Radiographs of h and s were obtained at the baseline and after 12 months of treatment . Images were evaluated by investigators blinded to chronology and clinical data , and assessed according to the Sharp/Van der Heijde methods . Results High intrareader agreements were reached ( mean intraobserver intraclass coefficients : 0.95 ) . No significant change in any imaging parameters of joint destruction was observed at 12 months in either group ; and the differences between the two groups were not significant ( P>0.05 ) . The mean of the changing score in the QRHXD group was 3.5±4.1 , and 2.4±3.5 in the QRHXD+MTX group , while the baseline radiographic score of patients in the QRHXD group was relatively higher ( 18.9±19.1 vs. 14.0±14.0 ) . The mean rates of the changing scores of the two groups were similar ( 0.24±0.28 vs. 0.25±0.44 , P=0.40 ) . The severity of progression in the two groups was also similar ( P=0.46 ) , 7 cases without radiographic progression in the QRHXD group and 8 in the QRHXD+MTX group , 3 cases with obvious radiographic progression in the QRHXD group and 1 in the QRHXD+MTX group . Conclusion Radiographic progression of RA patients in both groups is similar , indicating that the QRHXD Decoction has a potential role in preventing bone destruction Aim To monitor joint inflammation and destruction in rheumatoid arthritis ( RA ) patients receiving adalimumab/methotrexate combination therapy using MRI and ultrasonography . To assess the predictive value of MRI and ultrasonography for erosive progression on CT and compare MRI/ultrasonography/radiography for erosion detection/monitoring . Methods Fifty-two erosive biological-naive RA patients were followed with repeated MRI/ultrasonography/radiography ( 0/6/12 months ) and clinical /biochemical assessment s during adalimumab/methotrexate combination therapy . Results No overall erosion progression or repair was observed at 6 or 12 months ( Wilcoxon ; p>0.05 ) , but erosion progressors and regressors were observed using the smallest detectable change cut-off . Scores of MRI synovitis , grey-scale synovitis ( GSS ) and power Doppler ultrasonography decreased after 6 and 12 months ( p<0.05 ) , as did DAS28 , HAQ and tender and swollen joint counts ( p<0.001 ) . Patients with progression on CT had higher baseline MRI bone oedema scores . The RR for CT progression in bones with versus without baseline MRI bone oedema was 3.8 ( 95 % CI 1.5 to 9.3 ) and time-integrated MRI bone oedema , power Doppler and GSS scores were higher in bones/joints with CT progression ( Mann – Whitney ; p<0.05 ) . With CT as the reference method , sensitivities/specificities for erosion in metacarpophalangeal joints were 68%/92 % , 44%/95 % and 26%/98 % for MRI , ultrasonography and radiography , respectively . Median intraobserver correlation coefficient was 0.95 ( range 0.44–0.99 ) . Conclusion During adalimumab/methotrexate combination therapy , no overall erosive progression or repair occurred , whereas repair of individual erosions was documented on MRI , and MRI and ultrasonography synovitis decreased . Inflammation on MRI and ultrasonography , especially MRI bone oedema , was predictive for erosive progression on CT , at bone/joint level and MRI bone oedema also at patient level OBJECTIVE RANKL is essential for osteoclast development , activation , and survival . Denosumab is a fully human monoclonal IgG2 antibody that binds RANKL , inhibiting its activity . The aim of this multicenter , r and omized , double-blind , placebo-controlled , phase II study was to evaluate the effects of denosumab on structural damage in patients with rheumatoid arthritis ( RA ) receiving methotrexate treatment . METHODS RA patients received subcutaneous placebo ( n = 75 ) , denosumab 60 mg ( n = 71 ) , or denosumab 180 mg ( n = 72 ) injections every 6 months for 12 months . The primary end point was the change from baseline in the magnetic resonance imaging ( MRI ) erosion score at 6 months . RESULTS At 6 months , the increase in the MRI erosion score from baseline was lower in the 60-mg denosumab group ( mean change 0.13 ; P = 0.118 ) and significantly lower in the 180-mg denosumab group ( mean change 0.06 ; P = 0.007 ) than in the placebo group ( mean change 1.75 ) . A significant difference in the modified Sharp erosion score was observed as early as 6 months in the 180-mg denosumab group ( P = 0.019 ) as compared with placebo , and at 12 months , both the 60-mg ( P = 0.012 ) and the 180-mg ( P = 0.007 ) denosumab groups were significantly different from the placebo group . Denosumab caused sustained suppression of markers of bone turnover . There was no evidence of an effect of denosumab on joint space narrowing or on measures of RA disease activity . Rates of adverse events were comparable between the denosumab and placebo groups . CONCLUSION Addition of twice-yearly injections of denosumab to ongoing methotrexate treatment inhibited structural damage in patients with RA for up to 12 months , with no increase in the rates of adverse events as compared with placebo OBJECTIVE To observe the effect of Fengshi No. 1 ( FS1 ) in treating patients with active stage of rheumatoid arthritis ( RA ) . METHODS Patients with RA were r and omly divided into two groups , the 40 patients in the treated group were treated with combined therapy of methotrexate ( MTX ) , sulfasalazine ( SSZ ) and FS1 , and the 20 in the control groups were treated with MTX and SSZ alone . RESULTS In the treated group , the total effective rate was 97.5 % , the clinical controlled and markedly effective rate 95.0 % and the occurrence rate of side-toxic reaction 10.0 % , as compared with those in the control group , 60.0 % , 20.0 % and 45.0 % respectively , the difference was significant ( chi 2 = 11.91 , 32.23 and 7.67 respectively , all P < 0.01 ) . The effect in the treated group was superior to that in the control group in abating joint swelling and pain , improving function of joint , reducing immune indices and ameliorating iconographic features ( P < 0.01 or P < 0.05 ) . CONCLUSION FS1 not only has the effects of anti-inflammation , analgesis , regulating immune reaction , but also could retard the occurring of bone destruction , reduce the toxic-side effects of MTX and SSZ Objective To observe the efficacy of Hebi Formula ( HF ) combined Methotrexate ( MTX ) on early rheumatoid arthritis ( RA ) patients with disharmony of Gan and Pi syndrome ( DGPS ) and its effects on matrix metalloproteinase-3 ( MMP-3 ) activator of nuclear factor-KB/receptor activator of nu- clear factor-KB/osteoprotegerin ( RANK/RANKL/OPG ) . Methods Totally 72 early RA patients with DGPS were assigned to the treatment group and the control group according to r and om digit table , 36 in each group . Patients in the control group took MTX , while those in the treatment group additionally took HF . MTX dose was increased from 7 . 5 mg to 12 . 5 mg gradually , once per week , and the course of treatment was 24 weeks . Efficacy for Chinese medicine ( CM ) syndromes , ACR20 improvement rate , laboratory re- lated indices [ rheumatoid factor ( RF ) , erythrocyte sedimentation rate ( ESR ) , C-reactive protein ( CRP ) , anti-cyclic citrullinated peptide antibody ( CCP ) ] , serum levels of MMP-3 , OPG , RANKL , and adverse reactions were observed . Results The st and ard arriving rate of ACR20 was 82 . 86 % ( 2935 ) in the treatment group , higher than that in the control group [ 51 . 52 % ( 173 ) ; P < 0 . 05 ) . The effective rate of CM syndrome was 85 . 7 % ( 30f35 ) in the treatment group , higher than that in the control group [ 63 . 6 % ( 21/33 ) ; P < 0 . 05 ) . Compared with before treatment in the same group , levels of RF , ESR , CRP , MMP-3 , and RANKL decreased , the OPG level increased in the two groups after treatment ( P < 0 . 05 , P < 0 . 01 ) . Compared with the control group , levels of RF , ESR , CRP , and RANKL all decreased with statistical difference ( P < 0 . 01 , P < 0 . 05 ) . Liver dysfunction occurred in 1 case of the treatment group . Leucopenia occurred in 1 case and liver dysfunction occurred in 2 cases of the control group . Conclusion HF com- bined MTX could improve symptoms of early RA patients with DGPS , and regulate bone destruction in- duced by RANK/RANKL/OPG systems |
13,230 | 31,392,534 | The observed association was independent of the timing of QRS width measurement after CRT implantation .
Acute and late improvement of electrical dysynchrony as depicted by QRS narrowing following biventricular pacing is associated with clinical and echocardiographic response to CRT . | Prolonged QRS duration , which reflects a higher degree of mechanical dysynchrony , is a predictor of response to CRT .
However , the association of QRS narrowing after biventricular pacing with CRT response rates is not clear .
Our aim was to conduct a systematic review and meta- analysis on the association between QRS narrowing after cardiac resynchronization therapy ( CRT ) and clinical and echocardiographic response to CRT in patients with heart failure . | PURPOSE To investigate whether magnetic resonance imaging ( MRI ) cine-derived dyssynchrony indices provide additional information compared to conventional tagged MRI ( tMRI ) acquisitions in heart failure patients undergoing cardiac resynchronization therapy ( CRT ) . MATERIAL S AND METHODS Patients scheduled for CRT ( n = 52 ) underwent preprocedure MRI including cine and tMRI acquisitions . Segmental strain curves were calculated for both cine and tMRI to produce a range of st and ard indices for direct comparison between modalities . We also proposed and evaluated a novel index of " dyscontractility , " which detects the presence of focal areas with paradoxically positive circumferential strain . RESULTS Across conventional strain indices , there was only moderate-to-poor ( R = 0.3 - 0.6 ) correlation between modalities ; eight cine-derived indices showed statistically significant ( P < 0.05 ) relations to CRT outcome compared to just two tMRI-based counterparts . The novel dyscontractility index calculated on basal slice cine images ( cine dyscontractility index , " CDI " ) was the single best predictor of clinical response to CRT ( area under the curve AUC = 0.81 , P < 0.001 ) . While poorly correlated to its tMRI counterpart ( R = 0.33 ) , CDI performed significantly better in predicting response to CRT ( P < 0.005 ) , and was also numerically better than all other tMRI indices ( AUC 0.53 - 0.76 , all P for AUC comparisons < 0.17 ) . CONCLUSION Cine-derived strain indices offer potentially new information compared to tMRI . Specifically , the novel CDI is most strongly linked to response to cardiac resynchronization therapy in a contemporary patient cohort . It utilizes readily available MRI data , is relatively straightforward to process , and compares favorably with any conventional tagging index . J. Magn . Reson . Imaging 2016;44:1483 - 1492 AIMS The aim of the study was to assess the predictive value for outcomes of various response criteria currently used in patients undergoing cardiac resynchronization therapy ( CRT ) . METHODS AND RESULTS Data from TRUST CRT r and omized trial in patients with New York Heart Association ( NYHA ) III-IV class , QRS ≥ 120 ms , ejection fraction ≤ 35 % , and mechanical dyssynchrony was analysed . Ninety-seven subjects who survived 6 months after implantation of CRT-defibrillator were classified as responders or non-responders depending on 15 criteria used in most of the previous trials . Blindly adjudicated data on major adverse cardiac events ( MACEs ) within 1 year after classification were used to calculate the predictive value of response criteria . After adjustment for baseline confounding variables only eight criteria were significantly predictive for future MACEs . Sensitivity and specificity ranged substantially for clinical ( 32 - 94 % and 26 - 63 % ) and echocardiographic criteria ( 40 - 93 % and 22 - 70 % , respectively ) . The most powerful clinical predictor was > a NYHA class reduction ≥ 1 [ adjusted relative risk ( RR ) 4.41 for non-responders ; 95 % confidence interval ( CI ) 1.75 - 11.04 , P = 0.002 ] , while the strongest echocardiographic predictor was a reduction in the left ventricular end-systolic index by > 15 % ( RR 3.49 ; 95 % CI 1.59 - 7.64 , P = 0.002 ) . A combination of these two criteria did not improve the predictive value of a single parameter . Both criteria showed multiple significant interactions with baseline patients ' characteristics . CONCLUSION Only some of the commonly used response criteria predict outcome in patients undergoing CRT . The predictive value varies substantially across different criteria , with a higher sensitivity observed for the clinical parameters and a higher specificity observed for echocardiographic parameters . Combining various criteria adds little to their prognostic value . The predictive accuracy of various criteria can be different in various subgroups due to multiple interactions with baseline characteristics . CLINICAL TRIALS . GOV IDENTIFIER : NCT00814840 Background — Cardiac resynchronization therapy ( CRT ) decreases mortality , improves functional status , and induces reverse left ventricular remodeling in selected population s with heart failure . We aim ed to assess the impact of baseline QRS duration and morphology and the change in QRS duration with pacing on CRT outcomes in mild heart failure . Methods and Results — Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction ( REVERSE ) was a multicenter r and omized trial of CRT among 610 patients with mild heart failure . Baseline and CRT-paced QRS duration s and baseline QRS morphology were evaluated by blinded core laboratories . The mean baseline QRS duration was 151±23 milliseconds , and 60.5 % of subjects had left bundle-branch block ( LBBB ) . Patients with LBBB experienced a 25.3-mL/m2 mean reduction in left ventricular end-systolic volume index ( P<0.0001 ) , whereas non-LBBB patients had smaller decreases ( 6.7 mL/m2 ; P=0.18 ) . Baseline QRS duration was also a strong predictor of change in left ventricular end-systolic volume index with monotonic increases as QRS duration prolonged . Similarly , the clinical composite score improved with CRT for LBBB subjects ( odds ratio , 0.530 ; P=0.0034 ) but not for non-LBBB subjects ( odds ratio , 0.724 ; P=0.21 ) . The association between clinical composite score and QRS duration was highly significant ( odds ratio , 0.831 for each 10-millisecond increase in QRS duration ; P<0.0001 ) , with improved response at longer QRS duration s. The change in QRS duration with CRT pacing was not an independent predictor of any outcomes after correction for baseline variables . Conclusion — REVERSE demonstrated that LBBB and QRS prolongation are markers of reverse remodeling and clinical benefit with CRT in mild heart failure . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00271154 The aim of this study was to assess the effectiveness of cardiac resynchronization therapy ( CRT ) by intracardiac delay optimization using echocardiography . Sixty-five patients were implanted with a CRT device r and omly assigned to receive simultaneous biventricular pacing or echo-optimized sequential CRT . Forty-two patients were defined as responders and 23 patients were classified as non-responders . During a 12-month follow-up period , the positive response rate , QRS duration , New York Heart Association class , mitral insufficiency grade , left ventricular end-systolic volume and LV end-diastolic volume were similar in the optimized and non-optimized groups ( P>0.05 ) , whereas 6-minute walking distance , quality -of-life score , left ventricular ( LV ) ejection fraction and aortic velocity time integral were significantly improved in the optimized group ( P<0.05 ) . The baseline QRS duration s of the responders and non-responders were similar ( P>0.05 ) , whereas heart failure aetiology , clinical and echocardiographic measurements showed significant differences ( P<0.05 ) . The mean decrease in QRS duration after 12 months of CRT used for separating responders and non-responders was significantly different ( P<0.05 ) , and significant differences were observed in the mean decrease of QRS duration between responders and non-responders ( P<0.05 ) . Echocardiographic optimization may further improve the effectiveness of CRT . Moreover , severe mitral regurgitation and greater LV volume are likely to indicate a poor response to CRT In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias Background —Despite benefits of cardiac resynchronization therapy ( CRT ) in patients with severe but less symptomatic heart failure , approximately 30 % of patients do not fully respond to treatment . We hypothesized that a combined assessment of left ventricular ( LV ) dyssynchrony and contractile function by strain-based imaging would identify patients who would most benefit from CRT . Methods and Results —We studied 1077 patients with New York Heart Association class I/II , LV ejection fraction ⩽30 % and QRS width ≥130 ms enrolled in the Multicenter Automatic Defibrillator Implantation Trial – Cardiac Resynchronization Therapy trial with sufficient echocardiographic image quality for cardiac deformation analysis ( implantable cardioverter-defibrillator [ ICD ] , n=416 ; CRT , n=661 ) . Patients were assigned to CRT plus an ICD or to ICD alone in 3:2 r and om assignment . We assessed the degree to which baseline echocardiographic assessment s of dyssynchrony , measured as the st and ard deviation of time-to-peak transverse strain over 12 segments , contractile function , measured as global longitudinal strain , or both predicted the effect of treatment on the primary outcome of death or heart failure . With 213 primary events occurring over a mean of 2.4 years , the benefit of CRT plus an ICD relative to ICD alone was greatest in patients with mild to moderate dyssynchrony ( time-to-peak transverse strain st and ard deviation , 142 to 230 ms ) and greater baseline contractile function ( global longitudinal strain ⩽−8.7 % ) . Overall , those patients with mild to moderate dyssynchrony and those with best contractile function at baseline demonstrated the greatest benefit from CRT ( adjusted hazards ratio , 0.20 ; 95 % confidence interval , 0.09 to 0.44 ) . Dyssynchrony and global longitudinal strain predicted response to CRT independent of each other , QRS width , LV ejection fraction , and presence versus absence of left bundle-branch block , although the observed benefit remained greatest in patients with left bundle-branch block . Conclusions —Both mechanical dyssynchrony and contractile function are important independent correlates of benefit from CRT . Clinical Trial Registration —URL : http://www . clinical trials.gov . Unique identifier : NCT00180271 Biventricular pacing results in left ventricular ( LV ) reverse remodeling in heart failure patients with wide QRS complexes . This study examines potential predictors of reverse remodeling . Echocardiography with tissue Doppler imaging was performed at baseline and 3 months after biventricular pacing in 30 patients ( 21 men and 9 women , mean age 62 + /- 14 years ) . There were 17 responders to reverse remodeling ( defined as a reduction in LV end-systolic volume by > 15 % ) and 13 nonresponders . Responders had significant improvement in 6-minute hall-walking distance ( p = 0.006 ) , metabolic equivalents ( p = 0.02 ) , peak oxygen uptake ( p = 0.02 ) , New York Heart Association functional class ( p < 0.001 ) , and quality of life ( p < 0.001 ) ; an increase in the sphericity index ( p = 0.007 ) , ejection fraction ( p < 0.001 ) , and diastolic filling time ( p = 0.03 ) ; a decrease in myocardial performance index ( p = 0.02 ) , isovolumic relaxation time ( p = 0.004 ) , and mitral regurgitation ( p = 0.007 ) ; and an improvement in systolic dyssynchrony ( SD of the time to peak myocardial systolic contraction of the 12 LV segments as dyssynchrony index ) ( 45.0 + /- 8.3 vs 32.5 + /- 14.5 ms , p = 0.003 ) . In contrast , nonresponders only had a small degree of clinical improvement in New York Heart Association class ( p = 0.03 ) and quality -of-life scores ( p = 0.03 ) , without any change in cardiac function , and worsening of systolic dyssynchrony ( 24.8 + /- 4.5 vs 34.1 + /- 13.5 ms , p = 0.02 ) . When all the above factors were put into univariate and multivariate analyses models , systolic dyssynchrony was the only independent predictor of reverse remodeling ( r = -0.76 , p < 0.001 ) ( beta = -1.54 , p = 0.007 ) . A preimplant dyssynchrony index of 32.6 ms ( + 2 SDs from mean of 88 normal controls ) was able to totally segregate responders from nonresponders of biventricular pacing . Thus , responders of LV reverse remodeling were associated with improvement in clinical status , cardiac function , and systolic synchronicity . Direct assessment of systolic synchronicity by tissue Doppler imaging is highly accurate in predicting responders to therapy BACKGROUND L and mark reports have suggested that patients with QRS widening immediately after cardiac resynchronization therapy ( CRT ) experienced less frequently reverse left ventricular remodeling during follow-up . OBJECTIVE We sought to investigate the relationship between postoperative QRS widening relative to baseline and mortality in a prospect i ve cohort of heart failure patients receiving CRT . METHODS A 12-lead electrocardiogram was recorded for 237 heart failure patients ( New York Heart Association class II to IV , left ventricular ejection fraction ≤35 % , and QRS width ≥120 ms ) before and immediately after CRT device implantation . The relationships between QRS widening , all-cause and cardiovascular mortality , and echocardiographic response to CRT were studied . RESULTS During a median follow-up of 24 months , 39 patients died . Fifty patients ( 21 % ) experienced QRS widening after CRT [ QRS(+ ) group ] . During follow-up , all-cause mortality was higher in QRS(+ ) patients than in QRS(- ) patients ( 36-month survival free from death 81 % ± 7 % vs 64 % ± 16 % ; log rank , P = .029 ) . After adjustment for important prognostic confounders , QRS(+ ) patients remained associated with an excess overall mortality ( adjusted hazard ratio [ HR ] 2.67 ; 95 % confidence interval 1.07 - 6.65 ; P = .035 ) and cardiovascular mortality ( adjusted hazard ratio 3.63 ; 95 % confidence interval 1.13 - 11.65 ; P = .03 ) . QRS(+ ) patients were less frequent responders to CRT than were QRS(- ) patients ( 20 [ 47 % ] vs 136 [ 83 % ] ; P < .0001 ) . CONCLUSION Postoperative QRS widening relative to baseline after CRT is associated with a considerable increased mortality risk during follow-up . Whether QRS narrowing should be achieved to optimize CRT placement , and thereby increase the rate of CRT responders and improve outcome , deserves further research INTRODUCTION Biventricular pacing improves functional status in the majority of patients with drug-refractory heart failure , dilated cardiomyopathy , and interventricular conduction delay . The aim of this study was to analyze the baseline clinical and functional data of a cohort of patients implanted with a biventricular stimulation system in a single-center experience , to verify if the pathophysiologic characteristics of patients affect outcome , and to determine if preliminary identification of the right c and i date s for the new therapy is possible with noninvasive parameters . METHODS AND RESULTS Since March 1999 , 52 patients with advanced heart failure ( idiopathic cardiomyopathy 50 % , ischemic cardiomyopathy 35 % , other etiology 15 % ) and left bundle branch block underwent cardiac resynchronization and were followed prospect ively . Paired analysis over mean ( + /- SD ) follow-up of 348 + /- 154 days showed an overall significant decrease of QRS width ( baseline 194 + /- 33.2 msec vs follow-up 159.6 + /- 20.1 msec ) , New York Heart Association ( NYHA ) functional class ( baseline 3.2 + /- 0.5 vs follow-up 2.3 + /- 0.5 ) , quality -of-life score ( baseline 54 + /- 25 vs follow-up 25 + /- 16 ) , and increase of maximal VO2 ( baseline 12.6 + /- 2.5 mL/kg/min vs follow-up 15.0 + /- 3.3 mL/kg/min ) . There were 80 % responders ( documented , persistent decrease > or = 1 NYHA class ) and 20 % nonresponders ( same NYHA class or decline of status ; need for heart transplant ; death due to progressive pump failure ) . No significant differences in baseline clinical and functional variables between the two subgroups were observed . In responders , there was a highly significant global improvement of all variables ; in nonresponders , no parameters changed between baseline and follow-up . CONCLUSION These data confirm the role of biventricular pacing in improving the functional status of the great majority of a selected patient population having advanced heart failure and left bundle branch block with wide QRS complex . Basal demographic , clinical , and functional characteristics are not helpful in preliminary selection of responders . Simple evaluation of NYHA class confirms favorable outcome ( improvement of functional and hemodynamic status ) AIMS Strain delay index ( SDI ) allows quantification of the wasted contraction or gain of myocardial contractility expected after cardiac resynchronization therapy ( CRT ) . The present multicentre prospect i ve study aim ed to assess the accuracy of the SDI in predicting responses to CRT in real-life patients with wide and narrow ( < 130 ms ) QRS complexes . METHODS AND RESULTS Implantation of a CRT device was performed in 235 heart failure patients and echocardiography data were analysable in 80 % ( n= 189 ) of patients ( age 65 ± 12 years , left ventricular ejection fraction = 26 ± 8 % , 63 ischaemic , 51 with narrow QRS complexes ) . Mechanical dyssynchrony before CRT was quantified by the 12-segment st and ard deviation of peak longitudinal strain by speckle tracking ( 12SD-ε , 12 st and ard deviation of time to peak strain by speckle tracking ) , and SDI , defined as the sum of difference between end-systolic and peak-ε across the 16 segments . Response to CRT was defined as an end-systolic volume reduction ( ESVR ) at 6 months > 15 % . After CRT , ESVR>15 % was observed in 60 % ( n= 114/189 ) of patients , and was greater in non-ischaemic ( 68 vs. 44 % , P= 0.003 ) and wide QRS patients ( 65 vs. 49 % , P= 0.04 ) . Correlation between 12SD-ε and ESVR was poor ( r = 0.18 , P= 0.01 ) . In contrast , SDI correlated with reverse remodelling ( r = 0.61 , P < 0.0001 for all ) in both wide and narrow QRS patients and ischaemic and non-ischaemic patients . Decrease in SDI after CRT was greater in responders and correlated with ESVR . Finally , SDI > 25 % identified responders to CRT ( positive and negative predictive value of 80 and 84 % , respectively ) with 6 % inter-observer variability . CONCLUSION The present multicentre study suggests that SDI may identify responders to CRT in ischaemic and non-ischaemic patients AIMS To predict response to cardiac resynchronization therapy ( CRT ) in patients with heart failure ( HF ) and intraventricular conduction delay . METHODS AND RESULTS The study population consisted of 82 consecutive HF patients with st and ard CRT indications . Patients were classified as responders , if they were alive without cardiac decompensation and experienced > or=15 % decrease in left ventricular end-systolic volume . Sixty-eight percent of the enrolled patients responded to CRT . When compared with non-responders , responders had a wider baseline QRS width ( P = 0.001 ) , more marked QRS shortening ( DeltaQRS ) immediately after CRT ( P = 0.001 ) , and a better improvement in aortic velocity time integral ( VTI ) 24 h after CRT ( P = 0.02 ) . Moreover , there was a trend towards a greater baseline intraventricular dyssynchrony in the responder group ( P = 0.07 ) . By multivariable logistic regression , the baseline QRS width ( OR : 0.95 , 95 % CI : 0.90 - 0.97 , P = 0.001 ) , DeltaQRS ( OR : 1.038 , 95 % CI : 1.012 - 1.064 , P = 0.003 ) , and acute aortic VTI ( OR : 0.81 , 95 % CI : 0.68 - 0.96 , P = 0.017 ) emerged as independent predictors of response to CRT . Receiver operating characteristic curve analysis identified a QRS width > 145 ms , DeltaQRS > 20 ms , and aortic VTI > 14 cm to predict responders . CONCLUSION A positive response to CRT was observed in 68 % of the patients . Cardiac resynchronization therapy response is predictable using simple electrocardiographic and echocardiographic data OBJECTIVES This study sought to assess the prognostic utility of echocardiographic dyssynchrony for health status improvement after cardiac resynchronization therapy ( CRT ) . BACKGROUND Echocardiographic measures of dyssynchrony have been proposed for patient selection for CRT , but prospect i ve validation studies are lacking . METHODS A prospect i ve cohort of 324 patients from 53 centers with moderate to severe heart failure , left ventricular dysfunction , QRS > or = 130 ms , and available echocardiographic and health status information were identified from the PROSPECT ( Predictors of Response to Cardiac Re-Synchronization Therapy ) trial , which evaluated the prognostic utility of dyssynchrony measures in CRT recipients . The association of 12 echocardiographic dyssynchrony parameters with 6-month improvement in health status , as measured by the Kansas City Cardiomyopathy Question naire ( KCCQ ) , was assessed both as a continuous variable and by responder status ( DeltaKCCQ > or = + 10 points reflecting moderate to large improvement ) . RESULTS Of 12 pre-defined dyssynchrony parameters , only 3 were consistently reported : interventricular mechanical delay ( IVMD ) , left ventricular filling time relative to the cardiac cycle ( LVFT ) , and left ventricular pre-ejection interval . After multivariable adjustment , IVMD ( + 5.18 , 95 % confidence interval [ CI ] : + 0.76 to + 9.60 ; p = 0.02 ) and LVFT ( + 5.19 , 95 % CI : + 0.45 to + 0.94 ; p = 0.03 ) were independently associated with 6-month improvements in KCCQ . Patients with 6-month improvements in KCCQ had lower subsequent mortality ( adjusted hazard ratio [ HR ] for each 5-point improvement : 0.83 ; 95 % CI : 0.72 to 0.93 ; p = 0.03 ) . Additionally , IVMD was associated with CRT responder status ( for DeltaKCCQ > or = + 10 points : odds ratio [ OR ] : 1.85 ; 95 % CI : 1.12 to 3.05 ; p = 0.03 ) , whereas LVFT was not ( OR : 1.63 ; 95 % CI : 0.85 to 3.11 ; p = 0.14 ) . Patients classified as health status responders had a 76 % lower subsequent risk of all-cause mortality ( adjusted HR : 0.24 ; 95 % CI : 0.07 to 0.84 ; p = 0.03 ) . CONCLUSIONS The presence of pre-implantation IVMD and LVFT was associated with 6-month health status improvement , and IVMD was associated with a significant CRT response . These echocardiographic factors may help clinicians counsel patients regarding their likelihood of symptomatic improvement with CRT . ( PROSPECT Predictors of Response to Cardiac Re-Synchronization Therapy ; NCT00253357 ) INTRODUCTION Patients with end-stage heart failure and a wide QRS complex are considered c and i date s for cardiac resynchronization therapy ( CRT ) . However , 20 % to 30 % of patients do not respond to CRT . Lack of left ventricular dyssynchrony may explain the nonresponse . Accordingly , we evaluated the presence of left ventricular dyssynchrony using tissue Doppler imaging ( TDI ) in 90 consecutive patients with heart failure . METHODS AND RESULTS Ninety patients with severe heart failure ( left ventricular ejection fraction < 35 % , New York Heart Association class III-IV ) were prospect ively evaluated . Based on QRS duration , 30 consecutive patients with a narrow QRS complex were included ( QRS duration < or=120 ms ) , 30 patients with an intermediate QRS duration ( 120 - 150 ms ) , and 30 patients with a wide QRS complex ( > 150 ms ) . All patients underwent TDI to assess left ventricular dyssynchrony . Extensive left ventricular dyssynchrony was defined as an electromechanical delay on TDI between the septum and lateral wall , the so-called septal-to-lateral delay , of > 60 ms . Severe dyssynchrony was observed in 27 % of patients with narrow QRS complex , 60 % with intermediate QRS duration , and 70 % with wide QRS complex . No relation existed between QRS duration and septal-to-lateral delay . CONCLUSION From 30 % to 40 % of heart failure patients with QRS duration > 120 ms do not exhibit left ventricular dyssynchrony , which may explain the nonresponse to CRT . Alternatively , 27 % of patients with heart failure and a narrow QRS complex show significant left ventricular dyssynchrony and may be c and i date s for CRT INTRODUCTION Predicting reverse remodeling after cardiac resynchronization therapy ( CRT ) remains challenging and different etiologies of heart failure might hamper identification of predictors . OBJECTIVE Assess the incremental value of mechanical dyssynchrony besides electrical dyssynchrony for predicting CRT response . METHODS 227 patients ( 51 % ischemic ) received CRT . Response was defined as ≥15 % left ventricular end systolic volume decrease after six months . Prediction models were developed comprising clinical parameters and electrical dyssynchrony ( Model A ) , subsequently complemented with mechanical dyssynchrony ( Model B ) . Models were compared by area under the receiver-operating curve ( AUC ) , net reclassification index ( NRI ) and integrated discrimination improvement ( IDI ) for the complete cohort , ischemic ( ICM ) and non-ischemic ( NICM ) sub population s. RESULTS Model B performed significantly better than Model A supported by AUC , NRI and IDI . Furthermore , model B significantly better predicted response for NICM than ICM . CONCLUSION Electrical dyssynchrony and mechanical dyssynchrony are essential to predict CRT response . Nevertheless , response prediction for ICM remains challenging BACKGROUND This study examined factors that could predict response to cardiac resynchronization therapy ( CRT ) up grade in patients who developed heart failure ( HF ) after long-term right ventricular ( RV ) pacing . METHODS Twenty-five consecutive patients who received CRT up grade for long-term RV pacing ( RVP ) were enrolled in this study . None of these patients were eligible for CRT at the moment of starting RVP . After 5.7 ± 4.0 years chronic RVP , these 25 patients developed HF symptoms and received CRT up grade . Echocardiography was conducted at the moment of CRT up grade and 6 months after CRT . Remote past left ventricular ejection fraction ( RP-LVEF ) at the moment of starting RVP was retrospectively obtained from the echocardiographic and cardiac catherization reports . Responders were defined as a reduction in LV end-systolic volume ( LVESV ) ≥ 15 % . Their clinical and echocardiographic parameters were analyzed and compared . RESULTS Responders had significant higher RP-LVEF as compared to nonresponders ( 53.6 ± 16.5 % vs 31.4 ± 11.6 % , P = 0.002 ) . RP-LVEF correlated with reduction in LVESV after CRT up grade ( P < 0.001 ) . RP-LVEF ≥ 43.5 % as a cutoff value predicted response to CRT up grade with an area under the receiver-operating curve of 0.87 , a sensitivity of 78 % , and a specificity of 100 % . Intrinsic QRS width , septal-posterior wall motion delay , or tissue Doppler-derived dyssynchrony indexes did not predict responses to CRT up grade . CONCLUSION In long-term RVP patients who developed HF and received CRT up grade , RP-LVEF ≥ 43.5 % predicts good response . Conventional dyssynchrony indexes do not predict responses to CRT up grade in these patients Objective To determine the value of echocardiography in predicting response to cardiac resynchronisation therapy ( CRT ) . Methods This is a prospect i ve r and omised study that recruited patients with ( group 1 ) and without ( group 2 ) echocardiographic evidence of mechanical dyssynchrony . 73 heart failure patients ( NYHA III – IV ) with a requirement for an implantable cardioverter defibrillator , QRS ≥120 ms and LV ejection fraction ( EF ) < 35 % were studied . Group 1 patients received CRT-D ( 26 patients ) . Group 2 patients were r and omised to CRT-D ( group 2a : 23 patients ) or implantable cardioverter defibrillator ( group 2b : 21 patients ) . Main outcome measures were peak oxygen consumption ( VO2max ) , NYHA class , and echocardiography at baseline and at 6 months . Results 62 % of group 1 patients achieved ≥1 ml/kg/min increase in VO2max at 6 months versus 50 % in group 2a and 21 % in group 2b ( p=0.04 ) . Group 1 patients showed significant improvements in VO2max ( 15.8±2 to 18.0±4 ml/kg/min , p=0.01 ) , NYHA class ( 3.1±0.3 to 1.9±0.7 , p<0.001 ) and EF ( 22±7 % to 26±9 % , p=0.02 ) . Group 2a showed significant improvement in NYHA class ( 3.1±0.3 to 2.2±0.7 , p<0.001 ) but no change in EF or VO2max . Group 2b showed no change in NYHA class or EF with a decline in VO2max ( 16.4±4 to 14.1±4 , p=0.03 ) . A significantly higher proportion of patients in group 2b showed ≥1 ml/kg/min deterioration in VO2max compared to group 2a ( 68 % vs 23 % , HR for group 2b : 2.4 , 95 % CI 1.2 to 4.8 , p=0.005 ) . Conclusions The presence of echocardiographic dyssynchrony identifies patients who derive the most improvement from CRT . Patients without dyssynchrony also show more benefit and less deterioration with CRT than without and should not be denied CRT In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted BACKGROUND Cardiac resynchronization therapy ( CRT ) was shown to improve heart failure ( HF ) prognosis . But many patients do not benefit from CRT . Optimization of left ventricular ( LV ) lead position to the latest activated LV area is important to increase CRT response . We aim ed to detect the relationship between LV lead sensing delay and echocardiographic and electrocardiographic response to CRT treatment . METHODS We prospect ively included 156 consecutive patients with HF diagnosis , QRS ≥ 120 ms , left bundle branch block , New York Heart Association II-IV , LV ejection fraction ( LVEF ) < 35 % , and scheduled for CRT ( 100 male , 56 female ; mean age 65.8 ± 10.06 years ) . Echocardiographic CRT response was defined as ≥15 % reduction in LV end-systolic volume ( LVESV ) . LV lead sensing delay was calculated as the time interval from the onset of surface QRS wave to the onset of depolarization wave recorded from the LV lead by using the LV pacing lead as a bipolar electrode . RESULTS LVESV reduction was associated with baseline QRS width ( r = 0.292 , P = 001 ) , QRS narrowing ( r = 0.332 , P < 001 ) , and LV lead sensing delay ( r = 0.454 , P < 001 ) in bivariate analysis . In logistic regression analysis , LV lead sensing delay was found to be the only independent parameter for predicting significant LVESV reduction ( β = 0.423 , P < 0.001 ) . LV lead sensing delay was also found to be significantly associated with LVEF increase ( r = 0.320 , P < 0.001 ) and QRS narrowing ( r = 0.345 , P < 0.001 ) . CONCLUSION LV lead sensing delay is the only independent predictor for significant reduction in LVESV and was found to be significantly associated with LVEF increase and QRS narrowing after CRT treatment . We suggest that LV lead sensing delay may be used as a marker to predict the favorable response to CRT BACKGROUND Previous studies have suggested that cardiac resynchronization achieved through atrial-synchronized biventricular pacing produces clinical benefits in patients with heart failure who have an intraventricular conduction delay . We conducted a double-blind trial to evaluate this therapeutic approach . METHODS Four hundred fifty-three patients with moderate-to-severe symptoms of heart failure associated with an ejection fraction of 35 percent or less and a QRS interval of 130 msec or more were r and omly assigned to a cardiac-resynchronization group ( 228 patients ) or to a control group ( 225 patients ) for six months , while conventional therapy for heart failure was maintained . The primary end points were the New York Heart Association functional class , quality of life , and the distance walked in six minutes . RESULTS As compared with the control group , patients assigned to cardiac resynchronization experienced an improvement in the distance walked in six minutes ( + 39 vs. + 10 m , P=0.005 ) , functional class ( P<0.001 ) , quality of life ( -18.0 vs. -9.0 points , P= 0.001 ) , time on the treadmill during exercise testing ( + 81 vs. + 19 sec , P=0.001 ) , and ejection fraction ( + 4.6 percent vs. -0.2 percent , P<0.001 ) . In addition , fewer patients in the group assigned to cardiac resynchronization than control patients required hospitalization ( 8 percent vs. 15 percent ) or intravenous medications ( 7 percent vs. 15 percent ) for the treatment of heart failure ( P<0.05 for both comparisons ) . Implantation of the device was unsuccessful in 8 percent of patients and was complicated by refractory hypotension , bradycardia , or asystole in four patients ( two of whom died ) and by perforation of the coronary sinus requiring pericardiocentesis in two others . CONCLUSIONS Cardiac resynchronization results in significant clinical improvement in patients who have moderate-to-severe heart failure and an intraventricular conduction delay |
13,231 | 31,425,624 | Ground larviciding for non-extensive larval habitats may have an effect on malaria transmission , and we do not know if there is an effect in large-scale aquatic habitats .
We found no studies using larviciding application techniques that could cover large aquatic habitats , such as aerial spraying using aircraft | BACKGROUND Larviciding refers to the regular application of chemical or microbial insecticides to water bodies or water containers to kill the aquatic immature forms of the mosquito ( the larvae and pupae ) .
OBJECTIVES To summarize research evidence evaluating whether larviciding with chemical or microbial insecticides prevents malaria transmission .
AUTHORS ' CONCLUSIONS Most controlled studies on larviciding have been performed with microbial agents . | Objective Systematic review s can include cluster-r and omised controlled trials ( C- RCTs ) , which require different analysis compared with st and ard individual-r and omised controlled trials . However , it is not known whether review authors follow the method ological and reporting guidance when including these trials . The aim of this study was to assess the method ological and reporting practice of Cochrane review s that included C- RCTs against criteria developed from existing guidance . Methods Criteria were developed , based on method ological literature and personal experience supervising review production and quality . Criteria were grouped into four themes : identifying , reporting , assessing risk of bias , and analysing C- RCTs . The Cochrane Data base of Systematic Review s was search ed ( 2nd December 2013 ) , and the 50 most recent review s that included C- RCTs were retrieved . Each review was then assessed using the criteria . Results The 50 review s we identified were published by 26 Cochrane Review Groups between June 2013 and November 2013 . For identifying C- RCTs , only 56 % identified that C- RCTs were eligible for inclusion in the review in the eligibility criteria . For reporting C- RCTs , only eight ( 24 % ) of the 33 review s reported the method of cluster adjustment for their included C- RCTs . For assessing risk of bias , only one review assessed all five C- RCT -specific risk-of-bias criteria . For analysing C- RCTs , of the 27 review s that presented unadjusted data , only nine ( 33 % ) provided a warning that confidence intervals may be artificially narrow . Of the 34 review s that reported data from unadjusted C- RCTs , only 13 ( 38 % ) excluded the unadjusted results from the meta-analyses . Conclusions The method ological and reporting practice s in Cochrane review s incorporating C- RCTs could be greatly improved , particularly with regard to analyses . Criteria developed as part of the current study could be used by review authors or editors to identify errors and improve the quality of published systematic review s incorporating C- RCTs Background The massive scale-up of insecticide-treated nets ( ITNs ) and indoor residual spraying ( IRS ) has led to a substantial increase in malaria vector insecticide resistance as well as in increased outdoor transmission , both of which hamper the effectiveness and efficiency of ITN and IRS . Long-lasting microbial larvicide can be a cost-effective new supplemental intervention tool for malaria control . Methods / design We will implement the long-lasting microbial larvicide intervention in 28 clusters in two counties in western Kenya . We will test FourStar controlled release larvicide ( 6 % by weight Bacillus thuringiensis israelensis and 1 % Bacillus sphaerius ) by applying FourStar controlled release granule formulation , 90-day briquettes , and 180-day briquettes in different habitat types . The primary endpoint is clinical malaria incidence rate and the secondary endpoint is malaria vector abundance and transmission intensity . The intervention will be conducted as a two-step approach . First , we will conduct a four-cluster trial ( two clusters per county , with one of the two clusters r and omly assigned to the intervention arm ) to optimize the larvicide application scheme . Second , we will conduct an open-label , cluster-r and omized trial to evaluate the effectiveness and cost-effectiveness of the larvicide . Fourteen clusters in each county will be assigned to intervention ( treatment ) or no intervention ( control ) by a block r and omization on the basis of clinical malaria incidence , vector density , and human population size per site . We will treat each treatment cluster with larvicide for three rounds at 4-month intervals , followed by no treatment for the following 8 months . Next , we will switch the control and treatment sites . The former control sites will receive three rounds of larvicide treatment at appropriate time intervals , and former treatment sites will receive no larvicide . We will monitor indoor and outdoor vector abundance using CO2-baited CDC light traps equipped with collection bottle rotators . Clinical malaria data will be aggregated from government-run malaria treatment centers . Discussion Since current first-line vector intervention methods do not target outdoor transmission and will select for higher insecticide resistance , new methods beyond bed nets and IRS should be considered . Long-lasting microbial larviciding represents a promising new tool that can target both indoor and outdoor transmission and alleviate the problem of pyrethroid resistance . It also has the potential to diminish costs by reducing larvicide reapplications . If successful , it could revolutionize malaria vector control in Africa , just as long-lasting bed nets have done . Trial registration U.S. National Institute of Health , study ID NCT02392832 . Registered on 3 February 2015 The optimization of malaria control strategies is complicated by constraints posed by local health systems , infrastructure , limited re sources , and the complex interactions between infection , disease , and treatment . The purpose of this paper is to describe the protocol of a r and omized factorial study design ed to address this research gap . This project will evaluate two malaria control interventions in Mvomero District , Tanzania : ( 1 ) a disease management strategy involving early detection and treatment by community health workers using rapid diagnostic technology ; and ( 2 ) vector control through community-supported larviciding . Six study villages were assigned to each of four groups ( control , early detection and treatment , larviciding , and early detection and treatment plus larviciding ) . The primary endpoint of interest was change in malaria infection prevalence across the intervention groups measured during annual longitudinal cross-sectional surveys . Recurring entomological surveying , household surveying , and focus group discussion s will provide additional valuable insights . At baseline , 962 households across all 24 villages participated in a household survey ; 2,884 members from 720 of these households participated in subsequent malariometric surveying . The study design will allow us to estimate the effect sizes of different intervention mixtures . Careful documentation of our study protocol may also serve other research ers design ing field-based intervention trials Introduction The efficacy of Vectobac GR ( potency 200 ITU/mg ) , a new formulation of bacterial larvicide Bacillus thuringiensis var . israelensis Strain AM65 - 52 , was evaluated against Anopheles gambiae and Culex quinquefasciatus in simulated field and natural habitats in Benin . Methods In simulated field conditions , Vectobac GR formulation was tested at 3 dosages ( 0.6 , 0.9 , 1.2 g granules/m2 against An . gambiae and 1 , 1.5 , 2 g granules/m2 against Cx . quinquefasciatus ) according to manufacturer ’s product label recommendations . The dosage giving optimum efficacy under simulated field conditions were evaluated in the field . The efficacy of Vectobac GR in terms of emergence inhibition in simulated field conditions and of reduction of larval and pupal densities in rice fields and urban cesspits was measured following WHO guidelines for testing and evaluation of mosquito larvicides . Results Vectobac GR caused emergence inhibition of ≥80 % until 21 [20]–[22 ] days for An . gambiae at 1.2 g/m2 dose and 28 [ 27–29 ] days for Cx . quinquefasciatus at 2 g/m2 in simulated field habitats . The efficacy of Vectobac GR in natural habitats was for 2 to 3 days against larvae and up to 10 days against pupae . Conclusions Treatment with Vectobac GR caused complete control of immature mosquito within 2–3 days but did not show prolonged residual action . Larviciding can be an option for malaria and filariasis vector control particularly in managing pyrethroid-resistance in African malaria vectors . Since use of larvicides among several African countries is being emphasized through Economic Community of West Africa States , their epidemiological impact should be carefully investigated Background Outdoor malaria transmission is becoming an increasingly important problem in malaria control in Africa . Larval control is a promising intervention as it can target both indoor and outdoor biting mosquitoes . However , the currently available biolarvicide formulations have a short effective duration , and consequently larval control incurs a high operational expense due to the requirement for frequent re-treatment of larval habitats . Formulations of biolarvicides with long-lasting effects is highly desired . A recently developed FourStar ® slow-release briquet formulation of Bacillus thuringiensis israelensis and Bacillus sphaericus was evaluated to test its efficacy on malaria vectors . Methods The study evaluated FourStar ™ briquets 180-days formulation under semi-natural and natural conditions to test their efficacy in reducing the mosquito population in western Kenya . The semi-natural habitats used the formulation dissolved in rainwater with appropriate concentrations , and second-instar larvae of Anopheles gambiae were introduced and the number of surviving larvae and pupae produced was recorded daily as the outcome . The briquets formulation was then tested in natural habitats for efficacy on pupal productivity reduction in highl and and lowl and sites in western Kenya . The formulation was finally tested for efficacy in reducing adult mosquito population s in r and omized clusters in western Kenya highl and . Results In semi-natural conditions , the FourStar ™ briquets 180-days formulation completely inhibited mosquito pupal production in the first 3 months , and then reduced pupal productivity by 87–98 % ( P < 0.001 ) 4–6 months after application . In natural habitats , during the first 2 months no pupae were detected from any of the treated habitats in highl and sites , and Anopheles spp . pupal density was reduced by 60–90 % in the next 3–5 months ( P < 0.001 ) . In the lowl and site , pupal productivity reduction was 100 % in the first 3 months , and 75–90 % in the next 4–5 months ( P < 0.001 ) . The r and omized cluster trial found that the application of the briquets formulation reduced mean densities of indoor-biting mosquitoes by 76–82 % ( P < 0.001 ) and by 67–75 % ( P < 0.001 ) for outdoor-biting mosquitoes . Conclusion This study demonstrated that long-lasting biological larviciding was effective in reducing pupal productivity of larval habitats , and reducing indoor and outdoor resting mosquitoes . The study suggests that long-lasting microbial larviciding may be a promising complementary malaria vector control tool and warrants further large-scale evaluation Background The use of larval source management is not prioritized by contemporary malaria control programs in sub-Saharan Africa despite historical success . Larviciding , in particular , could be effective in urban areas where transmission is focal and accessibility to Anopheles breeding habitats is generally easier than in rural setting s. The objective of this study is to assess the effectiveness of a community-based microbial larviciding intervention to reduce the prevalence of malaria infection in Dar es Salaam , United Republic of Tanzania . Methods and Findings Larviciding was implemented in 3 out of 15 targeted wards of Dar es Salaam in 2006 after two years of baseline data collection . This intervention was subsequently scaled up to 9 wards a year later , and to all 15 targeted wards in 2008 . Continuous r and omized cluster sampling of malaria prevalence and socio-demographic characteristics was carried out during 6 survey rounds ( 2004–2008 ) , which included both cross-sectional and longitudinal data ( N = 64,537 ) . Bayesian r and om effects logistic regression models were used to quantify the effect of the intervention on malaria prevalence at the individual level . Effect size estimates suggest a significant protective effect of the larviciding intervention . After adjustment for confounders , the odds of individuals living in areas treated with larviciding being infected with malaria were 21 % lower ( Odds Ratio = 0.79 ; 95 % Credible Intervals : 0.66–0.93 ) than those who lived in areas not treated . The larviciding intervention was most effective during dry seasons and had synergistic effects with other protective measures such as use of insecticide-treated bed nets and house proofing ( i.e. , complete ceiling or window screens ) . Conclusion A large-scale community-based larviciding intervention significantly reduced the prevalence of malaria infection in urban Dar es Salaam Background Malaria control in Africa is most tractable in urban settlements yet most research has focused on rural setting s. Elimination of malaria transmission from urban areas may require larval control strategies that complement adult mosquito control using insecticide-treated nets or houses , particularly where vectors feed outdoors . Methods and Findings Microbial larvicide ( Bacillus thuringiensis var . israelensis ( Bti ) ) was applied weekly through programmatic , non-r and omized community-based , but vertically managed , delivery systems in urban Dar es Salaam , Tanzania . Continuous , r and omized cluster sampling of malaria infection prevalence and non-r and om programmatic surveillance of entomological inoculation rate ( EIR ) respectively constituted the primary and secondary outcomes surveyed within a population of approximately 612,000 residents in 15 fully urban wards covering 55 km2 . Bti application for one year in 3 of those wards ( 17 km2 with 128,000 residents ) reduced crude annual transmission estimates ( Relative EIR [ 95 % Confidence Interval ] = 0.683 [ 0.491–0.952 ] , P = 0.024 ) but program effectiveness peaked between July and September ( Relative EIR [ CI ] = 0.354 [ 0.193 to 0.650 ] , P = 0.001 ) when 45 % ( 9/20 ) of directly observed transmission events occurred . Larviciding reduced malaria infection risk among children ≤5 years of age ( OR [ CI ] = 0.284 [ 0.101 to 0.801 ] , P = 0.017 ) and provided protection at least as good as personal use of an insecticide treated net ( OR [ CI ] = 0.764 [ 0.614–0.951 ] , P = 0.016 ) . Conclusions In this context , larviciding reduced malaria prevalence and complemented existing protection provided by insecticide-treated nets . Larviciding may represent a useful option for integrated vector management in Africa , particularly in its rapidly growing urban centres The study was conducted in eight adjacent villages in central Sri Lanka where there are many shallow pits dug by gem miners that fill with water . These become breeding places of the main malarial vector Anopheles culicifacies , and of the second most important vector Anopheles subpictus , but not of Anopheles varuna , the third most important vector . With the help of local volunteers , data on the adult population s of these three species was collected by various st and ard methods , and data on the incidence of malaria cases was collected by two clinics set up for the project and through the existing hospitals . Prevalence of malaria infection in symptom-less people was investigated by mass blood surveys . On the basis of a year 's pre-intervention data the villages were stratified into four with high levels of malaria transmission and four with lower transmission . Within each stratum two villages were r and omly assigned for mosquito control by treating all the gem pits , as well as river bed pools , with a granular formulation of the insect growth regulator pyriproxyfen at a target dose of 0.01 mg a.i./litre . The intervention caused significant reductions in the adult population s of An . culicifacies and An . subpictus . Similarly , incidence of malaria was reduced in the intervention villages to about 24 % ( 95 % c.l . 20 - 29 % ) of that in the controls . Prevalence of parasitaemia also declined significantly . It is concluded that in this situation where , with active community participation , the breeding sites of the main vectors could be located ; vector control by a highly active and persistent insect growth regulator can be a very effective means of malaria control Background The communities of Namawala and Idete villages in southern Tanzania experienced extremely high malaria transmission in the 1990s . By 2001 - 03 , following high usage rates ( 75 % of all age groups ) of untreated bed nets , a 4.2-fold reduction in malaria transmission intensity was achieved . Since 2006 , a national-scale programme has promoted the use of longer-lasting insecticide treatment kits ( consisting of an insecticide plus binder ) co-packaged with all bed nets manufactured in the country . Methods The entomological inoculation rate ( EIR ) was estimated through monthly surveys in 72 houses r and omly selected in each of the two villages . Mosquitoes were caught using CDC light traps placed beside occupied bed nets between January and December 2008 ( n = 1,648 trap nights ) . Sub- sample s of mosquitoes were taken from each trap to determine parity status , sporozoite infection and Anopheles gambiae complex sibling species identity . Results Compared with a historical mean EIR of ~1400 infectious bites/person/year ( ib/p/y ) in 1990 - 94 ; the 2008 estimate of 81 ib/p/y represents an 18-fold reduction for an unprotected person without a net . The combined impact of longer-lasting insecticide treatments as well as high bed net coverage was associated with a 4.6-fold reduction in EIR , on top of the impact from the use of untreated nets alone . The scale-up of bed nets and subsequent insecticidal treatment has reduced the density of the anthropophagic , endophagic primary vector species , Anopheles gambiae sensu stricto , by 79 % . In contrast , the reduction in density of the zoophagic , exophagic sibling species Anopheles arabiensis was only 38 % . Conclusion Insecticide treatment of nets reduced the intensity of malaria transmission in addition to that achieved by the untreated nets alone . Impacts were most pronounced against the highly anthropophagic , endophagic primary vector , leading to a shift in the sibling species composition of the A. gambiae complex Background Recent efforts of accelerated malaria control towards the long-term goal of elimination had significant impacts in reducing malaria transmission . While these efforts need to be sustained over time , a scenario of low transmission could bring about changes in individual disease risk perception , hindering adherence to protective measures , and affecting disease-related knowledge . The goal of this study was to investigate the potential impact of a successful malaria vector control intervention on bed net usage and malaria-related knowledge . Methods Dar es Salaam ’s Urban Malaria Control Program was launched in 2004 with the aim of developing a sustainable larviciding intervention . Larviciding was scaled-up using a stepped-wedge design . Cross-sectional and longitudinal data were collected using a r and omized cluster sampling design ( 2004–2008 ) . Prevalence ratios ( PR ) for the effect of the larviciding intervention on bed net usage ( N = 64,537 ) and household heads ’ knowledge of malaria symptoms and transmission ( N = 11,254 ) were obtained from r and om effects regression models . Results The probability that individuals targeted by larviciding had used a bed net was reduced by 5 % as compared to those in non-intervention areas ( PR = 0.95 ; 95 % credible intervals ( CrI ) : 0.94 - 0.97 ) and the magnitude of this effect increased with time . Larviciding also led to a decline in household heads ’ knowledge of malaria symptoms ( PR = 0.88 ; 95 % CrI : 0.83 - 0.92 ) but no evidence of effect on knowledge of malaria transmission was found . ConclusionS uccessful control interventions could bring about further challenges to sustaining gains in reducing malaria transmission if not accompanied by strategies to avoid changes in individual knowledge and behaviour . This study points to two major research gaps . First , there is an urgent need to gather more evidence on the extent to which countries that have achieved significant decline in malaria transmission are also observing changes in individual behaviour and knowledge . Second , multidisciplinary assessment s that combine quantitative and qualitative data , utilizing theories of health behaviour and theories of knowledge , are needed to optimize efforts of national malaria control programmes , and ultimately contribute to sustained reduction in malaria transmission Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background Appropriate supervision , along with availability of an effective system for monitoring and evaluation , is a crucial requirement to guarantee sufficient coverage and quality of malaria vector control procedures . This study evaluated the efficacy of self- assessment practice as a possible innovative method towards achieving high coverage and excellent quality of larviciding operation in Iran . Methods The research was conducted on the r and omly selected rural health centre of Kanmbel Soliman with 10 staff and 30 villages , in three main steps : ( i ) assessment of effectiveness of larviciding operations in the study areas before intervention through external assessment by a research team ; ( ii ) self- assessment of larviciding operations ( intervention ) by staff every quarter for three rounds ; and , ( iii ) determining the effectiveness of applying self- assessment of larviciding operations in the study areas . Two toolkits were used for self- assessment and external evaluation . The impact of self- assessment of larviciding operations was measured by two indicators : percentage of missed breeding habitats and cleaned breeding habitats among r and omly selected breeding sites . Moreover , the correlation coefficients were measured between self- assessment measures and scores from external evaluation . The correlation coefficient and Mann Whitney test were used to analyse data . Results Following the utilization of self- assessment , the percentage of missed breeding habitats decreased significantly from 14.23 % to 1.91 % ( P < 0.001 ) . Additionally , the percentage of cleaned breeding habitats among r and omly selected breeding sites increased from 66.89 % to 95.28 % ( P < 0.001 ) . The external evaluation also showed significant effects of self- assessment in performance of vector control ; the maximum effect of intervention were seen in an action plan for monitoring and evaluation of larviciding operations at field level , geographical reconnaissance for the registration of breeding habitats and worker skills related to larviciding . Before intervention , the results of self- assessment practice were compatible with external evaluation in 76.3 % of 139 review ed reports of self- assessment . After intervention , the findings of self- assessment and external evaluation were similar in the vast majority of review ed reports ( 95 % ) . Conclusion The self- assessment tool seems to be valid and reliable in improving effectiveness of larviciding operations . Furthermore , the result of self- assessment is more compatible with external evaluation results if it would be applied frequently . Therefore , it can be used as an alternative assessment technique in the evaluation of larviciding operations in addition to traditional assessment methods A r and omised , controlled , blinded field trial was conducted in a large cantonment area , to study the efficacy of the biocide formulation ( Bacillus spp . ) indigenously produced by Central Drug Research Institute , Lucknow , India , as a mosquito larvicide , in comparison with Fenthion and Temephos . The study revealed that the biocide formulation in dosage of 5 grams per square metre brought about a very high level of control of culicine larvae from third day of application and the effect persisted till at least 28 days ( median values of percentage reduction achieved being 93 % to 100 % ) . This effect was statistically significant from 7th to 28th day , as compared to Fenthion , Temephos or the biocide in dosage of 2 grams per square metre . Fenthion , on the other h and was statistically more efficacious in bringing about a quick reduction , with a 100 % reduction being obtained within a day , but the effect declined to a low level by 7th day Background Due to outdoor and residual transmission and insecticide resistance , long-lasting insecticidal nets ( LLINs ) and indoor residual spraying ( IRS ) will be insufficient as st and -alone malaria vector control interventions in many setting s as programmes shift toward malaria elimination . Combining additional vector control interventions as part of an integrated strategy would potentially overcome these challenges . Larval source management ( LSM ) and structural house improvements ( HI ) are appealing as additional components of an integrated vector management plan because of their long histories of use , evidence on effectiveness in appropriate setting s , and unique modes of action compared to LLINs and IRS . Implementation of LSM and HI through a community-based approach could provide a path for rolling-out these interventions sustainably and on a large scale . Methods / design We will implement community-based LSM and HI , as additional interventions to the current national malaria control strategies , using a r and omised block , 2 × 2 factorial , cluster-r and omised design in rural , southern Malawi . These interventions will be continued for two years . The trial catchment area covers about 25,000 people living in 65 villages . Community participation is encouraged by training community volunteers as health animators , and supporting the organisation of village-level committees in collaboration with The Hunger Project , a non-governmental organisation . Household-level cross-sectional surveys , including parasitological and entomological sampling , will be conducted on a rolling , 2-monthly schedule to measure outcomes over two years ( 2016 to 2018 ) . Coverage of LSM and HI will also be assessed throughout the trial area . Discussion Combining LSM and /or HI together with the interventions currently implemented by the Malawi National Malaria Control Programme is anticipated to reduce malaria transmission below the level reached by current interventions alone . Implementation of LSM and HI through a community-based approach provides an opportunity for optimum adaptation to the local ecological and social setting , and enhances the potential for sustainability . Trial Registration Registered with The Pan African Clinical Trials Registry on 3 March 2016 , trial number PACTR201604001501493 Various vector control measures were applied in different endemic areas in two provinces , Saraburi and Chanthaburi , with comparison among different control measures . Application of IGR ( insect growth regurator , pyriproxyfen ) was introduced at Wat Tam Pra Pothisat , Tab-Kwang District , Saraburi Province . Some integration measures were performed at villages 6 and 8 , Patavee , Makham District , Chanthaburi Province . In Tab-Kwang District with low malaria endemicity at the study site predators were not able to be released due to rapid velocity of running water . IGR could effectively control malaria compared to the basin released predators . Another endemic areas villagers 6 and 8 , Patavee , Makham , Chanthaburi Province was chosen . Highly endemic multidrug resistant malaria has been prevalent for many years in this area . Integration of K and a 's trapping system , application of IGR , use of both residual spraying and impregnated bed-net methods with etofenprox successfully interrupted malaria infection . The application of these methods as an integrated control system could be adjusted to environmental conditions . The results of this study suggest rapid effective vector control An evaluation of pyriproxyfen as a larval control agent with the aim of reducing malaria vector population s and incidence of malaria was conducted in 12 villages in an irrigated settlement scheme in the dry zone of central Sri Lanka . In these villages , there are many pools in the beds of rivers , streams , and irrigation ditches during the dry season of the year . These are the major breeding places of the malaria vectors Anopheles culicifacies and An . subpictus . Collection s of adult mosquitoes were carried out by using st and ard methods and parasitological data were collected by daily malaria clinics set up for the project and through the 2 government hospitals . All villages in the study area were under residual house spraying with lambdacyhalothrin water-dispersible powder . Using the 1st year 's baseline data collection , the villages were stratified into 6 villages with high malaria incidence and 6 villages with low incidence . Within each group , 3 villages were r and omly assigned for larval control by treating all the pools in the beds of rivers , streams , and irrigation ditches and agricultural wells with a granular formulation of the insect growth regulator pyriproxyfen at the rate of 0.01 mg active ingredient/liter . The field bioassays indicated that a single treatment of pyriproxyfen effectively inhibited the emergence of adult mosquitoes in the riverbed pools for a period of 190 days . The treatment caused significant reduction of the adult population s of An . culicifacies ( 78 % ) and An . subpictus ( 72 % ) . Similarly , incidence of malaria was reduced in the treatment villages by about 70 % ( 95 % confidence interval 58 - 78 % ) compared with the controls . The conclusion is made that pyriproxyfen can be a very effective means of malaria control if all possible vector breeding places in the area can be located |
13,232 | 18,843,719 | When polyvalent immunoglobulins or hyperimmune cytomegalovirus (CMV)-IVIG was compared to control for HSCT , there was no difference in all-cause mortality .
Polyvalent immunoglobulins significantly reduced the risk for interstitial pneumonitis but increased the risk for veno-occlusive disease and adverse events .
In LPD , no benefit in terms of mortality IVIG could be demonstrated but there was a decrease in clinical ly and microbiologically documented infections .
AUTHORS ' CONCLUSIONS In patients undergoing HSCT , routine prophylaxis with IVIG is not supported . | BACKGROUND Patients undergoing hematopoietic stem cell transplantation ( HSCT ) and those with lymphoproliferative disorders ( LPD ) have a higher incidence of infections due to secondary hypogammaglobulinemia .
One approach is the prophylactic administration of intravenous immunoglobulins ( IVIG ) .
R and omized controlled trials ( RCTs ) showed conflicting results in terms of type , schedule , dose and hematological patients benefiting from IVIG .
We therefore performed a systematic review and meta- analysis to evaluate the role of IVIG in these patients .
OBJECTIVES To determine whether prophylaxis with IVIG reduces mortality or affects other outcomes in patients with hematological malignancies . | Polyclonal intravenous IgG ( IVIG ) was administered as an infusion 6 times every 3 weeks ( week 0 , 3 , 6 , 9 , 12 , 15 ) in doses of 0.1 , 0.4 and 0.8 g/kg BW to determine the dose causing an increase in 12 pneumococcal antibody types above the protective level of 200 ng/ml of antibody N. The dose of 0.4 g/kg BW was found to be optimal in patients with chronic lymphocytic leukaemia ( CLL ) . From the first infusion onwards at least 80 % of CLL patients had increases in all 12 antibodies . Five weeks after the last infusion the antibody levels were still elevated in 80 % of patients with CLL . The dose of 0.8 g/kg raised all 12 antibodies in 53 - 73 % of CLL patients when assessment s were made after each infusion . In multiple myeloma ( MM ) patients , 73 - 82 % and 73 - 91 % of patients had increased antibody levels , respectively , before and after the 4th-6th infusions at the 0.8 g/kg dose level . However , in only 45 - 50 % of patients did the antibodies remain increased 2 weeks after the treatment at this dose . The dose of 0.4 g/kg caused antibody increases in only 30 - 50 % of patients when measured before the 4th-6th infusion . Serum IgG increased significantly only in the CLL patients , whereas in the MM patients it was high from the beginning owing to the disease . Therefore , the pneumococcal antibody levels were a better marker for the purpose of dose finding . The dosage recommendation in CLL is 0.4 g/kg every 3 weeks until week 12 , when steady state is reached . The maintenance dose is 0.4 g/kg every 5 weeks . In MM patients , who have a faster elimination rate of antibodies , the recommended loading dose is 0.8 g/kg , followed by 0.4 g/kg every week as a continuous treatment . Treatment with IVIG in CLL and MM was generally well tolerated . Only 25 % of patients experienced minor side-effects , the most frequent being febrile reactions , shivering and headache Patients treated with allogeneic bone marrow transplantation ( BMT ) suffer from a deficient humoral immunity during the post-transplant period . To prevent infections patients may receive prophylactic intravenous immunoglobulin ( IVIG ) therapy from 1 week before to 3 months after BMT . We have studied the effect of IVIG treatment on reconstitution of immunoglobulin repertoires in transplanted patients . Sera obtained from 13 IVIG-treated and 31 non-IVIG-treated patients before and at different time points after BMT , ranging from 3 days to 3 years , and from 18 healthy controls , were analyzed using a quantitative immunoblot system . The average immunoglobulin (Ig)M and IgG reactivity profiles against antigens derived from human liver , muscle and skin as well as Staphylococcus epidermidis protein extracts were similar in both patient groups and in controls . Both IgG and IgM reactivity profiles are , however , less heterogeneous among the individuals in the IVIG-treated patient group . Around 1 year after BMT the heterogeneity of the IgM reactivity profiles against allogeneic protein extracts is much lower in the IVIG-treated group compared to the non-IVIG-treated group and the healthy controls . This effect remains months to years after the IVIG treatment has been completed . Our results suggest that IVIG influences selection of the natural antibody repertoire mediated by the variable (V)-region during reconstitution after BMT To determine whether intravenous immunoglobulin ( IVIg ) given monthly from day 90 to day 360 posttransplantation decreased the incidence of late infection , chronic graft-vs.-host disease ( GVHD ) , and obliterative bronchiolitis after marrow transplantation , patients were assigned r and omly to receive either IVIg ( 500 mg/kg/month ) or no IVIg prophylaxis . Participants were registered before transplantation , and 250 patients ( 123 IVIg and 127 control ) were evaluable for events after day 100 . The two groups were balanced for age , marrow source , cytomegalovirus ( CMV ) seropositivity , pretransplantation conditioning , and prophylaxis for infection and GVHD . Between days 100 and 365 posttransplantation , the incidence of bacteremia or septicemia per 100 patient-days of risk was 0.10 in the IVIg group and 0.12 in the controls ( p = not significant ) . During the same period , the incidence of localized infection was marginally higher in control patients than in IVIg recipients ( 0.44 vs. 0.24 , respectively ; relative risk [ RR ] 1.46 , p < 0.07 ) . Administration of IVIg prophylaxis had no effect on survival , the incidence of obliterative bronchiolitis , severity of airflow obstruction , or the incidence or mortality of chronic GVHD . After discontinuing IVIg prophylaxis at day 360 , subsequent recovery of endogeneous humoral immunity was impaired ( serum IgG1 and IgA levels were significantly lower than controls at day 730 ) , and total infections were less common in the second year in control patients than in former IVIg recipients ( 0.12 vs 0.19 , respectively ; RR 0.61 , p = 0.03 ) . We conclude that in the absence of hypogammaglobulinemia , monthly administration of IVIg given from day 90 to 360 does not reduce late complications and may impair long-term humoral immune recovery after marrow transplantation In a study of 63 allogeneic and autologous bone marrow transplants , patients were r and omized to receive the IgM and IgA enriched intravenous immunoglobulin ( IVIG ) preparation ( Pentaglobin ) . Pentaglobin has been postulated to have anti-endotoxin properties and one of the aims of the study was to measure endotoxin levels in these patients together with the clinical sequelae of infection . The anti-endotoxin effects of Pentaglobin were found to reside in the IgM fraction . Those patients who received Pentaglobin were significantly protected from dying from infection in the first 100 days after the transplant , although it was not actually possible to document bacterial infections as the cause of death in the control patients . Peak endotoxin levels were significantly reduced ( p = 0.02 ) in those patients receiving Pentaglobin . Liver damage as assessed by liver enzyme abnormalities correlated significantly with the presence of endotoxaemia greater than 25 pg/ml and up to 70 % of pyrexial episodes were associated with endotoxaemia . Our results suggest that Pentaglobin is useful in reducing hepatic toxicity and this may be related to a reduction in endotoxaemia Overwhelming infections cause significant morbidity and mortality in the immunocompromised host . There is considerable in vitro and in vivo evidence that the immune deficient state which accompanies acute leukaemia , and , is exacerbated by intensive chemotherapy , contributes to the infection risk in these patients . The most easily documented and corrected is that of impaired humoral immunity . In order to study the clinical significance of the deficit a double blind , r and omised , placebo controlled pilot study was set up design ed to test the feasibility , efficacy and toxicity of using prophylactic intravenous immunoglobulin to prevent infective complications in this patient group . Patients received 150 mg/kg of Pentaglobin , an immunoglobulin preparation specifically enriched in IgM and IgA , on days 0 , 10 and 20 of the chemotherapy regimes . There were no adverse side effects . Patients in the placebo group had a 25 % fall in IgM level whilst IgG and IgA remained unchanged . The treatment group maintained a stable IgM and IgG concentration throughout but had a rise in IgA. There was no difference in the total number of septicaemic episodes in each group but the placebo group had an increased number of non Staphylococcal infections ( P < 0.04 ) . We conclude that intravenous Pentaglobin protects patients against a fall in IgM during induction chemotherapy for acute leukaemia and decreases the number of non Staphylococcal infections A r and omized crossover study of prophylactic immunoglobulin ( IgG ) therapy was performed in patients with chronic lymphocytic leukaemia ( CLL ) or non-Hodgkin 's lymphoma ( NHL ) . Twelve patients with hypogammaglobulinemia or a history of recurrent infections received infusions of IgG or placebo intravenously ( IV ) every 3 weeks for 1 year . They were then switched to the alternative preparation for another year . The number of serious bacterial infections was significantly less ( P = .001 ; Mainl and 's cross-over method ) in the months in which patients received IgG. Serious bacterial infections showed a trend to be associated with an IgG level less than 6.4 g/L ( P = .046 ; Fisher 's exact test ) Forty-two patients with chronic lymphocytic leukaemia ( CLL ) , serum IgG levels < 5.5 milligrams and a history of two or more recent infections , were r and omized to receive infusions of 18 g human intravenous immunoglobulin ( IVIg ) or human albumin placebo every three weeks . During the 12 month study 122 infections were documented but only four were associated with neutropenia . Ten patients ( 24 % ) with IgG levels < 3.0 milligrams experienced 65 % of the infections . In response to IVIg there were immediate and accumulative increases in serum IgG levels and an associated decrease in total and serious infections . If three further infections occurred , placebo patients were commenced on 18 g IVIg , and IVIg patients were increased to 24 g IVIg . Approximately 50 % of these cases subsequently remained infection free . The study shows the usefulness of prophylactic S and oglobulin in CLL patients with hypogammaglobulinaemia , and suggests that this may be justified in those with recurrent infections and serum IgG levels < 3 milligrams Treatment with intense myelosuppressive therapy ( including bone marrow transplantation ) has improved survival in patients with various malignant neoplasms [ 1 , 2 ] . Unfortunately , this treatment increases the incidence of infectious complications , primarily during the period of myelosuppression [ 3 ] . Various methods have been used to limit infection during myelosuppression [ 4 - 7 ] . Despite these pre caution s , bacteremia and fungemia continue to occur in at least one third of patients with sustained neutropenia . Intravenous immunoglobulin ( IVIG ) therapy prevents infections in patients with inborn B-cell deficiencies and hypogammaglobulinemia secondary to hematologic disorders such as chronic lymphocytic leukemia [ 8 - 10 ] . Intravenous immunoglobulin has also been used successfully to treat immune thrombocytopenic purpura , alloimmunity to platelets , and other immune-mediated disorders by a mechanism of immune system modulation [ 11 ] . After allogeneic bone marrow transplantation , IVIG is commonly used to prevent graft-versus-host disease [ 12 ] . During these bone marrow transplant trials , a reduction in bacterial infection was also observed in patients who were not necessarily hypogammaglobulinemic . This finding was initially reported in small anecdotal series but was later confirmed by large prospect i ve studies [ 12 - 17 ] . This effect of IVIG was observed during the pre-engraftment ( neutropenic ) and myelosuppression recovery phases . Most patients in these studies were undergoing allogeneic bone marrow transplantation , for which graft-versus-host disease and its treatment contribute to the rate of infection [ 18 ] . Intravenous immunoglobulin is not routinely used during autologous bone marrow transplantation or severely myelosuppressive therapy because prevention of graft-versus-host disease is unnecessary . Because IVIG prevents infection after allogeneic bone marrow transplantation , it might also do so in other patients undergoing intense myelosuppression and thus may serve as a general prophylactic agent for infections . Intravenous immunoglobulin is expensive and thus should not be used indiscriminately . We design ed a prospect i ve study that r and omized patients who were expected to develop severe and sustained myelosuppression to receive IVIG or no treatment . We specifically wished to determine whether IVIG could reduce the incidence of severe infections in patients with neutropenia but without allogeneic cofactors such as graft-versus-host disease . We therefore sought to determine whether the benefits of IVIG after allogeneic bone marrow transplantation occur as a direct effect of the drug or as an indirect result of a reduced incidence of graft-versus-host disease . Methods Study Design We conducted a stratified , r and omized comparison of patients who either underwent autologous bone marrow transplantation or received substantial myelosuppressive therapy for acute leukemia or other malignant conditions . The protocol and consent forms were approved by the Institutional Review Boards of the three participating institutions : Baylor University Medical Center , Dallas , Texas ; The University of Louisville , Louisville , Kentucky ; and V and erbilt University , Nashville , Tennessee . Patients were stratified for treatment ( autologous bone marrow transplantation or myelosuppressive therapy ) and were r and omized at each study center by a computer-generated scheme to receive IVIG or no treatment . Neither tumor-specific cytoreductive therapy nor state of disease were used as strata . Patients with an ongoing infection , those younger than 17 years , and those with a previous intolerance to IVIG were ineligible for the study . The main end points were the development of proven clinical infection , positive blood cultures for bacteria or fungi , and survival until hospital discharge . Other analyses included the number of platelet transfusions and the development of clinical alloimmunity to platelet transfusion . Patients Between February 1990 and December 1991 , 170 patients entered the study . All patients were evaluable for efficacy and were included in the analysis . The distribution of study patients is shown in ( Table 1 ) . The duration of neutropenia , the most important determinant for infection , was similar between the two groups ( P > 0.2 ) . Patients in the treatment arm and those in the control arm had statistically similar distributions of overall cytotoxic regimens and disease diagnoses ( data not shown ) . Table 1 . Patient Characteristics Treatment Protocol The IVIG used ( S and oglobulin , S and oz Pharmaceuticals , East Hanover , New Jersey ) was commercially purchased , reconstituted as a 5 % solution , and administered intravenously at an initial rate of 0.02 mL/kg per minute for 30 minutes and , if tolerated , was increased every 30 minutes to a maximum rate of 0.08 mL/kg per minute . Administration of IVIG was not blinded , and controls received no placebo . Immunoglobulin was given at a weekly dose of 500 mg/kg beginning at the start of cytotoxic treatment . It was discontinued when severe side-effects occurred or when neutropenia resolved ( as defined by a neutrophil count of more than 500 109/L [ 500/L ] for 1 day ) . Supportive Care The patients were hospitalized in HEPA-filtered single rooms , observed strict h and -washing rules , and received low-bacterial diets . Prophylactic oral antibacterial agents were allowed , but prophylactic parenteral antibacterial drugs were not . Patients who were seropositive for Herpes simplex virus received prophylactic acyclovir . All administered blood products were leukofiltered , and patients undergoing autologous bone marrow transplantation also received irradiated blood products . During periods of neutropenia , patients with fever greater than 38 C had two blood cultures taken and received empiric broad-spectrum antibacterial therapy as determined by the study center . Patients whose fever persisted were recultured . If fever persisted for 3 days and no bacterial cause was found , amphotericin B was administered at a dose of 0.5 mg/kg per day . Definitions and Evaluation of Infection The duration of neutropenia was defined as the interval from the first day the absolute neutrophil count decreased below 500 109/L ( 500/L ) until the first day the count exceeded 500 109/L ( 500/L ) . In patients with neutropenia , the interval was measured from the first day of cytotoxic therapy until recovery from neutropenia . Each platelet transfusion , whether with single-donor platelets or r and om-donor pooled platelets , was denoted as one episode . Clinical alloimmunity was diagnosed when platelet counts measured 1 hour after transfusion increased by less than 5000 109/L ( < 5000/L ) per unit of r and om- or single-donor platelets transfused on two consecutive occasions . The diagnosis of bacteremia and fungemia required one or more positive blood cultures in patients with suspected infection . The diagnosis of clinical infection required evidence of a localized tissue infection with supporting features such as fever , chills , pain , or erythema with or without isolation of a pathogen . Fever without localized evidence of infection or without positive blood cultures was not considered to represent clinical infection . Statistical Analysis Assuming an infection rate of 40 % , the study was design ed to detect an anticipated decrease to 20 % with a power of 0.80 and an -error of 0.05 . Results were analyzed according to the intention to treat . For comparisons of patient groups , the Pearson chi-square test or the Mann-Whitney rank-sum test were used . The Pearson chi-square test with confirmation by the confidence interval method of Simon was used to evaluate study end points [ 19 ] . Confidence intervals of 95 % were used . Binary logistic regression was used to evaluate the influence of various clinical and laboratory parameters on the end points of bacteremia or fungemia . These parameters included age , diagnosis , study center , duration of neutropenia , baseline IgG value , use of prophylactic oral antibacterials , and use of IVIG . To evaluate hypogammaglobulinemia , 5 g/L ( 500 mg/dL ) was chosen as the lower limit of normal . To evaluate the duration of neutropenia , a threshold of 7 days was chosen . The trial ended with the resolution of neutropenia because this patient population rarely experiences serious infections after leukocyte recovery and because survival after hematopoietic recovery is largely determined by the underlying disease . Survival was reported using actual proportions . Results Infections Proven clinical infections were frequent , as shown in Table 2 . Of all study patients , 43.5 % had documented clinical infections . Bacteremia and fungemia occurred in 35 % and 7.6 % of patients , respectively . The incidences of proven clinical infection , bacteremia , and fungemia were 43 % , 35 % , and 6 % in the IVIG group and 44 % , 34 % , and 9 % in the control group , respectively . These differences were not statistically significant ( P > 0.2 ) . Analysis of bacteremia by organism ( gram positive , gram negative , and mixed ) showed no statistical difference . The most common infection in the study was bacteremia due to coagulase-negative Staphylococci . This organism was isolated in 58 % of all cases of bacteremia and was the sole organism in 38 % of all cases of bacteremia . Twenty-eight percent of the documented bloodstream infections were polymicrobial . Table 2 . Treatment Results Only 8 % of patients in this study had hypogammaglobulinemia . The distribution of these patients was similar in the IVIG ( 9 % ) and control ( 8 % ) groups . In multiple regression analysis , the pretreatment value of IgG ( < 5 g/L [ 500 mg/dL ] compared with > 5 g/L ) did not predict the development of bacteremia or fungemia . Bloodstream infections were frequent , but most were controlled by broad-spectrum antibiotics . Death from infection occurred in 3.5 % of study patients ( 4.9 % in the IVIG group compared with 2.3 % in the control group ) , yielding a difference of 2.6 % ( 95 % CI , 3.0 % to 8.2 % ; P > 0.2 ) . Platelet Transfusion Patients in the IVIG BACKGROUND In a recently reported study , low doses of intravenous immunoglobulins ( IVIG ) were shown to be as effective as high doses in protecting chronic lymphocytic leukemia ( CLL ) patients against infections , although a control group was not included . With this background we started a crossover study of low-dose IVIG prophylaxis aim ed at investigating its superiority over empirical treatment of infections . MATERIAL S AND METHODS Forty-two CLL patients with hypogammaglobulinemia ( IgG < 600 mg/dL ) and /or a history of at least one episode of severe infection in the 6 months preceding inclusion in the study were r and omly allocated to receive either an infusion of 300 mg/kg IVIG every 4 weeks for 6 months or no treatment . Then they were switched to observation or IVIG for another 12 months ; finally , they received IVIG or no therapy for 6 more months . RESULTS A significantly lower incidence of infectious episodes was observed during IVIG prophylaxis in 30 patients who completed the 6-month period of either observation or IVIG therapy . The same applied to the 17 patients who completed 12 months of either observation or IVIG prophylaxis . Interestingly , the restoration of serum IgG levels obtained in 17 out of 25 patients ( mean percent value of IgG increase , 41.8 % ) did not parallel a decrease in the number of infectious episodes . CONCLUSIONS A protective effect against infections is demonstrated for low-dose IVIG in the present study . A benefit was shown in patients who completed either 12 or 6 months of IVIG prophylaxis ; however , even this low-dose treatment is not a cost effective way to prevent infection in CLL patients Endotoxin was measured in over 1000 plasma sample s from bone marrow transplant patients in a r and omized trial of the IgM-enriched intravenous immunoglobulin ( IVIG ) Pentaglobin . Peak endotoxaemia was significantly reduced ( P = 0.02 ) in patients receiving Pentaglobin and 70 % of all pyrexias of unknown origin were associated with endotoxaemia . Gut mucosal damage , assessed by lactulose/mannitol ratios , was significantly associated ( P = 0.02 ) with endotoxaemia . Specific IgM antibody to endotoxin core-glycolipid was significantly raised ( P < 0.01 ) in patients receiving the IVIG , and the IgM fraction of Pentaglobin was found to contain most of the anti-endotoxin antibody activity of the IVIG . These results suggest a role for IgM-enriched IVIG as a prophylactic agent for the reduction of endotoxaemia and its consequences in bone marrow transplant patients The effects of prophylactic , polyvalent intravenous immune globulin on cytomegalovirus infection and interstitial pneumonia in allogenic marrow transplants were evaluated in an ongoing , r and omized controlled trial . Thirty-eight patients were given weekly doses ( 20 cc/kg ) of polyvalent intravenous immune globulin before and after transplantation , and 37 patients were controls . Both symptomatic cytomegalovirus infection ( 17 of 37 or 46 % vs. 8 of 38 or 21 % , p = 0.04 ) and interstitial pneumonia ( 17 of 37 or 46 % vs. 7 of 38 or 18 % , p = 0.02 ) occurred less frequently in the recipients of polyvalent intravenous immune globulin . In separate kinetic studies , a 5 cc/kg dose of a cytomegalovirus-specific hyperimmune globulin produced cytomegalovirus antibody titers in patients equivalent to those achieved after the 20 cc/kg dose of polyvalent intravenous immune globulin . All immune globulin preparations were well-tolerated . These preliminary results suggest that intravenous immune globulin can modify the severity of cytomegalovirus infection and prevent interstitial pneumonia in marrow transplants . Additional trials are now needed to define the minimal effective dose of intravenous immune globulin and to compare the effectiveness of different intravenous immune globulin formulations The most common complication of chronic lymphocytic leukaemia ( CLL ) is infection , which occurs mainly in advanced stages of disease or in those patients with hypogammaglobulinaemia . Intravenous immune globulin ( IVIG ) has been shown to be a useful prophylactic therapy against infections in such patients . A r and omized , double-blind study on 36 patients receiving either 500 mg/kg or 250 mg/kg IVIG every 4 weeks was undertaken to determine the dose regimen required . There was no significant difference in the two treatment groups and we found that CLL patients were equally protected with low-dose IVIG Context No placebo-controlled trials have evaluated potential benefits of immunoglobulin in patients undergoing hematopoietic stem-cell transplantation . Contribution This multicenter r and omized , double-blind trial involved 200 recipients of HLA-matched sibling transplants . At 6 months , the benefit of prophylactic immunoglobulin ( given weekly from day 7 to day 100 ) compared with placebo was not significant for the following outcomes : number of infections , interstitial pneumonia , graft-versus-host disease , and transplantation-related mortality . Implication s Prophylactic immunoglobulin is not indicated for patients undergoing allogeneic hematopoietic stem-cell transplantation from HLA-identical siblings . The Editors Despite controversy about the benefit of immunoglobulin in stem-cell transplantation , this agent has been given as part of most transplantation protocol s for more than 20 years . Several large controlled series showed that immunoglobulin prevented infection ( 1 , 2 ) , especially cytomegalovirus infection ( 3 ) , interstitial pneumonia ( 3 , 4 ) , and graft-versus-host disease ( 2 , 3 , 5 ) ; patients older than 20 years of age experienced the most benefit ( 1 , 6 ) . However , because of different products ( hyperimmune or polyvalent immunoglobulins ) , schedules , dosing regimens , and patient sample s , it has been difficult to definitively conclude that immunoglobulin is beneficial for transplant recipients . The varying conclusions of two large meta-analyses ( 6 , 7 ) have encouraged new trials to better define the optimal dose and duration of immunoglobulin therapy and its value . Immunoglobulin exposes patients to the potential transmission of new pathogens . It is very expensive in high doses and is not always well tolerated . Although immunoglobulin is still widely used , strong evidence supporting its use is lacking . None of the early trials , which led to the approval of immunoglobulin in most countries , were placebo controlled , and two recent trials comparing doses did not include a control group ( 8 , 9 ) . In addition , effective agents are now available to prevent and treat most of the infections that led to the original use of prophylactic immunoglobulin . To re-evaluate the benefit of immunoglobulin in allogeneic stem-cell transplantation using current protocol s , we conducted a r and omized , double-blind , dose effect , placebo-controlled study limited to recipients of transplants from an HLA-identical sibling . To our knowledge , this is the first placebo-controlled study evaluating immunoglobulin in this population . We assessed the value of immunoglobulin , given from day 7 to day 100 , in the prophylaxis of transplantation-related complications . Methods Study Design We design ed the study as a multi-institutional trial involving 19 centers of the Socit Franaise de Greffe de Molle in France ( Figure 1 ) . Patients were recruited at a visit 14 to 28 days before transplantation . They were r and omly assigned to receive 16 weekly doses , from day 7 to day 100 , of placebo ( group 1 ) or polyvalent immunoglobulin at 50 mg/kg of body weight ( group 2 ) , 250 mg/kg ( group 3 ) , or 500 mg/kg ( group 4 ) ; the proportion of patients in each group was equal . Day 0 was the day of transplantation . R and omization was central ized ; stratified by center , age , and disease status ; and performed 14 to 28 days before transplantation . The ethical committee of Hpital Piti-Salptrire , Paris , approved the protocol , and all patients gave informed consent . Data were collected prospect ively and verified on site with the original charts . Figure 1 . Flow diagram of the trial . R and omization We used a r and omization procedure with r and om permuted blocks to ensure the same number of patients at certain equally spaced points in the sequence of patient assignments in each center . The physicians responsible for recruitment in each center did not know the block size . Each sequence was computer generated . Eligibility Criteria We used the following inclusion criteria : age older than 2 years , first-time recipient of an allogeneic stem-cell transplant from an HLA-identical sibling , and no plans for T-cell depletion . Exclusion criteria were as follows : a syngeneic , unrelated , or haplo-mismatched donor ; nonmyeloablative conditioning ; previous autologous transplants conditioned with total-body irradiation or busulfan and cyclophosphamide ; active infection ; presence of hypogammaglobulinemia ( < 4 g/L ) at time of r and omization ; or presence of HIV . Immunoglobulin and Placebo Administration Immunoglobulin was provided from unselected , commercially available lots [ S and oglobulin , Novartis Pharma , Rueil-Malmaison ] . The placebo was a 5 % dextrose solution . We maintained blinding during the study by using two procedures : 1 ) The immunoglobulin was prepared by the pharmacist and delivered to the clinical unit in bottles with special plastic covers [ a small vertical slit allowed the nurse to watch the level of infusion without seeing the bubbles of the immunoglobulin infusion ] and 2 ) the final volume and flow rate of each infusion were adapted , according to manufacturer recommendations , to the highest immunoglobulin dose ( 500 mg/kg ) . The recommended flow rate was 0.5 mL/kg per hour during the initial 30 minutes of administration , and then , if tolerated , 4 mL/kg per hour . End Points The principal end point was the cumulative incidence of infection during the 6 months after transplantation . Secondary end points were time to first infection , occurrence and severity of acute or chronic graft-versus-host disease , occurrence and grade of veno-occlusive disease , interstitial pneumonia , treatment-related mortality at 6 months , overall survival at 2 years , and side effects . Concomitant Treatment , Anti-Infectious Prophylaxis , and Supportive Care All patients received prophylaxis against graft-versus-host disease with methotrexate ( 15 mg/m2 on day 1 and 10 mg/m2 on days 3 and 6 ) and cyclosporine ( 2 mg/kg per day from the day before transplantation ) to at least day 100 . No patient received prophylactic steroids . All patients were housed in high-efficiency particulate air-filtered or laminar airflow rooms . Intestinal decontamination , according to French practice s , was performed with nonabsorbable antibiotics ( mostly oral colimycin and gentamicin ) and antifungal drugs ( oral polyenes ) during the neutropenic phase . Prophylactic acyclovir was allowed if all patients included in a given center received the same prophylactic strategy . All patients received leukodepleted and irradiated blood products and Pneumocystis carinii prophylaxis until at least day 100 . Patients did not receive prophylactic growth factors or anticytomegalovirus drugs . All patients , except those who were seronegative for cytomegalovirus with seronegative donors , were screened weekly for cytomegalovirus ( using pp65 antigenemia detection or polymerase chain reaction ) until day 100 . Preemptive treatment with ganciclovir or foscarnet for at least 14 days was begun on the basis of one positive test result for pp65 antigenemia or two consecutive positive polymerase chain reaction results within 7 days . Definitions Acute graft-versus-host disease was diagnosed and grade d ( from 0 to IV ) , according to st and ard criteria , on the presence and severity of skin , liver , and intestinal tract injury ( 10 ) . Chronic graft-versus-host disease was grade d as absent , limited , or extensive according to the criteria of Shulman and colleagues ( 11 ) . Veno-occlusive disease was diagnosed by different criteria depending on whether it occurred before or after day 20 ; the criteria were those of Shulman and colleagues ( 12 ) . Criteria for veno-occlusive disease occurring before day 20 were the presence of at least two of the three following manifestations : serum bilirubin level of 34.2 mol/L or greater ( 2.0 mg/dL ) , painful hepatomegaly , or abrupt weight gain of 5 % or more above baseline body weight . Criteria for veno-occlusive disease occurring after day 20 were based on histologic evidence obtained at liver biopsy . The severity of veno-occlusive disease was also grade d : grade 1 , spontaneous resolution of liver symptoms ; grade 2 ( moderate ) , resolution of symptoms with specific treatments ; or grade 3 ( severe ) , no resolution before day 100 or death , whichever occurred first ( 12 ) . Cytomegalovirus infection and disease were defined according to the criteria of the Multidisciplinary International Workshop ( 13 ) . Bacteremia was defined by fever associated with at least one positive blood culture , except for coagulase-negative staphylococci , for which two positive blood cultures from two different sites were required . The diagnosis of bacterial pneumonia required 103 or more colony-forming units/mL in a protected bronchial sample or 104 or more colony-forming units/mL in bronchoalveolar lavage fluid . A definitive diagnosis of Aspergillus pneumonia was made if Aspergillus species were isolated from bronchoalveolar lavage fluid or from a lung biopsy specimen ; the diagnosis was considered probable if an air-crescent sign or characteristic fungus ball was present or results of a serum galactomannane test were positive . Interstitial pneumonia was defined by the presence of nonbacterial , nonfungal pneumonitis and hypoxemia of 75 mm Hg or less while breathing room air . If no cause of infection was identified on at least one bronchoalveolar lavage or lung biopsy ( which included stains for P. carinii and viral tests ) , the diagnosis was idiopathic pneumonia . The severity of infection was grade d as follows : Grade 1 infections were all episodes treated at home or all episodes of fever of unknown origin in neutropenic patients receiving broad-spectrum antibiotics ; grade 3 infections had an expected death rate greater than 60 % ( based on data in the literature ) and included infections associated with Aspergillus , fungemia , and cytomegalovirus disease and any type of pneumonia with a Pao 2 less than 65 mm Hg ; and grade 2 infections were all others ( usually requiring treatment in a hematology ward ) . One author , BACKGROUND AND OBJECTIVE The role of high dose intravenous IgG ( HDIgG ) and of hyperimmune CMV IgG ( CMV-IgG ) in patients undergoing allogeneic hemopoietic stem cell transplantation ( HSCT ) is still unclear . The aim of this study was to compare prophylactic CMV-IgG with HDIgGin a r and omized prospect i ve trial in allogeneic HSCT recipients : primary end point of the study was the occurrence of post-transplant CMV antigenemia ( CMVAg-emia ) . Secondary end-points were severity of acute and chronic graft-versus-host disease ( GvHD ) , infections and transplant related mortality ( TRM ) . DESIGN AND METHODS Patients were r and omized to receive 100 mg/kg/week of CMV-IgG ( group A ; n = 64 ) or 400 mg/kg/week of HDIgG ( group B ; n = 64 ) from day -7 to day + 100 . The two groups were comparable for age , diagnosis , disease status , and acute graft-versus host ( aGvHD ) prophylaxis . RESULTS The actuarial risk at 1 year of CMV antigenemia was lower for CMV-IgG ( 61 % vs. 71 % ) but not significantly ( p = 0.37 ) ; CMVAg-emia occurred at the same interval from HSCT ( 47 vs. 48 days , p = 0.9 ) , with a comparable number of CMVAg positive cells ( 3 vs. 3 p = 0.9 ) . Eight patients died of interstitial pneumonia ( IP ) ( 4 in each group ) , two in group A of CMV-IP . Acute GvHD was scored as O-I , II and III-IV in 39 vs. 35 , 23 vs. 22 and 2 vs. 7 patients respectively for the two groups ( p = not significant ) . The actuarial risk of developing acute GvHD grade II-IV was lower for CMV-IgG ( 39 % vs. 45 % ) but not significantly ( p = 0.43 ) . Chronic GvHD scored as absent in 7 vs. 10 patients , limited in 39 vs. 37 and extensive in 19 vs. 17 patients respectively ( p = not significant ) . Numbered days with intravenous antibiotics , days in hospital , days of fever , number of local and disseminated infections , number of patients with fever of unknown origin were not significantly different . Actuarial 1 year TRM is 18 % vs. 19 % , respectively ( p = 0.9 ) . INTERPRETATION AND CONCLUSIONS This study confirms that CMV antigenemia is comparable in recipients of hyperimmune CMV-IgG and of polyvalent HDIgG , although the former had a 32 % lower cost . It also shows that the potential immunomodulating effect on acute GvHD and transplant mortality is similar with 100 or 400 mg of IgG/kg/week : this is relevant , in view of the high cost of prophylactic Between May 1987 and September 1989 , 72 patients undergoing marrow transplantation at a single institution were r and omized to receive 50 mg/kg of a commercial gammaglobulin preparation or placebo daily in four divided doses for 28 days following transplantation . Patients receiving oral gammaglobulin had significantly increased concentrations of stool IgG ( p = 0.01 ) compared with the placebo group . There was no difference in the amount of diarrhea , frequency of GVHD , duration of hospitalization or survival in the two groups . The present study demonstrates that orally administered IgG can survive passage through the gastrointestinal tract of bone marrow transplantation recipients but there was no effect of oral administration of immunoglobulin on morbidity or mortality following bone marrow transplantation The effects of immune globulin intravenous , 5 percent in 10 percent maltose , on cytomegalovirus infection and interstitial pneumonia in bone marrow transplants were evaluated in a r and omized controlled trial . Eighteen patients were given weekly doses ( 20 cc/kg ) of intravenous immunoglobulin before and after transplantation , and 18 patients were controls . The incidence of cytomegalovirus infection was similar in the control and intravenous immunoglobulin-treated groups , but symptomatic cytomegalovirus infection ( eight of 18 versus three of 18 , p = 0.14 ) and interstitial pneumonia ( 10 of 18 versus four of 18 , p = 0.08 ) occurred less frequently in the group receiving intravenous immunoglobulin . Cytomegalovirus pneumonia developed in eight control patients and in three patients receiving intravenous immunoglobulin ( p = 0.14 ) , whereas two control patients and one patient receiving intravenous immunoglobulin experienced idiopathic interstitial pneumonia . These preliminary results suggest that intravenous immunoglobulin can modify the severity of cytomegalovirus infection and prevent interstitial pneumonia in bone marrow transplant recipients In an attempt to prevent primary cytomegalovirus infection after marrow transplantation , we r and omly assigned 97 patients who were seronegative for antibody to cytomegalovirus before transplantation to receive one of the following : ( 1 ) both intravenous cytomegalovirus immune globulin and seronegative blood products ( 23 patients ) ; ( 2 ) seronegative blood products alone ( 28 patients ) ; ( 3 ) globulin alone ( 22 patients ) ; or ( 4 ) neither treatment ( 24 patients ) . Patients not assigned to receive seronegative blood products received unscreened blood products from r and om donors . The incidence of cytomegalovirus infection according to study group among patients in the study for at least 62 days was 5 percent , 13 percent , 24 percent , and 40 percent , respectively . Among 57 patients with seronegative marrow donors , those who received seronegative blood products had significantly less infection ( 1 of 32 ) than those who received st and ard blood products ( 8 of 25 , P less than 0.007 ) . In contrast , the use of seronegative blood products did not appear to prevent cytomegalovirus infection among patients with seropositive marrow donors . The possibility that cytomegalovirus immune globulin as used in this study can prevent cytomegalovirus infection or ameliorate cytomegalovirus disease was not confirmed , and it can not be recommended for routine use without additional study Intravenous immunoglobulin is approved for use in allogeneic bone marrow transplant recipients for prevention of graft-versus-host disease ( GVHD ) and infections , but the minimally effective dose has not been established . In this multicenter , r and omized , double-blind trial , patients undergoing allogeneic marrow transplantation were r and omized to receive 100 mg/kg , 250 mg/kg , or 500 mg/kg doses of intravenous immunoglobulin . Each dose was given weekly for 90 days and then monthly until 1 year after transplant . Six hundred and eighteen patients were evaluated . Acute GVHD ( grade s 2–4 ) occurred in 39 % of the patients ( 80 of 206 ) in the 100 mg/kg group , 42 % of the patients ( 88 of 208 ) in the 250 mg/kg group , and in 35 % of the patients ( 72 of 204 ) in the 500 mg/kg group ( P = 0.344 ) . Among patients with unrelated marrow donors , a higher dose of intravenous immunoglobulin ( 500 mg/kg ) was associated with less acute GVHD ( P = 0.07 ) . The incidences of chronic GVHD , infection and interstitial pneumonia were similar for all three doses of intravenous immunoglobulin . The dose of intravenous immunoglobulin also had no effect on the types of infection , relapse of hematological malignancy or survival . Except for more frequent chills ( P = 0.007 ) and headaches ( P = 0.015 ) in patients given the 500 mg/kg or 250 mg/kg dose of immunoglobulin , adverse events were similar for all three doses . These results suggest that 100 mg/kg , 250 mg/kg , and 500 mg/kg doses of intravenous immunoglobulin are associated with similar incidences of GVHD and infections in most allogeneic marrow transplants . These results should be considered when design ing cost-effective strategies for the use of intravenous immunoglobulin in allogeneic marrow transplants receiving other current regimens for prophylaxis of GVHD and infection . Bone Marrow Transplantation ( 2001 ) 28 , 187–196 Bacterial infections were registered in 39 patients with myelomatosis during 18 months in a prospect i ve study . The infection incidence was 0.80 infections per patient year . 81 % of a total of 32 isolates were gram-negative . Urinary tract infections due to Escherichia coli were the most frequent infections . Pneumonia due to Streptococcus pneumoniae were infrequently seen compared to previous studies . Hence , the etiologic spectrum has clearly shifted from gram-positive to gram-negative bacteria in these patients . 53 % of all infections were hospital-acquired , and most of these were preceded by instrumentation of the urinary tract or indwelling venous catheters . The infections were nosocomial in 7/9 cases of septicemia registered . All 4 patients who died of infection , suffered from hospital-acquired infections . Patients who attracted infections had significantly higher serum creatinine levels and higher mortality compared to the rest of the patients 60 children with acute lymphoblastic leukemia were sequentially r and omized at the time of diagnosis : Immunoglobulin ( Endobulin , Immuno ) was administered intravenously to 30 patients at a dose 100 mg/kg/week during the first 3 months , followed by 2 x 200 mg/kg/month immunoglobulin during the 4 . , 5 . , 6 . months . No immunoglobulin was administered to the control patients . We studied the effect of immunoglobulin prophylaxis on the number of days with fever , number of cases with bacteriologically proved infections , length and frequency of antibiotic therapy . Our data confirm the efficacy of immunoglobulin prophylaxis during the intensive phase of leukemia therapy in children The effects of high doses of polyvalent intravenous immune globulin given for prophylaxis of cytomegalovirus infection and interstitial pneumonia in recipients of allogeneic marrow transplants were evaluated in a r and omized controlled trial . Both symptomatic cytomegalovirus infection ( 21 % compared with 46 % , p = 0.03 ) and interstitial pneumonia ( 18 % compared with 46 % , p = 0.02 ) occurred less frequently in the recipients of intravenous immune globulin than in control patients . Prophylactic intravenous immune globulin was also associated with a lower incidence of graft-versus-host disease ( 34 % in recipients compared with 65 % in controls , p = 0.01 ) , but its reduction in rates of interstitial pneumonia was independent of graft-versus-host disease and occurred in both patients with and without graft-versus-host disease . The high doses of immune globulin were well tolerated . Prophylactic intravenous immune globulin can modify the severity of cytomegalovirus infection and prevent interstitial pneumonia and possibly graft-versus-host disease in patients having allogeneic marrow transplantation BACKGROUND Graft-versus-host disease ( GVHD ) and infection are major complications of allogeneic bone marrow transplantation . Since intravenous immunoglobulin has shown benefit in several immunodeficiency and autoimmune disorders , we studied its antimicrobial and immunomodulatory role after marrow transplantation . METHODS In a r and omized trial of 382 patients , transplant recipients given immunoglobulin ( 500 mg per kilogram of body weight weekly to day 90 , then monthly to day 360 after transplantation ) were compared with controls not given immunoglobulin . By chance , the immunoglobulin group included more patients with advanced-stage neoplasms ; otherwise , the study groups were balanced for prognostic factors . RESULTS Control patients seronegative for cytomegalovirus who received seronegative blood products remained seronegative , but seronegative patients who received immunoglobulin and screened blood had a passive transfer of cytomegalovirus antibody ( median titer , 1:64 ) . Among the 61 seronegative patients who could be evaluated , none contracted interstitial pneumonia ; among the 308 seropositive patients evaluated , 22 percent of control patients and 13 percent of immunoglobulin recipients had this complication ( P = 0.021 ) . Control patients had an increased risk of gram-negative septicemia ( relative risk = 2.65 , P = 0.0039 ) and local infection ( relative risk = 1.36 , P = 0.029 ) and received 51 more units of platelets than did immunoglobulin recipients . Neither survival nor the risk of relapse was altered by immunoglobulin . However , among patients greater than or equal to 20 years old , there was a reduction in the incidence of acute GVHD ( 51 percent in controls vs. 34 percent in immunoglobulin recipients ; P = 0.0051 ) and a decrease in deaths due to transplant-related causes after transplantation of HLA-identical marrow ( 46 percent vs. 30 percent ; P = 0.023 ) . CONCLUSIONS Passive immunotherapy with intravenous immunoglobulin decreases the risk of acute GVHD , associated interstitial pneumonia , and infections after bone marrow transplantation The safety and pharmacokinetics of the two neutralizing human IgG1 monoclonal antibodies to cytomegalovirus ( CMV ) SDZ 89 - 104 and 89 - 109 in bone marrow transplant ( BMT ) recipients was assessed in an open phase I trial . Thirteen patients , 8 seropositive and 5 seronegative for CMV , were treated with allogeneic or autologous bone marrow transplantation . SDZ 89 - 104 was given to 5 and SDZ 89 - 109 to 8 patients . Patients were divided into high- and low-dose groups . A fixed pre study dose of 0.1 mg/kg was given 4 days before BMT . On days 3 , 17 , 31 , 45 , 59 , and 73 , patients were treated with either 0.5 or 2 mg/kg of the respective antibody . Results indicate that doses of 2 mg/kg of SDZ 89 - 104 or SDZ 89 - 109 in alternating weeks can be safely administered to BMT patients . Serum trough levels measured by antiidiotype ELISA were approximately 10 micrograms/ml after administration of 0.5 mg/kg and approximately 50 micrograms/ml after treatment with 2 mg/kg of SDZ 89 - 104 or SDZ 89 - 109 . High serum levels defined by antiidiotype ELISA techniques closely paralleled increased neutralizing activity . Serum half-lives calculated from these data were approximately 6 days In an effort to prevent cytomegalovirus infection among seronegative patients having marrow transplants , a globulin with high antibody levels against cytomegalovirus was given before and for 11 weeks after transplantation in a r and omized trial . Among 36 patients who received no prophylactic granulocyte transfusions , globulin recipients had significantly fewer infections than controls ( 2 of 17 versus 8 of 19 , p = 0.05 by Fisher 's exact test and p = 0.03 by Mantel-Cox test ) . Conversely , infection rates were high and unchanged by globulin use among patients who received granulocytes from seropositive donors ( 7 of 8 recipients versus 6 of 7 controls ) . The lack of effect of the globulin among patients receiving transfusions of granulocytes from seropositive donors may suggest that the dose of antibody was insufficient or that antibody is ineffective against virus transmitted in granulocytes . We conclude that cytomegalovirus infection can be prevented by immunoprophylaxis in seronegative patients having marrow transplants who are not given granulocyte transfusions The effects of passive immunization on cytomegalovirus infection and interstitial pneumonia in marrow transplants were evaluated in a r and omized , controlled trial . Twenty-four patients received cytomegalovirus immune plasma before and after transplantation , and 24 patients were controls . Although the incidence of cytomegalovirus infection was similar in the control and plasma groups , symptomatic infection ( 12 of 24 versus five of 24 , p = 0.07 ) and interstitial pneumonia ( 11 of 24 versus five of 24 , p = 0.12 ) occurred less frequently in the group receiving plasma . Cytomegalovirus infection occurred in 11 of 13 recipients of leukocyte transfusions and in 16 of 35 patients not given leukocyte transfusions ( p = 0.02 ) . Among patients not given leukocyte transfusions , the incidence of cytomegalovirus infection was similar in the control and plasma groups , but symptomatic infection ( eight of 18 versus one of 17 , p = 0.03 ) and interstitial pneumonia ( nine of 18 versus one of 17 , p = 0.01 ) were significantly less in the group receiving plasma . These results suggest that passive immunization modifies cytomegalovirus infection in humans and prevents interstitial pneumonia in marrow transplants especially when leukocyte transfusions are not used Summary . Previous studies have shown that intravenous immunoglobulin ( IVIg ) therapy is useful prophylaxis against infection in patients with secondary hypogammaglobulinaemia due to a low‐ grade lymphoproliferative disease . This r and omized double‐blind study was undertaken to determine prospect ively the dose regime required . 34 such patients received IVIg at either 500 or 250 mg/kg every 4 weeks for 1 year . There was no significant difference in the rates of serious infections between the two groups of patients , which were well matched for disease and laboratory parameters . The rates of infection seen were similar to those in IVIg groups of previous studies and strikingly different from those in the placebo group in the previously r and omized placebo‐controlled study Patients with plateau-phase multiple myeloma have an increased risk of life-threatening bacterial infections and polyclonal humoral immune suppression . We conducted a r and omised , double-blind , placebo-controlled , multicentre trial of intravenous immunoglobulin ( IVIg ) as prophylaxis against infection . 82 patients with stable multiple myeloma received monthly infusions of IVIg at 0.4 g/kg body weight or an equivalent volume of placebo ( 0.4 % albumin ) intravenously for 1 year . Other interventions , including chemotherapy , were not affected ; no patient received prophylactic antibiotics . There were no differences at entry or on study in clinical or laboratory variables between patients in the two groups . There were no episodes of septicaemia or pneumonia in patients receiving IVIg compared with 10 in placebo patients ( p = 0.002 ) . There were 57 serious infections ; 38 occurred in 470 patient-months on placebo , compared with 19 in 449 patient-months on IVIg ( p = 0.019 ) . IVIg also protected against recurrent infections ( p = 0.021 ) in 60 patients who completed a year . Before treatment , 54 patients were immunised with Pneumovax and specific IgG responses were measured . A poor pneumococcal IgG antibody response ( less than 2-fold increase ) identified patients who had maximum benefit from IVIg . Mild adverse reactions were noted in 12 % of IVIg infusions and 5 % of placebo infusions . IVIg can be given safely to plateau-phase myeloma patients . It protects against life-threatening infections and significantly reduces the risk of recurrent infections . The individuals who benefit most can be identified prospect ively by measuring IgG antibody responses to pneumococcal immunisation A r and omized multicentre study was conducted to evaluate the effect of anti-CMV hyperimmune globulin in the prophylaxis of CMV infections in CMV seronegative allogeneic BMT patients who received a transplant from a seropositive donor or who had received blood products unscreened for CMV during the treatment before BMT . Twenty-eight patients were included in the study . Thirteen were r and omized to receive and 15 not to receive intravenous CMV hyperimmune globulin . A dose of 0.4 g/kg of immunoglobulin was given on day −8 and 0.2 g/kg on days −1 , + 7 , + 14 , + 21 , + 28 , + 35 , + 42 , + 56 and + 70 in relation to the day of transplantation . Among the 15 patients not given immunoglobulin CMV was isolated in three , and two of them developed clinical CMV disease . In addition , one more patient developed CMV antibodies without virus isolation . In five of the 13 patients given immunoglobulin the virus could be isolated , and four of them developed CMV disease . One additional patient showed seroconversion but no other findings of CMV infection . The incidence of acute and chronic GVHD was similar in the two arms . There was no significant difference in survival . In conclusion , the present results do not indicate a beneficial effect of CMV hyperimmune globulin infusions in the prophylaxis of CMV infection or disease in seronegative allogeneic bone marrow transplant recipients from a seropositive donor Background . Allogeneic hematopoietic stem-cell transplantation is a widely used , cost-intensive procedure . Our purpose was to estimate costs and determine cost predictors . Methods . We used data from a prospect i ve French study comparing four doses of immunoglobulins . Re source use of hematopoietic stem-cell transplant recipients during the first 6 months posttransplant , both inpatient and ambulatory costs , in 85 patients from five centers were collected prospect ively and costed . Baseline data and clinical events were retrieved . Protocol -driven costs were excluded . Multivariable analysis evaluated the association between costs and patient ’s pretransplant status and transplant-related complications . Because of the absence of differences in outcome among the four r and omization groups , cost data for all patients were pooled . Results . Total costs per patient were the following : mean & U20AC;76,237 ; st and ard deviation & U20AC;32,565 ; median & U20AC;69,516 ; range & U20AC;183,758 to & U20AC;14,761 . The major cost driver was hospital days . No association was found between costs and baseline status . The “ predictors ” of higher costs ( adding an average & U20AC;20,000/patient ) were the occurrence of transplant-related complications : graft-versus-host disease and repeated infections that were unpredictable before transplant in this homogeneous group of patients . Conclusion . Our data highlight the discrepancy between the Diagnosis Related Group prospect i ve payment system and actual costs . The actual cost of geno-identical stem-cell transplantation results from posttransplant complications that can not be predicted prospect ively and require ex post cost adjustment We have completed a r and omized trial to evaluate the safety and effectiveness of hyperimmune cytomegalovirus intravenous human globulin in prevention of cytomegalovirus infection and related problems in bone marrow transplant recipients . Prophylactic intravenous administration of this native , intact , hyperimmune , cytomegalovirus IgG , at a dose of 200 mg/kg 25 , 50 , and 75 days following transplant result ed in complete protection against cytomegalovirus infection during the 120 days covered by the treatment ( p = 0.009 ) . There was no interstitial pneumonia or mortality in the group receiving the hyperimmune IgG. This is significant at the p = 0.014 when compared with the supporting treatment control group . In bone marrow transplant recipients , prophylaxis with a total dosage of 0.6 g/kg of an intravenous hyperimmune cytomegalovirus globulin was safe and afforded effective protection against cytomegalovirus infection and interstitial pneumonia in this high-risk population Patients with multiple myeloma suffer from serious bacterial infections throughout the course of the disease . This is probably associated with reduced polyclonal immunoglobulin synthesis . Prophylactic intravenous immune globulin ( IVIG ) reduces the incidence and recurrence of these infections in the stable phase of the disease . Infections at times of induction chemotherapy and /or relapse have a wider range of causative organisms . Such susceptibility may be associated with abnormal phagocytic function following chemotherapy MSL-109 is a monoclonal antibody specific to the cytomegalovirus ( CMV ) glycoprotein H with high neutralizing capacity . In a prospect i ve , r and omized , double-blind study , allogeneic hematopoietic stem cell transplantation ( HSCT ) recipients with positive donor and /or recipient serology for CMV before transplantation received either 60 mg/kg MSL-109 ( n = 59 ) , 15 mg/kg MSL-109 ( n = 60 ) , or placebo ( n = 60 ) intravenously every 2 weeks from day -1 until day 84 after transplantation . CMV pp65 antigenemia , CMV-DNA load in plasma , and viremia by culture were tested weekly . Primary end points were development of pp65 antigenemia at any level and /or viremia for which ganciclovir was given . There was no statistically significant difference in CMV pp65 antigenemia or viremia among patients in the 60-mg group ( pp65 antigenemia , 47 % ; viremia , 15 % ) , the 15-mg group ( 52 % ; 23 % ) , and the placebo group ( 45 % ; 17 % ) . There was also no difference in maximum levels of pp65 antigenemia , time to clearance of pp65 antigenemia after start of ganciclovir , CMV disease , invasive bacterial and fungal infections , time to neutrophil and platelet engraftment , acute graft-versus-host disease , days of hospitalization , and overall survival rate among the 3 groups . However , a subgroup analysis of CMV-seronegative recipients with a seropositive donor ( D+/R- ) showed a transiently improved survival rate by day 100 in MSL-109 recipients ( mortality : 60-mg group , 1/13 ; 15-mg group , 1/12 ; placebo group , 6/10 [ P = .02 for 60-mg versus placebo groups ; P = .08 for 15-mg versus placebo groups ] ) ; by the end of follow-up , the difference was no longer statistically significant . The improved survival rate in D+/R- patients could not be attributed to a reduction in CMV disease ; however , MSL-109 was associated with improved platelet engraftment and less grade III to IV acute graft-versus-host disease in this subgroup . In a subgroup analysis of CMV-seropositive recipients of MSL-109 ( D+/R+ and D-/R+ ) , overall mortality was increased compared to that of the placebo group ( P = .12 for the 60-mg versus placebo groups , P = .05 for the 15-mg versus placebo groups , and P = .04 for the dose levels combined versus placebo ) . MSL-109 was well tolerated and no immune response to the drug was observed . Thus , MSL-109 was safe but did not reduce CMV infection in allogeneic HSCT recipients . The transient survival advantage seen early after transplantation in CMV D+/R- patients and the negative effect on survival in seropositive patients remain unexplained . Thus , there is no evidence that MSL-109 is beneficial in CMV-seropositive HSCT recipients Intravenous immunoglobulin has been used after bone marrow transplants to prevent infections and acute graft-versus-host disease . However , the minimum dose required for protection is unknown . This may have significant economic implication s. A multicenter r and omized clinical trial compared the impact of two intravenous immunoglobulin doses on systemic infections and acute graft-versus-host disease in transplant recipients . Either 250 mg/kg or 500 mg/kg was given weekly from day −8 to day + 111 . Multivariate analysis was used to assess the effect of dose and other risk factors on event-free survival , systemic infection , and acute graft-versus-host disease . The two-dose cohorts had similar event-free survival and infection frequencies . The higher dose was associated with less acute graft-versus-host disease ( P = 0.03 ) Cytomegalovirus (CMV)-specific immunoglobulin ( IVIG ) was evaluated in a r and omized controlled trial in CMV-seronegative marrow transplant patients with seropositive marrow donors for the prevention of primary CMV infection during the first 100 days after transplant . Patients received 200 mg/kg CMV IVIG on days 8 and 6 before transplant , the day after transplant , weekly for the first month , and then every 2 weeks to complete 10 doses . Patients were followed with weekly CMV cultures and serologic studies and for clinical and histologic evidence of CMV disease . Sixty patients were evaluable in each group . There was significantly less CMV excretion ( P = .04 ) and viremia ( P = .01 ) in the treatment group . However , the incidence of CMV disease including CMV pneumonia , CMV enteritis , and CMV syndrome ( fever , leukopenia , hepatitis ) was not statistically different . There was also no difference in median time of onset of CMV infection or disease , median number of hospital days , or survival between the two groups Ninety-seven patients r and omized to receive ( 45 patients ) or not to receive ( 52 patients ) intravenous cytomegalovirus immune globulin before and after allogeneic marrow transplantation were evaluated retrospectively for the occurrence of bacterial and fungal septicemia in the first 100 days post-transplant . In a proportional hazards regression test , infection prevention regimens , immunoglobulin administration , age and occurrence of acute graft-versus-host disease were tested simultaneously for the occurrence of septicemia in the pre- and post-engraftment period . Of these factors , only patients receiving immunoglobulin had significantly fewer episodes of septicemia following engraftment with 11 ( 26 % ) patients in the globulin group having 14 episodes compared to 22 ( 42 % ) patients in the control group having 27 episodes ( p = 0.039 ) . None of the patients experienced complications with the immunoglobulin infusions . These results suggest that the administration of intravenous immunoglobulin may be a practical and effective method to decrease the incidence of septicemia following marrow transplantation Zymosan opsonisation was determined in sera of 38 normal individuals and 20 children with acute lymphocytic leukemia ( ALL ) . All patients underwent chemotherapy according to the CoALL 82 protocol . Intravenous gammaglobulin ( ivGG ) was given prophylactically to replace deficient specific antibodies . Zymosan opsonisation in normal sera ranged from 65 % to 133 % of a serum pool , whereas sera of children with ALL exhibited markedly decreased opsonisation ranging from 7 % to 141 % ( of the pooled serum st and ard ) at different times during an observation period of 20 months . No significant changes could be observed over time , neither induced by the ivGG infusion itself ( short term effect ) nor during the 20 months observation period ( long term effect ) . Before ivGG therapy was initiated , a positive correlation was found between zymosan opsonisation and complement parameters ( CH 50 : p less than 0.01 ; AP 50 ; p less than 0.001 ; C3 : p less than 0.05 ) . No correlation could be noted between zymosan opsonisation and IgG concentration . Experiments with complement deficient sera clearly demonstrated the dependence of zymosan opsonisation from complement function . In contrast , sera with little or no IgG but intact complement , showed normal zymosan opsonisation . Deficient zymosan opsonisation might contribute to the immune deficiency of ALL patients . The present study suggests , that the zymosan opsonisation can not be corrected by ivGG infusions The effects of i.v . cytomegalovirus ( CMV ) immunoglobulin given for prophylaxis of CMV infections in recipients of allogeneic and autologous marrow transplants were evaluated in a r and omized trial : 60 patients were r and omly assigned to receive ( 30 patients ) or not to receive ( 30 patients ) CMV immunoglobulin for a period of 90 days after transplantation . As to the allografted patients , the cumulative incidence of asymptomatic and symptomatic CMV infections was significantly reduced in the CMV immunoglobulin-treated group as compared to the control group ( 56.5 % versus 92.9 % , P less than 0.05 ) . No other statistically significant effect of CMV immunoglobulin could be found . In particular , the incidence of symptomatic CMV infections ( including interstitial pneumonia ) , the mean delay of post-transplant viraemia and haematopoietic recovery were similar in the control and CMV immunoglobulin-treated groups . We conclude that prophylactic CMV immunoglobulin administration , as design ed in our study , is no more than marginally effective and can not be recommended without additional trials Recent reports using historical controls or registry cohorts suggest , respectively , either an increase in the mortality or a decrease in the incidence of hepatic veno-occlusive disease ( VOD ) with the administration of intravenous immunoglobulin ( i.v . Ig ) after bone marrow transplantation . These divergent results prompted us to conduct a retrospective analysis of two r and omized clinical trials conducted at our center to determine the effect of i.v . Ig infusions on the development and severity of VOD . Patients were r and omized to receive ( n=318 ) or not to receive ( n=315 ) i.v . Ig prophylaxis after human leukocyte antigen-identical sibling ( n=414 ) , mismatched or unrelated ( n=178 ) , or autologous or syngeneic ( n=41 ) marrow transplantation . To determine the relationship of i.v . Ig to the development and severity of VOD , a single observer review ed data displays created for each patient for grading VOD without knowledge of patient i.v . Ig use . In this analysis , VOD was defined as hyperbilirubinemia > or = 2.0 mg/dL before day 20 and abrupt weight gain > or = 2 % before day 14 posttransplant in the absence of other causes of liver disease . Hepatic VOD developed in 235 ( 37 % ) of the 633 r and omized patients . No evidence for VOD was found in 230 ( 36 % ) patients . The remaining 168 ( 27 % ) patients were classified as having liver disease of uncertain etiology . Hepatic VOD was judged to be severe in 63 ( 10 % ) and mild or moderate in 172 ( 27 % ) patients . The number of patients developing any VOD or severe VOD was similar between those r and omized to i.v . Ig prophylaxis and untreated controls ( 115 vs. 120 and 32 vs. 31 , respectively ) . Logistic regression models identified several covariates as significant ( p < 0.01 ) factors associated with the development of severe VOD . Increased risk occurred with elevated pretransplant serum aspartate aminotransferase ( odds ratio [ OR ] = 2.64 ) and earlier year of transplant ( OR = 3.73 ) ; decreased risk occurred with autologous or twin donors ( OR = 0.09 ) and acute myeloid leukemia ( OR = 0.39 ) . The development of any VOD was associated with an elevated pretransplant alkaline phosphatase ( OR = 4.1 ) , pretransplant use of vancomycin ( OR = 1.6 ) or amphotericin ( OR = 3.0 ) , posttransplant use of cyclosporine ( OR = 2.5 ) , older patient age ( OR = 1.03 ) , and obesity ( OR = 0.78 ) . We concluded from the controlled trials of 633 patients that the administration of i.v . Ig did not influence the development or severity of VOD after bone marrow transplantation Graft-vs.-host disease ( GVHD ) and infection are major complications of allogeneic bone marrow transplantation . Intravenous immunoglobulin ( IVIg ) given at a dose of 500 mg/kg/wk has been shown to decrease the risk of acute GVHD , interstitial pneumonia , and infection in adults early after allogeneic transplantation . The current study is a controlled trial to determine whether a lower total dose of IVIg given with pretransplant loading reduces the incidence of transplant-related complications . In a r and omized trial of 241 patients > or = 20 years of age who were given related donor marrow allografts , 121 individuals receiving Ig prophylaxis ( 500 mg/kg/d loading from day -6 to -1 and then 100 mg/kg every 3 days from day 3 to 90 ) were compared with 120 control patients who did not receive IVIg . R and omization was stratified by human leucocyte antigen-matching , remission status of malignancy , GVHD prophylaxis , and cytomegalovirus ( CMV ) serology . The study was powered to detect a reduction in acute GVHD by 18 % and a decrease in transplant-related mortality by 17 % . Pretransplant IVIg loading and posttransplant maintenance achieved median serum IgG levels > 1350 mg/dL , which were approximately twofold greater than the untreated controls ( p<0.01 ) . White blood cell and platelet recoveries were similar for the two groups , although control patients required fewer units of platelets per day ( 2.5 vs. 3.3 , p = 0.008 ) . No significant differences in the incidence of CMV infection , interstitial pneumonia , or bacteremia were observed . The incidence of acute GVHD did not differ between the two groups ; however , acute GVHD was less frequent among IVIg recipients achieving maximum serum IgG levels > 3000 mg/dL ( 60 vs. 79 % ) . Neither transplant-related mortality nor disease-free survival was significantly altered by Ig prophylaxis . However , the cumulative incidence of relapse of malignancy was higher in IVIg recipients than in controls ( 31 vs. 18 % , p = 0.03 ) . Multivariable regression analysis demonstrated a 1.89 increased relative risk of relapse for individuals given IVIg ( p = 0.021 ) . We conclude that pretransplant loading and a shorter course and lower total dose of IVIg prophylaxis did not appear to decrease the risk of acute GVHD or mortality among adults receiving related donor marrow transplants . Note , IVIg administration may be associated with an increased risk of recurrent malignancy , a finding that warrants further investigation Bone marrow transplantation recipients who were cytomegalovirus ( CMV ) seropositive and /or had a CMV seropositive donor were r and omized for treatment with CMV hyperimmune plasma ( n = 27 ) or no treatment at all ( n = 27 ) . The CMV hyperimmune plasma had neutralization titers greater than 250 and enzyme-linked immunosorbent assay titers greater than 18,000 . Plasma ( 200 mg/kg body weight ) was given on four occasions ( during 2 days ) from day 3 to day 76 after transplantation . Patient characteristics were similar in the two groups . After transplantation , the median CMV titers increased with greater than 100 % in the group receiving the CMV plasma and decreased to less than 50 % in the controls ( p less than 0.01 ) . Asymptomatic CMV infections occurred in 26 % of the patients in the plasma group and 33 % of the controls . The frequency of patients with symptomatic CMV infections was also the same in the two groups ( 51 % vs 33 % ) . Three patients each in the two groups developed CMV-associated interstitial pneumonitis . Patient survival and causes of death were similar in the two groups . To conclude , no beneficial effect of CMV hyperimmune plasma was seen in patients at high risk of developing CMV infections In an attempt to reduce the incidence of lethal cytomegalovirus ( CMV ) interstitial pneumonitis after allogenic bone marrow transplantation 49 patients were r and omized in a multicenter controlled study to receive either CMV-hyperimmune globulin or a control immune globulin with low anticytomegalovirus titer . Immune globulin was administered intravenously 6 times with 20 days interval , starting on day 7 before transplantation . Patients receiving CMV hyperimmune globulin or control immune globulin were comparable with regard to age , diagnosis , pretransplant anti-CMV titer , incidence of graft-versus-host disease and transfusions . In each group , the incidence of histologically proven CMV interstitial pneumonitis during the first 110 days post BMT was recorded . Six of 23 patients in the control group versus 1 of 26 in the CMV hyperimmune globulin group died of CMV interstitial pneumonitis ( p less than 0.05 ) . No significant effect on idiopathic pneumonitis or survival was observed Intravenous immunoglobulin replacement therapy reduces the number of bacterial infections in B-cell chronic lymphocytic leukaemia ( B-CLL ) patients . However , due to the complexity of immunodeficiency in B-CLL and the cost-effectiveness of replacement therapy , it is important to identify patients who are likely to benefit from the treatment and to investigate which dose should be used . 15 patients with hypogammaglobulinaemia and a history of recurrent infections received a fixed dose of 10 grams of gammaglobulin intravenously every 3 weeks . Serum IgG levels were significantly higher after three doses ( p = 0.0002 ) , and stabilized just above lower reference value after 11 doses . The total number of infection-related events during 168 months before therapy was compared to the total number of infection-related events in 169 months during therapy . The number of antibiotic prescriptions was reduced from 78 to 54 ( N.S. ) , the number of admissions to hospital due to infections was reduced from 16 to 5 ( p = 0.047 ) and the number of febrile episodes was reduced from 63 to 31 ( p = 0.004 ) . We conclude that a fixed low dose of gammaglobulin intravenously can restore normal serum IgG levels in hypogammaglobulinaemic B-CLL patients , and leads to a decreased number of febrile episodes and admissions to hospital due infections Thirty-two patients undergoing allogeneic hematopoietic stem-cell transplantation were given respiratory syncytial virus ( RSV ) immune globulin ( RSVIG ) at the time of transplantation and again 3 weeks later . Antibody titers to RSV , human parainfluenza virus 3 , measles , and influenza H1N1 , H3N2 , and B were measured prior to administration of RSVIG and 6 more times over the course of the subsequent 6 weeks . Baseline antiviral titers and increases in antibody after administration of RSVIG were extremely variable for all the viruses . In 18 patients in whom the baseline titers of antibody titers to RSV-F protein were 1:640 - 1:2048 , there was a 7.7-fold initial increase in these titers after the first dose of RSVIG , compared with a 2.1-fold increase in 14 patients with baseline titers of 1:4096 - 1:20,840 ; increases in titers of antibody against the other viruses after the first dose of RSVIG reflected similar variability . The subset of patients with the lowest titers appear to receive the greatest benefit from administration of RSVIG BACTERIAL infection is one of the leading causes of morbidity and mortality in patients with multiple myeloma.1 , 2 Although most patients have large amounts of homogeneous myeloma immunoglobulin p The efficacy of i.v . immunoglobulin plus CMV-seronegative blood products or CMV-seronegative blood products alone for prevention of CMV infection , symptomatic CMV disease , other infections and GVHD after BMT was evaluated in a r and omized , controlled trial . Fifty-one CMV-seronegative allogeneic BMTs with a CMV-seronegative or CMV-seropositive marrow donor were r and omly assigned to receive either i.v . immunoglobulin ( 1.0 g/kg once weekly for 120 days after transplant ) plus CMV-seronegative blood products or CMV-seronegative blood products alone . CMV infection occurred in 2 of 25 patients ( 7 % ) receiving i.v . immunoglobulin plus CMV-seronegative blood and in 2 of 23 patients ( 9 % ) receiving CMV-seronegative blood alone . All CMV infections were asymptomatic and characterized by viral excretion with or without CMV seroconversion . There were no cases of CMV-related interstitial pneumonia . Grade > or = II GVHD was less frequent in patients given i.v . immunoglobulin ( 5 of 25 patients ( 20 % ) vs. 11 of 23 patients ( 48 % ) , p = 0.04 ) . The number of bacterial and fungal infections was similar in both groups . Fewer non-CMV viral infections ( 9 of 27 patients ( 33 % ) vs. 15 of 24 patients ( 63 % ) , p = 0.03 ) and fewer deaths associated with infection ( 1 of 27 patients ( 4 % ) vs. 5 of 24 patients ( 21 % ) , p = 0.07 ) occurred in recipients of immunoglobulin . Neither survival nor risk of leukemia relapse was changed by the immunoglobulin . The high doses of i.v . immunoglobulin were well tolerated . These results suggest that CMV-seronegative blood products alone prevent most CMV infections and CMV disease in CMV-seronegative allogeneic BMT recipients , even when the marrow donor is CMV-seropositive . ( ABSTRACT TRUNCATED AT 250 WORDS We have used sample s from the in vivo situation to compare antibody levels provided by the infusion of different IVIG products , a measure , albeit indirect , of potential therapeutic efficacy . The further correlation of in vivo antibody titers with functional activities of these antibodies ( eg , opsonization and viral neutralization ) would provide additive valuable information about the usefulness of this therapy The pharmacokinetics of an intravenous immunoglobulin ( IVIG ) , Gammagard ( Baxter Healthcare Corp. , Glendale , CA ) , were measured in 31 cytomegalovirus ( CMV ) antibody negative bone marrow transplant ( BMT ) patients as part of a multicenter efficacy trial of 2 weekly dose regimens . Since all patients lacked antibody to CMV and received only screened CMV negative blood products , the half-life of the exogenous CMV antibody could be measured with an ELISA assay . The CMV antibody titer was related to the immunoglobulin concentration using a st and ard curve . Compared with the 22-day half-life in normal subjects , the half-life in BMT patients was approximately 6 days for either the 250 mg/kg or 500 mg/kg dose regimen . The half-life did not change over the subsequent 3 weekly doses . Peak concentrations were 3.5 + /- 1.4 and 2.6 + /- 0.7 mg/mL of IVIG in week 1 as well as 5.5 + /- 2.6 and 3.4 + /- 1.2 mg/mL in week 3 after the 250 mg/kg and 500 mg/kg , respectively . Total body clearance of IVIG was 0.61 and 0.46 mL/kg/hr for the 500 mg/kg and 250 mg/kg , respectively |
13,233 | 32,186,518 | However , there was little evidence of changed behavior or health outcomes .
There was no strong evidence in support of the effectiveness of mobile apps in improving health behaviors or outcomes because few studies found significant differences between the app and control groups . | BACKGROUND With a growing focus on patient interaction with health management , mobile apps are increasingly used to deliver behavioral health interventions .
The large variation in these mobile health apps-their target patient group , health behavior , and behavioral change strategies-has result ed in a large but incohesive body of literature .
OBJECTIVE This systematic review aim ed to assess the effectiveness of mobile apps in improving health behaviors and outcomes and to examine the inclusion and effectiveness of behavior change techniques ( BCTs ) in mobile health apps . | OBJECTIVES Many individuals are advised to adhere to specific diet plans for their personal health ; hence , it is important that tools are available to support these behaviors . Smartphone applications ( apps ) may assist health care professionals in educating their clients on specific dietary modifications . This pilot study focused on a single dietary modification , reducing sodium intake , to determine whether a commercial health app is useful for promoting dietary change . METHODS Thirty healthy adults ( age 34.4 ± 15.7 y ; body mass index 25.6 ± 4.3 kg/m2 ) were recruited from a university community and completed this 4-wk r and omized parallel trial . Participants were instructed to reduce their sodium intake to ≤2300 mg/d by using the MyFitnessPal app to receive feedback on sodium content of foods or by paper tallying of estimated sodium intake . The predicted 24-h sodium excretion , estimated using the ratio of sodium to creatinine from the first morning urine void , and participant satisfaction were the main outcomes measured . RESULTS The change in the predicted 24-h sodium excretion differed between groups : -838 ± 1093 and + 236 ± 1333 mg/24 h predicted for the app and journal groups , respectively ( P = 0.010 ) . Moreover , participants in the app group reported significantly greater satisfaction with their method of diet tracking than the journal group ( P = 0.001 ) . CONCLUSIONS These data suggest that smartphone apps have the potential to facilitate the implementation of dietary advice . This was a small pilot study with limited scope , and more research is necessary to determine the value of smartphone apps for facilitating dietary change Background Mobile apps present a potentially cost-effective tool for delivering behavior change interventions at scale , but no known studies have tested the efficacy of apps as a tool to specifically increase vegetable consumption among overweight adults . Objective The purpose of this pilot study was to assess the initial efficacy and user acceptability of a theory-driven mobile app to increase vegetable consumption . Methods A total of 17 overweight adults aged 42.0 ( SD 7.3 ) years with a body mass index ( BMI ) of 32.0 ( SD 3.5 ) kg/m2 were r and omized to the use of Vegethon ( a fully automated theory-driven mobile app enabling self-monitoring of vegetable consumption , goal setting , feedback , and social comparison ) or a wait-listed control condition . All participants were recruited from an ongoing 12-month weight loss trial ( parent trial ) . Research ers who performed data analysis were blinded to condition assignment . The primary outcome measure was daily vegetable consumption , assessed using an adapted version of the vali date d Harvard Food Frequency Question naire administered at baseline and 12 weeks after r and omization . An analysis of covariance was used to assess differences in 12-week vegetable consumption between intervention and control conditions , controlling for baseline . App usability and satisfaction were measured via a 21-item post-intervention question naire . Results Using intention-to-treat analyses , all enrolled participants ( intervention : 8 ; control : 9 ) were analyzed . Of the 8 participants r and omized to the intervention , 5 downloaded the app and logged their vegetable consumption a mean of 0.7 ( SD 0.9 ) times per day , 2 downloaded the app but did not use it , and 1 never downloaded it . Consumption of vegetables was significantly greater among the intervention versus control condition at the end of the 12-week pilot study ( adjusted mean difference : 7.4 servings ; 95 % CI 1.4 - 13.5 ; P=.02 ) . Among secondary outcomes defined a priori , there was significantly greater consumption of green leafy vegetables , cruciferous vegetables , and dark yellow vegetables ( adjusted mean difference : 2.6 , 1.6 , and 0.8 servings ; 95 % CI 0.1 - 5.0 , 0.1 - 3.2 , and 0.3 - 1.4 ; P=.04 , P=.04 , and P=.004 , respectively ) . Participants reported positive experiences with the app , including strong agreement with the statements “ I have found Vegethon easy to use ” and “ I would recommend Vegethon to a friend ” ( mean 4.6 ( SD 0.6 ) and 4.2 ( SD 0.8 ) , respectively , ( on a 5-point scale ) . Conclusions Vegethon demonstrated initial efficacy and user acceptability . A mobile app intervention may be useful for increasing vegetable consumption among overweight adults . The small sample size prevented precise estimates of effect sizes . Given the improved health outcomes associated with increases in vegetable consumption , these findings indicate the need for larger , longer-term evaluations of Vegethon and similar technologies among overweight adults and other suitable target groups . Trial Registration Clinical Trials.gov NCT01826591 ; https:// clinical trials.gov/ct2/show/NCT01826591 ( Archived by WebCite at http://www.webcitation.org/6hYDw2AOB Background Conventional face-to-face weight loss and weight control programs are very labor intensive for both the patient and the provider . It is unclear to what extent conventional programs can be ( partially ) completed by mobile health ( mHealth ) apps . Objective The aim of this study was to compare the effectiveness of different weight loss programs using a combination of conventional and mobile programs among adults who are overweight ( body mass index [ BMI ] > 29 kg/m² ) . Methods A single-blinded r and omized controlled trial among obese adults was performed from September 2015 to March 2016 . The study took place in Leuven , Belgium . Of the 102 eligible ( BMI > 29 kg/m² ) adults , 81 ( 79 % ) completed the study . The three intervention groups consisted of a conventional face-to-face weight loss program , a weight loss app program ( app group ) , and a partial face-to-face and partial app program ( combi group ) . All intervention groups received the same advice from a dietician and a physical activity coach during a 12-week period . The control group did not receive any information during the same period . Primary outcomes were weight reduction ( 5 % decrease of baseline weight in kg ) , BMI , metabolic risk factors , dietary pattern , and physical activity . Results Significant more participants in all three intervention groups lost at least 5 % or more of their weight at baseline compared with the control group . No significant difference was found between the combi group and the conventional group . A trend was found that more participants in the combi group lost 5 % or more compared with the app group ( 19 % ) , P=.06 . A significant time x group effect was found for BMI and metabolic risk factors , with the control group having the worst results and the combi group being significantly better with regard to BMI compared with the app group . No significant group x time effects were found for the intake of different food and drinks and moderate to vigorous physical activity ( MVPA ) . Conclusions The results of this study show that a conventional weight loss program could partially be completed with an mHealth program without affecting the effectiveness . Trial Registration Clinical trials.gov NCT02595671 ; https:// clinical trials.gov/ct2/show/NCT02595671 ( Archived by WebCite at http://www.webcitation.org/6w1H0x1Q6 Background Obesity is a growing global issue that is linked to cognitive and psychological deficits . Objective This preliminary study investigated the efficacy of training to improve inhibitory control ( IC ) , a process linked to overeating , on consumption and cognitive control factors . Methods This study utilized a multisession mobile phone – based intervention to train IC in an overweight and obese population using a r and omized waitlist-control design . A combination of self- assessment question naires and psychophysiological measures was used to assess the efficacy of the intervention in terms of improved general IC and modified food consumption after training . Attitudes toward food were also assessed to determine their mediating role in food choices . A total of 58 participants ( 47 female ) completed 2 assessment sessions 3 weeks apart , with 2 weeks of intervention training for the training group during this time . The groups did not differ in baseline demographics including age , body mass index , and inhibitory control . Results Inhibitory control ability improved across the training sessions , with increases in P3 amplitude implying increased cognitive control over responses . Inhibitory control training was associated with increased healthy and reduced unhealthy food consumption in a taste test and in the week following training , as measured by the Healthy Eating Quiz and the food consumption test . Cognitive restraint was enhanced after training for the training but not the waitlist condition in the Three-Factor Eating Question naire , implying that attempts to avoid unhealthy foods in the future will be easier for the training group participants . Conclusions Inhibitory control training delivered via a purpose - design ed mobile phone app is easy to complete , is convenient , and can increase cognitive restraint and reduce unhealthy food consumption . Trial Registration Australian New Zeal and Clinical Trials Registry ACTRN12616000263493 ; http://www.ANZCTR.org.au/ACTRN12616000263493.aspx ( Archived by WebCite at http://www.webcitation.org/6ioHjGING Background Growing evidence shows that fixed , nonpersonalized daily step goals can discourage individuals , result ing in unchanged or even reduced physical activity . Objective The aim of this r and omized controlled trial ( RCT ) was to evaluate the efficacy of an automated mobile phone – based personalized and adaptive goal - setting intervention using machine learning as compared with an active control with steady daily step goals of 10,000 . Methods In this 10-week RCT , 64 participants were recruited via email announcements and were required to attend an initial in-person session . The participants were r and omized into either the intervention or active control group with a one-to-one ratio after a run-in period for data collection . A study -developed mobile phone app ( which delivers daily step goals using push notifications and allows real-time physical activity monitoring ) was installed on each participant ’s mobile phone , and participants were asked to keep their phone in a pocket throughout the entire day . Through the app , the intervention group received fully automated adaptively personalized daily step goals , and the control group received constant step goals of 10,000 steps per day . Daily step count was objective ly measured by the study -developed mobile phone app . Results The mean ( SD ) age of participants was 41.1 ( 11.3 ) years , and 83 % ( 53/64 ) of participants were female . The baseline demographics between the 2 groups were similar ( P>.05 ) . Participants in the intervention group ( n=34 ) had a decrease in mean ( SD ) daily step count of 390 ( 490 ) steps between run-in and 10 weeks , compared with a decrease of 1350 ( 420 ) steps among control participants ( n=30 ; P=.03 ) . The net difference in daily steps between the groups was 960 steps ( 95 % CI 90 - 1830 steps ) . Both groups had a decrease in daily step count between run-in and 10 weeks because interventions were also provided during run-in and no natural baseline was collected . Conclusions The results showed the short-term efficacy of this intervention , which should be formally evaluated in a full-scale RCT with a longer follow-up period . Trial Registration Clinical Trials.gov : NCT02886871 ; https:// clinical trials.gov/ct2/show/NCT02886871 ( Archived by WebCite at http://www.webcitation.org/6wM1Be1Ng ) Background : Evidence on the efficacy of smartphone applications ( apps ) for reducing body weight and other measurements of adiposity sustainably is not conclusive . Objective : To evaluate the effect of adding an app for 3 months to traditional counselling on physical activity ( PA ) and a heart-healthy diet for the modification of measurements of adiposity at 3 and 12 months after intervention . Methods : This r and omised clinical trial included 833 subjects . The counselling and app group ( IG ) had 415 subjects , while 418 were included in the counselling only group ( CG ) . The primary outcome was adiposity measurements at 3 and 12 months after intervention . The secondary outcome was the effect of the intervention by sex . Intervention : Counselling on a heart-healthy diet and PA was given to both groups . The IG also received training in the use of a smartphone app design ed to promote a heart-healthy diet and PA , and this group was given access to this application for 3 months . Outcome measurements included waist circumference ( WC ) , body mass index ( BMI ) and Clínica Universidad de Navarra – body adiposity estimator ( CUN-BAE ) . Results : In the IG at 12 months , the following decreased : WC −0.72 cm ( 95 % confidence interval [ CI ] : −2.35 to −0.02 ) and CUN-BAE −0.35 ( 95 % CI : −0.63 to −0.06 ) . These decreases were only observed in women . After baseline adjustment , the beneficial effect was maintained in the IG compared to the CG at 12 months in terms of WC ( −0.67 ; 95 % CI : −0.29 to −0.02 ) and CUN-BAE ( −0.57 ; 95 % CI : −1.10 to −0.04 ) , but only in women . Conclusions : An intervention of nutritional counselling and PA plus the smartphone app with personalised recommendations compared to CG showed beneficial results in terms of reduction of abdominal obesity and the percentage of body fat in women , but not in men Background Mobile applications ( apps ) have been heralded as transformative tools to deliver behavioral health interventions at scale , but few have been tested in rigorous r and omized controlled trials . We tested the effect of a mobile app to increase vegetable consumption among overweight adults attempting weight loss maintenance . Methods Overweight adults ( n=135 ) aged 18–50 years with BMI = 28–40 kg/m2 near Stanford , CA were recruited from an ongoing 12-month weight loss trial ( parent trial ) and r and omly assigned to either the st and -alone , theory-based Vegethon mobile app ( enabling goal setting , self-monitoring , and feedback and using “ process motivators ” including fun , surprise , choice , control , social comparison , and competition ) or a wait-listed control condition . The primary outcome was daily vegetables servings , measured by an adapted Harvard food frequency question naire ( FFQ ) 8 weeks post-r and omization . Daily vegetable servings from 24-hour dietary recalls , administered by trained , certified , and blinded interviewers 5 weeks post-r and omization , was included as a secondary outcome . All analyses were conducted according to principles of intention-to-treat . Results Daily vegetable consumption was significantly greater in the intervention versus control condition for both measures ( adjusted mean difference : 2.0 servings ; 95 % CI : 0.1 , 3.8 , p=0.04 for FFQ ; and 1.0 servings ; 95 % CI : 0.2 , 1.9 ; p=0.02 for 24-hour recalls ) . Baseline vegetable consumption was a significant moderator of intervention effects ( p=0.002 ) in which effects increased as baseline consumption increased . Conclusions These results demonstrate the efficacy of a mobile app to increase vegetable consumption among overweight adults . Theory-based mobile interventions may present a low-cost , scalable , and effective approach to improving dietary behaviors and preventing associated chronic diseases . Trial registration Clinical Trials.gov NCT01826591 . Registered 27 March 2013 Background The use of mobile phone apps for improving lifestyles has become generalized in the population , although little is still known about their effectiveness in improving health . Objective We evaluate the effect of adding an app to st and ard counseling on increased physical activity ( PA ) and adherence to the Mediterranean diet , 3 months after implementation . Methods A r and omized , multicenter clinical trial was carried out . A total of 833 participants were recruited in six primary care centers in Spain through r and om sampling : 415 in the app+counseling group and 418 in the counseling only group . Counseling on PA and the Mediterranean diet was given to both groups . The app+counseling participants additionally received training in the use of an app design ed to promote PA and the Mediterranean diet over a 3-month period . PA was measured with the 7-day Physical Activity Recall ( PAR ) question naire and an accelerometer ; adherence to the Mediterranean diet was assessed using the Mediterranean Diet Adherence Screener question naire . Results Participants were predominantly female in both the app+counseling ( 249/415 , 60.0 % ) and counseling only ( 268/418 , 64.1 % ) groups , with a mean age of 51.4 ( SD 12.1 ) and 52.3 ( SD 12.0 ) years , respectively . Leisure-time moderate-to-vigorous physical activity ( MVPA ) by 7-day PAR increased in the app+counseling ( mean 29 , 95 % CI 5 - 53 min/week ; P=.02 ) but not in the counseling only group ( mean 17.4 , 95 % CI –18 to 53 min/week ; P=.38 ) . No differences in increase of activity were found between the two groups . The accelerometer recorded a decrease in PA after 3 months in both groups : MVPA mean –55.3 ( 95 % CI –75.8 to –34.9 ) min/week in app+counseling group and mean –30.1 ( 95 % CI –51.8 to –8.4 ) min/week in counseling only group . Adherence to the Mediterranean diet increased in both groups ( 8.4 % in app+counseling and 10.4 % in counseling only group ) , with an increase in score of 0.42 and 0.53 points , respectively ( P<.001 ) , but no difference between groups ( P=.86 ) . Conclusions Leisure-time MVPA increased more in the app+counseling than counseling only group , although no difference was found when comparing the increase between the two groups . Counseling accompanied by printed material s appears to be effective in improving adherence to the Mediterranean diet , although the app does not increase adherence . Clinical Trial Clinical trials.gov NCT02016014 ; https:// clinical trials.gov/ct2/show/NCT02016014 ( Archived by WebCite at http://www.webcitation.org/6mnopADbf Background While gains in reducing smoking rates in Finl and have been made , prevalence rates are still substantial . Relapse rates among smokers engaged in quit-smoking programs are high . Physical activity has been proposed as one means to help smokers manage cravings . Software and apps on mobile phone and h and held devices offer an opportunity to communicate messages on how to use physical activity to manage cravings as part of quit-smoking programs . Objective We aim ed to test the feasibility , acceptability , usability , and preliminary efficacy of an mHealth mobile phone app , Physical activity over Smoking ( PhoS ) , to assist smokers in quitting smoking in a r and omized controlled trial . The app was design ed to prompt smokers to engage in physical activities to manage their smoking cravings . Methods Regular smokers ( n=44 ) attended a group-based behavioral counselling program aim ed at promoting physical activity as an additional aid to quit . After quit day , participants were r and omly allocated to an intervention ( n=25 ) or to a comparison ( n=19 ) group . Participants in the intervention group were provided with the PhoS app and training on how to use it to assist with relapse prevention . Participants in the comparison condition were provided with generalized relapse prevention training . Results Some participants reported that the PhoS app was useful in assisting them to successfully manage their cigarette cravings , although compliance across the sample was modest and participants reported low levels of usability . Participants receiving the PhoS app did not report greater abstinence than those who did not receive the app . However , participants receiving the app were more likely to report greater abstinence if they did not use pharmacological support , while those who did not receive the app reported greater abstinence when using pharmacological support . Participants receiving the app reported greater levels of physical activity than those who did not . Results revealed that the app result ed in better retention . Conclusions The PhoS app showed some potential to reduce abstinence among participants not using pharmacological therapy and to increase physical activity . However , problems with usability and lack of effects on abstinence raise questions over the app ’s long-term effectiveness . Future research should prioritize further development of the app to maximize usability and test effects of the intervention independent of quit-smoking programs . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 55259451 ; http://www.controlled-trials.com/IS RCT N55259451 ( Archived by WebCite at http://www.webcitation.org/6cKF2mzEI Background Smartphones are ideal for promoting physical activity in those with little intrinsic motivation for exercise . This study tested three hypotheses : H1 – receipt of social feedback generates higher step-counts than receipt of no feedback ; H2 – receipt of social feedback generates higher step-counts than only receiving feedback on one ’s own walking ; H3 – receipt of feedback on one ’s own walking generates higher step-counts than no feedback ( H3 ) . Methods A parallel group r and omised controlled trial measured the impact of feedback on steps-counts . Healthy male participants ( n = 165 ) aged 18–40 were given phones pre-installed with an app that recorded steps continuously , without the need for user activation . Participants carried these with them as their main phones for a two-week run-in and six-week trial . R and omisation was to three groups : no feedback ( control ) ; personal feedback on step-counts ; group feedback comparing step-counts against those taken by others in their group . The primary outcome measure , steps per day , was assessed using longitudinal multilevel regression analysis . Control variables included attitude to physical activity and perceived barriers to physical activity . Results Fifty-five participants were allocated to each group ; 152 completed the study and were included in the analysis : n = 49 , no feedback ; n = 53 , individual feedback ; n = 50 , individual and social feedback . The study provided support for H1 and H3 but not H2 . Receipt of either form of feedback explained 7.7 % of between-subject variability in step-count ( F = 6.626 , p < 0.0005 ) . Compared to the control , the expected step-count for the individual feedback group was 60 % higher ( effect on log step-count = 0.474 , 95 % CI = 0.166–0.782 ) and that for the social feedback group , 69 % higher ( effect on log step-count = 0.526 , 95 % CI = 0.212–0.840 ) . The difference between the two feedback groups ( individual vs social feedback ) was not statistically significant . Conclusions Always-on smartphone apps that provide step-counts can increase physical activity in young to early-middle-aged men but the provision of social feedback has no apparent incremental impact . This approach may be particularly suitable for inactive people with low levels of physical activity ; it should now be tested with this population BACKGROUND Recent studies suggest that about 6 out of 10 users have installed a fitness tracking application on their smartphone . Nevertheless , more than 59 % of adults do not engage in sufficient daily physical activity and much remains unknown with regard to the effectiveness of mobile applications . By adopting the Theory of Planned Behavior , we tested whether the use of fitness apps for daily steps tracking could positively influence people 's health behavior . METHODS Participants ( N.=78 ) were r and omly assigned to one of two experimental conditions ; in one condition , they were asked to adopt a fitness app for two weeks . No information regarding mobile apps was given for participants in the control condition . In order to test the effects of using a fitness app , a series of two-way mixed ANOVAs were conducted . RESULTS Participants in the experimental condition reported more favorable attitudes in the post-test compared to the pre-test , t(43)=4.09 , P<0.001 , d=0.65 . By contrast , in the control condition , the difference on attitudes between pre-test and post-test was not significant ( P=1.00 ) . They also reported higher perceived behavioral control ( PBC ) scores , t(43 ) = 4.97 , P<0.001 , d=0.75 , whereas the difference on PBC for the control condition was not significant ( P=0.27 ) . Participants who used a fitness app reported to have walked more in the post-test compared to the pre-test , t(43 ) = 2.41 , P=0.02 , d=0.36 , whereas self-reported behavior did not change for participants in the control condition ( P=0.46 ) . CONCLUSIONS The present study provides encouraging evidence for the positive effects of using a fitness-tracking app in promoting health behavior Background Mobile phone apps may be acceptable to users and could improve retention and adherence over more traditional methods , but there is mixed literature supporting their efficacy . In the weight management space , very little is known about how a mobile phone app integrating features beyond text messaging ( short message service ) can affect behavior , particularly when combined with face-to-face support . Objective The objective of this study was to examine the effectiveness of a mobile phone app when combined with a partial meal replacement program including face-to-face support . This paper compares a static versus supportive app over a 6-month r and omized trial for effects on weight loss , weight-related biomarkers , and psychological outcomes . Methods Overweight and obese adults ( 71.2 % female , 104/146 ; mean 48.11 , SD 11.75 years ) were recruited to participate in the weight loss study , and they were r and omized on a 1:1 basis using a computer algorithm . The supportive app ( n=75 ) provided information , food intake recording , rewards , prompts for regular interaction through reminders , and the opportunity to review personal compliance with the dietary program . The static app ( n=71 ) included only recipes and weight loss information . Both groups recieved equal amounts of face-to-face support in addition to app . Results The overall reduction in app usage over 24 weeks was lower for the supportive app in comparison with the static app ; approximately 39.0 % ( 57/146 ) of the users were still using the app at week 24 . Despite the promising results for app usage , there were no differences in weight loss between groups ( F1,128.12=0.83 , P=.36 ) . However , it should be noted that almost 60 % ( 49/84 ) of all participants lost 5 % or more of body weight during the trial . No weight-related biomarkers were significantly different between groups . Both groups experienced an increase in positive mood , but this was significantly higher for those who received the static app ( F1,118.12=4.93 , P=.03 ) . Conclusions Although the supportive app was well received by users , we found little evidence of the added benefit of this versus the static app in combination with face-to-face support in a community-delivered weight loss program . Future versions of the app may incorporate more unique behavioral techniques beyond those provided by the consultant to improve the potency of the app . Trial Registration Australian New Zeal and Clinical Trials Registry ACTRN12613000547741 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=364187 ( Archived by WebCite http://www.webcitation.org/6yivwfMI9 It is well-known that the United States is facing an obesity epidemic , and the long-term sequelae are costly ( 1 , 2 ) . Research ers continue to search for effective weight-loss interventions that can be applied in outpatient setting s , but these are often time-consuming and re source -intensive , requiring repeated counseling ( 3 ) . It is no surprise that primary care providers often omit discussing weight loss with obese patients and rarely spend adequate time on counseling ( 4 , 5 ) . Smartphone applications ( apps ) may provide an alternative to re source -intensive weight-loss programs . In December 2013 , a survey by the Pew Research Center found that 58 % of Americans own smartphones and ownership is increasing among every demographic group , including low-income population s ( 6 ) . The nascent field of mobile health is rapidly exp and ing ; experts estimate that as many as 40000 health-related apps were available in 2012 , comprising a $ 718 million industry ( 7 ) . Many of these apps aim to help persons change behaviors to improve health , including weight loss , yet few have been rigorously evaluated . An effective app for reducing body weight could produce tremendous cost savings by preventing long-term complications , such as diabetes and cardiovascular events . To our knowledge , however , no studies have examined the effectiveness of delivering or prescribing an app for weight loss to patients in a clinical setting . We evaluated one of the most popular publicly available apps for weight loss : MyFitnessPal ( MFP ) ( MyFitnessPal ) . MFP has received the highest possible rating , 5 out of 5 stars , from thous and s of review ers on the Apple and And roid ( Google ) app store Web sites . It has nearly 1 million likes on Facebook , and the company reports more than 50 million registered users . MFP incorporates elements of social cognitive theory , including self-monitoring , goal setting , and feedback . We sought to test the effect of providing this free , widely used smartphone app for weight loss to patients in their primary care clinic . Methods Design Overview mFit ( The Mobile Fitness Project ) was a r and omized , controlled trial in which participants were r and omly assigned to receive usual primary care ( n= 107 ) or usual primary care plus the MFP app ( n= 105 ) ( Figure 1 ) . Assessment s were completed at baseline , 3 months , and 6 months between August 2012 and May 2013 . The institutional review board of the University of California , Los Angeles ( UCLA ) , approved the study , and all participants provided written informed consent . Figure 1 . Study flow diagram . * Among the 6 intervention group participants who withdrew , 3 reported not having enough time to use the app , 2 did not have time to return for follow-up , and 1 was no longer interested in participating in the study . Among the 8 control group participants who withdrew , 6 reported not having time to return for follow-up and 2 were no longer interested in participating in the study . Study data were collected on Apple iPads using Research Electronic Data Capture ( REDCap ) tools hosted at UCLA . REDCap is a secure , Web-based application design ed to support data capture for research studies , providing an intuitive interface , audit trails , and automated export ( 8) . Setting and Participants Participants were recruited from 2 UCLA primary care clinics that serve ethnically and socioeconomically diverse patient population s. Eligibility criteria included age 18 years or older , body mass index ( BMI ) of 25 kg/m2 or greater , and smartphone ownership . Participants also had to answer yes when asked , Are you interested in losing weight ? Exclusion criteria were current , planned , or previous pregnancy within 6 months ; receipt of hemodialysis ; life expectancy less than 6 months ; lack of interest in weight loss ; or current use of a smartphone app for weight loss . Screening and R and omization Patients were recruited during routine primary care visits at their respective clinics . The research team provided a script to medical assistants to use with any patients with BMI greater than 25 kg/m2 . Patients interested in enrollment were referred to the on-site research assistant , who screened , received consent from , and completed surveys with each patient . Participants were r and omly assigned in blocks by BMI of 25 to 30 kg/m2 and BMI greater than 30 kg/m2 to ensure roughly equal distribution of overweight and obese patients between the intervention and control groups . Our statistician used R ( R Foundation for Statistical Computing ) to generate the permuted block sequence . We printed the sequence and placed it in opaque envelopes . Research assistants helped intervention group participants download the MFP app onto their smartphone and showed them an instructional video developed by MFP . These participants also received a telephone call from the same research assistant 1 week after enrollment to assist with any technical problems with the app . Research assistants told control group patients to choose any activities you 'd like to lose weight , without specifying any particular interventions . Control group participants were aware that they were participating in a study of a weight-loss app but were blinded to the name of the app . To minimize contamination of the control group , providers and clinic staff were also blinded to the name of the app and to group assignment . At the 3-month follow-up visit , all participants received a 1-page educational h and out on healthy eating from www.myplate.gov . Participants received a $ 20 gift card for attending each follow-up visit . Each participant 's primary care provider was notified of their enrollment in the study . Blood pressure was measured at baseline , 3 months , and 6 months by trained research assistants using an automated monitor ( Dinamap , GE Medical Systems ) . Intervention We selected MFP as our intervention on the basis of 2 focus groups held with overweight primary care patients . Patients were asked about their impressions of various text messagebased programs and smartphone apps . Overall , there was much more interest in smartphone apps than text-based programs . A few participants stated they enjoyed using MFP , and a majority expressed great interest in trying it . Although we selected MFP as our intervention , there are many similar , publicly available apps that may be as popular as MFP . Some of these apps have been assessed in prior studies , but to our knowledge , none have been evaluated in a r and omized trial ( 9 ) . MFP was design ed by software engineers in collaboration with dietitians to create an app for calorie counting . The app provides a data base of more than 3 million foods and an easy-to-use interface for logging food and exercise . Users enter their current weight , goal weight , and goal rate of weight loss ( limited to 0.23 to 0.90 kg/wk ) . The MFP app then shows the user their daily , individualized calorie goal . Each day , the app displays the user 's calorie goal relative to their recorded caloric intake . MFP also generates real-time reports showing users their weight trend , caloric intake in the past week , and nutritional summaries of their diet ( for example , grams of fat , carbohydrates , and protein and milligrams of sodium ) . The app also includes a bar code scanner for store-bought foods and a social networking feature that enables users to find friends and share their progress . Study participants were encouraged to use the social networking feature with friends and to set reminders to log their food . MFP incorporates an evidence -based and theory-based approach to weight loss . Setting a realistic weight-loss goal of 0.23 to 0.90 kg/wk is supported in self-regulation theory and is a st and ard setting of the MFP app ( 10 ) . The social networking feature of MFP may be important , given prior studies demonstrating the benefits of social support on weight loss ( 11 ) . Self-monitoring , consisting of recording dietary intake , physical activity , and weight , is also strongly associated with weight loss ( 12 ) . One pilot trial recently found that adherence to diet self-monitoring is higher among patients using a smartphone app than among those using a paper diary ( 13 ) . Outcomes and Follow-up The primary outcome was change in weight at 6 months in the intervention group compared with the usual primary care group . Weight was measured at baseline , 3 months , and 6 months . Secondary outcomes were systolic blood pressure and 3 self-reported behavioral mediators of weight loss : exercise , dieting , and self-efficacy in weight loss . Data on these outcomes were also collected at baseline , 3 months , and 6 months ( Appendix A in the Data Supplement ) . The behavioral survey items were adapted from the TRIAD ( Translating Research Into Action for Diabetes ) study ( 14 ) and the Diabetes Empowerment Scale ( 15 ) . Data Supplement . Appendices The MFP company also shared user data with the research team to investigate frequency of app logins over time . Each time a participant opened the app counted as a login . We assessed for contamination at the end of the trial by asking control group participants whether they had used MFP in the past 6 months . At 6 months , participants in the intervention group completed a survey on their experience using MFP ( Appendix B in the Data Supplement ) . In addition , we interviewed 6 participants who lost more than 4.5 kg to ask whether they thought MFP helped them lose weight and , if so , how . Statistical Analysis We determined that a total sample size of 82 patients ( 41 per group ) would allow us 80 % power to detect a 2.5-kg difference in weight change at 6 months between the groups , assuming an SD of 4.0 kg . We set a goal of enrolling 180 participants to account for rates of attrition as high as 55 % . We used a linear mixed-effects model ( PROC MIXED ) to compare changes in weight , systolic blood pressure , and behavioral survey items between groups from baseline to 3 and 6 months while controlling for clinic site . Month , including baseline , was modeled as a categorical term in the mixed-effects model . This model Objective To assess the efficacy of an interactive smoking cessation decision-aid application ( pp ) compared with a smoking cessation static information app on continuous abstinence . Design Automated double-blind r and omised controlled trial with 6 months follow-up ( 2014–2015 ) . Setting Smartphone-based . Participants 684 participants ( daily smokers of cigarettes , 18 years old or over ) recruited passively from app stores in the USA , Australia , UK and Singapore , and r and omised to one of two sub-apps . Intervention(s ) Behavioural , decision-aid , smartphone application . Main outcome ( s ) Continuous abstinence at 10 days , 1 month , 3 months and 6 months . Results Smokers who received the decision-aid app were more likely to be continuously abstinent at 1 month compared with the information-only app ( 28.5 % vs 16.9 % ; relative risk ( RR ) 1.68 ; 95 % CI 1.25 to 2.28 ) . The effect was sustained at 3 months ( 23.8 % vs 10.2 % ; RR 2.08 ; 95 % CI 1.38 to 3.18 ) and 6 months ( 10.2 % vs 4.8 % ; RR 2.02 ; 95 % CI 1.08 to 3.81 ) . Participants receiving the decision-aid app were also more likely to have made an informed choice ( 31.9 % vs 19.6 % ) and have lower decisional conflict ( 19.5 % vs 3.9 % ) . Conclusion A smartphone decision-aid app with support features significantly increased smoking cessation and informed choice . With an increasing number of smokers attempting to quit , unassisted evidence -based decision-aid apps can provide an effective and user-friendly option to many who are making quit decisions without healthcare professionals . Trial registration number ACTRN12613000833763 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Excessive uninterrupted sitting , also known as sedentary behavior , has been detrimentally associated with several health outcomes . However , the general population is often unaware of these health risks . Mobile phone technology offers great potential to increase awareness and to initiate behavior change . This study examined the short-term effects of stAPP , a smartphone-based intervention , on prolonged sitting behavior . Fifty-eight participants were r and omly assigned to an intervention group ( IG , n = 31 ) or a control group ( CG , n = 27 ) . After 1 week of baseline assessment , the IG received stAPP ( i.e. smartphone , smartphone app and corresponding motion sensor ) and used it during the following week . CG participants were monitored during 2 weeks without receiving stAPP . Total daily sitting time and prolonged sitting bouts ( > 30 min bouts of sitting ) were objective ly assessed using activPAL3 inclinometers . Although no significant changes emerged in the CG in any of the sitting parameters , total sitting time ( on weekdays ; p = 0.032 ) , number of prolonged sitting bouts ( > 30 min of sitting ) [ both on week- ( p < 0.001 ) and weekend days ( p = 0.008 ) ] and average duration of prolonged sitting bouts [ both on week- ( p = 0.004 ) and weekend days ( p = 0.029 ) ] decreased significantly in the IG . The stAPP smartphone-based intervention constitutes a promising intervention tool to interrupt and reduce prolonged sitting behavior . Further long-term studies on a larger scale are needed to further explore the effectiveness of a smartphone-based intervention aim ed at reducing prolonged sitting behavior Background While there has been an explosion of mobile device applications ( apps ) promoting healthful behaviors , including physical activity and sedentary patterns , surprisingly few have been based explicitly on strategies drawn from behavioral theory and evidence . Objective This study provided an initial 8-week evaluation of three different customized physical activity-sedentary behavior apps drawn from conceptually distinct motivational frames in comparison with a commercially available control app . Study Design and Methods Ninety-five underactive adults ages 45 years and older with no prior smartphone experience were r and omized to use an analytically framed app , a socially framed app , an affectively framed app , or a diet-tracker control app . Daily physical activity and sedentary behavior were measured using the smartphone ’s built-in accelerometer and daily self-report measures . Results Mixed-effects models indicated that , over the 8-week period , the social app users showed significantly greater overall increases in weekly accelerometry-derived moderate to vigorous physical activity relative to the other three arms ( P values for between-arm differences = .04-.005 ; Social vs. Control app : d = 1.05 , CI = 0.44,1.67 ; Social vs. Affect app : d = 0.89 , CI = 0.27,1.51 ; Social vs. Analytic app : d = 0.89 , CI = 0.27,1.51 ) , while more variable responses were observed among users of the other two motivationally framed apps . Social app users also had significantly lower overall amounts of accelerometry-derived sedentary behavior relative to the other three arms ( P values for between-arm differences = .02-.001 ; Social vs. Control app : d = 1.10,CI = 0.48,1.72 ; Social vs. Affect app : d = 0.94 , CI = 0.32,1.56 ; Social vs. Analytic app : d = 1.24 , CI = 0.59,1.89 ) . Additionally , Social and Affect app users reported lower overall sitting time compared to the other two arms ( P values for between-arm differences < .001 ; Social vs. Control app : d = 1.59,CI = 0.92 , 2.25 ; Social vs. Analytic app : d = 1.89,CI = 1.17 , 2.61 ; Affect vs. Control app : d = 1.19,CI = 0.56 , 1.81 ; Affect vs. Analytic app : d = 1.41,CI = 0.74 , 2.07 ) . Conclusion The results provide initial support for the use of a smartphone-delivered social frame in the early induction of both physical activity and sedentary behavior changes . The information obtained also sets the stage for further investigation of subgroups that might particularly benefit from different motivationally framed apps in these two key health promotion areas . Trial Registration Clinical Trials.gov Background Information and communication technologies are currently among the supporting elements that may contribute to improving health and changing lifestyles . Objective The aim of this study was to evaluate the long-term effectiveness of adding an app to st and ardized counseling in order to increase physical activity ( PA ) and adherence to the Mediterranean diet and to analyze the effects of app adherence in lifestyle changes . Methods A r and omized , multicenter clinical trial with a 12 month-follow up was conducted , involving 833 participants recruited by r and om sampling in 6 primary Spanish care centers ( 415 vs 418 ) . Counseling on PA and the Mediterranean diet was given to both groups by a research nurse ; however , the counseling + app group ( intervention group ) received additional training in the use of an app that was design ed to promote the Mediterranean diet and PA over a 3-month period . Main outcomes and measures included PA by accelerometer and the 7-day Physical Activity Recall ( PAR ) question naire and adherence to the Mediterranean diet by an adherence screener question naire . We considered adherence to the app to be high when it was used for more than 60 days . Results The mean age was 51 years ( SD 12 ) in the intervention group and 52.3 years ( SD 12.0 ) in the counseling-only group ; females predominated in both groups ( 60.0 % , 249/415 and 64.1 % , 268/418 , respectively ) . PA by accelerometer declined in both groups at 12 months ( P value for tendency in moderate to vigorous PA , [MVPA]=.15 ) . The intervention subgroup with high app adherence had better behavior than the low adherence subgroup ( P value for tendency in MVPA=.001 ) . PA analyzed by 7-day PAR did not show changes at 12 months in any of the groups ( P value for tendency=.25 ) . In the Mediterranean diet , an increase in adherence was observed in both groups at 12 months with no differences between them ( P value for tendency=.46 ) . In these two cases , the group with high app adherence also had better behavior , although without reaching significance for the tendency ( P>.05 ) . Conclusions The participants with strongest app adherence showed better outcomes in terms of maintenance of healthy lifestyles at 12 months than those with weaker adherence . Overall , however , we found no differences between intervention group and counseling-only group in PA increase and adherence to the Mediterranean diet in the long term . Trial Registration Clinical trials.gov NCT02016014 ; https:// clinical trials.gov/ct2/show/NCT02016014 ( Archived by WebCite at http://www.webcitation.org/6ymEXH6W4 Background Given the global prevalence of insufficient physical activity ( PA ) , effective interventions that attenuate age-related decline in PA levels are needed . Mobile phone interventions that positively affect health ( mHealth ) show promise ; however , their impact on PA levels and fitness in young people is unclear and little is known about what makes a good mHealth app . Objective The aim was to determine the effects of two commercially available smartphone apps ( Zombies , Run and Get Running ) on cardiorespiratory fitness and PA levels in insufficiently active healthy young people . A second aim was to identify the features of the app design that may contribute to improved fitness and PA levels . Methods Apps for IMproving FITness ( AIM FIT ) was a 3-arm , parallel , r and omized controlled trial conducted in Auckl and , New Zeal and . Participants were recruited through advertisements in electronic mailing lists , local newspapers , flyers posted in community locations , and presentations at schools . Eligible young people aged 14 - 17 years were allocated at r and om to 1 of 3 conditions : ( 1 ) use of an immersive app ( Zombies , Run ) , ( 2 ) use of a nonimmersive app ( Get Running ) , or ( 3 ) usual behavior ( control ) . Both smartphone apps consisted of a fully automated 8-week training program design ed to improve fitness and ability to run 5 km ; however , the immersive app featured a game-themed design and narrative . Intention-to-treat analysis was performed using data collected face-to-face at baseline and 8 weeks , and all regression models were adjusted for baseline outcome value and gender . The primary outcome was cardiorespiratory fitness , objective ly assessed as time to complete the 1-mile run/walk test at 8 weeks . Secondary outcomes were PA levels ( accelerometry and self-reported ) , enjoyment , psychological need satisfaction , self-efficacy , and acceptability and usability of the apps . Results A total of 51 participants were r and omized to the immersive app intervention ( n=17 ) , nonimmersive app intervention ( n=16 ) , or the control group ( n=18 ) . The mean age of participants was 15.7 ( SD 1.2 ) years ; participants were mostly NZ Europeans ( 61 % , 31/51 ) and 57 % ( 29/51 ) were female . Overall retention rate was 96 % ( 49/51 ) . There was no significant intervention effect on the primary outcome using either of the apps . Compared to the control , time to complete the fitness test was –28.4 seconds shorter ( 95 % CI –66.5 to 9.82 , P=.20 ) for the immersive app group and –24.7 seconds ( 95 % CI –63.5 to 14.2 , P=.32 ) for the nonimmersive app group . No significant intervention effects were found for secondary outcomes . Conclusions Although apps have the ability to increase reach at a low cost , our pragmatic approach using readily available commercial apps as a st and -alone instrument did not have a significant effect on fitness . However , interest in future use of PA apps is promising and highlights a potentially important role of these tools in a multifaceted approach to increase fitness , promote PA , and consequently reduce the adverse health outcomes associated with insufficient activity . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN12613001030763 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?ACTRN=12613001030763 ( Archived by WebCite at http://www.webcitation.org/6aasfJVTJ ) Objectives To determine the effect on weight of two Mobile technology-based ( mHealth ) behavioral weight loss interventions in young adults . Methods R and omized , controlled comparative effectiveness trial in 18–35 year olds with BMI ≥ 25 kg/m2 ( overweight/obese ) , with participants r and omized to 24 months of mHealth intervention delivered by interactive smartphone application on a cell phone ( CP ) ; personal coaching enhanced by smartphone self-monitoring ( PC ) ; or Control . Results The 365 r and omized participants had mean baseline BMI of 35 kg/m2 . Final weight was measured in 86 % of participants . CP was not superior to Control at any measurement point . PC participants lost significantly more weight than Controls at 6 months ( net effect −1.92 kg [ CI −3.17 , −0.67 ] , p=0.003 ) , but not at 12 and 24 months . Conclusions Despite high intervention engagement and study retention , the inclusion of behavioral principles and tools in both interventions , and weight loss in all treatment groups , CP did not lead to weight loss and PC did not lead to sustained weight loss relative to control . Although mHealth solutions offer broad dissemination and scalability , the CITY results sound a caution ary note concerning intervention delivery by mobile applications . Effective intervention may require the efficiency of mobile technology , the social support and human interaction of personal coaching , and an adaptive approach to intervention design . Trial Registration Clinical Trials.gov Identifier NCT01092364 . https:// clinical Background Use of mobile health ( mHealth ) technology is on an exponential rise . mHealth apps have the capability to reach a large number of individuals , but until now have lacked the integration of evidence -based theoretical constructs to increase exercise behavior in users . Objective The purpose of this study was to assess the effectiveness of a theory-based , self-monitoring app on exercise and self-monitoring behavior over 8 weeks . Methods A total of 56 adults ( mean age 40 years , SD 13 ) were r and omly assigned to either receive the mHealth app ( experimental ; n=28 ) or not to receive the app ( control ; n=28 ) . All participants engaged in an exercise goal - setting session at baseline . Experimental condition participants received weekly short message service ( SMS ) text messages grounded in social cognitive theory and were encouraged to self-monitor exercise bouts on the app on a daily basis . Exercise behavior , frequency of self-monitoring exercise behavior , self-efficacy to self-monitor , and self-management of exercise behavior were collected at baseline and at postintervention . Results Engagement in exercise bouts was greater in the experimental condition ( mean 7.24 , SD 3.40 ) as compared to the control condition ( mean 4.74 , SD 3.70 , P=.03 , d=0.70 ) at week 8 postintervention . Frequency of self-monitoring increased significantly over the 8-week investigation between the experimental and control conditions ( P<.001 , partial η2=.599 ) , with participants in the experimental condition self-monitoring significantly more at postintervention ( mean 6.00 , SD 0.93 ) in comparison to those in the control condition ( mean 1.95 , SD 2.58 , P<.001 , d=2.10 ) . Self-efficacy to self-monitor and perceived self-management of exercise behavior were unaffected by this intervention . Conclusions The successful integration of social cognitive theory into an mHealth exercise self-monitoring app provides support for future research to feasibly integrate theoretical constructs into existing exercise apps . In addition , findings provide preliminary support for theory-based apps to increase self-monitoring and exercise behavior in comparison to a control , no-app condition BACKGROUND There is a dual need for ( 1 ) innovative theory-based smartphone applications for smoking cessation and ( 2 ) controlled trials to evaluate their efficacy . Accordingly , this study tested the feasibility , acceptability , preliminary efficacy , and mechanism of behavioral change of an innovative smartphone-delivered acceptance and commitment therapy ( ACT ) application for smoking cessation vs. an application following US Clinical Practice Guidelines . METHOD Adult participants were recruited nationally into the double-blind r and omized controlled pilot trial ( n=196 ) that compared smartphone-delivered ACT for smoking cessation application ( SmartQuit ) with the National Cancer Institute 's application for smoking cessation ( QuitGuide ) . RESULTS We recruited 196 participants in two months . SmartQuit participants opened their application an average of 37.2 times , as compared to 15.2 times for QuitGuide participants ( p<0001 ) . The overall quit rates were 13 % in SmartQuit vs. 8 % in QuitGuide ( OR=2.7 ; 95 % CI=0.8 - 10.3 ) . Consistent with ACT 's theory of change , among those scoring low ( below the median ) on acceptance of cravings at baseline ( n=88 ) , the quit rates were 15 % in SmartQuit vs. 8 % in QuitGuide ( OR=2.9 ; 95 % CI=0.6 - 20.7 ) . CONCLUSIONS ACT is feasible to deliver by smartphone application and shows higher engagement and promising quit rates compared to an application that follows US Clinical Practice Guidelines . As results were limited by the pilot design ( e.g. , small sample ) , a full-scale efficacy trial is now needed Recent studies demonstrated that the duration of inactivity ( sedentary state ) is independently associated with increased risk of cardiovascular disease . Our goal was to develop the technology that can measure the amount of inactivity in real time , remind a person that a preprogrammed period of inactivity has occurred and encourage a period of activity , and provide web-based feedback with tailored information to the participant and investigators . Once it was developed , we carried out a pilot study in a group of sedentary overweight women . The objective of the study was to assess potential of the mobile app to reduce inactivity in our target population . A r and omized crossover design was employed with study subjects r and omly assigned to a 4-week each " message-on " and " message-off " periods . Out of 30 enrolled subjects , 27 completed the study . The average age of particpants was 52±12 ; BMI : 37±6 ; 47 % were white and 47 % were African American . Overall , inactivity was significantly lower ( p<0.02 ) during " message-on " periods ( 24.6 % ) as compared to the " message-off " periods ( 30.4 % ) . We conluded that mobile app monitoring inactivity and providing a real-time notification when inactivity period exceeds healthy limits was able to significantly reduce inactivity periods in overweight sedentary women Objectives This study developed a smartphone nutritional application ( app ) for making smart and healthy choices when purchasing food in grocery stores and tested its feasibility , usability , satisfaction and acceptability . Methods “ MyNutriCart ” was developed following the ADDIE ( analysis , design , development , implementation , and evaluation ) model . The goals of the app were to improve food selection when purchasing foods in the grocery stores based on a pre-defined budget , to improve dietary patterns based on the Dietary Guidelines for Americans , and to improve weight status . It was evaluated within a pilot r and omized trial using a convenient sample of 26 overweight or obese adults aged 21–45 years for 8 weeks . Results The developed app provided a grocery list of healthy foods to meet the individual requirements of all family members within a budget following the recommendations of the Dietary Guidelines for Americans . The average use of the app was 75 % on each purchase and only 37 % of the recommended products were purchased . The main reasons for not purchasing the recommended items were that participants did not like these ( 28.5 % ) and that the item was unavailable in the supermarket ( 24.3 % ) . Over 50 % of participants considered the app as feasible , usable , satisfactory , and acceptable ( p < 0.05 ) . Conclusions “ MyNutriCart ” is the first available app for making smart and healthy choices when purchasing food in grocery stores . This app could be used as a tool to translate recommendations into a practical grocery list that meet the needs of a family within a budget Background A dramatic rise in health-tracking apps for mobile phones has occurred recently . Rich user interfaces make manual logging of users ’ behaviors easier and more pleasant , and sensors make tracking effortless . To date , however , feedback technologies have been limited to providing overall statistics , attractive visualization of tracked data , or simple tailoring based on age , gender , and overall calorie or activity information . There are a lack of systems that can perform automated translation of behavioral data into specific actionable suggestions that promote healthier lifestyle without any human involvement . Objective MyBehavior , a mobile phone app , was design ed to process tracked physical activity and eating behavior data in order to provide personalized , actionable , low-effort suggestions that are context ualized to the user ’s environment and previous behavior . This study investigated the technical feasibility of implementing an automated feedback system , the impact of the suggestions on user physical activity and eating behavior , and user perceptions of the automatically generated suggestions . Methods MyBehavior was design ed to ( 1 ) use a combination of automatic and manual logging to track physical activity ( eg , walking , running , gym ) , user location , and food , ( 2 ) automatically analyze activity and food logs to identify frequent and nonfrequent behaviors , and ( 3 ) use a st and ard machine-learning , decision-making algorithm , called multi-armed b and it ( MAB ) , to generate personalized suggestions that ask users to either continue , avoid , or make small changes to existing behaviors to help users reach behavioral goals . We enrolled 17 participants , all motivated to self-monitor and improve their fitness , in a pilot study of MyBehavior . In a r and omized two-group trial , investigators r and omly assigned participants to receive either MyBehavior ’s personalized suggestions ( n=9 ) or nonpersonalized suggestions ( n=8 ) , created by professionals , from a mobile phone app over 3 weeks . Daily activity level and dietary intake was monitored from logged data . At the end of the study , an in-person survey was conducted that asked users to subjectively rate their intention to follow MyBehavior suggestions . Results In qualitative daily diary , interview , and survey data , users reported MyBehavior suggestions to be highly actionable and stated that they intended to follow the suggestions . MyBehavior users walked significantly more than the control group over the 3 weeks of the study ( P=.05 ) . Although some MyBehavior users chose lower-calorie foods , the between-group difference was not significant ( P=.15 ) . In a post study survey , users rated MyBehavior ’s personalized suggestions more positively than the nonpersonalized , generic suggestions created by professionals ( P<.001 ) . Conclusions MyBehavior is a simple-to-use mobile phone app with preliminary evidence of efficacy . To the best of our knowledge , MyBehavior represents the first attempt to create personalized , context ualized , actionable suggestions automatically from self-tracked information ( ie , manual food logging and automatic tracking of activity ) . Lessons learned about the difficulty of manual logging and usability concerns , as well as future directions , are discussed . Trial Registration Clinical Trials.gov NCT02359981 ; https:// clinical trials.gov/ct2/show/NCT02359981 ( Archived by WebCite at http://www.webcitation.org/6YCeoN8nv ) OBJECTIVE The purpose of this study was to develop and evaluate a 12-week weight management intervention involving computerized self-monitoring and technology-assisted feedback with and without an enhanced behavioral component . METHODS 120 overweight ( 30.5±2.6kg/m(2 ) ) adults ( 45.0±10.3 years ) were r and omized to one of three groups : computerized self-monitoring with Basic feedback ( n=45 ) , Enhanced behavioral feedback ( n=45 ) , or wait-list control ( n=30 ) . Intervention participants used a computer software program to record dietary and physical activity information . Weekly e-mail feedback was based on computer-generated reports , and participants attended monthly measurement visits . RESULTS The Basic and Enhanced groups experienced significant weight reduction ( -2.7±3.3 kg and -2.5±3.1 kg ) in comparison to the Control group ( 0.3±2.2 ; p<0.05 ) . Waist circumference and systolic blood pressure also decreased in intervention groups compared to Control ( p<0.01 ) . CONCLUSIONS A program using computerized self-monitoring , technology-assisted feedback , and monthly measurement visits produced significant weight loss after 12 weeks . However , the addition of an enhanced behavioral component did not improve the effectiveness of the program . PRACTICE IMPLICATION S This study suggests that healthcare professionals can effectively deliver a weight management intervention using technology-assisted strategies in a format that may complement and reduce face-to-face sessions Background Physical inactivity is a growing concern for society and is a risk factor for cardiovascular disease , obesity , and other chronic diseases . Objective This study aim ed to determine the efficacy of the Accupedo-Pro Pedometer mobile phone app intervention , with the goal of increasing daily step counts in young adults . Methods Mobile phone users ( n=58 ) between 17 - 26 years of age were r and omized to one of two conditions ( experimental and control ) . Both groups downloaded an app that recorded their daily step counts . Baseline data were recorded and followed-up at 5 weeks . Both groups were given a daily walking goal of 30 minutes , but the experimental group participants were told the equivalent goal in steps taken , via feedback from the app . The primary outcome was daily step count between baseline and follow-up . Results A significant time x group interaction effect was observed for daily step counts ( P=.04 ) . Both the experimental ( P<.001 ) and control group ( P=.03 ) demonstrated a significant increase in daily step counts , with the experimental group walking an additional 2000 steps per day . Conclusions The results of this study demonstrate that a mobile phone app can significantly increase physical activity in a young adult sample by setting specific goals , using self-monitoring , and feedback Background Mobile health ( mHealth ) interventions hold great promise for helping smokers quit since these programs can have wide reach and facilitate access to comprehensive , interactive , and adaptive treatment content . However , the feasibility , acceptability , and effectiveness of these programs remain largely untested . Objective To assess feasibility and acceptability of the My Mobile Advice Program ( MyMAP ) smoking cessation program and estimate its effects on smoking cessation and medication adherence to inform future research planning . Methods Sixty-six smokers ready to quit were recruited from a large regional health care system and r and omized to one of two mHealth programs : ( 1 ) st and ard self-help including psychoeducational material s and guidance how to quit smoking or ( 2 ) an adaptive and interactive program consisting of the same st and ard mHealth self-help content as controls received plus a ) real-time , adaptively tailored advice for managing nicotine withdrawal symptoms and medication side-effects and b ) asynchronous secure messaging with a cessation counselor . Participants in both arms were also prescribed a 12-week course of varenicline . Follow-up assessment s were conducted at 2 weeks post-target quit date ( TQD ) , 3 months post-TQD , and 5 months post-TQD . Indices of program feasibility and acceptability included acceptability ratings , utilization metrics including use of each MyMAP program component ( self-help content , secure messaging , and adaptively tailored advice ) , and open-ended feedback from participants . Smoking abstinence and medication adherence were also assessed to estimate effects on these treatment outcomes . Results Utilization data indicated the MyMAP program was actively used , with higher mean program log-ins by experimental than control participants ( 10.6 vs 2.7 , P<.001 ) . The majority of experimental respondents thought the MyMAP program could help other people quit smoking ( 22/24 , 92 % ) and consistently take their stop-smoking medication ( 17/22 , 97 % ) and would recommend the program to others ( 20/23 , 87 % ) . They also rated the program as convenient , responsive to their needs , and easy to use . Abstinence rates at 5-month follow-up were 36 % in the experimental arm versus 24 % among controls ( odds ratio 1.79 [ 0.61 - 5.19 ] , P=.42 ) . Experimental participants used their varenicline an average of 46 days versus 39 among controls ( P=.49 ) . More than two-thirds ( 22/33 , 67 % ) of experimental participants and three-quarters ( 25/33 , 76 % ) of controls prematurely discontinued their varenicline use ( P=.29 ) . Conclusions The MyMAP intervention was found to be feasible and acceptable . Since the study was not powered for statistical significance , no conclusions can be drawn about the program ’s effects on smoking abstinence or medication adherence , but the overall study results suggest further evaluation in a larger r and omized trial is warranted . Clinical Trial Clinical Trials.gov NCT02136498 ; https:// clinical trials.gov/ct2/show/NCT02136498 ( Archived by WebCite at http://www.webcitation.org/6jT3UMFLj BACKGROUND Physical inactivity is a major , potentially modifiable , risk factor for cardiovascular disease , cancer , and other chronic diseases . Effective , simple , and generalisable interventions that will increase physical activity in population s are needed . AIM To evaluate the effectiveness of a smartphone application ( app ) to increase physical activity in primary care . DESIGN AND SETTING An 8-week , open-label , r and omised controlled trial in rural , primary care in the west of Irel and . METHOD And roid smartphone users > 16 years of age were recruited . All participants were provided with similar physical activity goals and information on the benefits of exercise . The intervention group was provided with a smartphone app and detailed instructions on how to use it to achieve these goals . The primary outcome was change in physical activity , as measured by a daily step count between baseline and follow-up . RESULTS A total of 139 patients were referred by their primary care health professional or self-referred . In total , 37 ( 27 % ) were screened out and 12 ( 9 % ) declined to participate , leaving 90 ( 65 % ) patients who were r and omised . Of these , 78 provided baseline data ( intervention = 37 ; control = 41 ) and 77 provided outcome data ( intervention = 37 ; control = 40 ) . The mean daily step count at baseline for intervention and control groups was 4365 and 5138 steps per day respectively . After adjusting , there was evidence of a significant treatment effect ( P = 0.009 ) ; the difference in mean improvement in daily step count from week 1 to week 8 inclusive was 1029 ( 95 % confidence interval 214 to 1843 ) steps per day , favouring the intervention . Improvements in physical activity in the intervention group were sustained until the end of the trial . CONCLUSION A simple smartphone app significantly increased physical activity over 8 weeks in a primary care population BACKGROUND Text messaging has successfully supported smoking cessation . This study compares a mobile application with text messaging to support smoking cessation . MATERIAL S AND METHODS Young adult smokers 18 - 30 years old ( n = 102 ) participated in a r and omized pretest-posttest trial . Smokers received a smartphone application ( REQ-Mobile ) with short messages and interactive tools or a text messaging system ( onQ ) , managed by an expert system . Self-reported usability of REQ-Mobile and quitting behavior ( quit attempts , point-prevalence , 30-day point-prevalence , and continued abstinence ) were assessed in posttests . RESULTS Overall , 60 % of smokers used mobile services ( REQ-Mobile , 61 % , mean of 128.5 messages received ; onQ , 59 % , mean of 107.8 messages ) , and 75 % evaluated REQ-Mobile as user-friendly . A majority of smokers reported being abstinent at posttest ( 6 weeks , 53 % of completers ; 12 weeks , 66 % of completers [ 44 % of all cases ] ) . Also , 37 % ( 25%of all cases ) reported 30-day point-prevalence abstinence , and 32 % ( 22 % of all cases ) reported continuous abstinence at 12 weeks . OnQ produced more abstinence ( p<0.05 ) than REQ-Mobile . Use of both services predicted increased 30-day abstinence at 12 weeks ( used , 47 % ; not used , 20 % ; p = 0.03 ) . CONCLUSIONS REQ-Mobile was feasible for delivering cessation support but appeared to not move smokers to quit as quickly as text messaging . Text messaging may work better because it is simple , well known , and delivered to a primary inbox . These advantages may disappear as smokers become more experienced with new h and sets . Mobile phones may be promising delivery platforms for cessation services using either smartphone applications or text messaging Learning points R and omised controlled trials ( RCTs ) are the reference st and ard for study ing causal relationships between interventions and outcomes as r and omisation eliminates much of the bias inherent with other study design s. To provide a true , reliable assessment of effectiveness , RCTs need to be conducted robustly , i.e. with concealment of allocation , blinding , intention-to-treat analysis and sufficiently large sample size Obesity is partly driven by unhealthy food choices underpinned by cognitive biases , including approach bias ( a tendency to move towards food cues ) and delay discounting ( a preference for immediate rewards ) . Cognitive training strategies aim ed at modifying these biases , namely , approach-avoidance training ( AAT ) and episodic future thinking ( EFT ) , may improve food choice . This pilot r and omised trial examined the effect of these two trainings , delivered daily for 1 week via smartphone apps , on approach bias for healthy/unhealthy foods , delay discounting for money/food , and hypothetical food choice . Sixty overweight/obese participants ( 18 - 45 years ) were r and omly allocated to AAT , EFT , or control . Outcomes were measured at pretraining , posttraining , and 6-week follow-up . AAT reduced approach bias for unhealthy food and increased healthy food choice . However , EFT did not affect delay discounting or food choice . We conclude that AAT is useful for improving food choice in obesity and that smartphones are a feasible , engaging way to deliver training Many smartphone applications ( apps ) for mental health ( MHapps ) are available to the public . However , few have been the subject of a r and omized controlled trial ( RCT ) , and the change processes that are hypothesized to mediate cl aim ed effects have not been previously studied . This RCT compared the efficacy of three publicly available MHapps to a waitlist control condition in a community sample , in which no MHapp was provided . The three MHapps included cognitive behavioural therapy ( CBT ) toolkit app MoodKit , mood tracking app MoodPrism , and CBT strategy app MoodMission . Participants were r and omly allocated to each condition , completed a baseline assessment , downloaded their allocated MHapp , and completed a second assessment 30 days later , with n = 226 included in final analyses ( 81 % female ; M age = 34 years ) . Compared to the control condition , all MHapp groups experienced increases in mental wellbeing , MoodKit and MoodMission groups experienced decreases in depression , and no groups experienced effects on anxiety . Mediated regressions revealed that increasing coping self-efficacy , rather than emotional self-awareness or mental health literacy , was the underlying process contributing to effects on mental health for all three MHapps . MHapps appear to be an effective solution for improving public mental health , notably by improving users ' confidence in their ability to cope Background Mobile technologies have great potential to promote an active lifestyle in lower educated working young adults , an under research ed target group at a high risk of low activity levels . Objective The objective of our study was to examine the effect and process evaluation of the newly developed evidence - and theory-based smartphone app “ Active Coach ” on the objective ly measured total daily physical activity ; self-reported , context -specific physical activity ; and self-reported psychosocial variables among lower educated working young adults . Methods We recruited 130 lower educated working young adults in this 2-group cluster r and omized controlled trial and assessed outcomes at baseline , posttest ( baseline+9 weeks ) , and follow-up ( posttest+3 months ) . Intervention participants ( n=60 ) used the Active Coach app ( for 9 weeks ) combined with a Fitbit activity tracker . Personal goals , practical tips , and educational facts were provided to encourage physical activity . The control group received print-based generic physical activity information . Both groups wore accelerometers for objective measurement of physical activity , and individual interviews were conducted to assess the psychosocial variables and context -specific physical activity . Furthermore , intervention participants were asked process evaluation questions and generalized linear mixed models and descriptive statistics were applied . Results No significant intervention effects were found for objective ly measured physical activity , self-reported physical activity , and self-reported psychosocial variables ( all P>.05 ) . Intervention participants evaluated the Active Coach app and the combined use with the Fitbit wearable as self-explanatory ( 36/51 , 70.6 % ) , user friendly ( 40/51 , 78.4 % ) , and interesting ( 34/51 , 66.7 % ) . Throughout the intervention , we observed a decrease in the frequency of viewing graphical displays in the app ( P<.001 ) ; reading the tips , facts , and goals ( P<.05 ) ; and wearing the Fitbit wearable ( P<.001 ) . Few intervention participants found the tips and facts motivating ( 10/41 , 24.4 % ) , used them to be physically active ( 8/41 , 19.6 % ) , and thought they were tailored to their lifestyle ( 7/41 , 17.1 % ) . Conclusions The lack of significant intervention effects might be due to low continuous user engagement . Advice or feedback that was not perceived as adequately tailored and the difficulty to compete with many popular commercial apps on young people ’s smartphones may be responsible for a decrease in the engagement . A st and -alone app does not seem sufficient to promote an active lifestyle among lower educated working young adults ; therefore , multicomponent interventions ( using both technological and human support ) , as well as context -specific sensing to provide tailored advice , might be needed in this population . Trial Registration Clinical Trials.gov NCT02948803 ; https:// clinical trials.gov/ct2/show/ results /NCT02948803 ( Archived by WebCite at http://www.webcitation.org/71OPFwaoA Introduction Mobile phone messaging support and biomarker feedback independently show evidence of increasing an individual 's likelihood of quitting smoking . However , the combination of these two strategies to facilitate smoking cessation has not been adequately explored . Methods We conducted a r and omized controlled trial in Baltimore , Maryl and to assess the efficacy of COach2Quit , a smartphone application that provides exhaled carbon monoxide readings with message support . The primary outcome was self-reported and biochemically verified smoking cessation at 30-day follow-up . Secondary outcomes were smoking reduction , motivation to quit , use of , and satisfaction with COach2Quit . An intent to treat analysis was conducted . Results Adult smokers were r and omized 1:1 to receive brief advice and COach2Quit ( intervention , n=50 ) or brief advice only ( control , n=52 ) . Thirteen participants were lost to follow-up . At 30-day follow-up , one participant in each arm quit smoking . Median change in CO levels ( parts per million , ppm ) ( intervention : -3.0 IQR -12.0 , 2.0 ) ( control : -2.5 IQR -9.0 , 2.0 ) and median change in number of cigarettes smoked/day ( intervention : -5.5 IQR -14.0 , -1.0 ) ( control : -6.0 IQR -10.0 , -2.0 ) was similar between study arms . There was no significant difference in mean percent change in the reasons for quitting ( RFQ ) scale score ( intervention : 6.3 95 % CI -2.2 , 14.8 ) ( control : -3.6 95 % CI -9.2 , 2.1 ) . A majority ( n=32 , 91 % ) of participants liked having COach2Quit to help them quit smoking . Conclusions There were no significant differences in smoking cessation , smoking reduction and motivation to quit between study arms . However , high satisfaction with the COach2Quit application indicates its feasibility and acceptability as a smoking cessation tool . Implication s Smoking is the leading preventable cause of morbidity and mortality in the United States . Although counseling and pharmacotherapy are efficacious for smoking cessation , they are not easily accessible or desirable to all smokers , highlighting the need for identifying other interventions . There is evidence for the efficacy of mobile phone based messaging support for smoking cessation . However , there is limited research on the efficacy of biomarker feedback , much less interventions that combine these two approaches . This research contributes to filling this gap and identifying novel interventions to facilitate smoking cessation Background Digital mobile technology presents a promising medium for reaching young adults with smoking cessation interventions because they are the heaviest users of this technology . Objective The aim of this study was to determine the efficacy of an evidence -informed smartphone app for smoking cessation , Crush the Crave ( CTC ) , on reducing smoking prevalence among young adult smokers in comparison with an evidence -informed self-help guide , On the Road to Quitting ( OnRQ ) . Methods A parallel , double-blind , r and omized controlled trial with 2 arms was conducted in Canada to evaluate CTC . In total , 1599 young adult smokers ( aged 19 to 29 years ) intending to quit smoking in the next 30 days were recruited online and r and omized to receive CTC or the control condition OnRQ for a period of 6 months . The primary outcome measure was self-reported continuous abstinence at the 6-month follow-up . Results Overall follow-up rates were 57.41 % ( 918/1599 ) and 60.48 % ( 967/1599 ) at 3 and 6 months , respectively . Moreover , 45.34 % ( 725/1599 ) of participants completed baseline , 3- , and 6-month follow-up . Intention-to-treat analysis ( last observation carried forward ) showed that continuous abstinence ( N=1599 ) at 6 months was not significantly different at 7.8 % ( 64/820 ) for CTC versus 9.2 % ( 72/779 ) for OnRQ ( odds ratio ; OR 0.83 , 95 % CI 0.59 - 1.18 ) . Similarly , 30-day point prevalence abstinence at 6 months was not significantly different at 14.4 % ( 118/820 ) and 16.9 % ( 132/779 ) for CTC and OnRQ , respectively ( OR 0.82 , 95 % CI 0.63 - 1.08 ) . However , these rates of abstinence were favorable compared with unassisted 30-day quit rates of 11.5 % among young adults . Secondary measures of quit attempts and the number of cigarettes smoked per day at 6-month follow-up did not reveal any significant differences between groups . For those who completed the 6-month follow-up , 85.1 % ( 359/422 ) of young adult smokers downloaded CTC as compared with 81.8 % ( 346/423 ) of OnRQ , χ21(N=845)=1.6 , P=.23 . Furthermore , OnRQ participants reported significantly higher levels of overall satisfaction ( mean 3.3 [ SD 1.1 ] vs mean 2.6 [ SD 1.3 ] ; t644=6.87 , P<.001 ) , perceived helpfulness ( mean 5.8 [ SD 2.4 ] vs mean 4.3 [ SD 2.6 ] , t657=8.0 , P<.001 ) , and frequency of use ( mean 3.6 [ SD 1.2 ] vs mean 3.2 [ SD 1.1 ] , t683=5.7 , P<.001 ) compared with CTC participants . Conclusions CTC was feasible for delivering cessation support but was not superior to a self-help guide in helping motivated young adults to quit smoking . CTC will benefit from further formative research to address satisfaction and usage . As smartphone apps may not serve as useful alternatives to printed self-help guides , there is a need to conduct further research to underst and how digital mobile technology smoking cessation interventions for smoking cessation can be improved . Trial Registration Clinical Trials.gov NCT01983150 ; http:// clinical trials.gov/ct2/show/NCT01983150 ( Archived by WebCite at http://www.webcitation.org/6VGyc0W0i Objective We built an app to help clients of food pantries . The app offers vegetable-based recipes , food tips and no-cost strategies for making mealtimes healthier and for bargain-conscious grocery shopping , among other themes . Users customize material s to meet their own preferences . The app , available in English and Spanish , has been tested in a r and omized field trial . Design A r and omized controlled trial with repeated measures across 10 weeks . Setting Clients of fifteen community food pantry distributions in Los Angeles County , USA . Participants Distributions were r and omized to control and experimental conditions , and 289 household cooks and one of their 9–14-year-old children were enrolled as participants . Experimental dyads were given a smartphone with our app and a phone use-plan , then trained to use the app . ‘ Test vegetables ’ were added to the foods that both control and experimental participants received at their pantries . Results After 3–4 weeks of additional ‘ test vegetables ’ , cooks at experimental pantries had made 38 % more preparations with these items than control cooks ( P = 0·03 ) . Ten weeks following baseline , experimental pantries also scored greater gains in using a wider assortment of vegetables than control pantries ( P = 0·003 ) . Use of the app increased between mid-experiment and final measurement ( P = 0·0001 ) . Conclusions The app appears to encourage household cooks to try new preparation methods and widen their incorporation of vegetables into family diets . Further research is needed to identify specific app features that contributed most to outcomes and to test ways in which to disseminate the app widely Objective : To pilot test the effectiveness of “ MyNutriCart ” , a smartphone application ( app ) that generates healthy grocery lists , on diet and weight . Methods : A pilot r and omized trial was conducted to test the efficacy of using the “ MyNutriCart ” app compared to one face-to-face counseling session ( Traditional group ) in Hispanic overweight and obese adults . Household food purchasing behavior , three 24-h food recalls , Tucker ’s semi-quantitative food frequency question naire ( FFQ ) , and weight were assessed at baseline and after 8 weeks . Statistical analyses included t tests , a Poisson regression model , and analysis of covariance ( ANCOVA ) using STATA . Results : 24 participants in the Traditional group and 27 in the App group completed the study . Most participants were women ( > 88 % ) , with a mean age of 35.3 years , more than a high school education ( > 80 % ) , a family composition of at least three members , and a mean baseline body mass index ( BMI ) of 34.5 kg/m2 . There were significant improvements in household purchasing of vegetables and whole grains , in individual intakes of refined grains , healthy proteins , whole-fat dairies , legumes , 100 % fruit juices , and sweets and snacks ; and in the individual frequency of intake of fruits and cold cuts/cured meats within the intervention group ( p < 0.05 ) . However , no significant differences were found between groups . No changes were detected in weight . Conclusions : “ MyNutriCart ” app use led to significant improvements in food-related behaviors compared to baseline , with no significant differences when compared to the Traditional group . Cost and re source savings of using the app compared to face-to-face counseling may make it a good option for interventionists Background Previous evidence suggests that mindfulness training may improve aspects of psychosocial well-being . Whilst mindfulness is traditionally taught in person , consumers are increasingly turning to mindfulness-based smartphone apps as an alternative delivery medium for training . Despite this growing trend , few studies have explored whether mindfulness delivered via a smartphone app can enhance psychosocial well-being within the general public . Methods The present pilot r and omised controlled trial compared the impact of engaging with the self-guided mindfulness meditation ( MM ) app ‘ Headspace ’ ( n = 38 ) for a period of 10 or 30 days , to a wait-list ( WL ) control ( n = 36 ) , using a cohort of adults from the general population . The Satisfaction with Life Scale , Perceived Stress Scale , and Wagnild Resilience Scale were administered online at baseline and after 10 and 30 days of the intervention . Results Twelve participants ( MM n = 9 , WL n = 3 ) were lost to follow-up for unknown reasons . Relative to the WL control , the MM app positively impacted self-reported satisfaction with life , stress , and resilience at day 10 , with further improvements emerging at day 30 ( Cohen ’s d = 0.57 , 1.42 , 0.63 respectively ) . The rate of improvement was largest at the 10-day assessment point , dropping moderately by day 30 . Participants that rated the MM app as easy to engage with experienced the largest self-reported benefits . Moreover , the MM app was able to protect against an unexpected increase in perceived stress that emerged in the control group . Conclusions This pilot r and omised controlled trial shows that self-reported improvements in psychosocial outcomes can be achieved at low cost through short-term engagement with a mindfulness-based smartphone app , and should be followed up with more substantive studies . Trial registration IS RCT N IS RCT N34618894 Background Emotion dysregulation increases the risk of depression , anxiety , and substance use disorders . Music can help regulate emotions , and mobile phones provide constant access to it . The Music eScape mobile app teaches young people how to identify and manage emotions using music . Objective This study aim ed to examine the effects of using Music eScape on emotion regulation , distress , and well-being at 1 , 2 , 3 , and 6 months . Moderators of outcomes and user ratings of app quality were also examined . Methods A r and omized controlled trial compared immediate versus 1-month delayed access to Music eScape in 169 young people ( aged 16 to 25 years ) with at least mild levels of mental distress ( Kessler 10 score>17 ) . Results No significant differences between immediate and delayed groups on emotion regulation , distress , or well-being were found at 1 month . Both groups achieved significant improvements in 5 of the 6 emotion regulation skills , mental distress , and well-being at 2 , 3 , and 6 months . Unhealthy music use moderated improvements on 3 emotion regulation skills . Users gave the app a high mean quality rating ( mean 3.8 [ SD 0.6 ] ) out of 5 . Conclusions Music eScape has the potential to provide a highly accessible way of improving young people ’s emotion regulation skills , but further testing is required to determine its efficacy . Targeting unhealthy music use in distressed young people may improve their emotion regulation skills . Trial Registration Australian New Zeal and Clinical Trials Registry ACTRN12615000051549 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review BACKGROUND There is limited evidence of the efficacy of smartphone applications to reduce unhealthy alcohol use . We tested the efficacy of providing access to a smartphone-based brief intervention for unhealthy alcohol use . METHODS We conducted a two parallel-group r and omized controlled trial with follow-up at 6 months , among 977 individuals with an Alcohol Use Disorder Identification Test ≥8 and drinking 15 or more drinks/week . Participants were r and omized to receive ( or not ) access to a smartphone application consisting of personalized feedback , risk assessment and self-monitoring . The primary outcome was the mean number of drinks/week . An intention to treat analysis ( ITT ) and a per protocol analysis ( PP ) were conducted . RESULTS Mean age of participants was 34.2(9.8 ) , 46 % were female . The baseline mean number of drinks per week was 28.9(16.7 ) . Results differed by type of analysis : ITT : all 977 participants were included in the analysis . Follow-up rate was 70.7 % ( n = 691 ) . There was no significant intervention effect : the Incidence Rate Ratio ( IRR ) ( 95%CI ) for number of drinks per week was 0.93(0.84 ; 1.03 ) . PP : 702 participants were included in the analysis . Follow-up rate was 78.1 % ( n = 548 ) . There was a significant intervention effect : the IRR for number of drinks per week was 0.88(0.78 ; 0.99 ) . CONCLUSIONS Providing access to a smartphone-based brief intervention had no impact on drinking at 6 months and does not appear to be an effective intervention in reducing drinking . Those who downloaded the app appear to benefit from it , nevertheless downloads were limited and further development of similar apps should focus on increasing use Background : Smartphone applications ( apps ) are popular aids for smoking cessation . Smoke Free is an app that delivers behaviour change techniques used in effective face-to-face behavioural support programmes . The aim of this study was to assess whether the full version of Smoke Free is more effective than the reduced version . Methods : This was a two-arm exploratory r and omised controlled trial . Smokers who downloaded Smoke Free were r and omly offered the full or reduced version ; 28,112 smokers aged 18 + years who set a quit date were included . The full version provided up date s on benefits of abstinence , progress ( days smoke free ) , virtual ‘ badges ’ and daily ‘ missions ’ with push notifications aim ed at preventing and managing cravings . The reduced version did not include the missions . At baseline the app recorded users ’ : device type ( iPhone or And roid ) , age , sex , daily cigarette consumption , time to first cigarette of the day , and educational level . The primary outcome was self-reported complete abstinence from the quit date in a 3-month follow-up question naire delivered via the app . Analyses conducted included logistic regressions of outcome on to app version ( full versus reduced ) with adjustment for baseline variables using both intention-to-treat/missing-equals smoking ( MES ) and follow-up-only ( FUO ) analyses . Results : The 3-month follow-up rate was 8.5 % ( n=1,213 ) for the intervention and 6.5 % ( n=901 ) for the control . A total of 234 participants reported not smoking in the intervention versus 124 in the control , representing 1.6 % versus 0.9 % in the MES analysis and 19.3 % versus 13.8 % in the FUO analysis . Adjusted odds ratios were 1.90 , 95%CI=1.53 - 2.37 ( p<0.001 ) and 1.50 , 95%CI=1.18 - 1.91 ( p<0.001 ) in the MES and FUO analyses respectively . Conclusions : Despite very low follow-up rates using in-app follow up , both intention-to-treat/missing equals smoking and follow-up only analyses showed the full version of the Smoke Free app to result in higher self-reported 3-month continuous smoking abstinence rates than the reduced version BACKGROUND AND OBJECTIVE The last few years have seen the appearance many mobile applications aim ed at improving health , but studies analyzing their effectiveness on cardiovascular risk factors ( CVRFs ) are few and far between . Our aim was to assess the effect on CVRFs such as hypertension , dyslipidemia , diabetes and global CVR , of adding the use of a smartphone app to an intervention consisting of st and ard counseling on physical activity and the Mediterranean diet . METHOD This is a multicenter , r and omized and controlled clinical trial . From January 2014 and September 2016 , a total of 833 subjects selected by r and om sampling from six health centers participated . Of these , 415 were assigned to the counseling + app group ( IG ) and 418 to the counseling only group ( CG ) . The IG additionally received training in the use of a mobile application . The main outcome was the change in CVRFs and estimated CVR at 3 and 12 months in the IG compared to the CG . RESULTS No significant changes were observed at 3 or 12 months in terms of CVR . Nevertheless , an effect between groups was observed in favor of the CG at 12 months in some CVRFS : SBP , DBP , total cholesterol and triglycerides : 2.02 mmHg ( 95%CI : 0.43 - 3.61 ) , 1.21 mmHg ( 95%CI : 0.20 - 2.24 ) , 5.24 mg/dl ( 95%CI : 1.22 - 9.26 ) and 7.24 mg/dl ( 95%CI : 0.53 - 14.32 ) . CONCLUSION Adding an intervention with the use of an app for three months to st and ard counseling on diet and physical activity , does not provide additional benefits for improving CVRFs or the estimated CVR in the long term . TRIAL REGISTRATION NUMBER Clinical Trials.gov NCT02016014 Background ImpulsePal is a theory-driven ( dual-process ) , evidence -informed , and person-centered smartphone app intervention design ed to help people manage impulsive processes that prompt unhealthy eating to facilitate dietary change and weight loss . Objective The aims of this study were to ( 1 ) assess the feasibility of trial procedures for evaluation of the ImpulsePal intervention , ( 2 ) estimate st and ard deviations of outcomes , and ( 3 ) assess usability of , and satisfaction with , ImpulsePal . Methods We conducted an individually r and omized parallel two-arm nonblinded feasibility trial . The eligibility criteria included being aged ≥16 years , having a body mass index of ≥25 kg/m2 , and having access to an And roid-based device . Weight was measured ( as the proposed primary outcome for a full-scale trial ) at baseline , 1 month , and 3 months of follow-up . Participants were r and omized in a 2:1 allocation ratio to the ImpulsePal intervention or a waiting list control group . A nested action- research study allowed for data -driven refinement of the intervention across 2 cycles of feedback . Results We screened 179 participants for eligibility , and 58 were r and omized to the intervention group and 30 to the control group . Data were available for 74 ( 84 % , 74/88 ) participants at 1 month and 67 ( 76 % , 67/88 ) participants at 3 months . The intervention group ( n=43 ) lost 1.03 kg ( 95 % CI 0.33 to 1.74 ) more than controls ( n=26 ) at 1 month and 1.01 kg ( 95 % CI −0.45 to 2.47 ) more than controls ( n=43 and n=24 , respectively ) at 3 months . Feedback suggested changes to intervention design were required to ( 1 ) improve receipt and underst and ing of instructions and ( 2 ) facilitate further engagement with the app and its strategies . Conclusions The evaluation methods and delivery of the ImpulsePal app intervention are feasible , and the trial procedures , measures , and intervention are acceptable and satisfactory to the participants . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 14886370 ; http://www.is rct n.com/IS RCT N14886370 ( Archived by WebCite at http://www.webcitation.org/76WcEpZ51 Background Mobile health ( mHealth ) apps have the potential to increase smoking cessation , but little research has been conducted with Aboriginal communities in Australia . Objective We conducted a pilot study to assess the feasibility and acceptability and explore the effectiveness of a novel mHealth app to assist Aboriginal people to quit smoking . Methods A pilot r and omized controlled trial ( RCT ) and process evaluation comprising usage analytics data and in-depth interviews was conducted . Current Aboriginal smokers ( > 16 years old ) , who were willing to make a quit attempt in the next month , were recruited from Aboriginal Community Controlled Health Services and a government telephone coaching service . The intervention was a multifaceted And roid or iOS app comprising a personalized profile and quit plan , text and in-app motivational messages , and a challenge feature allowing users to compete with others . The comparator was usual cessation support services . Outcome data collection and analysis were conducted blinded to treatment allocation . The primary outcome was self-reported continuous smoking abstinence verified by carbon monoxide breath testing at 6 months . Secondary outcomes included point prevalence of abstinence and use of smoking cessation therapies and services . Results A total of 49 participants were recruited . Competing service delivery priorities , the lack of re sources for research , and lack of support for r and omization to a control group were the major recruitment barriers . At baseline , 23/49 ( 47 % ) of participants had tried to quit in recent weeks . At 6-month follow-up , only 1 participant ( intervention arm ) was abstinent . The process evaluation highlighted low to moderate app usage ( 3 - 10 new users per month and 4 - 8 returning users per month ) , an average of 2.9 sessions per user per month and 6.3 min per session . Key themes from interviews with intervention participants ( n=15 ) included the following : ( 1 ) the powerful influence of prevailing social norms around acceptability of smoking ; ( 2 ) high usage of mobile devices for phone , text , and social media but very low use of other smartphone apps ; ( 3 ) the role of family and social group support in supporting quit attempts ; and ( 4 ) low awareness and utilization of smoking cessation support services . Despite the broad acceptability of the app , participants also recommended technical improvements to improve functionality , greater customization of text messages , integration with existing social media platforms , and gamification features . Conclusions Smoking cessation apps need to be integrated with commonly used functions of mobile phones and draw on social networks to support their use . Although they have the potential to increase utilization of cessation support services and treatments , more research is needed to identify optimal implementation models . Robust evaluation is critical to determine their impact ; however , an RCT design may not be feasible in this setting . Trial Registration Australian and New Zeal and Clinical Trials Registry ACTRN12616001550493 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=371792 ( Archived by WebCite at http://www.webcitation.org/76TiV7HA6 ) Background The Ten Top Tips ( 10TT ) is an intervention based on the habit formation theory that promotes a set of weight management behaviors alongside advice about repetition in a consistent context . Overall , 3 studies have demonstrated that the 10TT can support individuals to lose weight when delivered in a leaflet format . Delivery of 10TT via new technology such as a mobile app could potentially improve its effectiveness and make it more convenient , appealing , and wide reaching . Objective This study aim ed to provide preliminary indications of the usage , effectiveness , and acceptability of an And roid app of the 10TT intervention ( Top Tips only app ) and a second version including self-regulatory strategies for dealing with tempting foods ( Top Tips plus app ) . Methods The 3-month pilot r and omized adults with overweight or obesity to ( 1 ) Top Tips only app , ( 2 ) Top Tips plus app , or ( 3 ) waiting list condition . Automated data from app users were collected . Vali date d question naires assessed self-regulatory skills , weight loss ( kg ) , and behaviors at baseline and 3 months . Users ’ feedback on their experience using the app was assessed using open questions . Results A total of 81 participants took part in the pilot ; 28 participants were r and omized to the Top Tips only app , 27 to the Top Tips plus app , and 26 to the waiting list condition . On average , participants viewed a mean of 43.4 ( SD 66.9 ) screens during a mean of 24.5 ( SD 44.07 ) log-ins and used the app for 124.2 ( SD 240.2 ) min over the 3-month period . Participants r and omized to the Top Tips only app reported the greatest improvement in self-regulatory skills ( mean 0.59 , SD 1.0 ) , weight loss ( mean 4.5 kg , SD 5.2 ) , and adherence to the target behaviors ( mean 0.59 , SD 0.49 ) compared with the Top Tips plus ( meanself-regulation 0.15 , SD 0.42 ; meanweight −1.9 , SD 3.9 ; and meanbehaviors 0.29 , SD 0.29 ) and waiting list condition ( meanself-regulation −0.02 , SD 0.29 ; meanweight −0.01 , SD 0.51 ; and meanbehaviors 0.08 , SD 0.38 ) . Participants who reported the largest improvements , on average , viewed pages 2 to 3 times more , had 2 to 3 times more log-ins , logged their weight 2 to 3 times more , and achieved the tips more than those who reported smaller changes in these outcomes . According to users ’ feedback , engagement with the app could be increased by making the app more interactive and allowing more tailoring . Conclusions This study suggests that the Top Tips app could potentially be a useful intervention for promoting eating self-regulatory skills , weight loss , and weight management behaviors among adults with overweight or obesity . Future research should develop the app further based on user feedback and test it in larger sample sizes . Trial Registration IS RCT N Registry IS RCT N10470937 ; http://www.is rct n.com/IS RCT N10470937 ( Archived by Webcite at http://www.webcitation.org/76j6rQibI Background Laboratory studies suggest that eating more ‘ attentively ’ ( e.g. attending to food being eaten and recalling eating episodes ) can reduce food intake among participants with both healthy weight and overweight . The aim of this trial was to assess whether a smartphone application that encourages a more attentive eating style reduces energy intake and promotes weight loss . Methods In an open-label , single centre , parallel groups , individually r and omised controlled trial , 107 adults with overweight/obesity in Merseyside , UK used an attentive eating smartphone application along with st and ard dietary advice ( intervention group ) or st and ard dietary advice only ( control group ) for 8 weeks . The primary outcomes were change in body weight at 8 weeks and energy intake at 4 and 8 weeks . Additional outcomes included self-reported eating behaviours measured at 8 weeks . Differences between groups were assessed with linear regression ( adjusted ) using multiple imputation for missing data . Study protocol registered prospect ively at ( https://doi.org/10.17605/osf.io/btzhw ) . Results There was no significant difference between the intervention and control group in weight lost at 8 weeks , or change in self-reported 24 h or objective taste-test energy intake at 4 or 8 weeks . Mean weight loss in the intervention group ( n = 53 ) was 1.2 kg and 1.1 kg in the control group ( n = 54 ) , adjusted difference of − 0.10 ( − 1.6 to 1.3 ) kg . Self-reported eating behaviours at 8 weeks also did not differ across groups . The intervention was largely used as intended and a per protocol analysis confined to participants in the intervention group that used the attentive eating smartphone application regularly and as intended also showed no effect on energy intake or weight loss . Conclusions A smartphone based attentive eating intervention and st and ard dietary advice did not result in reduced energy intake or greater weight loss at 4 or 8 week follow-up than st and ard dietary advice alone . Trial registration Clinical Trials.gov , NCT03602001 . Registered retrospectively on 26th July 2018 . Prospect ively registered on the Open Science Framework on 11th August 2017 BACKGROUND Dietary self-monitoring ( DSM ) of foods and beverages is associated with weight loss in behavioral interventions ; however , DSM may be burdensome , and adherence may decrease over time . Novel methods of DSM , including apps that track food using photographs , may decrease burden , increase DSM adherence , and improve weight loss . OBJECTIVE The objective was to test a mobile photo DSM app compared to a calorie-tracking DSM app on tracking frequency and weight loss in a remotely delivered behavioral weight-loss intervention . DESIGN This was a 6-month ( October 2016 to April 2017 ) r and omized trial . PARTICIPANTS / SETTING Participants were adults ( n=41 ) classified as overweight or obese ( body mass index 25 to 49.9 ) from South Carolina . INTERVENTION Participants received remotely delivered twice-weekly behavioral weight-loss podcasts and tracked diet using a calorie-tracking DSM app ( Calorie Group ) or a photo DSM app ( Photo Group ) . MAIN OUTCOME MEASURES Main outcomes were the number of days diet was tracked , podcasts downloaded , and weight change at 6 weeks and 6 months . STATISTICAL ANALYSES Research ers used nonparametric Wilcoxon rank sum tests and χ2 analysis to test for differences between groups at baseline ; repeated- measures models to estimate weight change and Spearman correlations to determine relationships between DSM frequency , podcasts downloaded , and weight change at 6 months . RESULTS There were no differences between groups for the number of days that diet was recorded ( P=0.18 ) , which was low overall ( < 30 % of days ) but was statistically significantly and strongly correlated with weight change for all participants pooled ( r=0.63 ; P<0.001 ) and for the calorie tracking group ( r=0.70 ; P=0.004 ) , but not the photo tracking group ( r=0.51 ; P=0.06 ) . Participants in both groups had significant weight loss at 6 months ( Photo Group , -2.5±0.9 kg ; P=0.008 ; Calorie Group -2.4±0.9 kg ; P=0.007 ) , with no differences between groups at either 6 weeks ( P=0.66 ) or at 6 months ( P=0.74 ) . CONCLUSIONS As part of a remotely delivered weight loss intervention , frequency of DSM was significantly associated with overall weight loss for participants using a calorie DSM app but not a photo DSM app . DSM was low regardless of group and weight loss was significant , although minimal . Increasing user engagement with any DSM may be important to increase self-monitoring and improve weight loss Background College students experience high levels of stress . Mindfulness meditation delivered via a mobile app may be an appealing , efficacious way to reduce stress in college students . Objective We aim ed to test the initial efficacy and sustained effects of an 8-week mindfulness meditation mobile app — Calm — compared to a wait-list control on stress , mindfulness , and self-compassion in college students with elevated stress . We also explored the intervention ’s effect on health behaviors ( ie , sleep disturbance , alcohol consumption [ binge drinking ] , physical activity , and healthy eating [ fruit and vegetable consumption ] ) and the feasibility and acceptability of the app . Methods This study was a r and omized , wait-list , control trial with assessment s at baseline , postintervention ( 8 weeks ) , and at follow-up ( 12 weeks ) . Participants were eligible if they were current full-time undergraduate students and ( 1 ) at least 18 years of age , ( 2 ) scored ≥14 points on the Perceived Stress Scale , ( 3 ) owned a smartphone , ( 4 ) were willing to download the Calm app , ( 5 ) were willing to be r and omized , and ( 7 ) were able to read and underst and English . Participants were asked to meditate using Calm at least 10 minutes per day . A P value ≤.05 was considered statistically significant . Results A total of 88 participants were included in the analysis . The mean age ( SD ) was 20.41 ( 2.31 ) years for the intervention group and 21.85 ( 6.3 ) years for the control group . There were significant differences in all outcomes ( stress , mindfulness , and self-compassion ) between the intervention and control groups after adjustment for covariates postintervention ( all P<.04 ) . These effects persisted at follow-up ( all P<.03 ) , except for the nonreacting subscale of mindfulness ( P=.08 ) . There was a significant interaction between group and time factors in perceived stress ( P=.002 ) , mindfulness ( P<.001 ) , and self-compassion ( P<.001 ) . Bonferroni posthoc tests showed significant within-group mean differences for perceived stress in the intervention group ( P<.001 ) , while there were no significant within-group mean differences in the control group ( all P>.19 ) . Similar results were found for mindfulness and self-compassion . Effect sizes ranged from moderate ( 0.59 ) to large ( 1.24 ) across all outcomes . A significant group × time interaction in models of sleep disturbance was found , but no significant effects were found for other health behaviors . The majority of students in the intervention group reported that Calm was helpful to reduce stress and stated they would use Calm in the future . The majority were satisfied using Calm and likely to recommend it to other college students . The intervention group participated in meditation for an average of 38 minutes/week during the intervention and 20 minutes/week during follow-up . Conclusions Calm is an effective modality to deliver mindfulness meditation in order to reduce stress and improve mindfulness and self-compassion in stressed college students . Our findings provide important information that can be applied to the design of future studies or mental health re sources in university programs . Trial Registration Clinical Trials.gov NCT03891810 ; https:// clinical Background Few people successfully maintain lost weight over the longer term . Mobile phones have the potential to deliver weight loss management programs that can encourage self-monitoring while also providing some behavioral therapy to assist users in developing personal skills that may be necessary for improved longer term weight loss maintenance . Objective The aim of this study was to evaluate a program supporting weight maintenance , which uses a behaviorally based mobile phone app to manage weight , food , exercise , mood , and stress . Methods In a r and omized controlled trial over 24 weeks , the full version of the app ( MotiMate ) was compared with a control app ( monitoring only ; excluding mood and stress ) for its effect on weight , diet , and psychological well-being . Both apps had the same visual appearance and were design ed to deliver all intervention content without face-to-face contact . The control version included features to track weight , food intake , and exercise with limited feedback and no encouraging/persuasive features . The intervention app included more persuasive and interactive features to help users track their weight , food intake , and physical activity and prompted users to enter data each day through notifications and included a mood and stress workshopping tool . Participants were recruited through advertising and existing data bases . Clinic visits occurred at baseline , 4 weeks , 8 weeks , 12 weeks , and 24 weeks . At all visits , the clinical trial manager recorded body weight , and participants then completed a computer-delivered survey , which measured psychological and lifestyle outcomes . Objective app usage data were recorded throughout the trial . Results A total of 88 adults who had lost and maintained at least 5 % of their body weight within the last 2 years were r and omized ( 45 MotiMate and 43 control ) . Overall , 75 % ( 66/88 ) were female , and 69 % ( 61/88 ) completed week 24 with no differences in dropout by condition ( χ21,87=0.7 , P=.49 ) . Mixed models suggested no significant changes in weight or psychological outcomes over 24 weeks regardless of condition . Of 61 completers , 53 % ( 32/61 ) remained within 2 % of their starting weight . Significant increases occurred over 24 weeks for satisfaction with life and weight loss self-efficacy regardless of app condition . Diet and physical activity behaviors did not vary by app or week . Negative binomial models indicated that those receiving the full app remained active users of the app for 46 days longer than controls ( P=.02 ) . Users of the full version of the app also reported that they felt more supported than those with the control app ( P=.01 ) . Conclusions Although some aspects of the intervention app such as usage and user feedback showed promise , there were few observable effects on behavioral and psychological outcomes . Future evaluation of the app should implement alternative research methods or target more specific population s to better underst and the utility of the coping interface . Trial Registration Australia New Zeal and Clinical Trials Registry ACTRN12614000474651 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review Background SaltSwitch is an innovative smartphone application ( app ) that enables shoppers to scan the barcode of a packaged food and receive an immediate , interpretive , traffic light nutrition label on the screen , along with suggestions for lower salt alternatives . Our aim was to determine the effectiveness of SaltSwitch to support people with cardiovascular disease to make lower salt food choices . Design Six-week , two-arm , parallel , r and omised controlled trial in Auckl and , New Zeal and ( 2 weeks baseline and 4 weeks intervention ) . Methods Sixty-six adults with diagnosed cardiovascular disease ( mean ( SD ) age 64 ( 7 ) years ) were r and omly assigned in a 1:1 ratio to either the SaltSwitch smartphone app or control ( usual care ) . The primary outcome was the salt content of household packaged food purchases during the 4-week intervention ( g/MJ ) . Secondary outcomes were the saturated fat content ( g/MJ ) , energy content ( kJ/kg ) and expenditure ( NZ$ ) of household food purchases ; systolic blood pressure ( mmHg ) , urinary sodium ( mg ) and use and acceptability of the SaltSwitch app . Results Thirty-three participants with cardiovascular disease were allocated to the SaltSwitch intervention , and 33 to the control group . A significant reduction in mean household purchases of salt was observed ( mean difference ( 95 % confidence interval ) , −0.30 ( −0.58 to −0.03 ) g/MJ ) , equating to a reduction of ∼0.7 g of salt per person per day during the 4-week intervention phase . There were no significant between-group differences in any secondary outcomes ( all P > 0.05 ) . Conclusions The SaltSwitch smartphone app is effective in supporting people with cardiovascular disease to make lower salt food purchases . A larger trial with longer follow-up is warranted to determine the effects on blood pressure . Trial registration Australian New Zeal and Clinical Trials Registry https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?id=365784&is Review = true |
13,234 | 28,356,114 | Conclusions We concluded that multi-drug regimens have a better effect on prolonging the PFS and OS of osteosarcoma patients , and the T12 protocol has a better effect on prolonging the PFS of osteosarcoma patients , particularly in combination with ifosfamide or vincristine .
The OS analysis showed that the T12 protocol plus vincristine or the T12 protocol with the removal of cisplatinum might be a better regimen for improving the OS of patients . | Background Osteosarcoma is the most common malignant bone tumour .
Due to the high metastasis rate and drug resistance of this disease , multi-drug regimens are necessary to control tumour cells at various stages of the cell cycle , eliminate local or distant micrometastases , and reduce the emergence of drug-resistant cells .
Many adjuvant chemotherapy protocol s have shown different efficacies and controversial results .
Therefore , we classified the types of drugs used for adjuvant chemotherapy and evaluated the differences between single- and multi-drug chemotherapy regimens using network meta- analysis . | Background . Osteosarcoma is a highly malignant bone tumour . After the second relapse , the 12-month postrelapse disease-free survival ( PRDFS ) rate decreases below 20 % . Oral Etoposide is often used in clinical practice after surgery as an “ adjuvant ” outside any protocol and with only limited evidence of improved survival . Viscum album fermentatum Pini ( Viscum ) is an extract of mistletoe plants grown on pine trees for subcutaneous ( sc ) injection with immunomodulatory activity . Methods . Encouraged by preliminary findings , we conducted a study where osteosarcoma patients free from disease after second metastatic relapse were r and omly assigned to Viscum sc or Oral Etoposide . Our goal was to compare 12-month PRDFS rates with an equivalent historical control group . Results . Twenty patients have been enrolled , with a median age of 34 years ( range 11–65 ) and a median follow-up time of 38.5 months ( 3–73 ) . The median PRDSF is currently 4 months ( 1–47 ) in the Etoposide and 39 months ( 2–73 ) in the Viscum group . Patients getting Viscum reported a higher quality of life due to lower toxicity . Conclusion . Viscum shows promise as adjuvant treatment in prolonging PRDFS after second relapse in osteosarcoma patients . A larger study is required to conclusively determine efficacy and immunomodulatory mechanisms of Viscum therapy in osteosarcoma patients Two hundred and thirty five patients with osteosarcoma , aged less than 40 years , and treated by amputation or radiotherapy , were entered in a r and omised trial of two forms of adjuvant chemotherapy . A two drug regimen , namely vincristine 2 mg m-2 ( maximum 2 mg ) followed by methotrexate 200 mgm-2 , given every three weeks , was compared with a three drug regimen , comprising the same vincristine-methotrexate treatment , alternating every three weeks with doxorubicin 60 mg m-2 . Both regimens were continued for 54 weeks . Forty-one patients were excluded , most because of inadequate histology , leaving 194 patients for analysis . One hundred and seventy of these had immediate amputation , 14 were treated by a policy of radiotherapy , with surgery delayed for 9 months , provided no distant metastases had appeared , and 10 by a policy of radiotherapy only . Patients have been followed-up for between 26 and 94 months after entry to the trial . The 2- and 5-year survival rates were 48 % and 27 % . No significant difference in survival was observed between the two regimens , but toxicity was less with the two drug regimen BACKGROUND Based on pre clinical data for the antitumour effect of zoledronate in osteosarcoma , we assessed whether zoledronate combined with chemotherapy and surgery improved event-free survival in children and adults with osteosarcoma . METHODS In this r and omised , multicentre , open-label , phase 3 trial ( OS2006 ) , patients aged between 5 years and 50 years with newly diagnosed high- grade osteosarcoma were r and omly assigned to receive st and ard chemotherapy with or without ten zoledronate intravenous infusions ( four preoperative and six postoperative ) . Adults older than 25 years received 4 mg zoledronate per infusion , patients aged 18 - 25 years received 0·05 mg/kg for the first two infusions and 4 mg for the remaining eight infusions , and younger patients received 0·05 mg/kg per infusion . Chemotherapy comprised high-dose methotrexate based chemotherapy in patients younger than 18 years , and doxorubicin , ifosfamide , and cisplatin in adults older than 25 years ; patients aged 18 - 25 years were treated with either regime at the discretion of the treating centre . Balanced r and omisation between the two groups was done central ly with online r and omisation software , based on a minimisation algorithm taking into account centre , age , combined with chemotherapy regimen , and risk group ( resectable primary and no metastasis vs other ) . Patients and investigators were not masked to treatment assignment , but the endpoint adjudication committee members who review ed suspected early progressions were masked to group allocation . The primary endpoint was event-free survival , estimated from the r and omisation to the time of first failure ( local or distant relapse , progression , death ) or to the last follow-up visit for the patients in first complete remission , analysed on a modified intention-to-treat population , which excluded patients found not to have a malignant tumour after central review . Three interim analyses were planned . This trial is registered with Clinical Trials.gov , number NCT00470223 . FINDINGS Between April 23 , 2007 , and March 11 , 2014 , 318 patients , median age 15·5 years ( range 5·8 - 50·9 ) , were enrolled from 40 French centres ; of whom 158 were assigned to the control group ( chemotherapy alone ) and 160 to the zoledronate group , including 55 ( 17 % ) patients with definite metastases . The trial was stopped for futility after the second interim analysis . With a median follow-up of 3·9 years ( IQR 2·7 - 5·1 ) , 125 events occurred ( 55 in the control group and 70 in the with zoledronate group ) . Event-free survival at 3 years for all 315 r and omly assigned patients was 60·3 % ( 95 % CI 64·5 - 65·9 ) ; 3-year event-free survival was 63·4 % ( 55·2 - 70·9 ) for the control group and 57·1 % ( 48·8 - 65·0 ) for the zoledronate group . The risk of failure was not reduced and was even marginally higher in the zoledronate group than in the control group ( hazard ratio [ HR ] 1·36 [ 95 % CI 0·95 - 1·96 ] ; p=0·094 ) . No major increase in severe toxic effects of grade 3 or higher associated with zoledronate , barring expected hypocalcaemia ( 45 [ 29 % ] of 153 participants in the zoledronate group vs ten [ 6 % ] of 155 participants in the control group ; p<0·0001 ) and hypophosphataemia ( 61 [ 40 % ] of 151 in the zoledronate group vs 26 [ 17 % ] of 156 in the control group ; p<0·0001 ) . No significant difference in orthopaedic complications was noted between the two groups ( 27 in the control group and 29 in the zoledronate group ) . Two treatment-related deaths were reported ( one from cardiomyopathy in the control group and one from multiorgan failure in the zoledronate group before the first zoledronate infusion ) . INTERPRETATION From the results observed in this study , we do not recommend zoledronate in osteosarcoma patients . Further biological studies are required to underst and the discordance between the results of OS2006 trial and pre clinical data . FUNDING French National Cancer Institute ( INCa ) , Novartis , Chugai , Ligue Nationale contre le Cancer , Fédération Enfants et Santé , Société Française des Cancers et Leucémies de l'Enfant Summary Background We design ed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy ( ≥10 % viable tumour ) improved event-free survival in patients with high- grade osteosarcoma . Methods EURAMOS-1 was an open-label , international , phase 3 r and omised , controlled trial . Consenting patients with newly diagnosed , resectable , high- grade osteosarcoma aged 40 years or younger were eligible for r and omisation . Patients were r and omly assigned ( 1:1 ) to receive either postoperative cisplatin , doxorubicin , and methotrexate ( MAP ) or MAP plus ifosfamide and etoposide ( MAPIE ) using concealed permuted blocks with three stratification factors : trial group ; location of tumour ( proximal femur or proximal humerus vs other limb vs axial skeleton ) ; and presence of metastases ( no vs yes or possible ) . The MAP regimen consisted of cisplatin 120 mg/m2 , doxorubicin 37·5 mg/m2 per day on days 1 and 2 ( on weeks 1 and 6 ) followed 3 weeks later by high-dose methotrexate 12 g/m2 over 4 h. The MAPIE regimen consisted of MAP as a base regimen , with the addition of high-dose ifosfamide ( 14 g/m2 ) at 2·8 g/m2 per day with equidose mesna uroprotection , followed by etoposide 100 mg/m2 per day over 1 h on days 1–5 . The primary outcome measure was event-free survival measured in the intention-to-treat population . This trial is registered with Clinical Trials.gov , number NCT00134030 . Findings Between April 14 , 2005 , and June 30 , 2011 , 2260 patients were registered from 325 sites in 17 countries . 618 patients with poor response were r and omly assigned ; 310 to receive MAP and 308 to receive MAPIE . Median follow-up was 62·1 months ( IQR 46·6–76·6 ) ; 62·3 months ( IQR 46·9–77·1 ) for the MAP group and 61·1 months ( IQR 46·5–75·3 ) for the MAPIE group . 307 event-free survival events were reported ( 153 in the MAP group vs 154 in the MAPIE group ) . 193 deaths were reported ( 101 in the MAP group vs 92 in the MAPIE group ) . Event-free survival did not differ between treatment groups ( hazard ratio [ HR ] 0·98 [ 95 % CI 0·78–1·23 ] ) ; hazards were non-proportional ( p=0·0003 ) . The most common grade 3–4 adverse events were neutropenia ( 268 [ 89 % ] patients in MAP vs 268 [ 90 % ] in MAPIE ) , thrombocytopenia ( 231 [ 78 % in MAP vs 248 [ 83 % ] in MAPIE ) , and febrile neutropenia without documented infection ( 149 [ 50 % ] in MAP vs 217 [ 73 % ] in MAPIE ) . MAPIE was associated with more frequent grade 4 non-haematological toxicity than MAP ( 35 [ 12 % ] of 301 in the MAP group vs 71 [ 24 % ] of 298 in the MAPIE group ) . Two patients died during postoperative therapy , one from infection ( although their absolute neutrophil count was normal ) , which was definitely related to their MAP treatment ( specifically doxorubicin and cisplatin ) , and one from left ventricular systolic dysfunction , which was probably related to MAPIE treatment ( specifically doxorubicin ) . One suspected unexpected serious adverse reaction was reported in the MAP group : bone marrow infa rct ion due to methotrexate . Interpretation EURAMOS-1 results do not support the addition of ifosfamide and etoposide to postoperative chemotherapy in patients with poorly responding osteosarcoma because its administration was associated with increased toxicity without improving event-free survival . The results define st and ard of care for this population . New strategies are required to improve outcomes in this setting . Funding UK Medical Research Council , National Cancer Institute , European Science Foundation , St Anna Kinderkrebsforschung , Fonds National de la Recherche Scientifique , Fonds voor Wetenschappelijk Onderzoek-Vla and eren , Parents Organization , Danish Medical Research Council , Academy of Finl and , Deutsche Forschungsgemeinschaft , Deutsche Krebshilfe , Federal Ministry of Education and Research , Semmelweis Foundation , ZonMw ( Council for Medical Research ) , Research Council of Norway , Sc and inavian Sarcoma Group , Swiss Paediatric Oncology Group , Cancer Research UK , National Institute for Health Research , University College London Hospitals , and Biomedical Research Centre Following observation of the predictive value of the histologic extent of tumor cell destruction after preoperative chemotherapy for metastasis-free survival ( MFS ) in osteosarcoma , a r and omized study was undertaken with the aim of ( 1 ) sparing some patients the unpleasant side effects of highly toxic drugs like doxorubicin ( DOX ) and cisplatin ( CPDD ) by administering these drugs postoperatively only after poor response with a milder preoperative regimen , and ( 2 ) improving the prognosis of patients responding poorly to the initial treatment by use of a salvage chemotherapy postoperatively . The available patients were divided into two groups . Those in the study arm received a preoperative chemotherapy consisting of high-dose methotrexate ( HDMTX ) and the triple drug combination of bleomycin , cyclophosphamide , and dactinomycin ( BCD ) and were switched to DOX/CPDD postoperatively in case of poor response . DOX/CPDD was used besides HDMTX for initial treatment in the control arm , and BCD alternatively with CPDD/ifosfamide ( IFO ) for postoperative salvage treatment . The response rate of the study arm was significantly inferior to the control arm ( 26 % v 60 % ; P less than .001 ) . The actuarial 4-year MFS rate of poor responders after salvage chemotherapy also was poorest in the study arm ( 41 % ) ; it was unchanged in the control arm ( 53 % ) as compared with that of poor responders from the COSS-80 study without salvage chemotherapy ( 52 % ) . The actuarial 4-year MFS rate of good responders was 73 % in the study arm , 79 % in the control arm , and not significantly different from that of the COSS-80 study ( 84 % ) , although postoperative chemotherapy of good responders had been markedly shortened as compared with the COSS-80 study . The actuarial 4-year MFS rate of the study arm as a whole was inferior to that of the control arm ( 49 % v 68 % ; P less than .1 ) and also inferior to the COSS-80 study ( 68 % ; P less than .01 ) , indicating a failure of the employed salvage strategy in general and especially of the effort to restrict the use of the very effective but highly toxic drugs DOX and CPDD to patients resistant to a less toxic initial treatment PURPOSE To compare three-drug chemotherapy with cisplatin , doxorubicin , and methotrexate with four-drug chemotherapy with cisplatin , doxorubicin , methotrexate , and ifosfamide for the treatment of osteosarcoma . To determine whether the addition of muramyl tripeptide ( MTP ) to chemotherapy enhances event-free survival ( EFS ) and overall survival in newly diagnosed patients with osteosarcoma . PATIENTS AND METHODS Six hundred sixty-two patients with osteosarcoma without clinical ly detectable metastatic disease and whose disease was considered resectable received one of four prospect ively r and omized treatments . All patients received identical cumulative doses of cisplatin , doxorubicin , and methotrexate and underwent definitive surgical resection of primary tumor . Patients were r and omly assigned to receive or not to receive ifosfamide and /or MTP in a 2 x 2 factorial design . The primary end points for analysis were EFS and overall survival . RESULTS In the current analysis , there was no evidence of interaction , and we were able to examine each intervention separately . The chemotherapy regimens result ed in similar EFS and overall survival . There was a trend toward better EFS with the addition of MTP ( P = .08 ) . The addition of MTP to chemotherapy improved 6-year overall survival from 70 % to 78 % ( P = .03 ) . The hazard ratio for overall survival with the addition of MTP was 0.71 ( 95 % CI , 0.52 to 0.96 ) . CONCLUSION The addition of ifosfamide to cisplatin , doxorubicin , and methotrexate did not enhance EFS or overall survival for patients with osteosarcoma . The addition of MTP to chemotherapy result ed in a statistically significant improvement in overall survival and a trend toward better EFS The European Organization for Research on Treatment of Cancer ( EORTC ) trial 20781 , concerning osteosarcoma of the limbs is reported . After definitive treatment of the primary tumor with amputation or irradiation , adjuvant treatment was given , r and omized into either 9 months of chemotherapy according to a modified Rosen schedule , or elective bilateral lung irradiation of 20 Gy , or 3 months of chemotherapy followed by lung irradiation . The 4‐year disease‐free survival and total survival were 24 % and 43 % , respectively , with no difference between the treatment arms . In the radiotherapy arms the lung metastases were more frequently suitable for surgical treatment . The survival of patients with either tibia localizations or higher age was somewhat better . Local recurrences occurred in 16 % of patients , 50 % of them with distant metastases . The trial was executed from 1978 to 1983 ; 205 patients were evaluable and eligible , and three toxic deaths occurred in the chemotherapy arms . Elective lung irradiation provided the same survival as the adjuvant chemotherapy given in that time Twenty-six patients with classic osteosarcoma were r and omized to receive either transfer factor or combination chemotherapy . Eight of 14 patients who received transfer factor converted their skin test markers , evidence of activity of the transfer factor . Of these eight patients , all are alive ; four are free of disease . Of the 18 patients who received combination chemotherapy , 14 are alive , 12 of whom are free of disease . The immunologic test procedures performed sequentially reveal that transfer factor appears to enhance cell-mediated immunity , but it is evident that in this study , a control ( saline ) arm in the protocol could not be included . It is of interest that the chemotherapy regimen used does not appear to suppress such activity permanently . The individual test results , however , are not very helpful for predicting response to treatment . The small numbers of patients and the short duration of this study , combined with the exclusion of parosteal osteogenic sarcomas and jaw tumors , do not permit a meaningful comparison with other published studies Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Osteosarcoma is the commonest type of primary malignant bone tumor , frequently found in adolescents at sites of rapid bone growth . Despite current management protocol s , up to half of the patients succumb to this disease . Moreover , there is no well-characterized molecular marker for diagnosis and prognosis . Since phage display methodology allows the selection of human antibody fragments with potential use in clinical applications , we applied this procedure to construct a recombinant Fab ( antigen binding fragment ) library from patients with osteosarcoma . We used peripheral blood lymphocyte total RNA from 11 osteosarcoma patients and cloned recombinant Fab representing the micro , gamma and kappa chain antibody repertoires of these individuals . The result ing library was cloned in the pComb3X vector and attained 1.45 x 10(8 ) different functional forms . BstO I fingerprinting and DNA sequencing analysis of r and omly selected clones revealed the diversity of the library , demonstrating that Fab harbors Vkappa chains from subgroups I to V , biased towards the A27 fragment , as normally reported for the human repertoire . Analysis of the VH repertoire revealed that our library has a slight bias towards the VH4 family , instead of the usually reported VH3 . This is the first description of a phage display library from osteosarcoma patients . We believe these human Fab fragments will provide a valuable tool for the study of this neoplasia and could also contribute to improvements in the diagnosis of this disease Purpose EURAMOS-1 , an international r and omized controlled trial , investigated maintenance therapy with pegylated interferon alfa-2b ( IFN-α-2b ) in patients whose osteosarcoma showed good histologic response ( good response ) to induction chemotherapy . Patients and Methods At diagnosis , patients age ≤ 40 years with resectable high- grade osteosarcoma were registered . Eligibility after surgery for good response r and om assignment included ≥ two cycles of preoperative MAP ( methotrexate , doxorubicin , and cisplatin ) , macroscopically complete surgery of primary tumor , < 10 % viable tumor , and no disease progression . These patients were r and omly assigned to four additional cycles MAP with or without IFN-α-2b ( 0.5 to 1.0 μg/kg per week subcutaneously , after chemotherapy until 2 years post registration ) . Outcome measures were event-free survival ( EFS ; primary ) and overall survival and toxicity ( secondary ) . Results Good response was reported in 1,041 of 2,260 registered patients ; 716 consented to r and om assignment ( MAP , n = 359 ; MAP plus IFN-α-2b , n = 357 ) , with baseline characteristics balanced by arm . A total of 271 of 357 started IFN-α-2b ; 105 stopped early , and 38 continued to receive treatment at data freeze . Refusal and toxicity were the main reasons for never starting IFN-α-2b and for stopping prematurely , respectively . Median IFN-α-2b duration , if started , was 67 weeks . A total of 133 of 268 patients who started IFN-α-2b and provided toxicity information reported grade ≥ 3 toxicity during IFN-α-2b treatment . With median follow-up of 44 months , 3-year EFS for all 716 r and omly assigned patients was 76 % ( 95 % CI , 72 % to 79 % ) ; 174 EFS events were reported ( MAP , n = 93 ; MAP plus IFN-α-2b , n = 81 ) . Hazard ratio was 0.83 ( 95 % CI , 0.61 to 1.12 ; P = .214 ) from an adjusted Cox model . Conclusion At the preplanned analysis time , MAP plus IFN-α-2b was not statistically different from MAP alone . A considerable proportion of patients never started IFN-α-2b or stopped prematurely . Long-term follow-up for events and survival continues Osteosarcoma ( OS ) is the most common primary malignant tumor of bone and the third most common cancer in childhood and adolescence . However , controversy concerning the ideal combination of chemotherapy agents ensued throughout the last quarter of the 20th century because of conflicting and often nonr and omized data . Collaborative efforts to increase underst and ing of the biology of osteosarcoma and the use of pre clinical models to test novel protein targets will be critical to identify the path toward improving outcomes for patients . We attempted to identify potential protein markers or therapy targets of osteosarcoma and give a glance at tumorigenesis of osteosarcoma . A sensitive and accurate method was employed in comparative proteomic analysis between benign tumor and osteosarcoma . Tumor tissues obtained by open biopsy before induction chemotherapy were investigated With 2D DIGE and MALDI-TOF/TOF MS , 22 differentially expressed proteins were identified after data base search ing , including 8 up-regulated and 14 down-regulated proteins . We also vali date d the expression levels of interesting proteins(have higher Ratios(tumor/normal ) ) by Western blotting assay . Annotating by bioinformatic tools , we found structural and signal transduction associated proteins were in large percentage among altered level proteins . In particular , some low abundant proteins involving translation and transcription , such as EEF2(Elongation Factor 2 ) , LUM Lumican 23 kDa Protein ) and GTF2A2(Transcription Initiation Factor Iia Gamma Chain . ) , were firstly reported by our study comparing to previous observations . Our findings suggest that these differential proteins may be potential biomarkers for diagnosis or molecules for underst and ing of osteosarcoma tumorigenesis , coming with biologic , pre clinical , and clinical trial efforts being described to improve outcomes for patients AIM Our experience of pre-operative intraarterial ( i.a . ) vs intravenous ( i.v . ) infusion of cisplatinum ( CDP ) in a multiagent neo-adjuvant chemotherapy for osteosarcoma of the extremity is reported . METHODS Two successive r and omized studies were performed . In the first , pre-operatively , CDP i.a . vs CDP i.v . was applied in combination with high-dose methotrexate ( HDMTX ) and adriamycin ( ADM ) within a three-drug regimen . In the second , a combination of HDMTX , ADM and IFO , within a four-drug regimen was tested . RESULTS The rate of responses to chemotherapy ( tumour necrosis > or = 90 % ) was significantly higher ( P<0.04 ) for the 142 patients treated with the four-drug regimen than in the 79 patients treated with a three-drug regimen ( 76%vs 62 % ) . According to the route of CDP infusion , in the three-drug regimen the rate of responses was significantly higher ( P=0.004 ) in patients treated with i.a . CDP ( 77 % ) than in patients treated i.v . ( 46 % ) ; with the four-drug regimen the rate of response was not significantly different in patients treated i.a . ( 81 % ) and in patients treated i.v . ( 71 % ) . No significant differences in the rates of limb salvages , local recurrence and event-free survival ( EFS ) were seen between the i.a . and the i.v . groups . CONCLUSION In the treatment of osteosarcoma of the extremity , the i.a . infusion of CDP does not offer any significant advantage when this drug is used within an aggressive , multiagent , pre-operative four-drug regimen In osteosarcoma , intraarterial ( IA ) administration of systemic treatment has been advocated to improve local tumor response preparing for , or even obviating , definitive surgery . Because data from the literature did not unequivocally support the local superiority of IA infusion , a comparative study was started in 1986 . Preoperative chemotherapy consisted of 45 mg/m2 of doxorubicin on days 1 and 2 ; 12 g/m2 of high‐dose methotrexate on days 15 and 22 ; and 3 g/m2 of ifosfamide on days 29 , 30 , 50 , and 51 followed on days 31 and 52 by intravenous ( IV ) versus IA tourniquet infusion of cisplatin ( DDP ) . A strict r and omization of patients was not feasible . A balanced distribution of risk factors was strived for by stratifying and allocating the appropriate patients central ly . The infusion time was prolonged from 1 to 5 hours in the IV group , and the DDP dose was reduced from 150 to 120 mg/m2 in both arms when intolerable ototoxicity became apparent . A multivariate analysis was performed to exclude a bias on the response rates from risk factor distribution and from modifications of DDP infusion time and dosage . The overall fraction of histologic good responders ( > 90 % necrosis ) was not found to be different after IA versus IV treatment ( 34/50 [ 68 % ] vs. 41/59 [ 69 % ] ) . Intraarterial instead of IV use of DDP within an aggressive systemic treatment does not seem to improve the local tumor response From December 1979 to August 1982 158 patients were registered for an adjuvant chemotherapy ( CT ) study COSS -80 . To compare the effect of cisplatin ( CPL ) to that of the drug combination bleomycin , cyclophosphamide , and dactinomycin ( BCD ) , patients were r and omized to receive either drug(s ) within a course of sequential multidrug CT including doxorubicin and high-dose methotrexate ( HDMTX ) . Definite surgery was done 10 - 18 weeks after the start of CT . Patients were r and omized a second time to receive or not to receive fibroblast interferon in addition to CT beginning at week 16 . At a median observation time of 19.5 months ( range , 4 - 34 months ) , 116 ( 73 % ) of 158 patients were continuously disease-free ( CDF ) . After exclusion of 42 patients because of some deviation in history and /or management , 86 ( 74 % ) of 116 patients actually were CDF with a 30-month calculated CDF-rate of 68 % . There was no difference in CDF rates in the patients receiving BCD versus CPL or receiving interferon versus no interferon . Whereas , in comparison to the previous study COSS -77 , the over-all increase in CDF rate does not reach statistical significance , it does , however , for the younger ( less than or equal to 12 years ) and for male patients , which is assumed to be the effect of increasing the methotrexate dose from 6 to 12 g/m2 in the COSS -80 study The SFOP-OS94 r and omised multi-centre trial was design ed to determine whether preoperative chemotherapy regimen combining high-dose methotrexate courses and etoposide-ifosfamide could improve the proportion of good histologic response ( 5 % viable cells ) compared to a regimen based on high-dose methotrexate and doxorubicin , in children/adolescents with localised high- grade limb osteosarcoma . Postoperative chemotherapy was adapted to the histologic response . Overall , 234 patients were r and omised between 1994 and 2001 . There were 56 % good responders in the etoposide-ifosfamide arm versus 39 % in the doxorubicin arm ( p-value=0.009 ) . With a median follow-up of 77 months , the 5-year event-free survival of the entire population was 62 % , slightly greater in the etoposide-ifosfamide arm than in the doxorubicin arm , but the difference was not significant ( Hazard Ratio : HR=0.71 , 95%CI : 0.5 - 1.06 , p-value=0.09 ) . Five-year overall survival of the entire population was 76 % , similar in both arms ( HR=0.95 , 95%CI : 0.6 - 1.6 , p-value=0.85 ) . Toxicity was manageable with different acute toxicity profiles between treatment arms . No acute toxicity related death was reported . About 43 % of the patients in the etoposide-ifosfamide arm were event-free at 3 years without having received any doxorubicin or cisplatin , thus avoiding the risk of long-term cardio- and ototoxicity In neoadjuvant treatment of osteosarcoma of the extremities intra-arterial ( IA ) instead of intravenous ( IV ) administration of cisplatinum ( CDDP ) has been advocated to improve local response and consequently increase the percentage of limb salvages and the cure rate . Since the major local advantages from the IA use of CDDP have been recently question ed , a comparative prospect i ve study was performed at the Rizzoli Institute between July 1990 and September 1991 . Preoperative chemotherapy consisted of two cycles of high-dose methotrexate ( HDMTX ) , followed 6 days later by CDDP and adriamycin ( ADM ) , HDMTX and ADM were delivered intravenously while CDDP was delivered according to previous r and omization , either intra-arterially or intravenously . Of the 79 patients who entered the study 40 received CDDP IA and 39 CDDP IV . The percentage of clinical and radiological response of the tumor as well as the percentage of limb salvage procedures performed was the same in the two groups . However the rate of good histological response ( tumor necrosis greater than 90 % ) was significantly higher in the group of patients who received IA CDDP than in the patients who received the drug intravenously ( 77.5 % vs 46 % : p less than 0.01 ) . No differences in terms of local or systemic side effects were found in the two groups . A longer follow-up is necessary to establish if this improved good response rate achieved with IA CDDP will lead to an improved cure rate . ( ABSTRACT TRUNCATED AT 250 WORDS Adjuvant chemotherapy comprising Adriamycin ( ADM ) and Methotrexate ( MTX ) with Citrovorum Factor ( CF ) was administered on a r and omization basis to 2 groups of patients with osteosarcoma after surgical ablation of the primary tumor . One group received high dose MTX ( regimen I ) and the other moderate dose MTX ( regimen II ) . In both groups a short period of heparin treatment was also administered to prevent neoplastic emboli during surgery . All patients were free of metastasis at the beginning of therapy . The efficacy of therapy was determined by recording the percentage of continuously disease-free patients . This was compared to the disease-free survival in 132 patients previously treated with other ADM or ADM-MTX regimens and to a group of 39 patients treated during this period with amputation only . The latter did not receive adjuvant chemotherapy for a variety of reasons and are equated to a concurrent control group . Over the ensuing 27 - 66 months , 31 of 56 patients ( 55 % ) treated with regimen I and 25 of 50 ( 50 % ) treated with regimen II were disease-free . The overall disease-free survival in both regimens was 53 % . This is similar to the 132 patients treated with previous adjuvant chemotherapy protocol s ( 45 - 50 % ) . However , the percentage of continuously disease-free patients treated with adjuvant chemotherapy was significantly better than the 39 patients ( 12 % ) treated contemporaneously with surgery only ( P less than 0.0005 ) . Survival in the latter is similar to that of historical control patients . These results do not suggest any change in the natural history of osteosarcoma and reveal benefits which may accrue with adjuvant chemotherapy . These results also demonstrate that in adjuvant treatment of osteosarcoma performed with ADM and MTX the high and the moderate doses of MTX are equally efficacious PURPOSE A r and omized pilot study was undertaken to assess the acute and chronic toxicities of two short intensive chemotherapy regimens , and to evaluate the feasibility of conservative surgery in this setting . Additional aims were to determine the clinical and radiologic response and the degree of histologic necrosis after chemotherapy . With extension of the study , eventual accrual was sufficient to compare disease-free survival ( DFS ) and overall survival ( OS ) . PATIENTS AND METHODS Between July 1983 and December 1986 , the European Osteosarcoma Intergroup ( EOI ) entered 198 eligible patients with classic high- grade extremity osteosarcoma onto a r and omized trial that compared doxorubicin ( DOX ) 25 mg/m2/d times three , intravenous ( IV ) bolus plus cisplatin ( CDDP ) 100 mg/m2 , 24 hour infusion , every 3 weeks times six ; the same combination was preceded 10 days earlier by high-dose methotrexate ( HDMTX ) 8 g/m2 , 6-hour infusion , every 4.5 weeks times four . In the majority of patients ( 179 ) , chemotherapy was commenced after biopsy ; definitive surgery was scheduled at 9 weeks in both groups . RESULTS Toxicities for both regimens did not differ substantially from those that occurred in other trials of adjuvant chemotherapy in osteosarcoma . Local recurrence ( 9 % ) and surgical complications ( 18 % ) after conservative surgery were acceptable . With a median follow-up of 53 months , DFS at 5 years is superior ( P = .02 ) for DOX/CDDP , 57 % versus 41 % , although OS , 64 % versus 50 % , is not different significantly ( P = .10 ) . In a subset of 66 patients for whom pathologic data on the resected specimen were available , DFS ( P = .003 ) and OS ( P = .008 ) were better for those who demonstrated > or = 90 % necrosis . CONCLUSION A brief intensive chemotherapy regimen of DOX/CDDP has produced excellent long-term results , which are similar to those that have been achieved in cooperative group studies of longer , more complex multiagent chemotherapy , and provide the basis for a direct comparison in the next EOI study PURPOSE It has been observed previously in osteosarcoma ( OS ) that the degree of necrosis of the resected primary tumor following a period of preoperative chemotherapy is predictive of subsequent event-free survival ( EFS ) . The aim of this study was to determine if more intensive preoperative chemotherapy would increase the proportion of patients with a good histologic response and improve EFS . PATIENTS AND METHODS Seventy-three patients with OS were treated at Memorial-Sloan Kettering Cancer Center ( MSKCC ) on the T12 protocol between 1986 and 1993 . Patients were r and omized between therapy based on the T10 protocol and therapy with more intensive preoperative chemotherapy . The more intensive preoperative regimen consisted of two courses of cisplatin ( CDDP ) and doxorubicin ( DOX ) in addition to the usual preoperative regimen of high-dose methotrexate ( HD MTX ) and bleomycin , cyclophosphamide , and dactinomycin ( BCD ) . RESULTS The regimen with more intensive preoperative chemotherapy achieved a modest increase in the proportion of patients with a good histologic response ( 44 % with a grade III or IV histologic response v 37 % in the control arm , 33 % with grade IV histologic response v 13 % in the control arm ) . EFS continued to correlate with histologic response . The actuarial 5-year EFS in patients with localized disease was 78 % for the regimen with more intensive preoperative chemotherapy and 73 % for the control arm . CONCLUSION Despite modest increases in the proportion of patients with good histologic response with intensified preoperative chemotherapy , no improvement in EFS was observed BACKGROUND Neoadjuvant chemotherapy improves outcome in osteosarcoma . Determination of optimum regimens for survival , toxicity and prognostic factors requires r and omised controlled trials to be conducted . PATIENTS AND METHODS Between 1983 and 2002 , the European Osteosarcoma Intergroup recruited 1067 patients with localised extremity osteosarcoma to three r and omised controlled trials . St and ard treatment in each was doxorubicin 75 mg/m(2 ) and cisplatin 100 mg/m(2 ) . Comparators were addition of methotrexate ( BO02/80831 ) , a multidrug regimen ( BO03/80861 ) and a dose-intense schedule ( BO06/80931 ) . St and ard survival analysis methods were used to identify prognostic factors , temporal and other influences on outcome . RESULTS Five- and 10-year survival were 56 % ( 95 % confidence interval 53 % to 59 % ) and 52 % , respectively ( 49 % to 55 % ) , with no difference between trials or treatment arms . Median follow-up was 9.4 years . Age range was 3 - 40 years ( median 15 ) . Limb salvage was achieved in 69 % . Five hundred and thirty-three patients received the st and ard arm , 79 % completing treatment . Good histological response to preoperative chemotherapy , distal tumour location ( all sites other than proximal humerus/femur ) and female gender were associated with improved survival . CONCLUSIONS Localised osteosarcoma will be cured in 50 % of patients with cisplatin and doxorubicin . Large r and omised trials can be conducted in this rare cancer . Failure to improve survival over 20 years argues for concerted collaborative international efforts to identify and rapidly test new treatments Intra-arterial ( IA ) and intravenous ( IV ) cisplatinum ( CDP ) were studied in a multiagent regimen of neoadjuvant chemotherapy for osteosarcoma of the extremities . Preoperatively two cycles of high-dose methotrexate ( HDMTX ) were administered , followed 5 days later by CDP and Adriamycin ( ADM ) . MTX and ADM were administered IV , and CDP was delivered IA or IV . Postoperatively , good responders received 3 more cycles of the same drugs , while poor responders had a longer chemotherapy including ifosfamide . The rate of good histological response to chemotherapy was significantly higher in patients treated intraarterially ( 78 % vs 46 % : P < .004 ) , while no significant differences in terms of disease-free survival were observed between patients who received CDP IA and patients who received CDP IV ( 55 % vs 51 % ) . In the IA group , however , there was only one local recurrence vs 5 in the IV group . The IA infusion of CDP is more active on the primary tumor than the IV infusion Thirty-eight patients whose primary extremity or limb girdle osteosarcomas had been completely excised ( 37 amputations , one limb sparing procedure ) were allocated at r and om to two treatment groups receiving respectively regular follow-up examinations plus a high-dose methotrexate ( HDMTX ) regimen or regular follow-up without primary adjuvant chemotherapy . Although the vincristine , HDMTX , leucovorin regimen was generally quite tolerable when given at three-week intervals for one year and most of the chemotherapy patients followed the planned HDMTX dose escalations from 3 to 6 to 7.5 g/m2 , delayed methotrexate excretion limited dosage escalations in 25 % . An estimated 52 % of the 38 patients were surviving five years after r and omization and an estimated 42 % remained continuously relapse-free after five years . No significant differences between the outcomes of the 20 treated and the 18 untreated patients were apparent ; however , power to detect differences was low . Furthermore , no significant differences in postmetastasis survival were apparent between the 12 treated and 10 untreated patients who relapsed . Approximately 20 % of these failing patients appear to have been salvaged for long-term survival . This pilot study of HDMTX confirms the continuing need for controlled clinical trials in determining the therapeutic value of adjuvant chemotherapy programs for patients with primary osteosarcoma The Multi-institutional Osteosarcoma Study ( MIOS ) was initiated in June 1982 and was design ed to test the role of adjuvant chemotherapy in the treatment of osteosarcoma of the extremity . At the time of initiation of this trial , the role of adjuvant chemotherapy in the treatment of osteosarcoma was controversial , because the outcome of patients treated with only surgery and without adjuvant chemotherapy appeared to be improving over time at certain institutions [ 1,2 ] . Preliminary [ 3 ] and up date d [ 4 ] results of this trial have been published and have confirmed the favorable impact of adjuvant chemotherapy on event-free survival for patients with osteosarcoma of the extremity ; the outcome for patients treated with immediate adjuvant chemotherapy was significantly better than for those treated with only surgery To determine the role of chemotherapy in the multidisciplinary treatment of patients with osteosarcoma , a r and omized prospect i ve trial of postoperative adjuvant chemotherapy was begun in 1981 . Fifty-nine patients with nonmetastatic classic intramedullary osteosarcoma were r and omized ; 32 received postoperative adjuvant chemotherapy consisting of high-dose methotrexate , Adriamycin ( Adria Laboratories , Columbus , OH ) , and BCD ( bleomycin , cytoxan , actinomycin D ) , and 27 patients received no adjuvant chemotherapy . At a median follow-up of 2 years , there was a statistically significant improvement in both disease-free and overall survival in those who received adjuvant chemotherapy . In addition , there was no difference in the less than 20 % disease-free or overall survival of patients treated in the 1970s who did not receive chemotherapy , as compared with the concurrent nontreatment controls . Therefore , with identical staging procedures , uniform surgical management , and st and ard pathologic evaluation , postoperative adjuvant chemotherapy definitely improves disease-free and overall survival in patients with osteosarcoma BACKGROUND A previous trial by the European Osteosarcoma Intergroup ( EOI ) suggested that a short intensive chemotherapy regimen with doxorubicin and cisplatin might produce survival of operable , non-metastatic osteosarcoma similar to that obtained with complex and longer- duration drug regimens based on the widely used T10 multi-drug protocol . We undertook a r and omised multicentre trial to compare these two approaches . METHODS 407 patients with operable , non-metastatic osteosarcoma were r and omly assigned the two-drug regimen ( six cycles [ 18 weeks ] of doxorubicin 25 mg/m2 on days 1 - 3 and cisplatin 100 mg/m2 on day 1 ) or a multi-drug regimen ( preoperatively vincristine , high-dose methotrexate , and doxorubicin ; postoperatively bleomycin , cyclophosphamide , dactinomycin , vincristine , methotrexate , doxorubicin , and cisplatin ; this protocol took 44 weeks ) . Surgery was scheduled for week 9 for the two-drug group and week 7 for the multi-drug group . Analyses of survival and progression-free survival were by intention to treat . FINDINGS Of 407 r and omised patients , 391 were eligible and have been followed up for at least 4 years ( median 5 - 6 years ) . Toxic effects were qualitatively similar with the two regimens . However , 188 ( 94 % ) of 199 patients completed the six cycles of two-drug treatment , whereas only 97 ( 51 % ) of 192 completed 18 or more of the 20 cycles of the multi-drug regimen . The proportion showing a good histopathological response ( > 90 % tumour necrosis ) to preoperative chemotherapy was about 29 % with both regimens and was strongly predictive of survival . Overall survival was 65 % at 3 years and 55 % at 5 years in both groups ( hazard ratio 0.94 [ 95 % CI 0.69 - 1.27 ] ) . Progression-free survival at 5 years was 44 % in both groups ( hazard ratio 1.01 [ 0.77 - 1.33 ] ) . INTERPRETATION We found no difference in survival between the two-drug and multi-drug regimens in operable , non-metastatic osteosarcoma . The two-drug regimen is shorter in duration and better tolerated , and is therefore the preferred treatment . However , 5-year survival is still unsatisfactory and new approaches to treatment , such as dose intensification , are needed to improve results |
13,235 | 28,433,237 | Significant benefits in lung function and quality of life were also identified .
In patients with chronic renal failure on dialysis , inspiratory muscle training with a fixed load significantly improves respiratory muscle strength , functional capacity , lung function and quality of life .
de Medeiros AIC , Fuzari HKB , Rattesa C , Br and ão DC , de Melo Marinho PÉ ( 2017 ) Inspiratory muscle training improves respiratory muscle strength , functional capacity and quality of life in patients with chronic kidney disease : a systematic review . | QUESTION Does inspiratory muscle training improve respiratory muscle strength , functional capacity , lung function and quality of life of patients with chronic kidney disease ?
Does inspiratory muscle training improve these outcomes more than breathing exercises ? | Background Esophageal resection is associated with a high incidence of postoperative pneumonia . Respiratory complications account for almost half of the readmissions to the critical care unit . Postoperative complications can result in prolonged hospital stay and consequently increase healthcare costs . In cardiac surgery a preoperative inspiratory muscle training program has shown to prevent postoperative pneumonia and reduce length of hospital stay . While in some surgical centers inspiratory muscle training is already used in the preoperative phase in patients undergoing esophageal resection , the added value of this intervention on the reduction of pulmonary complications has not yet been investigated in large surgical population s other than cardiac surgery in a r and omized and controlled study design . Methods / Design The effect of a preoperative inspiratory muscle training program on the incidence of postoperative pneumonia in patients undergoing esophageal resection will be studied in a single blind multicenter r and omized controlled trial ( the PREPARE study ) . In total 248 patients ( age > 18 years ) undergoing esophageal resection for esophageal cancer will be included in this study . They are r and omized to either usual care or usual care with an additional inspiratory muscle training intervention according to a high-intensity protocol which is performed with a tapered flow resistive inspiratory loading device . Patients have to complete 30 dynamic inspiratory efforts twice daily for 7 days a week until surgery with a minimum of 2 weeks . The starting training load will be aim ed to be 60 % of maximal inspiratory pressure and will be increased based on the rate of perceived exertion . The main study endpoint is the incidence of postoperative pneumonia . Secondary objectives are to evaluate the effect of preoperative inspiratory muscle training on length of hospital stay , duration of mechanical ventilation , incidence of other postoperative ( pulmonary ) complications , quality of life , and on postoperative respiratory muscle function and lung function . Discussion The PREPARE study is the first multicenter r and omized controlled trial to evaluate the hypothesis that preoperative inspiratory muscle training leads to decreased pulmonary complications in patients undergoing esophageal resection . Trial registration NCT01893008 BACKGROUND Aging results in a decline in the function of the respiratory muscles . Inspiratory muscle training is emerging as a possible intervention to attenuate the decline of respiratory muscles in the elderly . The aim of this study was to evaluate the efficacy of inspiratory muscle training on respiratory strength , diaphragm thickness , and diaphragmatic mobility in elderly women . METHODS This was a controlled , r and omized , and double-blind clinical trial , performed on 22 elderly women distributed in two groups , training ( TG ) and control ( CG ) . Over an 8-week period a moderate intensity inspiratory muscle training protocol was followed in the TG , while CG followed a sham protocol . In addition maximum expiratory and inspiratory pressure , mobility of the diaphragm and diaphragmatic thickness were evaluated by ultrasound . RESULTS After training , in TG maximal inspiratory pressure , maximal expiratory pressure , diaphragm thickness , and mobility increased by 37 % , 13 % , 11 % , and 9 % respectively , and their values were significantly higher than CG ( p < .005 , p = .013 , p = .001 , and p = .001 ) . CONCLUSION Inspiratory muscle training of moderate intensity improves respiratory muscle strength , diaphragm thickness , and diaphragm mobility in elderly women and it should be considered to minimize changes associated with senescence Our aim was to determine the minimal important difference ( MID ) for 6-min walk distance ( 6MWD ) and maximal cycle exercise capacity ( MCEC ) in patients with severe chronic obstructive pulmonary disease ( COPD ) . 1,218 patients enrolled in the National Emphysema Treatment Trial completed exercise tests before and after 4–6 weeks of pre-trial rehabilitation , and 6 months after r and omisation to surgery or medical care . The St George 's Respiratory Question naire ( domain and total scores ) and University of California San Diego Shortness of Breath Question naire ( total score ) served as anchors for anchor-based MID estimates . In order to calculate distribution-based estimates , we used the st and ard error of measurement , Cohen 's effect size and the empirical rule effect size . Anchor-based estimates for the 6MWD were 18.9 m ( 95 % CI 18.1–20.1 m ) , 24.2 m ( 95 % CI 23.4–25.4 m ) , 24.6 m ( 95 % CI 23.4–25.7 m ) and 26.4 m ( 95 % CI 25.4–27.4 m ) , which were similar to distribution-based MID estimates of 25.7 , 26.8 and 30.6 m. For MCEC , anchor-based estimates for the MID were 2.2 W ( 95 % CI 2.0–2.4 W ) , 3.2 W ( 95 % CI 3.0–3.4 W ) , 3.2 W ( 95 % CI 3.0–3.4 W ) and 3.3 W ( 95 % CI 3.0–3.5 W ) , while distribution-based estimates were 5.3 and 5.5 W. We suggest a MID of 26±2 m for 6MWD and 4±1 W for MCEC for patients with severe COPD AIM To investigate the effects of inspiratory muscle training ( IMT ) on functional capacity and balance , respiratory and peripheral muscle strength , pulmonary function , dyspnea , fatigue , depression , and quality of life in heart failure patients . METHODS A prospect i ve , r and omized controlled , double-blinded study . Thirty patients with heart failure ( NYHA II-III , LVEF<40 % ) were included . Sixteen patients received IMT at 40 % of maximal inspiratory pressure ( MIP ) , and 14 patients received sham therapy ( 15 % of MIP ) for 6 weeks . Functional capacity and balance , respiratory muscle strength , quadriceps femoris muscle strength , pulmonary function , dyspnea , fatigue , quality of life , and depression were evaluated . RESULTS Functional capacity and balance , respiratory and peripheral muscle strength , dyspnea , depression were significantly improved in the treatment group compared with controls ; quality of life and fatigue were similarly improved within groups ( p < 0.05 ) . Functional capacity ( 418.59 ± 123.32 to 478.56 ± 131.58 m , p < 0.001 ) , respiratory ( MIP = 62.00 ± 33.57 to 97.13 ± 32.63 cmH(2)O , p < 0.001 ) and quadriceps femoris muscle strength ( 240.91 ± 106.08 to 301.82 ± 111.86 N , p < 0.001 ) , FEV(1)% , FVC% and PEF% , functional balance ( 52.73 ± 3.15 to 54.25 ± 2.34 , p < 0.001 ) , functional dyspnea ( 2.27 ± 0.88 to 1.07 ± 0.79 , p < 0.001 ) , depression ( 11.47 ± 7.50 to 3.20 ± 4.09 , p < 0.001 ) , quality of life , fatigue ( 42.73 ± 11.75 to 29.07 ± 13.96 , p < 0.001 ) were significantly improved in the treatment group . Respiratory muscle strength ( MIP = 78.64 ± 35.95 to 90.86 ± 30.23 cmH(2)O , p = 0.001 ) , FVC% , depression ( 14.36 ± 9.04 to 9.50 ± 10.42 , p = 0.011 ) , quality of life and fatigue ( 42.86 ± 12.67 to 32.93 ± 15.87 , p = 0.008 ) were significantly improved in the control group . CONCLUSION The IMT improves functional capacity and balance , respiratory and peripheral muscle strength ; decreases depression and dyspnea perception in patients with heart failure . IMT should be included effectively in pulmonary rehabilitation programs Chronic renal failure can result in a variety of conditions leading to muscle weakness . We investigated inspiratory muscle ( IM ) performance and functional capacity in chronic renal failure before and after specific inspiratory muscle training ( SIMT ) . 9 men and 1 woman , ranging in age from 22 - 78 years , while on chronic hemodialysis received SIMT 3 times a week , for 3 months , while 10 others received sham training . Static inspiratory pressures , IM endurance and functional capacity were reduced in most subjects . Following SIMT , IM performance improved significantly and was associated with improved functional capacity , but not in the control group . We conclude that patients with chronic renal failure undergoing maintenance hemodialysis have reduced IM performance , and SIMT improves functional capacity BACKGROUND Exercise training increasingly is recommended as an important part of the management of cardiovascular disease . However , few studies have evaluated the effectiveness of exercise training in patients with chronic kidney disease ( CKD ) , and those that have included very selective population s. STUDY DESIGN Analysis of secondary outcomes of a r and omized controlled trial , with participants r and omly assigned to either lifestyle intervention or usual care ( control ) . SETTING & PARTICIPANTS Patients with CKD stages 3 to 4 and one or more uncontrolled cardiovascular risk factor were recruited from an outpatient clinic at a large tertiary hospital . INTERVENTION Lifestyle intervention included access to multidisciplinary care through a nurse practitioner-led CKD clinic , exercise training , and a lifestyle program . The exercise training was a 2-phased program in which participants received 8 weeks of supervised training before commencing 10 months of home-based training . OUTCOMES & MEASUREMENTS Efficacy , as assessed by metabolic equivalent tasks ( METs ) , 6-minute walk distance , Timed Get-Up- and -Go test , grip strength , and anthropomorphic measures ; adherence , as assessed by self-reported physical activity ; and safety , as assessed by reported serious adverse events , were recorded . RESULTS 83 patients were r and omly assigned and 72 patients completed follow-up testing ( intervention , n=36 ; control , n=36 ) . The intervention result ed in a significant improvement in METs ( pre , 7.2±3.3 ; post , 9.7±3.6 ) , 6-minute walk distance ( pre , 485±110 m ; post , 539±82 m ) , and body mass index ( pre , 32.5±6.7kg/m(2 ) ; post , 31.9±7.3kg/m(2 ) ) . Reported physical activity levels significantly increased in the intervention group at 6 months , but decreased at 12 months . There were no serious adverse events related to the exercise training . LIMITATIONS This study was not powered to evaluate the safety of exercise training on serious adverse events . CONCLUSIONS The findings from the present study suggest that an exercise program that includes a supervised and home-based training phase is effective , adhered to , and safe in patients with CKD Resistance respiratory muscle training ( RRMT ) increases respiratory muscle and swimming performance at depths down to 17 msw . It is unknown if RRMT improves swimming performance at greater depths and if the improvements are associated with a reduced work of breathing ( WOB ) , altered respiratory mechanics and /or improved respiratory muscle performance . Eight male subjects ( 30.3 ± 6.0 years ) were tested swimming underwater in a hyperbaric chamber at 37 m of depth against a pre-determined load ( 70 % $ $ \dot{V}_{{{\text{O } } _ { 2 } } } $ $ ) until exhausted . End expiratory lung volume ( EELV ) was determined by subtracting inspiratory capacity from total lung capacity throughout the swims . The mechanical WOB on the lung was calculated as the integrated product of the transpulmonary pressure and ventilatory flow . Maximal expiratory ( PEMAX ) and inspiratory pressures ( PIMAX ) were measured pre- and post-RRMT . RRMT was performed every 30 s against spring loaded inspiratory and expiratory valves 30 min/day , 5 days/week , for 4 weeks . RRMT increased PIMAX and PEMAX by 40 % ( 110 ± 11 cmH2O ( SD ) vs. 155 ± 22 , p < 0.001 ) and 30 % ( 148 ± 33 cmH2O vs. 192 ± 49 , p < 0.001 ) , respectively , respiratory endurance by 75 % ( 19.7 ± 15.4 min vs. 34.4 ± 27.3 , p = 0.010 ) , and swimming endurance by 87 % ( 26.4 ± 9.7 min vs. 49.4 ± 21.6 , p = 0.004 ) . The longer swimming time was associated with reduced $ $ \dot{V}_{\text{E } } $ $ and $ $ \dot{V}_{\text{A } } $ $ ( p < 0.001 ) , fb ( p < 0.001 ) , $ $ \dot{V}_{{{\text{CO}}_{2 } } } $ $ ( p < 0.001 ) and WOB ( p < 0.001 ) . There were no changes in EELV post-RRMT . These results suggest the improved exercise performance post-RRMT was associated with stronger respiratory muscles , a decreased fb , and a reduced WOB Muscle weakness and progressive loss of skeletal muscle mass are serious complications of chronic kidney disease ( CKD ) . The pathogenesis of this condition is still poorly understood . The study investigated fibre type distribution and diameter in functionally different skeletal muscles : locomotor , gastrocnemius muscle ( MG ) and postural , longissimus thoracis muscle ( ML ) together with an evaluation of metabolic disturbances and nutritional parameters of rats with different stages of CKD . Wistar rats were r and omized to a sham operation - CON , uninephrectomy - CKD1/2 or subtotal nephrectomy - CKD5/6 . After 4 weeks , serum concentration haemoglobin ( Hb ) , haptoglobin ( Hp ) , MCP-1 , advanced glycation end products ( AGEs ) , and homocysteine ( Hcy ) were measured . Muscle specimens were stained for myofibrillary ATPase and NADH-diaphoreses activity according to Ziegan 's method . There was a significant increase in the percentage of IID/X with a concomitant decrease of IIB fibres in ML in CKD1/2 vs. CON and CKD5/6 . IIB fibre diameters in ML were smaller ( 53.4±7.3 vs. 58.1±8.1 and 59.8±11.2 ; p=0.08 ) for CKD5/6 vs. CKD1/2 and CON , respectively . There were significant differences for CKD5/6 and CKD1/2 vs. CON in : Hb ( 11.4±3.1 ; 13.7±0.7 and 14.1±1 g/dl ) , Hp ( 1.6±0.6 ; 1.6±0.6 and 0.7±0.4 mg/ml ) , AGEs ( 5.1±0.6 ; 4.3±1.2 and 4.6±0.9 AU ) , Hcy ( 7.2±1.2 ; 5.1±0.5 and 4.9±0.5 M ) , MCP-1 ( 609±255 ; 489±265 and 292±113 pg/ml ) , respectively . We concluded that early stages of CKD could induce the process of compensatory fast to slow fibre transformation , while in more advanced CKD this process may be blocked and atrophy of fast-twitch fibres may occur , predominantly in non-locomotor muscles . These disturbances can be secondary to CKD-related metabolic burden and inflammation Objective : To analyse respiratory biofeedback effects on respiratory muscle strengthening in chronic renal failure patients . Design : R and omized controlled study . Setting : Nephrology and dialysis centre . Subjects and intervention : Forty-one end-stage renal patients on haemodialysis treatment were allocated into three groups : control ( n = 10 ) , G-1 ( inspiratory muscle training using Threshold IMT device ; n = 16 ) and G-2 ( biofeedback ; n = 15 ) and given respiratory muscle training ( three sessions/week for six weeks ) . Main measures : Forced vital capacity ( FVC ) , expiratory volume in the first second ( FEV1 ) , FEV1/FVC ratio , maximal voluntary ventilation ( MVV ) and maximal inspiratory ( MIP ) and expiratory ( MEP ) pressures were measured before and after the respiratory muscle training programme . Results : Both training methods were efficient since we found an increase after training in the FVC in the G-1 group ( from 2.45 ± 0.17 to 2.85 ± 0.16 ; P = 0.001 ) and in the G-2 group ( from 2.35 ± 0.19 to 2.55 ± 0.19 ; P = 0.007 ) , in the FEV1 in G-1 ( from 2.18 ± 0.16 to 2.46 ± 0.14 ; P = 0.01 ) and in G-2 ( from 1.97 ± 0.17 to 2.20 ± 0.15 ; P < 0.0001 ) , MIP in G-1 ( from 70.63 ± 4.03 to 108.75 ± 7.41 ; P < 0.0001 ) and in G-2 ( from 67.67 ± 5.02 to 96.33 ± 8.30 ; P < 0.001 ) and MEP in G-1 ( from 73.13 ± 5.10 to 82.50 ± 6.74 ; P = 0.007 ) and in G-2 ( from 67.67 ± 5.41 to 76.00 ± 4.29 ; P = 0.002 ) . Conclusions : Respiratory biofeedback is efficient as a respiratory muscle training modality for patients with chronic renal failure Patients on hemodialysis ( HD ) show changes in muscle structure and function reducing their functional capacity . This study was conduted to assess the effects of respiratory muscle training ( RMT ) and peripheral muscle training ( PMT ) during dialysis on functional parameters , inflammatory state , and quality of life ( QoL ) in patients on HD . R and omized controlled trial included 39 patients on HD , and they were divided into three groups : RMT ( n = 11 ) , PMT ( n = 14 ) , and controls ( C , n = 14 ) . Training was performed during the HD session for 10 weeks . Maximal inspiratory pressure ( PImax ) , maximal expiratory pressure ( PEmax ) , forced vital capacity ( FVC ) , six-minute walk test ( 6MWT ) , Kt/Vsp , biochemical parameters , and inflammatory state ( i.e. , level of high sensitivity C-reactive protein ) were evaluated . Variation from baseline was calculated by Analysis of Covariance ( ANCOVA ) . The ΔPImax was 22.5 ± 3.2 , 9.1 ± 2.9 , and −4.9 ± 2.8 cmH2O in the RMT , PMT and C , respectively ( p < 0.001 ) ; ΔPEmax was 10.8 ± 6.6 , 3.7 ± 5.9 , and −15.6 ± 5.9 cmH2O respectively ( p = 0.014 ) . The Δ6MWT was significantly greater in RMT and PMT ( 65.5 ± 9 ; 30.8 ± 8 m ) than in C ( −0.5 ± 8.1 m ) , p < 0.001 . Although biochemical parameters decreased after training , Kt/V remained unchanged . CRP decreased only in the RMT and PMT groups . There was a significant increase in QoL scores in the training groups ( vs. C ) in energy/fatigue ( p = 0.002 ) , sleep ( p < 0.001 ) , pain ( p < 0.001 ) , and list of symptoms/problems ( p = 0.014 ) . A short period of RMT or PMT during HD significantly improved functional capacity , with RMT showing greater effect than PMT . Muscle training improved biochemical and inflammatory markers , but a direct cause and effect relationship could not be established by this study Introduction Inspiratory muscle training ( IMT ) has been applied during pulmonary rehabilitation in patients with chronic obstructive pulmonary disease ( COPD ) . However , it remains unclear if the addition of IMT to a general exercise training programme leads to additional clinical ly relevant improvements in patients with COPD . In this study , we will investigate whether the addition of IMT to a general exercise training programme improves 6 min walking distance , health-related quality of life , daily physical activity and inspiratory muscle function in patients with COPD with inspiratory muscle weakness . Methods and analysis Patients with COPD ( n=170 ) with inspiratory muscle weakness ( Pi , max < 60 cm H2O or < 50%pred ) will be recruited to a multicentre r and omised placebo controlled trial of IMT and allocated into one of the two groups . Patients in both groups will follow a 3 month general exercise training programme , in combination with home-based IMT . IMT will be performed with a recently developed device ( POWERbreathe KH1 ) . This device applies an inspiratory load that is provided by an electronically controlled valve ( variable flow resistive load ) . The intervention group ( n=85 ) will undertake an IMT programme at a high intensity ( ≥50 % of their Pi , max ) , whereas the placebo group ( n=85 ) will undertake IMT at a low training intensity ( ≤10 % of Pi , max ) . Total daily IMT time for both groups will be 21 min ( 6 cycles of 30 breaths ) . Improvement in the 6 min walking distance will be the primary outcome . Inspiratory muscle function , health-related quality of life and daily physical activity will be assessed as secondary outcomes . Ethics and dissemination Ethics approval has been obtained from relevant centre committees and the study has been registered in a publicly accessible clinical trial data base . The results will be easily interpretable and should immediately be communicated to healthcare providers , patients and the general public . Results This can be incorporated into evidence -based treatment recommendations for clinical practice . Clinical Trials.gov NCT01397396 |
13,236 | 22,563,637 | While the overall quality of existing clinical trials varies considerably , there appears to be some positive evidence from relatively high- quality RCTs to support the use of MBT for cancer patients and survivors with symptoms of anxiety and depression | OBJECTIVE The use of mindfulness-based therapy ( MBT ) in oncology setting s has become increasingly popular , and research in the field has rapidly exp and ed .
The objective was by means of a systematic review and meta- analysis to evaluate the current evidence for the effect of MBT on symptoms of anxiety and depression in adult cancer patients and survivors . | BACKGROUND The eight-item Patient Health Question naire depression scale ( PHQ-8 ) is established as a valid diagnostic and severity measure for depressive disorders in large clinical studies . Our objectives were to assess the PHQ-8 as a depression measure in a large , epidemiological population -based study , and to determine the comparability of depression as defined by the PHQ-8 diagnostic algorithm vs. a PHQ-8 cutpoint > or = 10 . METHODS R and om-digit-dialed telephone survey of 198,678 participants in the 2006 Behavioral Risk Factor Surveillance Survey ( BRFSS ) , a population -based survey in the United States . Current depression as defined by either the DSM-IV based diagnostic algorithm ( i.e. , major depressive or other depressive disorder ) of the PHQ-8 or a PHQ-8 score > or = 10 ; respondent sociodemographic characteristics ; number of days of impairment in the past 30 days in multiple domains of health-related quality of life ( HRQoL ) . RESULTS The prevalence of current depression was similar whether defined by the diagnostic algorithm or a PHQ-8 score > or = 10 ( 9.1 % vs. 8.6 % ) . Depressed patients had substantially more days of impairment across multiple domains of HRQoL , and the impairment was nearly identical in depressed groups defined by either method . Of the 17,040 respondents with a PHQ-8 score > or = 10 , major depressive disorder was present in 49.7 % , other depressive disorder in 23.9 % , depressed mood or anhedonia in another 22.8 % , and no evidence of depressive disorder or depressive symptoms in only 3.5 % . LIMITATIONS The PHQ-8 diagnostic algorithm rather than an independent structured psychiatric interview was used as the criterion st and ard . CONCLUSIONS The PHQ-8 is a useful depression measure for population -based studies , and either its diagnostic algorithm or a cutpoint > or = 10 can be used for defining current depression Background There is increasing recognition of mindfulness and mindfulness training as a way to decrease stress and increase psychological functioning . Purpose The aims of this study were to examine the effects of mindfulness stress reduction training on perceived stress and psychological well-being and to examine if changes in mindfulness mediate intervention effects on these outcomes . Methods Seventy women and one man with a previous cancer diagnosis ( mean age 51.8 years , st and ard deviation = 9.86 ) were r and omized into an intervention group or a wait-list control group . The intervention consisted of an 8-week mindfulness training course . Results Compared to participants in the control group , participants in the mindfulness training group had significantly decreased perceived stress and posttraumatic avoidance symptoms and increased positive states of mind . Those who participated in the intervention reported a significant increase in scores on the five-facet mindfulness question naire ( FFMQ ) when compared to controls . The increase in FFMQ score mediated the effects of the intervention on perceived stress , posttraumatic avoidance symptoms , and positive states of mind . Conclusions This study indicates that the improvements in psychological well-being result ing from mindfulness stress reduction training can potentially be explained by increased levels of mindfulness as measured with the FFMQ . The importance of these findings for future research in the field of mindfulness is discussed Sleep disturbance is a very common problem for cancer patients that has largely not been addressed in the clinical intervention literature . Mindfulness meditation has demonstrated clinical benefits for a variety of patient population s in other areas of functioning . This study examined the effects of an 8-week Mindfulness-Based Stress Reduction ( MBSR ) program on the sleep quality of a heterogeneous sample of 63 cancer patients . Overall sleep disturbance was significantly reduced ( p < .001 ) and participants reported that their sleep quality had improved ( p < .001 ) . There was also a significant reduction in stress ( p < .001 ) , mood disturbance ( p = .001 ) , and fatigue ( p < .001 ) . The associations among these changes and implication s for improving quality of life of cancer patients are discussed BACKGROUND A self-rating inventory has been developed to measure DSM-IV and ICD-10 diagnoses of major ( moderate to severe ) depression by the patients ' self-reported symptoms . This Major Depression Inventory ( MDI ) can be scored both according to the DSM-IV and the ICD-10 algorithms for depressive symptomatology and according to severity scales by the simple total sum of the items . METHODS The Schedule for Clinical Assessment in Neuropsychiatry ( SCAN ) was used as index of validity for the clinician 's DSM-IV and ICD-10 diagnosis of major ( moderate to severe ) depression . The sensitivity and specificity of MDI was assessed in a sample of 43 subjects covering a spectrum of depressive symptoms . RESULTS The sensitivity of the MDI algorithms for major depression varied between 0.86 and 0.92 . The specificity varied between 0.82 and 0.86 . When using the total score of MDI the optimal cut-off score was estimated 26 and the total score was shown to be a sufficient statistic . LIMITATIONS The sample of subjects was limited . Patients with psychotic depression were not included . CONCLUSION The MDI was found to have a sensitivity and specificity which is acceptable . The question naire is brief and can be scored diagnostically by the DSM-IV and ICD-10 algorithms as well as by its simple total score OBJECTIVES Considerable morbidity persists among survivors of breast cancer ( BC ) including high levels of psychological stress , anxiety , depression , fear of recurrence , and physical symptoms including pain , fatigue , and sleep disturbances , and impaired quality of life . Effective interventions are needed during this difficult transitional period . METHODS We conducted a r and omized controlled trial of 84 female BC survivors ( Stages 0-III ) recruited from the H. Lee Moffitt Cancer and Research Institute . All subjects were within 18 months of treatment completion with surgery and adjuvant radiation and /or chemotherapy . Subjects were r and omly assigned to a 6-week Mindfulness-Based Stress Reduction ( MBSR ) program design ed to self-regulate arousal to stressful circumstances or symptoms ( n=41 ) or to usual care ( n=43 ) . Outcome measures compared at 6 weeks by r and om assignment included vali date d measures of psychological status ( depression , anxiety , perceived stress , fear of recurrence , optimism , social support ) and psychological and physical subscales of quality of life ( SF-36 ) . RESULTS Compared with usual care , subjects assigned to MBSR(BC ) had significantly lower ( two-sided p<0.05 ) adjusted mean levels of depression ( 6.3 vs 9.6 ) , anxiety ( 28.3 vs 33.0 ) , and fear of recurrence ( 9.3 vs 11.6 ) at 6 weeks , along with higher energy ( 53.5 vs 49.2 ) , physical functioning ( 50.1 vs 47.0 ) , and physical role functioning ( 49.1 vs 42.8 ) . In stratified analyses , subjects more compliant with MBSR tended to experience greater improvements in measures of energy and physical functioning . CONCLUSIONS Among BC survivors within 18 months of treatment completion , a 6-week MBSR(BC ) program result ed in significant improvements in psychological status and quality of life compared with usual care For people at risk of depressive relapse , mindfulness-based cognitive therapy ( MBCT ) has an additive benefit to usual care ( H. F. Coelho , P. H. Canter , & E. Ernst , 2007 ) . This study asked if , among patients with recurrent depression who are treated with antidepressant medication ( ADM ) , MBCT is comparable to treatment with maintenance ADM ( m-ADM ) in ( a ) depressive relapse prevention , ( b ) key secondary outcomes , and ( c ) cost effectiveness . The study design was a parallel 2-group r and omized controlled trial comparing those on m-ADM ( N = 62 ) with those receiving MBCT plus support to taper/discontinue antidepressants ( N = 61 ) . Relapse/recurrence rates over 15-month follow-ups in MBCT were 47 % , compared with 60 % in the m-ADM group ( hazard ratio = 0.63 ; 95 % confidence interval : 0.39 to 1.04 ) . MBCT was more effective than m-ADM in reducing residual depressive symptoms and psychiatric comorbidity and in improving quality of life in the physical and psychological domains . There was no difference in average annual cost between the 2 groups . Rates of ADM usage in the MBCT group was significantly reduced , and 46 patients ( 75 % ) completely discontinued their ADM . For patients treated with ADM , MBCT may provide an alternative approach for relapse prevention Statistical procedures for missing data have vastly improved , yet misconception and unsound practice still abound . The authors frame the missing- data problem , review methods , offer advice , and raise issues that remain unresolved . They clear up common misunderst and ings regarding the missing at r and om ( MAR ) concept . They summarize the evidence against older procedures and , with few exceptions , discourage their use . They present , in both technical and practical language , 2 general approaches that come highly recommended : maximum likelihood ( ML ) and Bayesian multiple imputation ( MI ) . Newer developments are discussed , including some for dealing with missing data that are not MAR . Although not yet in the mainstream , these procedures may eventually extend the ML and MI methods that currently represent the state of the art Background Surgeons , along with the Centers for Disease Control and Prevention , emphasize the importance of managing symptoms and improving the quality of life of cancer survivors . A 2008 meta- analysis of mindfulness-based stress reduction ( MBSR ) concluded that this technique might improve patients ’ adjustment to their disease . However , r and omized controlled trials using st and ardized measures for evaluating MBSR are limited . The primary objective of this study was to evaluate , using valid and reliable measures , the effects of a unique , interactive , 8-week cancer recovery and wellness program on symptoms and quality of life of female cancer survivors . Methods Sixty-eight female cancer patients were r and omized into either an intervention or waitlisted control group . Patients were evaluated using the Symptoms Checklist ( SCL-90-R ) , the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-30 ) , and the Symptoms of Stress Inventory ( SOSI ) . Results Of the participants , 70.6 % were breast cancer survivors . Mean age was 57.5 years ( treatment group ) and 56.4 years ( control group ) . Between-group demographic differences were not significant ( P > 0.6 ) . The treatment group improved significantly on the EORTC QLQ-30 ( P = 0.005 ) , on six of the eight SOSI subscales ( P ≤ 0.049 ) , and on both SCL-90-R subscales ( P ≤ 0.023 ) , while the control group did not improve on any of these measures ( P > 0.2 ) . Conclusion The MBSR-based cancer recovery and wellness intervention improved the symptoms and quality of life of this largely breast cancer survivor population across a variety of cancer symptoms and quality -of-life measures 424 BMJ | 24 FEBRUARY 2007 | VOLUME 334 Almost all studies have some missing observations . Yet textbooks and software commonly assume that data are complete , and the topic of how to h and le missing data is not often discussed outside statistics journals . There are many types of missing data and different reasons for data being missing . Both issues affect the analysis . Some examples are : ( 1 ) In a postal question naire survey not all the selected individuals respond ; ( 2 ) In a r and omised trial some patients are lost to follow-up before the end of the study ; ( 3 ) In a multicentre study some centres do not measure a particular variable ; ( 4 ) In a study in which patients are assessed frequently some data are missing at some time points for unknown reasons ; ( 5 ) Occasional data values for a variable are missing because some equipment failed ; ( 6 ) Some laboratory sample s are lost in transit or technically unsatisfactory ; ( 7 ) In a magnetic resonance imaging study some very obese patients are excluded as they are too large for the machine ; ( 8) In a study assessing quality of life some patients die during the follow-up period OBJECTIVE This study explores satisfaction and changes in well-being in cancer patients following mindfulness-based stress reduction training . METHOD Data were collected in 47 cancer patients before and after the training , and also 1 year later . St and ardized question naires were used to measure quality of life , joy in life , mood disturbances ( depression , anger , vigor , fatigue , and tension ) , meaning in life and physical symptoms . RESULTS Participants were highly satisfied and said they had reached their goals with the training . The results show that directly after the training patients reported a better quality of life , more joy in life , less tension , and fewer physical symptoms . These effects appeared even stronger at follow-up . A year after the training a decrease was also found in depression , anger , vigor and total mood disturbance . No changes could be established for meaning in life and fatigue . Effect sizes varied between 0.28 and 0.60 , indicating small-to-moderate changes . CONCLUSION Mindfulness training potentially supports cancer patients in h and ling the stress due to their life-threatening disease and increases their well-being . Several suggestions for further research are discussed . PRACTICE IMPLICATION S Mindfulness training provides cancer patients with tools to deal with their limitations and worries , both during and after their treatment OBJECTIVE Major depression is the most common psychiatric disorder among breast cancer patients and is associated with substantial impairment . Although some research has explored the utility of psychotherapy with breast cancer patients , only 2 small trials have investigated the potential benefits of behavior therapy among patients with well-diagnosed depression . METHOD In a primarily Caucasian , well-educated sample of women ( age = 55.4 years , SD = 11.9 ) diagnosed with breast cancer and major depression ( n = 80 ) , this study was a r and omized clinical trial testing the efficacy of 8 sessions of behavioral activation treatment for depression ( BATD ) compared to problem-solving therapy . Primary outcome measures assessed depression , environmental reward , anxiety , quality of life , social support , and medical outcomes . RESULTS Across both treatments , results revealed strong treatment integrity , excellent patient satisfaction with treatment protocol s , and low patient attrition ( 19 % ) . Intent-to-treat analyses suggested both treatments were efficacious , with both evidencing significant pre-post treatment gains across all outcome measures . Across both treatments , gains were associated with strong effect sizes , and based on response and remission criteria , a reliable change index , and numbers-needed-to-treat analyses , approximately ¾ of patients exhibited clinical ly significant improvement . No significant group differences were found at posttreatment . Treatment gains were maintained at 12-month follow-up , with some support for stronger maintenance of gains in the BATD group . CONCLUSIONS BATD and problem-solving interventions represent practical interventions that may improve psychological outcomes and quality of life among depressed breast cancer patients . Study limitations and future research directions are discussed Mindfulness-based cognitive therapy ( MBCT ) is an efficacious psychosocial intervention for recurrent depression ( Kuyken et al. , 2008 ; Ma & Teasdale , 2004 ; Teasdale et al. , 2000 ) . To date , no compelling research addresses MBCT 's mechanisms of change . This study determines whether MBCT 's treatment effects are mediated by enhancement of mindfulness and self-compassion across treatment , and /or by alterations in post-treatment cognitive reactivity . The study was embedded in a r and omized controlled trial comparing MBCT with maintenance antidepressants ( mADM ) with 15-month follow-up ( Kuyken et al. , 2008 ) . Mindfulness and self-compassion were assessed before and after MBCT treatment ( or at equivalent time points in the mADM group ) . Post-treatment reactivity was assessed one month after the MBCT group sessions or at the equivalent time point in the mADM group . One hundred and twenty-three patients with ≥3 prior depressive episodes , and successfully treated with antidepressants , were r and omized either to mADM or MBCT . The MBCT arm involved participation in MBCT , a group-based psychosocial intervention that teaches mindfulness skills , and discontinuation of ADM . The mADM arm involved maintenance on a therapeutic ADM dose for the duration of follow-up . Interviewer-administered outcome measures assessed depressive symptoms and relapse/recurrence across 15-month follow-up . Mindfulness and self-compassion were measured using self-report question naire . Cognitive reactivity was operationalized as change in depressive thinking during a laboratory mood induction . MBCT 's effects were mediated by enhancement of mindfulness and self-compassion across treatment . MBCT also changed the nature of the relationship between post-treatment cognitive reactivity and outcome . Greater reactivity predicted worse outcome for mADM participants but this relationship was not evident in the MBCT group . MBCT 's treatment effects are mediated by augmented self-compassion and mindfulness , along with a decoupling of the relationship between reactivity of depressive thinking and poor outcome . This decoupling is associated with the cultivation of self-compassion across treatment OBJECTIVE To assess the impact of an 8-week structured mindfulness-based cognitive therapy ( MBCT ) program on individuals experiencing distress as a consequence of cancer . DESIGN , SETTING AND PARTICIPANTS Prospect i ve study of 16 participants with a history of cancer and five carers of people with cancer recruited from August 2008 to February 2009 through calls to the Cancer Council South Australia Helpline . Participants were assessed for anxiety and depression before and after undergoing a course in MBCT between 30 September and 18 November 2008 and 20 February and 10 April 2009 . MAIN OUTCOME MEASURES Depression , anxiety and mindfulness as measured by the Beck Depression Inventory-II ( BDI-II ) , State-Trait Anxiety Inventory ( STAI ) , and Freiburg Mindfulness Inventory ( FMI ) , respectively , and a consumer-centred evaluation . RESULTS There were significant reductions in depression ( F[1,24 ] = 6.37 ; P = 0.012 ; partial-eta2 = 0.27 ) and anxiety ( F[2,34 ] = 9.43 ; P = 0.001 , partial-eta2 = 0.36 ) and mindfulness ( F[2,32 ] = 8.36 ; P = 0.001 ; partial-eta2 = 0.34 ) following the intervention , and these effects were sustained at the 3-month follow-up . Reliable change indices further support these findings . Participants ' scores on measures of depression and anxiety decreased as a function of increased mindfulness , as reflected by significant ( P < 0.05 ) negative correlations between FMI scores and BDI-II scores ( ranging from r = -0.46 to r = -0.79 ) and STAI scores ( ranging from r = -0.46 to r = -0.50 ) scores at all time points . CONCLUSION The MBCT program appears to be an efficacious intervention for use among people affected by cancer who also experience symptoms of depression and anxiety OBJECTIVE This study evaluated the effectiveness of mindfulness-based cognitive therapy ( MBCT ) for individuals with a diagnosis of cancer . METHOD Participants ( N = 115 ) diagnosed with cancer , across site and stage , were r and omly allocated to either the treatment or the wait-list condition . Treatment was conducted at 1 site , by a single therapist , and involved participation in 8 weekly 2-hr sessions that focused on mindfulness . Participants meditated for up to 1 hr daily and attended an additional full-day session during the course . Participants were assessed before treatment and 10 weeks later ; this second assessment occurred immediately after completion of the program for the treatment condition . The treatment condition was also assessed at 3 months postintervention . All postinitial assessment s were completed by assessors who were blind to treatment allocation . RESULTS There were large and significant improvements in mindfulness ( effect size [ ES ] = 0.55 ) , depression ( ES = 0.83 ) , anxiety ( ES = 0.59 ) , and distress ( ES = 0.53 ) as well as a trend for quality of life ( ES = 0.30 ) for MBCT participants compared to those who had not received the training . The wait-list group was assessed before and after receiving the intervention and demonstrated similar change . CONCLUSIONS These improvements represent clinical ly meaningful change and provide evidence for the provision of MBCT within oncology setting Background There is increasing evidence showing beneficial effects of mindfulness and mindfulness training on various indicators of mental and physical health . Purpose This paper reports the 6-month follow-up effects of a mindfulness stress reduction training program among patients treated for cancer on perceived stress , depression , anxiety , post-traumatic stress symptoms , positive states of mind , coping self-efficacy , and mindfulness . Methods Patients with a previous cancer diagnosis were recruited and r and omized into an intervention group or a waiting list control group . The intervention consisted of an 8-week mindfulness training course . Results Compared to participants in the control group , the intervention group showed a larger increase in mindfulness at 6-month follow-up . However , there were no differences on any of the other outcomes between the intervention and control groups . Continued meditation practice was associated with a significant reduction in post-traumatic stress symptoms of avoidance . Conclusions The study draws attention to the need to better underst and the mechanisms behind the effect of mindfulness training and to potential modification of mindfulness interventions to promote sustained benefits over time PURPOSE To determine the prevalence of psychiatric disorders during hospitalization for hematopoietic stem-cell transplantation ( SCT ) and to estimate their impact on hospital length of stay ( LOS ) . PATIENTS AND METHODS In a prospect i ve inpatient study conducted from July 1994 to August 1997 , 220 patients aged 16 to 65 years received SCT for hematologic cancer at a single institution . Patients received a psychiatric assessment at hospital admission and weekly during hospitalization until discharge or death , yielding a total of 1,062 psychiatric interviews performed . Psychiatric disorders were determined on the basis of the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition . Univariate and multivariate linear regression analyses were used to identify variables associated with LOS . RESULTS Overall psychiatric disorder prevalence was 44.1 % ; an adjustment disorder was diagnosed in 22.7 % of patients , a mood disorder in 14.1 % , an anxiety disorder in 8.2 % , and delirium in 7.3 % . After adjusting for admission and in-hospital risk factors , diagnosis of any mood , anxiety , or adjustment disorder ( P = .022 ) , chronic myelogenous leukemia ( P = .003 ) , Karnofsky performance score less than 90 at hospital admission ( P = .025 ) , and higher regimen-related toxicity ( P < .001 ) were associated with a longer LOS . Acute lymphoblastic leukemia ( P = .009 ) , non-Hodgkin 's lymphoma ( P = .04 ) , use of peripheral-blood stem cells ( P < .001 ) , second year of study ( P < .001 ) , and third year of study ( P < .001 ) were associated with a shorter LOS . CONCLUSION Our data indicate high psychiatric morbidity and an association with longer LOS , underscoring the need for early recognition and effective treatment Objective The objective of this study was to assess the effects of participation in a mindfulness meditation – based stress reduction program on mood disturbance and symptoms of stress in cancer out patients . Methods A r and omized , wait-list controlled design was used . A convenience sample of eligible cancer patients enrolled after giving informed consent and were r and omly assigned to either an immediate treatment condition or a wait-list control condition . Patients completed the Profile of Mood States and the Symptoms of Stress Inventory both before and after the intervention . The intervention consisted of a weekly meditation group lasting 1.5 hours for 7 weeks plus home meditation practice . Results Ninety patients ( mean age , 51 years ) completed the study . The group was heterogeneous in type and stage of cancer . Patients ’ mean preintervention scores on dependent measures were equivalent between groups . After the intervention , patients in the treatment group had significantly lower scores on Total Mood Disturbance and subscales of Depression , Anxiety , Anger , and Confusion and more Vigor than control subjects . The treatment group also had fewer overall Symptoms of Stress ; fewer Cardiopulmonary and Gastrointestinal symptoms ; less Emotional Irritability , Depression , and Cognitive Disorganization ; and fewer Habitual Patterns of stress . Overall reduction in Total Mood Disturbance was 65 % , with a 31 % reduction in Symptoms of Stress . Conclusions This program was effective in decreasing mood disturbance and stress symptoms in both male and female patients with a wide variety of cancer diagnoses , stages of illness , and ages OBJECTIVES This study investigated the ongoing effects of participation in a mindfulness-based stress reduction ( MBSR ) program on quality of life ( QL ) , symptoms of stress , mood and endocrine , immune and autonomic parameters in early stage breast and prostate cancer patients . METHODS Forty-nine patients with breast cancer and 10 with prostate cancer enrolled in an eight-week MBSR program that incorporated relaxation , meditation , gentle yoga and daily home practice . Demographic and health behaviors , QL , mood , stress symptoms , salivary cortisol levels , immune cell counts , intracellular cytokine production , blood pressure ( BP ) and heart rate ( HR ) were assessed pre- and post-intervention , and at 6- and 12-month follow-up . RESULTS Fifty-nine , 51 , 47 and 41 patients were assessed pre- and post-intervention and at 6- and 12-month follow-up , respectively , although not all participants provided data on all outcomes at each time point . Linear mixed modeling showed significant improvements in overall symptoms of stress which were maintained over the follow-up period . Cortisol levels decreased systematic ally over the course of the follow-up . Immune patterns over the year supported a continued reduction in Th1 ( pro-inflammatory ) cytokines . Systolic blood pressure ( SBP ) decreased from pre- to post-intervention and HR was positively associated with self-reported symptoms of stress . CONCLUSIONS MBSR program participation was associated with enhanced quality of life and decreased stress symptoms , altered cortisol and immune patterns consistent with less stress and mood disturbance , and decreased blood pressure . These pilot data represent a preliminary investigation of the longer-term relationships between MBSR program participation and a range of potentially important biomarkers The efficacy of problem-solving therapy ( PST ) to reduce psychological distress was assessed among a sample of 132 adult cancer patients . A second condition provided PST for both the patient and a significant other . At posttreatment , all participants receiving PST fared significantly better than waiting list control patients . Further , improvements in problem solving were found to correlate significantly with improvements in psychological distress and overall quality of life . No differences in symptom reduction were identified between the 2 treatment protocol s. At a 6-month follow-up , however , patients who received PST along with their significant other reported lower levels of psychological distress as compared with members of the PST-alone condition on approximately half of the outcome measures . These effects were further maintained 1-year posttreatment The present prospect i ve study aim ed at ( 1 ) investigating the frequency of high levels of psychological distress in women with early-stage breast cancer almost two years after diagnosis and ( 2 ) identifying characteristics associated with long-term distress . One hundred and seventy women participated on two occasions . Two months after surgery , patients completed question naires measuring psychosocial variables ( e.g. , stressful life-events , health complaints , sleep problems , social support , subjective distress , personality factors ) , demographic and biomedical variables ( e.g. , TNM status , type of surgery ) . At the second measurement , subjective distress was assessed for a second time by means of the Impact of Events Scale ( IES ) . Almost two years after diagnosis , 16 % of the women reported a high level of psychological distress as measured by the Intrusion scale ( IES ) . Best predictors of a high level of distress were : intrusive thoughts about the disease , trait-anxiety , health complaints and problems with sleeping . No significant association was found between previous life-events , social support or biomedical variables and levels of distress PURPOSE To assess the effectiveness of mindfulness-based stress reduction ( MBSR ) for mood , breast- and endocrine-specific quality of life , and well-being after hospital treatment in women with stage 0 to III breast cancer . PATIENTS AND METHODS A r and omized , wait-listed , controlled trial was carried out in 229 women after surgery , chemotherapy , and radiotherapy for breast cancer . Patients were r and omly assigned to the 8-week MBSR program or st and ard care . Profile of Mood States ( POMS ; primary outcome ) , Functional Assessment of Cancer Therapy-Breast ( FACT-B ) , Functional Assessment of Cancer Therapy-Endocrine Symptoms ( FACT-ES ) scales and the WHO five-item well-being question naire ( WHO-5 ) evaluated mood , quality of life , and well-being at weeks 0 , 8 , and 12 . For each outcome measure , a repeated- measures analysis of variance model , which incorporated week 0 measurements as a covariate , was used to compare treatment groups at 8 and 12 weeks . RESULTS There were statistically significant improvements in outcome in the experimental group compared with control group at both 8 and 12 weeks ( except as indicated ) for POMS total mood disturbance ( and its subscales of anxiety , depression [ 8 weeks only ] , anger [ 12 weeks only ] , vigor , fatigue , and confusion [ 8 weeks only ] ) , FACT-B , FACT-ES , ( and Functional Assessment of Cancer Therapy subscales of physical , social [ 8 weeks only ] , emotional , and functional well-being ) , and WHO-5 . CONCLUSION MSBR improved mood , breast- and endocrine-related quality of life , and well-being more effectively than st and ard care in women with stage 0 to III breast cancer , and these results persisted at three months . To our knowledge , this study provided novel evidence that MBSR can help alleviate long-term emotional and physical adverse effects of medical treatments , including endocrine treatments . MBSR is recommended to support survivors of breast cancer The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials Abstract The goals of this work were to assess the effects of participation in a mindfulness meditation-based stress reduction program on mood disturbance and symptoms of stress in cancer out patients immediately after and 6 months after program completion . A convenience sample of eligible cancer patients were enrolled after they had given informed consent . All patients completed the Profile of Mood States ( POMS ) and Symptoms of Stress Inventory ( SOSI ) both before and after the intervention and 6 months later . The intervention consisted of a mindfulness meditation group lasting 1.5 h each week for 7 weeks , plus daily home meditation practice . A total of 89 patients , average age 51 , provided pre-intervention data . Eighty patients provided post-intervention data , and 54 completed the 6-month follow-up The participants were heterogeneous with respect to type and stage of cancer . Patients ' scores decreased significantly from before to after the intervention on the POMS and SOSI total scores and most subscales , indicating less mood disturbance and fewer symptoms of stress , and these improvements were maintained at the 6-month follow-up . More advanced stages of cancer were associated with less initial mood disturbance , while more home practice and higher initial POMS scores predicted improvements on the POMS between the pre- and post-intervention scores . Female gender and more education were associated with higher initial SOSI scores , and improvements on the SOSI were predicted by more education and greater initial mood disturbance . This program was effective in decreasing mood disturbance and stress symptoms for up to 6 months in both male and female patients with a wide variety of cancer diagnoses , stages of illness , and educational background , and with disparate ages |
13,237 | 27,265,510 | Symptom outcomes for dose-specific probiotics were heterogeneous . | BACKGROUND Probiotics are often taken by individuals with irritable bowel syndrome ( IBS ) .
Which products are effective is unclear , despite an increasing research base .
This project will systematic ally review which strain- and dose- specific probiotics can be recommended to adults with IBS to improve symptoms and quality of life ( QoL ) .
It is part of a broader systematic review to up date British Dietetic Association guidelines for the dietary management of IBS in adults . | Abstract Objective . The effect of probiotics on IBS symptoms has been mixed , but remains an intriguing treatment option with appeal to the patient . Material and methods . Patients fulfilling the Rome II criteria were r and omized double-blind to a daily intake of 500 ml of fermented milk containing at least 5 × 107 CFU/ml of Lactobacillus paracasei ssp paracasei F19 , Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 or an equal volume of acidified milk for 8 weeks . Symptoms were assessed at baseline and weekly using a disease-specific vali date d symptom rating scale ( IBS-SSI ) . The predefined primary outcome measure was patient reported adequate symptom relief . Adherence to study protocol were assessed by performing stool sample s at the of the treatment period . Results . Eight-one patients were screened . Sixty-four patients were r and omized ; 18 patients did not complete the study due to protocol violations or withdrew due to lack of effect . Fifty-two patients ( 13 males ) completed the study as per protocol ; mean age was 51.3 years ( range 29–67 ) . The proportion of patients reporting adequate symptom relief increased in both patient groups , but there was not any statistical difference between the groups . IBS-SSI scores did not differ statistically between the groups at the end of the treatment period , but improved during the study period in both groups . Conclusions . During this 8-week trial gastrointestinal symptoms improved . However , there was no difference between treatment with fermented milk containing probiotics or acidified milk . The effect of probiotics on IBS symptoms remains uncertain and further studies are warranted Introduction . Although combination therapy with herbal medicine and probiotics is gaining popularity for controlling diarrhea-dominant irritable bowel syndrome ( D-IBS ) symptoms , few studies have investigated its clinical effects . Material s and Methods . Fifty-three patients with D-IBS were r and omly allocated into 1 of the following 4 groups : herbal medicine ( Gwakhyangjeonggisan ; GJS ) plus probiotics ( Duolac7S ; DUO ) , GJS plus placebo DUO , placebo GJS plus DUO , and placebo GJS plus placebo DUO . The study period consisted of a 2-week run-in , 8 weeks of administration , and 2 weeks of follow-up . The primary outcomes were weekly adequate relief ( AR ) of overall IBS symptoms and the proportion of responders ( PR ) during the administration period . The secondary outcomes included individual IBS symptoms , stool assessment , and quality of life . Changes of intestinal microbiota and intestinal permeability were also analyzed . Results and Discussion . Weekly AR was not different among the 4 groups throughout the treatment period . However , the 3 treatment groups exhibited significant improvements in PR compared to the findings in the placebo group . In the intestinal microbiota assessment , herbal medicine and probiotics synergistically increased beneficial bacteria counts . Conclusion . Combination therapy with herbal medicine and probiotics appears to relieve overall IBS symptoms by synergistically increasing beneficial intestinal microbe counts AIM To evaluate the effects of a combination probiotic on symptoms and colonic transit in patients with irritable bowel syndrome ( IBS ) and significant bloating . METHODS Forty-eight patients with Rome II IBS were r and omized in a parallel group , double-blind design to placebo or VSL # 3 twice daily ( 31 patients received 4 weeks and 17 patients 8 weeks of treatment ) . Pre- and post-treatment colonic transit measurements were performed using scintigraphy with (111)In charcoal . Symptoms were summarized as an average daily score for the entire period of treatment and separately for the first 4 weeks of treatment . Weekly satisfactory relief of abdominal bloating was assessed . RESULTS Treatment with VSL # 3 was associated with reduced flatulence over the entire treatment period ( placebo 39.5 + /- 2.6 vs VSL # 3 29.7 + /- 2.6 , P = 0.011 ) ; similarly , during the first 4 weeks of treatment , flatulence scores were reduced ( placebo 40.1 + /- 2.5 vs VSL # 3 30.8 + /- 2.5 , P = 0.014 ) . Proportions of responders for satisfactory relief of bloating , stool-related symptoms , abdominal pain and bloating scores were not different . Colonic transit was retarded with VSL # 3 relative to placebo ( colon geometric center 2.27 + /- 0.20 vs 2.83 + /- 0.19 , P = 0.05 respectively ) . CONCLUSION VSL # 3 reduces flatulence scores and retards colonic transit without altering bowel function in patients with IBS and bloating Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut , but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change . Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression . The animal-based diet increased the abundance of bile-tolerant microorganisms ( Alistipes , Bilophila and Bacteroides ) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides ( Roseburia , Eubacterium rectale and Ruminococcus bromii ) . Microbial activity mirrored differences between herbivorous and carnivorous mammals , reflecting trade-offs between carbohydrate and protein fermentation . Foodborne microbes from both diets transiently colonized the gut , including bacteria , fungi and even viruses . Finally , increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat , bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease . In concert , these results demonstrate that the gut microbiome can rapidly respond to altered diet , potentially facilitating the diversity of human dietary lifestyles BACKGROUND : Probiotic bacteria exhibit a variety of properties , including immunomodulatory activity , which are unique to a particular strain . Thus , not all species will necessarily have the same therapeutic potential in a particular condition . We have preliminary evidence that Bifidobacterium infantis 35624 may have utility in irritable bowel syndrome ( IBS ) . OBJECTIVES : This study was design ed to confirm the efficacy of the probiotic bacteria B. infantis 35624 in a large-scale , multicenter , clinical trial of women with IBS . A second objective of the study was to determine the optimal dosage of probiotic for administration in an encapsulated formulation . METHODS : After a 2-wk baseline , 362 primary care IBS patients , with any bowel habit subtype , were r and omized to either placebo or freeze-dried , encapsulated B. infantis at a dose of 1 × 106 , 1 × 108 , or 1 × 1010 , cfu/mL for 4 wk . IBS symptoms were monitored daily and scored on to a 6-point Likert scale with the primary outcome variable being abdominal pain or discomfort . A composite symptom score , the subject 's global assessment of IBS symptom relief , and measures of quality of life ( using the IBS-QOL instrument ) were also recorded . RESULTS : B. infantis 35624 at a dose of 1 × 108 cfu was significantly superior to placebo and all other bifidobacterium doses for the primary efficacy variable of abdominal pain as well as the composite score and scores for bloating , bowel dysfunction , incomplete evacuation , straining , and the passage of gas at the end of the 4-wk study . The improvement in global symptom assessment exceeded placebo by more than 20 % ( p < 0.02 ) . Two other doses of probiotic ( 1 × 106 and 1 × 1010 ) were not significantly different from placebo ; of these , the 1 × 1010 dose was associated with significant formulation problems . No significant adverse events were recorded . CONCLUSIONS : B. infantis 35624 is a probiotic that specifically relieves many of the symptoms of IBS . At a dosage level of 1 × 108 cfu , it can be delivered by a capsule making it stable , convenient to administer , and amenable to widespread use . The lack of benefits observed with the other dosage levels of the probiotic highlight the need for clinical data in the final dosage form and dose of probiotic before these products should be used in practice Abstract Background : Symptoms of irritable bowel syndrome ( IBS ) can have a profound impact on emotional health and quality of life , and current treatments are sometimes unsatisfactory for patients facing this lifelong disease . Probiotics , which can normalize gastrointestinal microflora , may alleviate symptoms of IBS . Objective : This preliminary controlled study was conducted to evaluate the effects of the probiotic Bacillus coagulans GBI-30 , 6086 on IBS symptoms . Methods : This was a r and omized , double-blind , parallel-group , placebo-controlled clinical trial involving 44 subjects who received either placebo or B coagulans GBI-30 , 6086 once a day for 8 weeks . Self- assessment s of the severity of IBS symptoms ( abdominal pain and bloating ) were recorded every day for 8 weeks . Because baseline values were significantly different between the 2 study groups , within-group analysis was conducted . Results : Improvements from baseline abdominal pain and bloating scores in the B coagulans GBI-30 , 6086 group were statistically significant for all 7 weekly comparisons ( P < 0.01 ) . In the placebo group , only changes in abdominal pain scores at weeks 6 and 8 achieved statistical significance ( P < 0.05 ) . No treatment-related adverse events or serious adverse events were reported during the 8-week study period . Conclusions : Preliminary data suggest that the patented B coagulans GBI-30 , 6086 probiotic may be a safe and effective option for the relief of abdominal pain and bloating for patients with IBS . Larger , extended trials are needed to verify these results Abstract Objective . Meta-analyses have indicated effect of probiotics on irritable bowel syndrome ( IBS ) . However , few long-term trials have been conducted and uncertainty remains as to effectiveness and long-term effect in a primary care setting . We aim ed to investigate the effect of probiotics compared with placebo in the management of IBS in primary care during a 6-month treatment period and with a 6-month follow-up . Material and methods . We r and omized IBS patients fulfilling Rome III criteria to receive two capsules twice daily either containing placebo or a probiotic mixture of Lactobacillus paracasei ssp paracasei F19 , Lactobacillus acidophilus La5 and Bifidobacterium Bb12 in an amount of 1.3 × 1010 CFU per capsule . Primary endpoint was proportion of responders defined as patients reporting adequate relief ( AR ) at least 50 % of the time in the 6-month treatment period . Secondary outcomes were proportions of patients reporting AR at different time points , and change in gastrointestinal symptoms and health-related quality of life ( HrQOL ) from baseline to 6 and 12 months . Results . A total of 131 patients were included in this study . The proportion of responders in the treatment period was 52 % ( 35/67 ) in the probiotic group versus 41 % ( 26/64 ) in the placebo group , p = 0.18 . Overall we found no difference between the groups in change in gastrointestinal symptoms after treatment . Patients improved in HrQOL , but with no statistically significant difference between the groups . Conclusion . During a 6-month treatment period , we were not able to detect a positive effect of probiotic when compared with placebo Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background Some probiotics have shown efficacy for patients with irritable bowel syndrome ( IBS ) . Lactobacillus ( L. ) plantarum MF1298 was found to have the best in vitro probiotic properties of 22 strains of lactobacilli . The aim of this study was to investigate the symptomatic effect of L. plantarum MF1298 in subjects with IBS . Primary outcome was treatment preference and secondary outcomes were number of weeks with satisfactory relief of symptoms and IBS sum score . Methods The design was a r and omised double blind placebo-controlled crossover trial . 16 subjects with IBS underwent two three-week periods of daily intake of one capsule of 1010 CFU L. plantarum MF 1298 or placebo separated by a four-week washout period . Results Thirteen participants ( 81 % ; 95 % CI 57 % to 93 % ; P = 0.012 ) preferred placebo to L. plantarum MF1298 treatment . The mean ( SD ) number of weeks with satisfactory relief of symptoms in the periods with L. plantarum MF1298 and placebo were 0.50 ( 0.89 ) and 1.44 ( 1.26 ) , respectively ( P = 0.006 ) . IBS sum score was 6.44 ( 1.81 ) in the period with L. plantarum MF1298 treatment compared with 5.35 ( 1.77 ) in the period with placebo ( P = 0.010 ) . With a clinical ly significant difference in the IBS sum score of 2 in disfavour of active treatment , the number needed to harm was 3.7 , 95 % CI 2.3 to 10.9 . Conclusions This trial shows for the first time an unfavourable effect on symptoms in subjects with IBS after intake of a potential probiotic . The trial registration number Clinical trials NCT00355810 BACKGROUND & AIMS A diet low in fermentable oligosaccharides , disaccharides , monosaccharides , and polyols ( FODMAPs ) often is used to manage functional gastrointestinal symptoms in patients with irritable bowel syndrome ( IBS ) , yet there is limited evidence of its efficacy , compared with a normal Western diet . We investigated the effects of a diet low in FODMAPs compared with an Australian diet , in a r and omized , controlled , single-blind , cross-over trial of patients with IBS . METHODS In a study of 30 patients with IBS and 8 healthy individuals ( controls , matched for demographics and diet ) , we collected dietary data from subjects for 1 habitual week . Participants then r and omly were assigned to groups that received 21 days of either a diet low in FODMAPs or a typical Australian diet , followed by a washout period of at least 21 days , before crossing over to the alternate diet . Daily symptoms were rated using a 0- to 100-mm visual analogue scale . Almost all food was provided during the interventional diet periods , with a goal of less than 0.5 g intake of FODMAPs per meal for the low-FODMAP diet . All stools were collected from days 17 - 21 and assessed for frequency , weight , water content , and King 's Stool Chart rating . RESULTS Subjects with IBS had lower overall gastrointestinal symptom scores ( 22.8 ; 95 % confidence interval , 16.7 - 28.8 mm ) while on a diet low in FODMAPs , compared with the Australian diet ( 44.9 ; 95 % confidence interval , 36.6 - 53.1 mm ; P < .001 ) and the subjects ' habitual diet . Bloating , pain , and passage of wind also were reduced while IBS patients were on the low-FODMAP diet . Symptoms were minimal and unaltered by either diet among controls . Patients of all IBS subtypes had greater satisfaction with stool consistency while on the low-FODMAP diet , but diarrhea-predominant IBS was the only subtype with altered fecal frequency and King 's Stool Chart scores . CONCLUSIONS In a controlled , cross-over study of patients with IBS , a diet low in FODMAPs effectively reduced functional gastrointestinal symptoms . This high- quality evidence supports its use as a first-line therapy . CLINICAL TRIAL NUMBER ACTRN12612001185853 OBJECTIVES Irritable bowel syndrome ( IBS ) is a common diagnosis in gastroenterology . Its etiology is unknown and therapeutic options limited . Trials suggest probiotics may be beneficial . The aim of this study was to assess the symptomatic efficacy of Lactobacillus plantarum 299 v ( L. plantarum 299 v ) for the relief of abdominal pain in patients with IBS fulfilling Rome II criteria . METHODS This study was conducted in a referral hospital . Trial participants were r and omized to receive either two capsules of L. plantarum 299 v at a dosage of 5 × 10(9 ) cfu per capsule or placebo daily for 8 wk . Severity of abdominal pain was assessed using a visual analog scale at each visit and a quality -of-life IBS ( QoL-IBS ) question naire was also completed . RESULTS There was no significant difference in abdominal pain relief between the study and placebo groups ( P = 0.800 ) . There was also no difference in QoL- IBS scores between the groups ( P = 0.687 ) . Both groups had a significant improvement in abdominal pain scores over the study period , from an average of 251.55 to 197.90 ( P < 0.0001 ) indicating a large placebo effect . CONCLUSION An 8-wk treatment with L. plantarum 299 v did not provide symptomatic relief , particularly of abdominal pain and bloating , in patients fulfilling the Rome II criteria BACKGROUND AND AIM The efficacy of treatment with multispecies probiotics on irritable bowel syndrome ( IBS ) symptoms and the alterations of gut microbiota in patients who have taken probiotics were investigated . METHODS This r and omized , double-blind , placebo-controlled trial involved 49 IBS patients ( probiotics : 25 , placebo : 24 ) diagnosed according to the Rome III criteria . Patients were r and omly assigned to two groups : either to receive multispecies probiotics ( a mixture of Bifidobacterium longum , B. bifidum , B. lactis , Lactobacillus acidophilus , L. rhamnosus , and Streptococcus thermophilus ) twice a day for 4 weeks or to receive a placebo twice a day for 4 weeks . The primary efficacy end-point was the proportion of participants whose IBS symptoms were substantially relieved at week 4 . Secondary end-points were the intensity of abdominal pain/discomfort , bloating , stool frequency/consistency , alterations in fecal microflora over the 4 weeks . Fecal microflora were analyzed in 34 patients ( probiotics : 17 , placebo : 17 ) by quantitative real-time polymerase chain reaction assays . RESULTS The proportion of patients whose IBS symptoms were substantially relieved at week 4 was significantly higher in the probiotics group than in the placebo group : 68.0 % ( 17/25 ) versus 37.5 % ( 9/24 ) ( P < 0.05 ) . Secondary end-points such as improvement in abdominal pain/discomfort and bloating occurred in the probiotics group but not in the placebo group . Fecal analysis revealed that B. lactis , L. rhamnosus , and S. thermophilus had increased significantly in the probiotics group after 4 weeks and that B. lactis had increased in the placebo group . CONCLUSIONS Multispecies probiotics are effective in IBS patients and induce the alterations in the composition of intestinal microbiota BACKGROUND Irritable bowel syndrome ( IBS ) is a common disorder in Iran with challenging treatment . Although trials have suggested that probiotics alleviate the complaints of patients with minimal side effects , they have not been investigated in Iranian adults . METHODS In a r and omized double-blind study , 108 eligible IBS patients ( Rome III Criteria ) aged 20 - 70 years who referred consecutively to a clinical center in Tehran with abdominal bloating from 2010 to 2012 received a combination probiotics or placebo twice daily for 4 weeks . The objective was to evaluate the efficacy and safety of a multi-strain probiotics combination . One week prior to and throughout the treatment , the participants recorded their abdominal symptoms on a daily basis , using visual analogue scale and reported satisfactory relief of general symptoms at the end of each week . Adverse events were evaluated by self-reporting and physical examination . Continuous variables were analyzed by independent t-test and chi-square was used for binomials . RESULTS The baseline characteristics were balanced ( 60 % female , mean age 36.7 ± 11.5 ) . A total of 97 ( 51 intervention , 46 control ) completed the treatment . Intention to treat analysis was done on 108 allocated subjects . 85 % of the probiotic group reported satisfactory relief of general symptoms compared with 47 % in the control group ( P < 0.01 ) . A reduction in abdominal bloating and pain with probiotic was superior to placebo [ -13.0 vs. -3.7 ( P < 0.01 ) , -8.2 vs. -2.1 ( P = 0.02 ) , respectively ] . No severe adverse drug reaction was seen in either group . CONCLUSIONS A 4-week period of treatment with the combination probiotics twice daily was safe , well tolerated , and effective in our patients . Further investigation is recommended for other subgroups of IBS . Trial Registration : I RCT .ir I RCT 2012071010230N1 BACKGROUND Irritable bowel syndrome ( IBS ) is characterized by heterogeneous pathophysiology and low response to treatment . Up to 60 % of IBS patients suffers from visceral hypersensitivity , which is associated with symptom severity and underlying pathophysiological mechanisms . Recently , positive effects of probiotics in IBS have been reported , but overall the response was modest . We performed a study in IBS patients , characterized by visceral hypersensitivity measured with the rectal barostat , aim ing to assess the effect of 6 weeks of multispecies probiotic mix on visceral pain perception . METHODS We conducted a r and omized , placebo-controlled , double-blind trial in forty Rome III IBS patients with visceral hypersensitivity . Prior to intake , patients kept a 2-week symptom diary and underwent a rectal barostat measurement . When hypersensitivity was confirmed , participation was allowed and patients received a multispecies probiotic with in vitro proven potential beneficial effects on mechanisms contributing to visceral hypersensitivity ( six different probiotic strains ; 10(9 ) cfu/g ) , or a placebo product of one sachet ( 5 g ) per day for 6 weeks . At the end of the intervention period , visceroperception and symptoms were reassessed . KEY RESULTS Thirty-five patients completed the trial . The percentage of patients with visceral hypersensitivity decreased significantly in the probiotic and placebo group ( 76.5 % and 71.4 % , respectively ; N.S. between groups ) . Improvement in pain scores and mean symptom score did not differ between the probiotic and placebo group . CONCLUSIONS & INFERENCES In this placebo-controlled trial in IBS patients with visceral hypersensitivity , no significant effect of a multispecies probiotic on viscerperception was observed . The study has been registered in the US National Library of Medicine ( http://www . clinical trials.gov , NCT00702026 ) Certain r and omized , placebo-controlled trials of oral supplementation with B. infantis 35624 have demonstrated the amelioration of symptoms of irritable bowel syndrome . Potential GI colonization by B. infantis 35624 or effects of supplementation on resident GI microbiota may pertain to these clinical observations . In this study , fecal excretion of B. infantis 35624 before , during and after 8 weeks of daily treatment was compared in subjects with IBS who received either the encapsulated oral supplement ( n = 39 ) or placebo ( n = 37 ) and in healthy subjects who received the supplement ( n = 41 ) . Secondarily , changes in assessed fecal microbiota and IBS symptoms were determined . Supplementation significantly increased fecal B. infantis 35624 excretion vs. placebo in IBS subjects ; excretion in healthy subjects receiving supplement was quantitatively similar . Fecal levels of the probiotic declined and approached baseline once dosing ceased , documenting that colonization is transient . Although supplementation increased numbers of B infantis 35624 within the GI tract , limited changes in 10 other fecal taxa were observed either in healthy subjects or those with IBS . No impact on IBS symptoms was observed . Detection of bacterial DNA in fecal sample s suggests that the probiotic is able to survive transit through the GI tract , although strain selective culture techniques were not performed to confirm viability of B. infantis 35624 in the feces . Continuous probiotic administration was necessary to maintain steady-state transit . Given the complex spectrum of GI microbiota , however , monitoring perturbations in selected taxa may not be not a useful indicator of probiotic function Background Irritable Bowel Syndrome ( IBS ) is a common condition characterised by pain , distension and altered bowel habit . Evidence suggests functional foods containing probiotics improve gastrointestinal transit , however , data are limited by short follow-up periods and evaluation in selected population s. Methods A multi-centre , r and omized , double blind , controlled trial to evaluate the effect of a probiotic vs non-probiotic dairy product on symptoms in IBS with a constipation element ( IBS – Constipation or IBS – Mixed profile ) . Set in 13 general practice s within central Engl and . Individuals meeting the ROME III criteria for IBS , aged 18–65 completed a pre- study diary . Eligible individuals were r and omized to consume dairy ‘ yoghurt ’ products which either did or did not contain active probiotics twice daily and to complete a daily diary . Primary outcome was subjective global assessment of symptom relief at week 4 . Other outcomes comprised , IBS symptom scores , pain , bloating and flatulence levels , stool frequency , stool consistency , ease of bowel movement and quality of life . Results 179 were r and omized ( 91 active , 88 placebo ) . 76 ( 43 active , 33 placebo ) completed the study . No significant between group differences existed at 4 weeks ( 57 % active vs 53 % placebo , reported adequate relief ( p = 0.71 ) ) . By week 8 , 46 % active vs 68 % placebo reported adequate relief ( p = 0.03 ) . This was sustained at week 12 . Conclusions Significant improvements were reported for most outcomes in all trial participants but improvement did not differ by group . This trial does not provide evidence for effectiveness of a probiotic in IBS , in variance with a body of published literature and review conclusions . Differential drop out may however cloud interpretation of data .UK Trial registration IS RCT Purpose To study the therapeutic effects of probiotic Escherichia coli Nissle 1917 ( EcN ) in irritable bowel syndrome ( IBS ) and identify subgroups benefiting most . Background Some trials investigating therapeutic effects in irritable bowel syndrome have shown benefits in IBS subgroups only . Probiotic treatment seems to be promising . Methods Patients with irritable bowel syndrome ( 120 ; Rome II ) were recruited to a prospect i ve double-blind study and r and omized to either EcN ( n = 60 ) or placebo ( n = 60 ) given for 12 weeks . Objectives were to describe efficacy and safety of EcN in different groups of irritable bowel syndrome . Outcome was assessed by ‘ Integrative Medicine Patient Satisfaction Scale ’ . Results Altogether , the responder rate was higher in the EcN than in the placebo group . However , only after 10 and 11 weeks , the differences were significant ( Δ 20.0 % points [ 95 % CI 2.6 ; 37.4 ] , p = 0.01 and Δ 18.3 % points [ 95 % CI 1.0 ; 35.7 ] , p = 0.02 , respectively ) . The best response was observed in the subgroup of patients with gastroenteritis or antibiotics prior to irritable bowel syndrome onset ( Δ 45.7 % points , p = 0.029 ) . No significant differences were observed in any other subgroup . Both treatment groups showed similar adverse events and tolerance . Conclusions Probiotic EcN shows effects in irritable bowel syndrome , especially in patients with altered enteric microflora , e.g. after gastroenterocolitis or administration of antibiotics Background / Aims Despite numerous r and omized clinical trials and meta-analyses , there is no increased evidence for the efficacy of probiotics in the treatment of irritable bowel syndrome ( IBS ) . We review this evidence , identify and analyse the reasons for this lack of evidence and propose method ological improvements for future studies . Methods Based on a literature search , we identified 56 papers that matched the purpose of our analyses . Twenty-seven studies used multi-species bacterial preparations and 29 used single-strain probiotics . They were analysed regarding patients included , treatment duration , probiotic dosage , and outcome measures . Results Trials in both groups suffered from heterogeneity with respect to probiotic concentration , duration of treatment , and other method ological issues ( crossover design and underpowered studies ) . This heterogeneity did not allow the application of a meta-analytic approach and a systematic review was therefore performed instead . Multi-strain preparations combined 2 to 8 different bacterial subspecies , mostly lactobacilli or bifidobacteria , and used variable lengths of treatments . Overall , more than 50 % of trials presented negative outcomes . The majority of the single-strain probiotic trials employing lactobacilli or Saccharomyces were negative , whereas trials employing bifidobacteria showed positive results . Conclusions The heterogeneity of the studies of probiotics in IBS questions the value of meta-analyses . The use of different bacterial strains and different mixtures of these strains , as well as different dosages , are the main contributors to this heterogeneity . Current data provides limited evidence for the efficacy of a small number of single-strain probiotics in IBS ( mostly bifidobacteria ) and sound studies following strict trial guidelines ( Food and Drug Administration and European Medicines Agency guidelines for clinical trials ) are needed . We summarised and proposed some method ological issues for future studies in the field Background / Aims Irritable bowel syndrome ( IBS ) is a troublesome disease . Some strains of probiotics reportedly exert remarkable immunomodulatory effects , and so we design ed a prospect i ve double-blind r and omized placebo-controlled clinical study to assess their effects in Korean adults with IBS . Methods IBS patients who met Rome III criteria were r and omly assigned to receive composite probiotics or placebo . A total of 20 billion lyophilized bacteria were administered twice daily for 8 weeks . Primary outcome variables were symptom scores consisting of abdominal pain , flatulence , defecation discomfort , and sum of symptom scores . A visual analogue scale was used to quantify the severity . Secondary outcome variables consisted of the quality of life and bowel habits including defecation frequency and stool form . Results Thirty-six and 34 patients were r and omized to the probiotics and placebo groups , respectively . Intention-to-treat analysis showed significant reductions in pain after 8 weeks of treatment : -31.9 and -17.7 in the probiotics and placebo groups , respectively ( p=0.045 ) . The reductions in abdominal pain , defecation discomfort , and sum of scores were more significant in 58 patients with a score of at least 3 on the baseline stool-form scale . Conclusions Composite probiotics containing Bifidobacterium bifidum BGN4 , Lactobacillus acidophilus AD031 , and other species are safe and effective , especially in patients who excrete normal or loose stools BACKGROUND Irritable bowel syndrome ( IBS ) is a chronic debilitating functional gastrointestinal disorder . Diet and lifestyle changes are important management strategies . The aim of these guidelines is to systematic ally review key aspects of the dietary management of IBS , with the aim of providing evidence -based guidelines for use by registered dietitians . METHODS Questions relating to diet and IBS symptom management were developed by a guideline development group . These included the role of milk and lactose , nonstarch polysaccharides ( NSP ) , fermentable carbohydrates in abdominal bloating , probiotics and empirical or elimination diets . A comprehensive literature search was conducted and relevant studies from January 1985 to November 2009 were identified using the electronic data base search engines : Cinahl , Cochrane Library , Embase , Medline , Scopus and Web of Science . Evidence statements , recommendations , good practice points and research recommendations were developed . RESULTS Thirty studies were critically appraised . A dietetic care pathway was produced following a logical sequence of treatment and formed the basis of these guidelines . Three lines of dietary management were identified . first line : Clinical and dietary assessment , healthy eating and lifestyle management with some general advice on lactose and NSP . Second line : Advanced dietary interventions to improve symptoms based on NSP , fermentable carbohydrates and probiotics . Third line : Elimination and empirical diets . Research recommendations were also identified relating to the need for adequately powered and well design ed r and omised controlled trials . CONCLUSIONS These guidelines provide evidence -based details of how to achieve the successful dietary management of IBS Probiotic bacteria exhibit a variety of properties , which are unique to a particular strain . Lactobacillus acidophilus-SDC 2012 , 2013 are new strains isolated from Korean infants ’ feces . The potential utility of Lactobacillus acidophilus-SDC 2012 , 2013 in irritable bowel syndrome ( IBS ) was studied . Forty IBS patients were r and omized into a placebo ( n = 20 ) and probiotics group ( n = 20 ) . Four weeks of treatment with L. acidophilus-SDC 2012 , 2013 was associated with a reduced score for abdominal pain or discomfort compared to the baseline ( P = 0.011 ) . The percent reduction in abdominal pain or discomfort exceeded the placebo scores by more than 20 % ( 23.8 and 0.2 % for probiotics and placebo , respectively , P = 0.003 ) . There was a significant difference in the proportion of responders between the probiotics and placebo groups ( P = 0.011 ) . There was no drop out or adverse events for either group during the study period . Lactobacillus acidophilus-SDC 2012 , 2013 appeared to have a beneficial effect in patients with IBS . Further studies are warranted BACKGROUND Symptoms of at least a subgroup of patients with irritable bowel syndrome may be associated with an alteration in gut flora . Studies on bacterial based therapy have yielded mixed results . AIMS To determine if oral administration of the probiotic Lactobacillus casei strain GG under r and omized placebo controlled conditions improves symptoms in irritable bowel syndrome patients with bloating related symptoms . PATIENTS A total of 25 patients with clinical ly confirmed irritable bowel syndrome ( Rome criteria ) were enrolled in the study . METHODS This was a r and omised double-blind placebo-controlled crossover trial . Lactobacillus GG was administered as enterocoated tablets constituting a daily dosage of 10(10 ) colony forming units . Symptoms were assessed by daily symptom diaries and periodic question naires . RESULTS Twenty-four patients were r and omised ; 19 ( 80 % ) female , mean age 40 years ( range 24 - 60 ) , mean duration of symptoms 4.9 years ( range 0.5 - 18 ) . Nineteen ( 80 % ) patients completed the study . No significant differences were found between Lactobacillus casei strain GG and placebo mean symptom scores for pain , urgency or bloating . A trend was noted , however , for a reduction in the number of unformed bowel motions on Lactobacillus casei strain GG treatment for patients with diarrhoea . CONCLUSIONS Lactobacillus casei strain GG alone did not significantly improve symptoms in this irritable bowel syndrome subgroup . A " diarrhoea predominant " subgroup may warrant further investigation Background : The clinical effect of probiotics on irritable bowel syndrome ( IBS ) is still controversial . Aims : We aim ed to evaluate the effects of a probiotic mixture on IBS symptoms and the composition of fecal microbiota in patients with diarrhea-dominant IBS ( D-IBS ) . Methods : Fifty patients with D-IBS were r and omized into placebo or probiotic mixture ( Lactobacillus acidophilus , Lactobacillus plantarum , Lactobacillus rhamnosus , Bifidobacterium breve , Bifidobacterium lactis , Bifidobacterium longum , and Streptococcus thermophilus 1.0 × 1010 CFU ) groups . Treatment was taken daily for 8 weeks . The primary outcome was adequate relief ( AR ) of overall IBS symptoms , which was assessed weekly for 10 weeks . A responder was defined as a patient who experienced AR for at least half of the 10-week study period . Secondary outcomes included the effects on individual symptoms , stool parameters , and IBS quality of life . The fecal flora compositions were analyzed by polymerase chain reaction denaturing gradient gel electrophoresis ( DGGE ) . Results : The proportion of AR was consistently higher in the probiotics group than in the placebo group throughout the 10-week period ( P<0.05 ) . The proportion of responders was significantly higher in the probiotics group than in the placebo group ( 48 % vs. 12 % , P=0.01 ) . Stool consistency improved significantly in the probiotics group compared with the placebo group . Percent changes in individual symptom scores were similar in the 2 groups , but IBS quality of life improvement tended to be higher in the probiotics group . Comparison of denaturing gradient gel electrophoresis profiles of fecal flora showed that the concordance rate between bacterial compositions before and after treatment was significantly higher in the probiotics group than in the placebo group ( 69.5 % vs. 56.5 % , P=0.005 ) . Conclusions : The probiotic mixture was effective in providing AR of overall IBS symptoms and improvement of stool consistency in D-IBS patients , although it had no significant effect on individual symptoms . The therapeutic effect of probiotics is associated with the stabilization of intestinal microbiota A number of recent clinical trials have promoted the use of probiotic bacteria as a treatment for irritable bowel syndrome ( IBS ) . The recent demonstration of abnormal colonic fermentation in some patients with this condition provides an opportunity for the objective assessment of the therapeutic value of these bacteria . This study was design ed to investigate the effects of Lactobacillus plantarum 299V on colonic fermentation . We conducted a double-blind , placebo-controlled , cross-over , four-week trial of Lactobacillus plantarum 299V in 12 previously untreated patients with IBS . Symptoms were assessed daily by a vali date d composite score and fermentation by 24-hr indirect calorimetry in a 1.4-m3 canopy followed by breath hydrogen determination for 3 hr after 20 ml of lactulose . On placebo , the median symptom score was 8.5 [ 6.25–11.25 interquartile range ( IQR ) ] , the median maximum rate of gas production was 0.55 ml/min ( 0.4–1.1 IQR ) , and the median hydrogen production was 189.7 ml/24 hr ( 118.3–291.1 IQR ) . On Lactobacillus plantarum 299V the median symptom score was 8 ( 6.75–13.5 IQR ) , the median maximum rate of gas production 0.92 ml/min ( 0.45–1.5 IQR ) , and the median hydrogen production 208.2 ml/24 hr ( 146–350.9 IQR ) . There was no significant difference . Breath hydrogen excretion after lactulose was reduced by the probiotic ( median at 120 min , 6 ppm ; placebo , 17 ppm ; P = 0.019 ) . In conclusion , Lactobacillus plantarum 299V in this study did not appear to alter colonic fermentation or improve symptoms in patients with the irritable bowel syndrome AIM To determine the dose-related effects of a novel probiotic combination , I.31 , on irritable bowel syndrome (IBS)-related quality of life ( IBS-QoL ) . METHODS A multicenter , r and omized , double-blind , placebo-controlled intervention clinical trial with three parallel arms was design ed . A total of 84 patients ( 53 female , 31 male ; age range 20 - 70 years ) with IBS and diarrhea according to Rome-III criteria were r and omly allocated to receive one capsule a day for 6 wk containing : ( 1 ) I.31 high dose ( n = 28 ) ; ( 2 ) I.31 low dose ( n = 27 ) ; and ( 3 ) placebo ( n = 29 ) . At baseline , and 3 and 6 wk of treatment , patients filled the IBSQoL , Visceral Sensitivity Index ( VSI ) , and global symptom relief question naires . RESULTS During treatment , IBS-QoL increased in all groups , but this increment was significantly larger in patients treated with I.31 than in those receiving placebo ( P = 0.008 ) . After 6 wk of treatment , IBS-QoL increased by 18 ± 3 and 22 ± 4 points in the high and the low dose groups , respectively ( P = 0.041 and P = 0.023 vs placebo ) , but only 9 ± 3 in the placebo group . Gut-specific anxiety , as measured with VSI , also showed a significantly greater improvement after 6 wk of treatment in patients treated with probiotics ( by 10 ± 2 and 14 ± 2 points , high and low dose respectively , P < 0.05 for both vs 7 ± 1 score increment in placebo ) . Symptom relief showed no significant changes between groups . No adverse drug reactions were reported following the consumption of probiotic or placebo capsules . CONCLUSION A new combination of three different probiotic bacteria was superior to placebo in improving IBS-related quality of life in patients with IBS and diarrhea Background Probiotics confer health benefits to the host . However , its clinical effect on irritable bowel syndrome ( IBS ) is controversial . Aims This study was aim ed to evaluate the effects of Saccharomyces boulardii on quality of life ( QOL ) and symptoms in patients with diarrhea-predominant IBS or mixed-type IBS . Methods Sixty-seven patients with IBS were r and omized either to receive S. boulardii at 2 × 1011 live cells as a daily dose ( n=34 ) , or placebo ( n=33 ) for 4 weeks . IBS-QOL was assessed at the beginning and end of the treatment phase . IBS-related symptoms , bowel movement frequency , and stool consistency were recorded on a daily basis and assessed each week . Results The overall improvement in IBS-QOL was higher in S. boulardii group than placebo ( 15.4 % vs 7.0 % ; P<0.05 ) . All eight domains of IBS-QOL were significantly improved in S. boulardii group ; however , placebo group only showed improvements in dysphoria and health worry . Composite scores for IBS symptoms were significantly reduced in both groups to a similar extent . Bowel frequency and stool consistency did not change in either group . Conclusions S. boulardii improved IBS-QOL better than placebo but was not superior for individual symptoms in patients with diarrhea-predominant IBS or mixed-type IBS BACKGROUND Dyspepsia and irritable bowel syndrome are suitable conditions for assessment of quality of life . Their similarities justify the elaboration of a single specific question naire for the two conditions . AIMS To examine the process leading to the validation of the psychometric properties of the functional digestive disorders quality of life question naire ( FDDQL ) . METHODS Initially , the question naire was given to 154 patients , to assess its acceptability and reproducibility , analyse its content , and reduce the number of items . Its responsiveness was tested during two therapeutic trials which included 428 patients . The question naire has been translated into French , English , and German . The psychometric validation study was conducted in France , United Kingdom , and Germany by 187 practitioners . A total of 401 patients with dyspepsia or irritable bowel syndrome , defined by the Rome criteria , filled in the FDDQL and generic SF-36 question naires . RESULTS The structure of the FDDQL scales was checked by factorial analysis . Its reliability was expressed by a Cronbach ’s α coefficient of 0.94 . Assessment of its discriminant validity showed that the more severe the functional digestive disorders , the more impaired the quality of life ( p<0.05 ) . Concurrent validity was supported by the correlation found between the FDDQL and SF-36 question naire scales . The final version of the question naire contains 43 items belonging to eight domains . CONCLUSIONS The properties of the FDDQL question naire , available in French , English , and German , make it appropriate for use in clinical trials design ed to evaluate its responsiveness to treatment among patients with dyspepsia and irritable bowel syndrome OBJECTIVE : The influence of the gastrointestinal ( GI ) microflora in patients with irritable bowel syndrome ( IBS ) has not been clearly eluci date d. This study was undertaken to see if patients with IBS have an imbalance in their normal colonic flora , as some bacterial taxa are more prone to gas production than others . We also wanted to study whether the flora could be altered by exogenous supplementation . In a previous study we have characterized the mucosa-associated lactobacilli in healthy individuals and found some strains with good colonizing ability . Upon colonization , they seemed to reduce gas formation . METHODS : The study comprised 60 patients with IBS and a normal colonoscopy or barium enema . Patients fulfilling the Rome criteria , without a history of malabsorption , and with normal blood tests underwent a sigmoidoscopy with biopsy . They were r and omized into two groups , one receiving 400 ml per day of a rose-hip drink containing 5 × 107 cfu/ml of Lactobacillus plantarum ( DSM 9843 ) and 0.009 g/ml oat flour , and the other group receiving a plain rose-hip drink , comparable in color , texture , and taste . The administration lasted for 4 wk . The patients recorded their own GI function , starting 2 wk before the study and continuing throughout the study period . Twelve months after the end of the study all patients were asked to complete the same question naire regarding their symptomatology as at the start of the study . RESULTS : All patients tolerated the products well . The patients receiving Lb . plantarum had these bacteria on rectal biopsies . There were no major changes of Enterobacteriaceae in either group , before or after the study , but the Enterococci increased in the placebo group and remained unchanged in the test group . Flatulence was rapidly and significantly reduced in the test group compared with the placebo group ( number of days with abundant gas production , test group 6.5 before , 3.1 after vs 7.4 before and 5.6 after for the placebo group ) . Abdominal pain was reduced in both groups . At the 12-month follow-up , patients in the test group maintained a better overall GI function than control patients . There was no difference between the groups regarding bloating . Fifty-nine percent of the test group patients had a continuous intake of fermented products , whereas the corresponding figure for the control patients was 73 % . CONCLUSIONS : The results of the study indicate that the administration of Lb . plantarum with known probiotic properties decreased pain and flatulence in patients with IBS . The fiber content of the test solution was minimal and it is unlikely that the fiber content could have had any effect . This type of probiotic therapy warrants further studies in IBS patients A comparison of Paraghurt tablets ( freeze-dried culture of Streptococcus faecium ) and placebo was carried out in patients with irritable bowel syndrome in a double-blind trial in Danish general practice s. Fifty-four patients ( 42 females and 12 males ) with an average duration of the disease of seven years were treated for four weeks . The clinical symptoms were registered prior to the treatment and after two and four weeks . The clinical effect was assessed according to changes in number of abdominal symptoms , the patients ' registration s on rating scales , and the physicians ' overall estimations . According to all three parameters a markedly better effect of Paraghurt was seen . Thus , after four weeks 81 % of the Paraghurt- and 41 % of the placebo-treated patients had improved according to the physicians ' overall assessment ( p = 0.002 ) . The result of the trial suggests that Paraghurt is a valuable alternative in the treatment of irritable bowel syndrome AIM To assess the effects and safety of Lactobacillus casei rhamnosus LCR35 complete freeze-dried culture ( LCR35 ) in patients suffering from irritable bowel syndrome ( IBS ) . METHODS A r and omized , double-blind pilot study was performed in 50 patients complaining of IBS symptoms complying with Rome III criteria . Patients were allocated to receive either LCR35 ( n = 25 ) at a minimum daily dose of 6 × 10(8 ) colony forming units or placebo ( n = 25 ) for 4 wk . At inclusion , after treatment and 2 wk later , patients completed the IBS severity scale . Change from baseline in the IBS severity score at the end of treatment was the primary efficacy criterion . Changes were compared between groups in the whole population and in IBS subtypes ( IBS with predominance of constipation , IBS with predominance of diarrhoea , mixed IBS , unsubtyped IBS ) . The presence of lactobacillus casei rhamnosus in stools was investigated at inclusion and at the end of treatment . The gastrointestinal quality of life question naire and the hospital anxiety and depression ( HAD ) scale were also completed . RESULTS Both groups were balanced for baseline characteristics . In 85 % of patients , stool analyses showed that lactobacillus casei rhamnosus able to survive in the digestive tract . In the whole population , improvements in the IBS severity score did not differ significantly between treatments with a 25 % decrease after 4-wk treatment , and a 15 % decrease from baseline 2 wk later in both groups . In IBS subgroups , statistical analysis could not be performed due to small sample size , but a clinical response in favour of LCR35 was observed in IBS patients with predominance of diarrhoea : no change in the symptom severity score was seen with the placebo after 4 wk treatment , whereas a clinical ly relevant decrease occurred with LCR35 ( -37 % vs -3 % ) . Furthermore , in spite of an increase in symptom intensity , the IBS severity score was maintained below the baseline value 2 wk later with LCR35 ( -19 % from baseline ) , whilst a slight 5 % increase from baseline was observed with placebo . In the IBS subgroup with predominance of diarrhoea only , a clinical ly relevant decrease in abdominal pain severity score ( -36 % ) was observed with LCR35 , whereas no change occurred with placebo . In mixed IBS patients , the 20 % and 30 % decreases in the IBS severity score observed after treatment with LCR35 and placebo , respectively , were maintained 2 wk later in both groups . A clinical response slightly in favour of placebo was observed at the end of the treatment period in IBS patients with predominance of constipation ( -41 % vs -20 % ) and unsubtyped IBS patients ( -47 % vs -17 % ) , with the same value maintained 2 wk later . In both groups , no clinical ly relevant changes were observed either for the gastrointestinal quality of life index or HAD score . Thus , these results suggest that sub-grouping of IBS patients may be important for optimizing treatment responses by the physician . CONCLUSION This pilot study suggests that LCR35 could have some efficacy in IBS patients complaining of diarrhoea . These preliminary results need to be confirmed in larger studies AIM To assess the symptomatic efficacy of Lactobacillus plantarum 299v ( L. plantarum 299v ) ( DSM 9843 ) for the relief of abdominal symptoms in a large subset of irritable bowel syndrome ( IBS ) patients fulfilling the Rome III criteria . METHODS In this double blind , placebo-controlled , parallel- design ed study , subjects were r and omized to daily receive either one capsule of L. plantarum 299v ( DSM 9843 ) or placebo for 4 wk . Frequency and intensity of abdominal pain , bloating and feeling of incomplete rectal emptying were assessed weekly on a visual analogue scale while stool frequency was calculated . RESULTS Two hundred and fourteen IBS patients were recruited . After 4 wk , both pain severity ( 0.68 + 0.53 vs 0.92 + 0.57 , P < 0.05 ) and daily frequency ( 1.01 + 0.77 vs 1.71 + 0.93 , P < 0.05 ) were lower with L. plantarum 299v ( DSM 9843 ) than with placebo . Similar results were obtained for bloating . At week 4 , 78.1 % of the patients scored the L. plantarum 299v ( DSM 9843 ) symptomatic effect as excellent or good vs only 8.1 % for placebo ( P < 0.01 ) . CONCLUSION A 4-wk treatment with L. plantarum 299v ( DSM 9843 ) provided effective symptom relief , particularly of abdominal pain and bloating , in IBS patients fulfilling the Rome III criteria BACKGROUND & AIMS The aim of this study was to compare the response of symptoms and cytokine ratios in irritable bowel syndrome ( IBS ) with ingestion of probiotic preparations containing a lactobacillus or bifidobacterium strain . METHODS Seventy-seven subjects with IBS were r and omized to receive either Lactobacillus salivarius UCC4331 or Bifidobacterium infantis 35624 , each in a dose of 1 x 10 10 live bacterial cells in a malted milk drink , or the malted milk drink alone as placebo for 8 weeks . The cardinal symptoms of IBS were recorded on a daily basis and assessed each week . Quality of life assessment , stool microbiologic studies , and blood sampling for estimation of peripheral blood mononuclear cell release of the cytokines interleukin (IL)-10 and IL-12 were performed at the beginning and at the end of the treatment phase . RESULTS For all symptoms , with the exception of bowel movement frequency and consistency , those r and omized to B infantis 35624 experienced a greater reduction in symptom scores ; composite and individual scores for abdominal pain/discomfort , bloating/distention , and bowel movement difficulty were significantly lower than for placebo for those r and omized to B infantis 35624 for most weeks of the treatment phase . At baseline , patients with IBS demonstrated an abnormal IL-10/IL-12 ratio , indicative of a proinflammatory , Th-1 state . This ratio was normalized by B infantis 35624 feeding alone . CONCLUSIONS B infantis 35624 alleviates symptoms in IBS ; this symptomatic response was associated with normalization of the ratio of an anti-inflammatory to a proinflammatory cytokine , suggesting an immune-modulating role for this organism , in this disorder Until recently many clinical trials of functional gastrointestinal disorders ( FGIDs ) suffered from important weaknesses in trial design , study execution , and data analysis . This makes it difficult to determine whether truly efficacious therapies exist for these disorders . One of the important method ologic problems is the absence of vali date d outcome measures and lack of consensus among stakeholders on how to measure outcome . Currently much of the effort is being put into the development of vali date d outcome measures for several of the FGIDs . The r and omized , controlled trial with parallel groups is the design of choice . In this report , guidelines are given for the basic architecture of intervention studies of FGIDs . Further studies on design issues are required to ensure the recommendations will become evidence based in the future Background : Irritable bowel syndrome is a gastrointestinal disorder of unknown aetiology . The effect of probiotics in this syndrome remains unclear BACKGROUND We aim ed to evaluate clinical symptoms in subjects with irritable bowel syndrome receiving Saccharomyces cerevisiae in a r and omized double-blind placebo-controlled clinical trial . METHODS Overall , 179 adults with irritable bowel syndrome ( Rome III criteria ) were r and omized to receive once daily 500 mg of Saccharomyces cerevisiae , delivered by one capsule ( n = 86 , F : 84 % , age : 42.5 ± 12.5 ) , or placebo ( n = 93 , F : 88 % , age : 45.4 ± 14 ) for 8 weeks followed by a 3-week washout period . After a 2-week run-in period , cardinal symptoms ( abdominal pain/discomfort , bloating/distension , bowel movement difficulty ) and changes in stool frequency and consistency were recorded daily and assessed each week . A safety assessment was carried out throughout the study . RESULTS The proportion of responders , defined by an improvement of abdominal pain/discomfort , was significantly higher ( p = 0.04 ) in the treated group than the placebo group ( 63 % vs 47 % , OR = 1.88 , 95 % , CI : 0.99 - 3.57 ) in the last 4 weeks of treatment . A non-significant trend of improvement was observed with Saccharomyces cerevisiae for the other symptoms . Saccharomyces cerevisiae was well tolerated and did not affect stool frequency and consistency . CONCLUSION Saccharomyces cerevisiae is well tolerated and reduces abdominal pain/discomfort scores without stool modification . Thus , Saccharomyces cerevisiae may be a new promising c and i date for improving abdominal pain in subjects with irritable bowel syndrome Preliminary studies indicate that dietary restriction of fermentable short-chain carbohydrates improves symptoms in irritable bowel syndrome ( IBS ) . Prebiotic fructo-oligosaccharides and galacto-oligosaccharides stimulate colonic bifidobacteria . However , the effect of restricting fermentable short-chain carbohydrates on the gastrointestinal ( GI ) microbiota has never been examined . This r and omized controlled trial aim ed to investigate the effects of fermentable carbohydrate restriction on luminal microbiota , SCFA , and GI symptoms in patients with IBS . Patients with IBS were r and omized to the intervention diet or habitual diet for 4 wk . The incidence and severity of symptoms and stool output were recorded for 7 d at baseline and follow-up . A stool sample was collected and analyzed for bacterial groups using fluorescent in situ hybridization . Of 41 patients r and omized , 6 were withdrawn . At follow-up , there was lower intake of total short-chain fermentable carbohydrates in the intervention group compared with controls ( P = 0.001 ) . The total luminal bacteria at follow-up did not differ between groups ; however , there were lower concentrations ( P < 0.001 ) and proportions ( P < 0.001 ) of bifidobacteria in the intervention group compared with controls when adjusted for baseline . In the intention-to-treat analysis , more patients in the intervention group reported adequate control of symptoms ( 13/19 , 68 % ) compared with controls ( 5/22 , 23 % ; P = 0.005 ) . This r and omized controlled trial demonstrated a reduction in concentration and proportion of luminal bifidobacteria after 4 wk of fermentable carbohydrate restriction . Although the intervention was effective in managing IBS symptoms , the implication s of its effect on the GI microbiota are still to be determined Symptoms of irritable bowel syndrome ( IBS ) have a profound impact on quality of life for many patients and current treatments are sometimes unsatisfactory . This controlled pilot study was conducted to evaluate effects of the proprietary GanedenBC(30 ) ( Bacillus coagulans GBI-30 , 6086 ) probiotic on IBS symptoms , in a r and omized , double-blind , placebo-controlled clinical trial including patients with diarrhea-predominant IBS ( IBS-D ) . Patients were r and omized to receive either B. coagulans GBI-30 , 6086 or placebo once a day for 8 weeks . Patients filled out a quality -of-life question naire , and self- assessment diaries were provided to record stool count and consistency , symptom severity , and medication consumption . Of the 61 patients enrolled , six did not meet the inclusion criteria and three were lost to follow-up . Of the remaining 52 patients with IBS-D , the average number of bowel movements per day was significantly reduced for patients treated with B. coagulans GBI-30 , 6086 when compared to placebo ( P = 0.042 ) . Large variability in baseline scores prevented the assessment of severity scores and quality of life . This small pilot study provides evidence that the proprietary B. coagulans GBI-30 , 6086 probiotic is safe and effective for reducing daily bowel movements in patients with BACKGROUND It was suggested that the intestinal microflora may play a role in the pathogenesis of irritable bowel syndrome ( IBS ) . Probiotics may ease symptoms in IBS patients by changing gut microflora , reducing mucosal inflammation and exerting antibacterial effects . AIM To assess the short- and long-term effects of Lactobacillus reuteri administration on clinical symptoms of IBS . METHODS This is a double blind , placebo-controlled 6-month trial . Subjects consumed 1x10(8)cfu/tablet twice a day . The clinical severity of the IBS symptoms was evaluated by the Francis Severity score and the IBS quality -of-life score at study entry and then monthly . RESULTS In total , 54 subjects were r and omized for treatment and 39 concluded the study . Both groups ( treatment and placebo ) improved significantly in all the studied parameters with no significant differences between groups . Two parameters , constipation and passing gases , were marginally different between the main groups ( P=0.0714 and 0.0971 , respectively ) . CONCLUSIONS IBS symptoms did not improve with probiotic treatment with L. reuteri . A strong placebo effect and a lack of uniformity of the IBS population may have hindered a clearer demonstration of the effect Background Irritable bowel syndrome ( IBS ) is a widespread functional disorder of the digestive tract . Its aetiology is unknown and therapeutic options are limited . Recent reports suggest that probiotics may have a role in regulating the motility of the digestive tract . Aim To assess the efficacy of Lactobacillus plantarum 299V ( LP299V ) in patients with IBS . Patients and methods Forty patients were r and omized to receive either LP299V in liquid suspension ( 20 patients ) or placebo ( 20 patients ) over a period of 4 weeks . Clinical examination was performed at baseline and at the end of the study . Additionally , patients assessed their symptoms by applying a scoring system . Results All patients treated with LP299V reported resolution of their abdominal pain as compared to 11 patients from a placebo group ( P = 0.0012 ) . There was also a trend towards normalization of stools frequency in constipated patients in six out of 10 patients treated with LP299V compared with two out of 11 treated with placebo ( P = 0.17 ) . With regards to all IBS symptoms an improvement was noted in 95 % of patients in the LP299V group vs 15 % of patients in the placebo group ( P < 0.0001 ) . Conclusions LP299V seems to have a beneficial effect in patients with IBS . Further studies on larger cohorts of patients and with longer duration of therapy are required in order to establish the place of L. plantarum in the treatment of IBS OBJECTIVES : Adequate relief ( AR ) of irritable bowel syndrome ( IBS ) symptoms ( IBS-AR ) has been used as a primary end point in many r and omized controlled trials of IBS and is considered by the Rome III committee to be an acceptable primary end point . However , controversy exists on whether baseline severity confounds the effect of the treatment outcome . The aim ( 1 ) is to compare a subjective report of IBS-AR with global assessment of improvement ( IBS-GAI ) , change in IBS symptom severity scale ( IBS-SSS ) , and IBS quality of life ( IBS-QOL ) ; ( 2 ) to explore whether initial IBS symptom severity influences the ability of these outcome measures to detect differences post treatment ; and ( 3 ) to determine whether psychological symptoms influence the sensitivity of these measures , in a r and omized controlled treatment trial . METHODS : A total of 289 adult IBS patients were recruited to a treatment trial . Baseline IBS-SSS scores were used to classify IBS severity as mild ( < 175 ) , moderate ( 175–300 ) , or severe ( > 300 ) . Question naires were completed at baseline and after 3 weeks of treatment with sham acupuncture or wait-list control . RESULTS : IBS baseline severity ( IBS-SSS ) significantly affected the proportion of patients who reported IBS-AR at 3 weeks ( mild , 70 % ; moderate , 49.7 % ; severe , 38.8 % ) ( P<0.05 ) . However , once the patients who reported IBS-AR at baseline ( 28.0 % ) were excluded from the analysis , baseline severity no longer affected the proportion of patients reporting IBS-AR . Baseline severity did not have a significant effect on patients reporting moderate or significant improvement on the IBS-GAI ( mild , 30 % ; moderate , 25.3 % ; severe , 18.8 % ) ( P = NS ) . Psychological symptoms had no significant correlations with responders after adjusting for baseline severity . CONCLUSIONS : These data suggest that IBS-AR as an end point is inversely related to baseline symptom severity . However , if patients who report AR at screening were excluded from study participation , baseline symptom severity was no longer confounded with a report of AR at the study end point Therapy trials with bacterial compounds in irritable bowel syndrome ( IBS ) have produced conflicting results . This study was performed in 1988 and 1989 , and was re-analysed according to current IBS st and ards . Two hundred ninety-seven patients with lower abdominal symptoms diagnosed as IBS were treated for 8 weeks by the compound ProSymbioflor((R ) ) ( Symbiopharm GmbH , Herborn , Germany ) , an autolysate of cells and cell fragments of Enterococcus faecalis and Escherichia coli , or placebo in a double-blinded , r and omized fashion . Patients were seen weekly by the physician , who assessed the presence of core IBS symptoms . Responders had at least a 50 % decrease in global symptom score ( GSS ) and in abdominal pain score ( APS ) reports at > /=1 visit during treatment . The responder rate in GSS to the drug was 102/149 ( 68.5 % ) in comparison to placebo with 56/148 ( 37.8 % ) ( P < 0.001 ) , the improvement in APS was 108/149 ( 72.5 % ) and 66/148 ( 44.6 % ) respectively ( P = 0.001 ) . The number-needed-to-treat was 3.27 for GSS and 3.59 for the APS report . Kaplan-Meier analysis revealed a mean response time of 4 - 5 weeks for active treatment and more than 8 weeks for placebo ( P < 0.0001 ) . Treatment of IBS with the bacterial lysate ProSymbioflor is effective and superior to placebo in reducing typical symptoms of IBS patients seen by general practitioners |
13,238 | 28,827,614 | In summary , neither preparation was shown to be consistently superior across all outcome measures .
The difference in effect between preparations on SH and TBUT was not clinical ly significant | This systematic review and meta- analysis compares sodium hyaluronate ( HY ) with non-HY based artificial tears in the treatment of dry eye syndrome . | PURPOSE To evaluate the efficacy and safety of 0.18 % sodium hyaluronate ophthalmic solution ( Rejena , Vismed ) compared with its vehicle for the treatment of signs and symptoms of dry eye disease . DESIGN R and omized , placebo-controlled clinical trial . METHODS A total of 444 subjects with dry eye disease were r and omized 1:1 to active study drug ( n = 221 ) or vehicle control ( n = 223 ) in this multicenter , double-masked trial . Subjects instilled 1 to 2 drops , 3 to 6 times daily for 14 days , with evaluations at Days 7 and 14 . The study 's 2 primary efficacy endpoints were change from baseline at Day 7 in lissamine green staining scores ( objective ) and in global symptom frequency scores ( subjective ) . Results were analyzed using Wilcoxon rank sum test and Student t test in the intent-to-treat ( ITT ) population with last observation carried forward ( LOCF ) . RESULTS At Day 7 , the differences between the active and vehicle groups in change from baseline for lissamine green staining score ( P = .050 , Wilcoxon ; P = .029 , t test ) and global symptom frequency score ( P = .050 , Wilcoxon ; P = .017 , t test ) were both statistically significant . There were no clinical ly relevant safety findings related to the use of Rejena . CONCLUSIONS This study demonstrated the clinical efficacy of Rejena in the treatment of dry eye disease in both a primary objective endpoint and a primary subjective endpoint when compared to its vehicle . The study results also supported the well-known safety profile of Rejena Background Dry eye is a common condition , affecting approximately 10–20 % of the adult population . Artificial tears are often effective in relieving symptoms in mild and moderate dry eye by replenishing deficient tear volume . Sodium hyaluronate has been proposed as a component in artificial tears , due to its viscoelastic rheology . This paper reports on a study carried out to assess the efficacy of two recently developed eyedrops containing 0.1 % and 0.3 % sodium hyaluronate ( SH ) in the treatment of moderate dry eye . Methods Thirteen subjects were recruited with moderate dry eye . Forty microlitres of 0.1 % SH , 0.3 % SH , or 0.9 % saline were instilled in both eyes , and the subjects ’ symptom intensity and non-invasive break-up time ( NIBUT ) were measured at 5 , 15 , 30 , 45 , and 60 min , and then hourly , until 6 h after drop instillation . This was repeated twice following an interval of 7(±1 ) days , but with a different treatment so that at the end of the final visit each subject had trialled all products . Drop allocation was r and omized and double-masked . Results Both symptoms and NIBUT improved with all treatments . These changes were of a larger magnitude and longer duration with the SH containing eyedrops than with saline . SH of 0.3 % tended to perform better than 0.1 % SH and achieved statistical significance ( P=0.04 ) for NIBUT when considered over the whole 6-h study period . Conclusions Sodium hyaluronate of 0.1 % and 0.3 % reduces symptoms of ocular irritation and lengthens NIBUT in subjects with moderate dry eye more effectively than saline , in terms of peak effect and duration of action BACKGROUND / AIMS Hyaluronan ( sodium hyaluronate ) has been shown to confer objective and subjective improvement in patients with dry eye syndrome . This study compared the efficacy and safety of a 0.1 % solution of hyaluronan with 0.9 % saline , when administered topically to the eye , in the treatment of symptoms of severe dry eye syndrome . METHODS A r and omised , double blind , crossover clinical trial in which subjects were r and omised to receive either hyaluronan or saline , applied as one or two drops to the eye , three or four times a day or as required . After 28 days ’ treatment , subjects crossed over to the other study medication for a further 28 days ’ treatment . RESULTS 70 subjects were included in the analyses of efficacy and significant improvements in Schirmer ’s score ( p=0.0006 ) and rose bengal staining score ( p=0.0001 ) were observed during treatment with hyaluronan . In a subjective assessment of the effectiveness of two treatments , a majority of subjects felt that hyaluronan was more effective than saline in alleviating the symptoms of burning and grittiness ( p<0.001 ) . No adverse events attributable to hyaluronan treatment were reported . CONCLUSION The study demonstrates a clear benefit of hyaluronan over saline , in both subjective and objective assessment s of dry eye syndrome . Hyaluronan was shown to be well tolerated Aims To assess the safety and performance of a 0.1 % ( w/v ) solution of sodium hyaluronate ( HA , Fermavisc ® , in the alleviation of symptoms of severe dry eye in comparison with a 1.4 % ( w/v ) solution of polyvinyl alcohol . Methods A r and omised , crossover , multicentre study carried out at eight centres in the UK . Eligible patients giving written informed consent were r and omised to the order in which they would receive the two study products . Each treatment period lasted for 4 weeks , then the patient crossed over to the other study product . Symptoms of burning and grittiness were assessed by visual analogue scale ( VAS ) at each study visit and other objective clinical assessment s of ocular structure and function were carried out at baseline and the end of each treatment period . Results Thirty-nine patients were entered into the study and 32 completed both treatment periods and were included in the statistical analyses . A significant improvement in the patients ’ VAS assessment of burning was seen after treatment with HA ( P = 0.03 , 95 % Confidence Interval : −23.5 to −1.1 ) . This treatment also result ed in a significantly lower rose bengal staining score ( P = 0.04 , 95 % Confidence Interval : −1.62 to −0.05 for the right eye ) . Conclusion The results show a significant clinical benefit in terms of relief of the symptom of burning when HA is applied topically to the eye three or four times per day or as required . HA also appears to have a protective effect on the corneal epithelium , as shown by a reduction in the level of staining of corneal epithelial cells by rose bengal . This study confirms that Fermavisc ® is a safe and effective product for use in the alleviation of symptoms of severe dry eye syndrome Background The ocular surface changes of keratoconjunctivitis sicca ( KCS ) could be the result of the effect of an altered tear film on the epithelial environment . Purpose To evaluate the possibility of improving the environmental conditions of the ocular surface by lowering tear osmolarity , increasing tear film volume and stabilising the tear film . Also , to study the effect of such an improvement on the epithelial cells of the ocular surface . Methods One hundred and thirty-five patients with a diagnosis of KCS were treated on a r and omised basis with either unpreserved hypotonic 0.4 % hyaluronic acid ( HHA ) eye drops or 0.3 % hydroxypropylmethylcellulose plus 0.1 % Dextran 70 ( HPMC ) eye drops 6 times a day for 60 or 90 days . In all patients a Schirmer I test , break-up time ( BUT ) , ocular surface staining with 1 % Bengal Rose , or 2 % fluorescein , as well as subjective symptoms , were recorded before and 15 , 30 and 60 days after the beginning of the study . Patients were divided into three subgroups and the effect of the treatment was studied using three different techniques : the tear ferning test , conjunctival impression cytology and tear osmolarity measurement . Results Improvements in BUT , vital staining , Schirmer I and symptoms were recorded in both groups of treatment , with significant differences for patients treated with 0.4 % HHA . On day 60 , 30 min after installation : tear ferning patterns changed from 100 % pathological ( types III – IV ) to 93 % physiological ( types I – II ) in the 0.4 % HHA group and from 100 % pathological to 78 % physiological in the 0.3 % HPMC group ( p < 0.01 between groups ) . Tear osmolarity shifted from 353 ± 23 to 305 ± 6 mosmolA in the 0 - 4 % HHA group and from 346 ± 15 to 336 ± 8 mosmol/l in the 0.3 % HPMC group ( p < 0.001 between groups ) . On day 90 , the impression cytology score improved from 1.2 to 1.9 in the 0.4 % HHA group while it did not change in the 0.3 % HPMC group ( p < 0.05 between groups ) . Conclusion In KCS appropriate treatment with a hypotonic 0.4 % HHA tear substitute can change the tear environment and results in improvement of the epithelial conditions of the ocular surface This study assessed the repeatability of various methods of measuring tear break-up time ( TBUT ) with and without soft contact lenses ( CLs ) . TBUT was measured on 22 subjects with the tearscope , videokeratoscope and slit-lamp before and after 30 min of soft CL wear , and immediately after CL removal . Slit-lamp corneal TBUT was measured with fluorescein and without fluorescein while wearing CLs . TBUT was measured three times on the right eye only , using each technique in r and omised order . TBUT measurements on CLs were repeated a second day . TBUT measurements were highly variable under all conditions and our results indicated a lack of correlation between techniques . The videokeratoscope was the least repeatable ; while the tearscope was the most repeatable technique Between mid-May and mid-July 1987 we performed a prospect i ve crossover study of two unit-dose preservative-free artificial tear solutions , 1.4 % polyvinyl alcohol ( Refresh ) and 0.1 % sodium hyaluronate ( Hylorin ) in 14 female patients with severe dry eye syndrome . The patients were examined before treatment and after each of two trials with both products . A significant reduction in the mean score for dry-eye-induced keratitis ( p = 0.001 ) and for mucous str and s ( p = 0.03 ) was observed following the second of two trials with sodium hyaluronate . A significant reduction in the mean score for burning and irritation was observed with both solutions ( p = 0.009 ) . We believe that the elimination of preservatives from artificial tear preparations may substantially reduce the iatrogenic effects of these frequently applied medications Clinical trials to evaluate the effectiveness of therapy for dry eye disease are challenging because of the nature of the disease , the multiple palliative methods used by patients to control their symptoms , and the potential limitations of the techniques available to evaluate therapeutic outcomes . This review identifies some of the pitfalls encountered in recent clinical trials in dry eye disease . The peculiarities of dry eye disease with respect to symptoms , signs , and patho- physiological changes are discussed . Potential problems that apply to all clinical trials , including patient selection , r and omization in small population s , and assessment of the placebo effect , are presented with respect to dry eye clinical trials . Considerations regarding study design address inclusion /exclusion criteria and selection of outcome measures . Special attention is given to methods of symptom analysis , techniques of staining of the ocular surface , and grading systems for surface staining . Alternative methods to the st and ard clinical trial are mentioned to place them in perspective for overall evaluation of dry eye disease therapy . Finally , caveats are provided to encourage investigators to vigorously conduct future clinical trials in dry eye therapy Purpose : To compare the effects of Viscofresh 0.5 % ( carmellose sodium 0 . 5 % ) versus Lubristil ( sodium hyaluronate 0.15 % ) in dry eye syndrome and to study the influence of these two treatments on the expression of various inflammatory markers by flow cytometry in impression cytology specimens . Methods : In this r and omized , masked-observer , parallel group , single-center study , 15 patients with dry eye syndrome were r and omized to sodium carmellose 0.5 % or sodium hyaluronate 0.15 % 1-month treatment after a 1-week washout period . Corneal staining with flurescein , breakup time , Schirmer 1 test with anesthesia ( Jones test ) , and tear clearance were assessed . Besides , conjunctival impression cytology was performed to investigate inflammatory markers ( CD3 , CD11b , and HLA-DR ) using flow cytometry . Results : Carmellose group shows statistical improvement compared with the hyaluronate group in breakup time , corneal staining , and HLA-DR . The two other inflammatory markers had also a tendency for a decreased expression in both groups , with no statistical significance . There were neither visual acuity loss nor other complications related to treatment . Conclusion : Both artificial tears improve dry eye signs and symptoms and inflammatory markers expression , with significant better results in carmellose group Background / aims : Several studies have reported that sodium hyaluronate is able to improve both symptoms and signs in patients with dry eye but none have demonstrated an improvement of conjunctival epithelial cell abnormalities of the ocular surface . The aim of this study was to explore the effect of sodium hyaluronate-containing eye drops on the ocular surface of patients with dry eye during long term treatment . Methods : A r and omised double blind study was undertaken in 86 patients with medium to severe dry eye ( that is , rose bengal and /or fluorescein test score of at least 3 , tear film break up time < 10 seconds , or Schirmer 's test < 5.5 mm ) . Patients were treated with either preservative-free sodium hyaluronate or saline for 3 months at a dose of one drop 4–8 times a day . Bulbar impression cytology , slit lamp examinations , and subjective symptoms were evaluated after 1 , 2 , and 3 months . Impression cytology was considered the primary efficacy parameter of the study . Results : The efficacy analysis was performed on a total of 44 patients who were able to fully adhere to the protocol . After 3 months of treatment sodium hyaluronate improved impression cytology score ( p = 0.024 v baseline ) . At the same time also the difference with respect to placebo was statistically significant ( p = 0.036 ) . Study medication was well tolerated and no treatment related adverse events occurred during the study . Conclusions : Sodium hyaluronate may effectively improve ocular surface damage associated with dry eye syndrome Background Sodium hyaluronate ( SH ) is used in patients with dry eye . We evaluated the efficacy and safety of SH and carboxymethylcellulose ( CMC ) in the treatment of dry eye syndrome with superficial keratitis . Methods A total of 22 patients with moderate dry eye and superficial keratitis were enrolled in a prospect i ve , r and omised , masked-observer , parallel-group , single-centre study . Patients were r and omly assigned to a 0.18 % SH or 1 % CMC solution for a 2-month period . In addition to the commonly assessed parameters in patients with dry eye ( among others symptoms and corneal staining with fluorescein ) , flow cytometry analysis of CD44 , HLA DR expressions in impression cytology was investigated as a potential efficacy parameter . Results Both treatments improved the symptoms and ocular surface and were well tolerated . SH significantly ( p<0.05 ) decreased CD44 values compared with CMC . Comfort was significantly ( P<0.05 ) better in the SH group than that in the CMC group throughout the study . Recovery in keratitis ( type , extent and depth ) and symptoms were faster in the SH group than in the CMC group . Blurred vision was reported by patients in the CMC group only . Conclusions SH was well tolerated and tended to show a faster efficacy than did the CMC-based formulation in patients with moderate dry eye and superficial keratitis . SH could therefore advantageously be prescribed from the early stages of dry eye disease . This study also showed that flow cytometry in impression cytology specimens is a reliable tool for exploring the ocular surface at the epithelial level and that CD44 , in addition to HLA DR , could be an interesting endpoint for future trials in dry eye syndrome with products based on SH Purpose To determine which subjective assessment s and objective tests have clinical utility as diagnostic tools in ocular irritation associated with Sjögren 's syndrome — related aqueous tear deficiency ( ATD ) , non-Sjögren ATD , inflammatory meibomian gl and disease ( MGD ) associated with rosacea , and atrophic MGD . Methods Forty adults with ocular irritation and 10 with normal ocular surfaces were enrolled in a nonr and omized , nonblinded clinical trial . Symptoms were evaluated . Tests included biomicroscopy ; evaluation of tear-film integrity , production , and clearance ; fluorescein and rose bengal staining ; and serum autoantibody screening . Results Symptoms were similar among groups and most severe in the Sjögren 's group . Fluorescein tear break-up time was significantly faster in the ATD and MGD groups than that in controls . Schirmer scores were significantly lower in the ATD group than those in MGD and control groups . Tear clearance was delayed in the ATD and atrophic MGD groups . Xeroscope grid distortion was noted only with ATD . The Sjögren 's group had greater loss of nasolacrimal reflex , slower fluorescein clearance , and greater ocular-surface fluorescein and rose bengal staining than did the others . More MGD subjects had meibomian gl and orifice metaplasia and acinar dropout than did those with Sjögren-related ATD and controls . Schirmer scores correlated inversely with rose bengal staining , corneal fluorescein staining , and grid distortion . Rose bengal staining correlated with grid distortion and loss of nasal — lacrimal reflex , but not with MGD . Conclusion Subjective assessment s and objective diagnostic tests have clinical utility as diagnostic tools in tear-film disorders . ATD is correlated with ocular-surface disease . An algorithm summarizing the diagnostic utility of these tests is included PURPOSE To evaluate the efficacy of three commercially available lubricant eye drops for the treatment of mild , dry , irritated eyes . METHODS R and omized , investigator-masked evaluation of 60 patients in which 20 patients used carboxymethylcellulose sodium ( CMC ) , 0.5 % ( Cellufresh ) , Allergan Inc. , Irvine , CA ) ( group 1 ) ; 20 patients used a drop containing polyethylene glycol 400 , 2.5 % and sodium hyaluronate ( Blink Intensive Tears , Abbott Medical Optics Inc. , Santa Ana , CA ) ( group 2 ) ; and 20 patients used HP Guar 0.18 % ( Systane , Alcon Laboratories Inc. , Ft . Worth , TX ) ( group 3 ) . Study visits were at baseline and 1 month . Tests performed at both visits included Schirmer , tear-film break-up time ( TBUT ) , visual acuity , fluorescein staining , tear osmolarity and wavefront aberrometry . Osmolarity testing was performed prior to instillation of the lubricant eye drops and then a final time 5min after instillation of the drop at both day 1 and day 30 . Tear osmolarity was performed only in the right eye and only one time before and after instillation of lubricant eye drops . RESULTS At day 1 the mean reduction in osmolarity 5min after instillation of the lubricant eye drop was , -5.0+/-1.9 in group 1 , -9.0+/-4.2 in group 2 and -5.0+/-2.2 in group 3 . At day 30 the mean reduction in osmolarity 5min after instillation of the lubricant eye drop was , -5.6+/-2.3mOsm/L in group 1 ; -9.9+/-2.8mOsm/L in group 2 and -4.5+/-1.8mOsm/L in group 3 . The differences were statistically significant between groups 1 and 2 , and 2 and 3 . There was a reduction of osmolarity from day 1 to day 30 but the differences were not statistically significant . We feel that after a 30-day treatment with the lubricant eye drops , the lower osmolarity values could indicate that the tear film is progressing towards a more normal osmolarity value . A future study could examine the tear osmolarity value after 60 or 90 days of usage . LogMAR best-corrected visual acuity ( BCVA ) results showed an improvement in group 2 compared with baseline with no change in BCVA in groups 1 and 3 . There was no statistically significant change from day 1 to 1 month in TBUT , while the Schirmer test showed an improvement in all groups at 1 month . CONCLUSIONS Assessment of tear osmolarity provides the most objective , measurable test for determining improvement in dry eye patients . The instillation of any artificial tear or lubricant eye drop should decrease the tear-film osmolarity . The results found that polyethylene glycol 400 , 0.25 % and sodium hyaluronate ( Blink Intensive Tears ) significantly improved tear osmolarity compared with carboxymethylcellulose sodium ( CMC ) , 0.5 % ( Cellufresh ) and HP Guar 0.18 % ( Systane after instillation An unpreserved artificial tear substitute containing 0.1 % sodium hyaluronate was compared with a preparation containing 1.4 % polyvinyl alcohol and 0.5 % chlorobutanol in a controlled , double-masked , r and omized study in patients with moderately severe keratoconjunctivitis sicca . Patients were evaluated initially , at 1 , 4 , and 8 weeks . The dry-eye status was evaluated by means of tear-film osmolality , tear breakup time , rose bengal staining , Schirmer 's test ( without anesthesia ) , and ocular surface-impression cytology . In general , neither preparation was found to be superior to the other . In both study groups , the mean tear-film osmolality and rose bengal staining score improved over the eight-week study , but the degree of squamous metaplasia of the bulbar conjunctival surface , as shown by impression cytology , did not change significantly Tear osmolarity and Rose Bengal staining were studied in a group of patients with keratoconjunctivitis sicca ( KCS ) before and after treatment with isotonic and one-half isotonic saline to compare treatment with these two solutions and to ascertain whether tear film osmolarity could be correlated with ocular surface disease . When 20 KCS eyes were treated with isotonic saline drops every three hours for one week , the average ( + /-SD ) tear osmolarity decreased from 365 + /- 77 mOsm/L to 329 + /- 47 mOsm/L , and the average ( + /-SD ) Rose Bengal staining score decreased from 4.1 + /- 3.1 to 3.6 + /- 3.3 . There was no objective difference between treatment with isotonic and one-half isotonic solutions , in a double-masked comparison , however , four of five patients with diagnostically significant Rose Bengal staining preferred the half isotonic solution . There was a significant positive correlation between tear film osmolarity and Rose Bengal staining BACKGROUND / AIMS To compare the safety and efficacy of hypotonic 0.18 % sodium hyaluronate solution ( 0.18 % SH ) versus saline and versus 0.3 % carbomer for the treatment of signs and symptoms of moderate dry eye syndrome . METHODS A total of 304 patients were r and omized ( 1:1:1 ) in this parallel-group , multi-center , phase III trial . They were instructed to instill one drop of the allocated product in each eye two to four times per day over 84 days . The primary efficacy criterion was the change from baseline at Day 28 in symptom frequency score . The superiority of 0.18 % SH ( Vismed ( ® ) ) over saline and its non-inferiority versus carbomer were statistically tested . RESULTS At Day 28 , there was a statistically significant superiority of 0.18 % SH over saline in change from baseline for subjective symptom frequency score ( P=0.0376 , primary endpoint ) and objective fluorescein staining score ( P=0.0074 , secondary endpoint ) . 0.18 % SH had an excellent safety profile over 84 days . A strong trend was observed in favour of 0.18 % SH to cause less blurred vision than carbomer throughout the trial ( P=0.0798 at Day 28 ) . CONCLUSION 0.18 % SH caused a statistically significant improvement in both a subjective endpoint ( symptom frequency score ) and an objective endpoint ( fluorescein staining score ) . 0.18 % SH was well tolerated and result ed in low incidence of adverse events Twenty patients with keratoconjunctivitis sicca used three different viscoelastic tear formulations and a polyvinyl alcohol artificial tear for two weeks each . Each formulation was used once every two waking hours in a controlled double-masked study . Eighteen patients reported marked improvement over the course of the study , in terms of the severity of itching , burning , and foreign body sensation . Corneal staining and mucous str and formation were also reduced in patients with these manifestations . No formulation was preferred by a majority of patients or proved superior in treating signs of keratoconjunctivitis sicca . However , patients with low Schirmer test scores uniformly preferred a solution containing chondroitin sulfate , while patients with moderate Schirmer test scores tended to prefer a solution of polyvinyl alcohol or hyaluronic acid Introduction The clinical diagnosis of dry-eye is confirmed by a suitable test of tear production and the technique commonly used today to diagnose dry eye is the Schirmer ’s test ( ST ) . Although the ST is easy to perform it gives variable results , poor reproducibility and low sensitivity for detecting dry eyes . Another test , the tear break up time ( TBUT ) is used to assess the stability of tears which if abnormal may also cause symptomatic dry-eye . We present the results of both these tests and a new test , which shows greater sensitivity than the ST in detecting aqueous tear deficiency . The fluorescein meniscus time ( FMT ) is a new test developed in conjunction with one of the authors ( CL ) and the Department of Ophthalmology at the University Hospital of Wales . The FMT is a measure of the rate at which a fluorescent tear meniscus is formed using 2 % sodium fluorescein , a stopwatch and suitable illumination with a slit lamp . Method An open controlled study in 62 patients and 51 controls was conducted to compare the ability of ST , FMT and TBUT to detect dry-eye in a group of patients diagnosed with rheumatoid arthritis and symptomatic dry eyes for a minimum period of 6 months . A separate control group of 15 subjects was tested on three separate occasions to assess the reproducibility of the FMT test . Results All three tests showed a statistically significant difference between the patient and control population s ; Mann – Whitney P < 0.001 . There was a correlation between the right and left eye for all three tests in the control group ( ST r2 = 0.77 , FMT r2 = 0.98 , TBUT r2 = 0.94 ) . This correlation was markedly reduced for FMT and TBUT in the patient population and was in keeping with the symptoms reported as being worse on one side in a proportion of the patients ( FMT r2 = 0.52 , TBUT r2 = 0.54 , ST r2 = 0.75 ) . A correlation with age was also observed for all the three tests in the control group ( ST r2 = 0.74 , FMT r2= 0.92 , TBUT r2 = 0.51 ) , but not in the patient population ( ST r2 = 0.06 , FMT r2 = 0.18 , TBUT r2 = 0.03 ) . A significant correlation was observed between the ST and FMT in both the control ( ST vs FMT r2 = 0.65 ) and patient population ( ST vs FMT r2 = 0.44 ) . There was no value greater than 200 seconds for FMT recorded in the control group . Using this value to define an abnormal FMT , 85 % of the patients ( 72 % of the eyes tested ) had an abnormal result . This was in contrast to 35 % of patients ( 26 % of the eyes tested ) with abnormal results detected by ST.Using ANOVA and Student ’s paired t-test , there were no significant differences between the three sets of values recorded serially over 3 months to assess the reproducibility of the FMT . The average st and ard error of the mean was 2.72 % and the average co-efficient of variation 4.07 % . Conclusion Our study suggests that the FMT is a more sensitive test with good reproducibility compared to the Schirmer ’s test . The FMT correlates with the ST and suggests that both tests measure aqueous tear deficiency . The FMT therefore is a better alternative to ST currently being used to test aqueous tear deficiency Purpose : We compared the efficacy and safety of sodium hyaluronate ( SH ) and carboxymethylcellulose ( CMC ) in treating mild to moderate dry eye . Methods : Sixty-seven patients with mild to moderate dry eye were enrolled in this prospect i ve , r and omized , blinded study . They were treated 6 times a day with preservative-free unit dose formula eyedrops containing 0.1 % SH or 0.5 % CMC for 8 weeks . Corneal and conjunctival staining with fluorescein , tear film breakup time , subjective symptoms , and adverse reactions were assessed at baseline , 4 weeks , and 8 weeks after treatment initiation . Results : Thirty-two patients were r and omly assigned to the SH group and 33 were r and omly assigned to the CMC group . Both the SH and CMC groups showed statistically significant improvements in corneal and conjunctival staining sum scores , tear film breakup time , and dry eye symptom score at 4 and 8 weeks after treatment initiation . However , there were no statistically significant differences in any of the indices between the 2 treatment groups . There were no significant adverse reactions observed during follow-up . Conclusions : The efficacies of SH and CMC were equivalent in treating mild to moderate dry eye . SH and CMC preservative-free artificial tear formulations appropriately manage dry eye sign and symptoms and show safety and efficacy when frequently administered in a unit dose formula Purpose To compare a treatment containing carboxymethylcellulose ( CMC ) and the osmoprotective ( OsPr ) compatible osmolytes erythritol , L-carnitine , and glycerin ( OsPr-CMC ) with a st and ard sodium hyaluronate ( Na-HY ) formulation in patients with dry eye disease . Methods This was a 3-month , phase III , noninferiority study . Patients were r and omized 1:1 to receive OsPr-CMC ( OPTIVE ® ) or Na-HY ( VISMED ® ) . The primary efficacy outcome was the mean change from baseline in total ocular staining at day 35 , scored using the 15-point Oxford scale . Noninferiority was assessed using the adjusted means . The secondary efficacy outcome was change in ocular surface disease index ( OSDI ) score from baseline to day 35 . Other outcomes included tear osmolarity , Schirmer-I test score , OSDI , ease of use , patient acceptability , tolerability , and safety . Results A total of 82 patients were r and omized . The primary efficacy analysis was per protocol ( OsPr-CMC , n=37 ; Na-HY , n=29 ) . OsPr-CMC was noninferior to Na-HY in terms of adjusted mean change ( SE ) in ocular staining score at day 35 : −2.0 ( 0.33 ) with OsPr-CMC vs −1.7 ( 0.37 ) with Na-HY . Similar improvements were seen in tear osmolarity , Schirmer-I test score , OSDI , and ocular staining for OsPr-CMC and Na-HY . More patients treated with OsPr-CMC vs Na-HY liked using their eyedrops , reported that their eyes felt comfortable , and found the treatment easy to use . Both treatments were well tolerated , with no serious treatment-related adverse events . Conclusions Compared with Na-HY , OsPr-CMC was noninferior in terms of efficacy and safety , preferred by patients , and easier to use . Osmoprotection using OsPr-CMC therefore represents a viable option for dry eye disease management Abstract . The effect of sodium hyaluronate eye drops in the treatment of severe keratoconjunctivitis sicca ( KCS ) was evaluated in a double masked crossover trial , comparing the effect of a 0.1 % solution , a 0.2 % solution and placebo in 20 patients . We found significantly decreased rose bengal staining and increased break‐up time following 0.2 % treatment compared to placebo . No significant difference was found in the Schirmer values and the cornea sensitivity . The patients significantly preferred sodium hyaluronate treatment . We conclude that sodium hyaluronate eye drops seem to be a valuable new agent in the management of KCS Purpose : To compare the efficacies of sodium hyaluronate , hydroxypropyl methylcellulose ( HPMC ) , and a new oil-in-water emulsion ( Emustil unidose ; SIFI ) in the management of lipid-deficient dry eye . Methods : Seventy-five subjects with dry eye were r and omly divided into 3 groups . Each was allocated sodium hyaluronate , HPMC , or emulsion eyedrops to be used four times daily for 90 days . Parameters were measured at baseline , 30 days , and 90 days . A compliance visit was performed at days 7 and 60 . Results : Significant reduction ( P < 0.05 ) in evaporation and improvement in symptoms in all groups were found . No statistically significant increase in tear turnover rate ( TTR ) was found with any solution . A significant difference in tear stability and noninvasive tear break-up time ( NITBUT ) was found in the emulsion and sodium hyaluronate groups but not in the HPMC group ( P > 0.05 ) . There was a significant decrease in osmolarity and corneal staining in the emulsion group ( P < 0.001 ) but not in the sodium hyaluronate or HPMC group ( P > 0.05 ) . Conclusions : A significant reduction in evaporation and improvement in symptoms in all therapy groups were found from baseline to 90 days . However , no significant effect was seen on TTR for any group . The emulsion drops were shown to perform best , improving tear stability , and decreasing osmolarity and corneal staining . These results are consistent with improvements in the lipid layer of the tear film as a result of prolonged use of emulsion drops |
13,239 | 26,379,862 | More importantly , after lenalidomide treatment , the patients with non-GCB DLBCL did not show significantly worse progression-free survival ( PFS ) and overall survival ( OS ) compared with GCB subtype .
Lenalidomide as treatments for DLBCL patients , non-GCB DLBCL patients did not show significantly worse prognosis compared with GCB DLBCL | Lenalidomide has been shown to produce durable responses in patients with relapsed or refractory diffuse large B cell lymphoma ( DLBCL ) .
In order to gain better underst and ing of the efficacy of lenalidomide and compared the difference in clinical outcome between two subtypes of DLBCL . | Despite improvements in st and ard therapy with rituximab , cyclophosphamide , doxorubicin , vincristine and prednisone for patients with untreated , diffuse large B-cell lymphoma , up to 40 % of these patients relapse . Lenalidomide alone or in combination with rituximab has been shown to be active in relapsed/refractory aggressive lymphomas . In this phase I study we determined the maximum tolerated dose of lenalidomide plus rituximab , cyclophosphamide , doxorubicin , vincristine and prednisone in untreated , elderly ( median age 68 years ) patients with diffuse large B-cell lymphoma . Four lenalidomide doses ( 5 , 10 , 15 , and 20 mg/day on days 1–14 ) allocated using the continual re assessment method were planned to be administered for 14 days in combination with each course of rituximab , cyclophosphamide , doxorubicin , vincristine and prednisone for a total of six courses . Seven cohorts of patients ( n=3 in each cohort ) were treated ( total n=21 ) at 10 , 20 , 15 , 15 , 15 , 10 , and 10 mg of lenalidomide . Dose-limiting toxicities occurred in seven patients during the first three courses of treatment . The third dose-level of lenalidomide ( 15 mg/day ) was selected as the maximum tolerated dose , with an estimated probability of dose-limiting toxicities of 0.345 ( 95 % credibility interval 0.164–0.553 ) . Grade 3–4 hematologic adverse events were : neutropenia in 28 % of the courses , thrombocytopenia in 9 % , and anemia in 3 % . Non-hematologic toxicities were moderate : grade 4 increase of creatinine phosphokinase ( n=1 ) , grade 3 cardiac ( n=2 ) , grade 3 neurological ( n=3 ) , and grade 3 gastrointestinal ( n=1 ) . In this phase I study , the overall response rate was 90 % , with 81 % achieving complete remission . This combination regimen appears safe in elderly patients with diffuse large B-cell lymphoma and its efficacy will be assessed in the ongoing phase II trial . This trial was registered at www . clinical trials.gov as NCT00907348 BACKGROUND Cyclophosphamide , doxorubicin , vincristine , and prednisolone ( CHOP ) is used to treat patients with non-Hodgkin lymphoma . Interval decrease from 3 weeks of treatment ( CHOP-21 ) to 2 weeks ( CHOP-14 ) , and addition of rituximab to CHOP-21 ( R-CHOP-21 ) has been shown to improve outcome in elderly patients with diffuse large B-cell lymphoma ( DLBCL ) . This r and omised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14 . METHODS 1222 elderly patients ( aged 61 - 80 years ) were r and omly assigned to six or eight cycles of CHOP-14 with or without rituximab . Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement . The primary endpoint was event-free survival ; secondary endpoints were response , progression during treatment , progression-free survival , overall survival , and frequency of toxic effects . Analyses were done by intention to treat . The trial is registered on National Cancer Institute website , number NCT00052936 and as EU-20243 . FINDINGS 3-year event-free survival was 47.2 % after six cycles of CHOP-14 ( 95 % CI 41.2 - 53.3 ) , 53.0 % ( 47.0 - 59.1 ) after eight cycles of CHOP-14 , 66.5 % ( 60.9 - 72.0 ) after six cycles of R-CHOP-14 , and 63.1 % ( 57.4 - 68.8 ) after eight cycles of R-CHOP-14 . Compared with six cycles of CHOP-14 , the improvement in 3-year event-free survival was 5.8 % ( -2.8 - 14.4 ) for eight cycles of CHOP-14 , 19.3 % ( 11.1 - 27.5 ) for six cycles of R-CHOP-14 , and 15.9 % ( 7.6 - 24.2 ) for eight cycles of R-CHOP-14 . 3-year overall survival was 67.7 % ( 62.0 - 73.5 ) for six cycles of CHOP-14 , 66.0 % ( 60.1 - 71.9 ) for eight cycles of CHOP-14 , 78.1 % ( 73.2 - 83.0 ) for six cycles of R-CHOP-14 , and 72.5 % ( 67.1 - 77.9 ) for eight cycles of R-CHOP-14 . Compared with treatment with six cycles of CHOP-14 , overall survival improved by -1.7 % ( -10.0 - 6.6 ) after eight cycles of CHOP-14 , 10.4 % ( 2.8 - 18.0 ) after six cycles of R-CHOP-14 , and 4.8 % ( -3.1 - 12.7 ) after eight cycles of R-CHOP-14 . In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference , and adjusting for known prognostic factors , all three intensified regimens improved 3-year event-free survival ( eight cycles of CHOP-14 : RR [ relative risk ] 0.76 [ 0.60 - 0.95 ] , p=0.0172 ; six cycles of R-CHOP-14 : RR 0.51 [ 0.40 - 0.65 ] , p<0.0001 ; eight cycles of R-CHOP-14 : RR 0.54 [ 0.43 - 0.69 ] , p<0.0001 ) . Progression-free survival improved after six cycles of R-CHOP-14 ( RR 0.50 [ 0.38 - 0.67 ] , p<0.0001 ) , and eight cycles of R-CHOP-14 ( RR 0.59 [ 0.45 - 0.77 ] , p=0.0001 ) . Overall survival improved only after six cycles of R-CHOP-14 ( RR 0.63 [ 0.46 - 0.85 ] , p=0.0031 ) . In patients with a partial response after four cycles of chemotherapy , eight cycles were not better than six cycles . INTERPRETATION Six cycles of R-CHOP-14 significantly improved event-free , progression-free , and overall survival over six cycles of CHOP-14 treatment . Response-adapted addition of chemotherapy beyond six cycles , though widely practice d , is not justified . Of the four regimens assessed in this study , six cycles of R-CHOP-14 is the preferred treatment for elderly patients , with which other approaches should be compared Lenalidomide – rituximab therapy is effective in grade 1–2 follicular and mantle cell lymphoma , but its efficacy in diffuse large B-cell lymphoma ( DLBCL ) , transformed large cell lymphoma ( TL ) and grade 3 follicular lymphoma ( FLG3 ) is unknown . In this phase II trial , 45 patients with relapsed or refractory DLBCL ( n=32 ) , TL ( n=9 ) or FLG3 ( n=4 ) who had received 1–4 prior lines of treatment were given 20 mg oral lenalidomide on days 1–21 of each 28-day cycle , and intravenous rituximab ( 375 mg/m2 ) weekly during cycle 1 . Grade 3/4 hematological toxicities included neutropenia ( 53 % ) , lymphopenia ( 40 % ) , thrombocytopenia ( 33 % ) , leukopenia ( 27 % ) and anemia ( 18 % ) , with a median follow-up time of 29.1 months ( range 14.7–52.0 months ) . Overall response ( OR ) rate was 33 % ; median response duration was 10.2 months . Median progression-free survival ( PFS ) and overall survival ( OS ) were 3.7 and 10.7 months , respectively . Nine of the 15 responding patients ( three partial response ( PR ) , six complete response ( CR ) ) proceeded with stem cell transplantation ( SCT ) and were censored at the time of transplantation . When data were analyzed without censoring , median PFS remained 3.7 months and response duration increased to 30.9 months . Rituximab plus oral lenalidomide is well tolerated and effective for patients with relapsed/refractory DLBCL and TL . SCT after lenalidomide – rituximab is associated with prolonged response duration Relapsed/refractory diffuse large B‐cell lymphoma ( DLBCL ) is associated with a poor prognosis . Outcomes are particularly poor following immunochemotherapy failure or relapse within 12 months of induction . We conducted a Phase I/II trial of lenalidomide plus RICE ( rituximab , ifosfamide , carboplatin , and etoposide ) ( RICER ) as a salvage regimen for first‐relapse or primary refractory DLBCL . Dose‐escalated lenalidomide was combined with RICE every 14 d. After three cycles of RICER , patients with chemosensitive disease underwent stem cell collection and consolidation with BEAM [ BCNU ( carmustine ) , etoposide , cytarabine , melphalan ] followed by autologous stem cell transplantation ( autoSCT ) . Patients who recovered from autoSCT toxicities within 90 d initiated maintenance treatment with lenalidomide 25 mg daily for 21 d every 28 d for 12 months . No dose‐limiting or unexpected toxicities occurred with lenalidomide 25 mg plus RICE . Grade 3/4 haematological toxicities resolved appropriately , and planned dose density and dose intensity of RICER were preserved . No lenalidomide or RICE dose reductions were required in any of the three cycles . After two cycles of RICER , nine of 15 patients ( 60 % ) achieved a complete response , and two achieved a partial response ( 13 % ) . Combining lenalidomide with RICE is feasible , and results in promising response rates ( particularly complete response rates ) in high‐risk DLBCL patients BACKGROUND Lenalidomide is an immunomodulatory agent with antitumor activity in B-cell malignancies . This phase II trial aim ed to demonstrate the safety and efficacy of lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma ( DLBCL ) , mantle cell lymphoma ( MCL ) , follicular grade 3 lymphoma ( FL-III ) , or transformed lymphoma ( TL ) . METHODS Patients received oral lenalidomide 25 mg on days 1 - 21 every 28 days as tolerated or until progression . The primary end point was overall response rate ( ORR ) . RESULTS Two hundred and seventeen patients enrolled and received lenalidomide . The ORR was 35 % ( 77/217 ) , with 13 % ( 29/217 ) complete remission ( CR ) , 22 % ( 48/217 ) partial remission , and 21 % ( 45/217 ) with stable disease . The ORR for DLBCL was 28 % ( 30/108 ) , 42 % ( 24/57 ) for MCL , 42 % ( 8/19 ) for FL-III , and 45 % ( 15/33 ) for TL . Median progression-free survival for all 217 patients was 3.7 months [ 95 % confidence interval ( CI ) 2.7 - 5.1 ] . For 77 responders , the median response duration lasted 10.6 months ( 95 % CI 7.0-NR ) . Median response duration was not reached in 29 patients who achieved a CR and in responding patients with FL-III or MCL . The most common adverse event was myelosuppression with grade 4 neutropenia and thrombocytopenia in 17 % and 6 % , respectively . CONCLUSION Lenalidomide is well tolerated and produces durable responses in patients with relapsed or refractory aggressive non-Hodgkin 's lymphoma BACKGROUND Up to 40 % of elderly patients with untreated diffuse large B-cell lymphoma ( DLBCL ) given a regimen of rituximab , cyclophosphamide , doxorubicin , vincristine , and prednisolone every 21 days ( R-CHOP21 ) relapse or develop refractory disease . Lenalidomide has high activity in relapsed or refractory aggressive B-cell lymphomas . In phase 2 of the REAL07 trial , we aim ed to establish the safety and efficacy of the combination of lenalidomide and R-CHOP21 in elderly patients with untreated DLBCL . METHODS REAL07 was an open-label , multicentre trial that was done in 13 centres in Italy and one in Germany . Eligible patients were aged 60 - 80 years ; had newly diagnosed , untreated , CD20-positive , Ann Arbor stage II-IV DLBCL or grade 3b follicular lymphoma ; had an Eastern Cooperative Oncology Group performance status of 0 - 2 ; had an International Prognostic Index ( IPI ) risk of low-intermediate , intermediate-high , or high ; and were fit according to comprehensive geriatric assessment . Participants were to receive 15 mg oral lenalidomide on days 1 - 14 of six 21-day cycles , and st and ard doses of R-CHOP21 chemotherapy ( 375 mg/m(2 ) intravenous rituximab , 750 mg/m(2 ) intravenous cyclophosphamide , 50 mg/m(2 ) intravenous doxorubicin , and 1·4 mg/m(2 ) intravenous vincristine on day 1 , and 40 mg/m(2 ) oral prednisone on days 1 - 5 ) . The primary endpoint was frequency of overall response ( complete response [ CR ] and partial response [ PR ] ) , which was assessed by (18)F-fluorodeoxyglucose ( (18)F-FDG ) PET at the end of the treatment . Analyses were by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00907348 . FINDINGS 49 patients were included in phase 2 : nine had been enrolled into phase 1 between Oct 23 , 2008 , and June 4 , 2009 , and had received the maximum tolerated dose of 15 mg lenalidomide ; and 40 were enrolled into phase 2 between April 28 , 2010 , and June 3 , 2011 . 45 patients ( 92 % , 95 % CI 81 - 97 ) achieved a response ( 42 [ 86 % ] CR ; three [ 6 % ] PR ) . Three patients ( 6 % ) did not respond and one ( 2 % ) died for reasons unrelated to treatment or disease . 277 ( 94 % ) of 294 planned cycles of lenalidomide and R-CHOP21 were completed . Grade 3 - 4 neutropenia was reported in 87 cycles ( 31 % ) , grade 3 - 4 leukopenia in 77 ( 28 % ) , and grade 3 - 4 thrombocytopenia in 35 ( 13 % ) . No grade 4 non-haematological adverse events were reported . No patients died during the study as a result of toxic effects . INTERPRETATION Lenalidomide with R-CHOP21 is effective and safe in elderly patients with untreated DLBCL . FUNDING Fondazione Italiana Linfomi and Celgene PURPOSE To address early and late treatment failures in older patients with diffuse large B-cell lymphoma ( DLBCL ) , we design ed a two-stage r and omized trial of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) versus rituximab plus CHOP ( R-CHOP ) , with a second r and om assignment to maintenance rituximab ( MR ) or observation in responding patients . PATIENTS AND METHODS Untreated DLBCL patients who were 60 years or older were r and omly assigned to R-CHOP ( n = 318 ) or CHOP ( n = 314 ) ; 415 responders were r and omly assigned to MR ( n = 207 ) or observation ( n = 208 ) . The primary end point was failure-free survival ( FFS ) . All P values were two sided . RESULTS Three-year FFS rate was 53 % for R-CHOP patients and 46 % for CHOP patients ( P = .04 ) at a median follow-up time of 3.5 years . Two-year FFS rate from second r and om assignment was 76 % for MR compared with 61 % for observation ( P = .009 ) . No significant differences in survival were seen according to induction or maintenance therapy . FFS was prolonged with MR after CHOP ( P = .0004 ) but not after R-CHOP ( P = .81 ) with 2-year FFS rates from second r and om assignment of 77 % , 79 % , 74 % , and 45 % for R-CHOP , R-CHOP + MR , CHOP + MR , and CHOP , respectively . In a secondary analysis excluding MR patients , R-CHOP alone reduced the risks of treatment failure ( P = .003 ) and death ( P = .05 ) compared with CHOP alone . CONCLUSION Rituximab administered as induction or maintenance with CHOP chemotherapy significantly prolonged FFS in older DLBCL patients . After R-CHOP , no benefit was provided by MR . These results , which are consistent with an additive effect of rituximab , suggest that future studies could focus on maintenance strategies with novel agents as well as new induction therapies BACKGROUND Immunochemotherapy with rituximab and cyclophosphamide , doxorubicin , vincristine , and prednisone ( R-CHOP ) has become the st and ard of care for elderly patients with diffuse large B-cell lymphoma . We aim ed to ascertain if a dose-dense R-CHOP regimen administered every 2 weeks ( R-CHOP14 ) was superior to the st and ard 3-week schedule ( R-CHOP21 ) . METHODS We did a r and omised phase 3 trial at 83 centres in four countries . 602 patients aged 60 - 80 years with untreated diffuse large B-cell lymphoma and at least one adverse prognostic factor ( age-adjusted international prognostic index ≥ 1 ) were eligible for the study . We r and omly allocated individuals to R-CHOP-ie , rituximab ( 375 mg/m(2 ) ) , cyclophosphamide ( 750 mg/m(2 ) ) , doxorubicin ( 50 mg/m(2 ) ) , vincristine ( 1.4 mg/m(2 ) , up to 2 mg ) all on day 1 , and prednisone 40 mg/m(2 ) daily for 5 days-administered every 14 days ( n=304 ) or every 21 days ( n=298 ) for eight cycles . We did permuted-block r and omisation ( block size four , allocation ratio 1:1 ) stratified by centre and number of adverse prognostic factors . The primary endpoint was event-free survival . Our analysis was of the intention-to-treat population , and we present the final analysis . This study is registered with Clinical Trials.gov , number NCT00144755 . FINDINGS Two patients allocated R-CHOP21 were ineligible for the study and were excluded from analyses . After median follow-up of 56 months ( IQR 27 - 60 ) , 3-year event-free survival was 56 % ( 95 % CI 50 - 62 ) in the R-CHOP14 group and 60 % ( 55 - 66 ) in the R-CHOP21 group ( hazard ratio 1.04 , 95 % CI 0.82 - 1.31 ; p=0.7614 ) . Grade 3 - 4 neutropenia occurred in 224 ( 74 % ) of 304 patients allocated R-CHOP14 and 189 ( 64 % ) of 296 assigned R-CHOP21 , despite increased use of granulocyte colony-stimulating factor in the R-CHOP14 group compared with the R-CHOP21 group . 143 ( 47 % ) patients in the R-CHOP14 group received at least one red-blood-cell transfusion versus 93 ( 31 % ) in the R-CHOP21 group ( p=0.0001 ) . 35 ( 12 % ) patients allocated R-CHOP14 received at least one platelet transfusion versus 25 ( 8 % ) assigned R-CHOP21 ( p=0.2156 ) . 155 ( 51 % ) patients who were assigned R-CHOP14 had at least one serious adverse event compared with 140 ( 47 % ) who were allocated R-CHOP21 . INTERPRETATION In elderly patients with untreated diffuse large B-cell lymphoma and at least one adverse prognostic factor , a 2-week dose-dense R-CHOP regimen did not improve efficacy compared with the 3-week st and ard schedule . The frequency of toxic side-effects was similar between regimens , but R-CHOP14 was associated with increased need for red-blood-cell transfusion . FUNDING Groupe d'Etude des Lymphomes de l'Adulte ( GELA ) , Amgen Lenalidomide was shown to have significant single-agent activity in relapsed aggressive non-Hodgkin 's lymphoma ( NHL ) . We conducted a phase I trial to establish the maximum tolerated dose of lenalidomide that could be combined with R-CHOP ( rituximab – cyclophosphamide , doxorubicin , vincristine , and prednisone ) . Eligible patients were adults with newly diagnosed , untreated CD20 positive diffuse large cell or follicular grade III NHL . Patients received oral lenalidomide on days 1–10 with st and ard dose R-CHOP every 21 days . All patients received pegfilgrastim on day 2 of the cycle and aspirin prophylaxis . The lenalidomide dose levels tested were 15 , 20 and 25 mg . A total of 24 patients were enrolled . The median age was 65 ( 35–82 ) years and 54 % were over 60 years . Three patients received 15 mg , 3 received 20 mg and 18 received 25 mg of lenalidomide . No dose limiting toxicity was found , and 25 mg on days 1–10 is the recommended dose for phase II . The incidence of grade IV neutropenia and thrombocytopenia was 67 % and 21 % , respectively . Febrile neutropenia was rare ( 4 % ) and there were no toxic deaths . The overall response rate was 100 % with a complete response rate of 77 % . Lenalidomide at the dose of 25 mg/day administered on days 1 to 10 of 21-day cycle can be safely combined with R-CHOP in the initial chemotherapy of aggressive B-cell lymphoma PURPOSE Lenalidomide has significant single-agent activity in relapsed diffuse large B-cell lymphoma ( DLBCL ) . We demonstrated that lenalidomide can be safely combined with R-CHOP ( rituximab plus cyclophosphamide , doxorubicin , vincristine , and prednisone ) ; this new combination is known as R2CHOP . The goal of this phase II study was to evaluate the efficacy of this combination in newly diagnosed DLBCL . PATIENTS AND METHODS Eligible patients were adults with newly diagnosed untreated stages II to IV CD20(+ ) DLBCL . Patients received lenalidomide 25 mg orally per day on days 1 through 10 with st and ard-dose R-CHOP every 21 days for six cycles . All patients received pegfilgrastim on day 2 of each cycle and aspirin prophylaxis throughout . DLBCL molecular subtype was determined by tumor immunohistochemistry and classified as germinal center B-cell ( GCB ) versus non-GCB in the R2CHOP patients and 87 control patients with DLBCL from the Lymphoma Data base who were treated with conventional R-CHOP . RESULTS In all , 64 patients with DLBCL were enrolled , and 60 were evaluable for response . The overall response rate was 98 % ( 59 of 60 ) with 80 % ( 48 of 60 ) achieving complete response . Event-free survival and overall survival ( OS ) rates at 24 months were 59 % ( 95 % CI , 48 % to 74 % ) and 78 % ( 95 % CI , 68 % to 90 % ) , respectively . In R-CHOP patients , 24-month progression-free survival ( PFS ) and OS were 28 % versus 64 % ( P < .001 ) and 46 % versus 78 % ( P < .001 ) in non-GCB DLBCL versus GCB DLBCL , respectively . In contrast , there was no difference in 24-month PFS or OS for R2CHOP patients on the basis of non-GCB and GCB subtype ( 60 % v 59 % [ P = .83 ] and 83 % v 75 % [ P = .61 ] at 2 years , respectively ) . CONCLUSION R2CHOP shows promising efficacy in DLBCL . The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome |
13,240 | 10,796,356 | The results of the qualitative analysis showed that there is conflicting evidence ( level 3 ) that NSAIDs are more effective than paracetamol for acute low back pain , and that there is moderate evidence ( level 2 ) that NSAIDs are not more effective than other drugs for acute low back pain .
There is strong evidence ( level 1 ) that various types of NSAIDs are equally effective for acute low back pain .
REVIEW ER 'S CONCLUSIONS In conclusion , the evidence from the 51 trials included in this review suggests that NSAIDs are effective for short-term symptomatic relief in patients with acute low back pain .
Furthermore , there does not seem to be a specific type of NSAID which is clearly more effective than others . | BACKGROUND Non-steroidal anti-inflammatory drugs ( NSAIDs ) are the most frequently prescribed medications worldwide and are widely used for patients with low back pain .
OBJECTIVES The objective of this systematic review was to assess the effects of NSAIDs in the treatment of non-specific low back pain and to assess which type of NSAID is most effective . | Study Design . A prospect i ve , r and omized , single ( investigator ) blind , comparative efficacy trial was conducted . Objective . To compare the efficacy of continuous low-level heat wrap therapy ( 40 C , 8 hours/day ) with that of ibuprofen ( 1200 mg/day ) and acetaminophen ( 4000 mg/day ) in subjects with acute nonspecific low back pain . Summary of Background Data . The efficacy of topical heat methods , as compared with oral analgesic treatment of low back pain , has not been established . Methods . Subjects ( n = 371 ) were r and omly assigned to heat wrap ( n = 113 ) , acetaminophen ( n = 113 ) , or ibuprofen ( n = 106 ) for efficacy evaluation , or to oral placebo ( n = 20 ) or unheated back wrap ( n = 19 ) for blinding . Outcome measures included pain relief , muscle stiffness , lateral trunk flexibility , and disability . Efficacy was measured over two treatment days and two follow-up days . Results . Day 1 pain relief for the heat wrap ( mean , 2 ) was higher than for ibuprofen ( mean , 1.51;P = 0.0007 ) or acetaminophen ( mean , 1.32;P = 0.0001 ) . Extended mean pain relief ( Days 3 to 4 ) for the heat wrap ( mean , 2.61 ) also was higher than for ibuprofen ( mean , 1.68;P = 0.0001 ) or acetaminophen ( mean , 1.95;P = 0.0009 ) . Lateral trunk flexibility was improved with the heat wrap ( mean change , 4.28 cm ) during treatment ( P ≤ 0.009 vs acetaminophen [ mean change , 2.93 cm ] , P ≤ 0.001 vs ibuprofen [ mean change , 2.51 cm ] ) . The results were similar on Day 4 . Day 1 reduction in muscle stiffness with the heat wrap ( mean , 16.3 ) was greater than with acetaminophen ( mean , 10.5;P = 0.001 ) . Disability was reduced with the heat wrap ( mean , 4.9 ) , as compared with ibuprofen ( mean , 2.7;P = 0.01 ) and acetaminophen ( mean , 2.9;P = 0.0007 ) , on Day 4 . None of the adverse events were serious . The highest rate ( 10.4 % ) was reported in the ibuprofen group . Conclusion . Continuous low-level heat wrap therapy was superior to both acetaminophen and ibuprofen for treating low back pain A double-blind , 18-center , balanced trial of diflunisal vs. cyclobenzaprine HCl vs. these two drugs combined vs. placebo produced complete results from 175 patients . They had sought treatment at the cooperating centers for acute painful spasms of the back within a day or two of trauma or strain . Global results over the 7 to 10 days of observations revealed a clinical ly and statistically significant superiority of the combined therapy by Day 4 ( P=0.006 ) and almost all patients recovered within a week to 10 days . A combination therapy with an effective safe analgesic and a true muscle relaxant for less than a week appears to be an excellent relief measure for acute back problems The study objective was to assess the efficacy and patient acceptance of ketorolac as an alternative to meperidine for the treatment of severe musculoskeletal low back pain ( LBP ) . A double blinded prospect i ve trial in a convenience sample of patients > 18 years of age presenting to an urban university hospital emergency department ( ED ) was conducted over a 19-month period . Patients were included if the pain was musculoskeletal in origin and was severe enough to warrant parenteral analgesics . Patients were r and omized to receive 1 mg/kg meperidine intramuscularly ( IM ) or 60 mg ketorolac IM . Pain intensity was measured preadministration and at 60 minutes via a 100 mm Visual Analog Scale ( VAS ) . Outcomes measured at 60 minutes were pain intensity decrease ( PID ) , patient satisfaction , rescue analgesia requirement , sedation level , and adverse effects . Clinical ly significant pain reduction was defined as a PID of at least 13 mm or a reduction in pain of least 30 % . One hundred fifty-five patients were enrolled ( meperidine = 75 , ketorolac = 80 ) and 153 patients completed the study . At 60 minutes the mean PID was 7 mm less in the ketorolac group ( 95 % confidence interval [ CI ] - 15 mm to 2.6 mm ) . Pain reduction of at least 30 % occurred in 63 % of the ketorolac group versus 67 % of the meperidine group ( 95 % CI , odds ratio [ OR ] .43 to 1.61 ) . Rescue analgesia was required in 35 % of the ketorolac group versus 37 % of the meperidine group ( 95 % CI , OR .47 to 1.74 ) . Patient satisfaction was less in the ketorolac group ( ketorolac 68 % satisfied versus meperidine 74 % satisfied ) however this was not significant ( 95 % CI , OR .66 to 2.72 ) . Sedation level and adverse effects were significantly greater in the meperidine group . Ketorolac shows comparable single dose analgesic efficacy to a single moderate dose of meperidine with less sedation and adverse effects in an ED population with severe musculoskeletal LBP . The trend for greater pain reduction and patient satisfaction with meperidine needs further investigation This study reports on 105 patients with acute low-back pain given tizanidine ( 4 mg three times daily ) plus ibuprofen ( 400 mg three times daily ) or placebo plus ibuprofen ( 400 mg three times daily ) . Patients assessed their pain using visual analogue scales in a daily diary and the doctor assessed their condition at baseline and on days 3 and 7 . Both groups were treated effectively , but earlier improvement occurred in patients given tizanidine/ibuprofen , particularly regarding pain at night and at rest . Doctors assessed the helpfulness of treatment : tizanidine/ibuprofen was significantly better than placebo/ibuprofen at day 3 ( P = 0.05 ) . Significant differences between treatments in favour of tizanidine/ibuprofen occurred in patients with moderate and severe pain at night ( P<0.05 ) , at rest ( P<0.05 ) and those with moderate or severe sciatica ( P<0.05 ) . Significantly more patients given placebo/ibuprofen had gastro-intestinal side-effects compared with tizanidine/ibuprofen ( P = 0.002 ) . This supports previous work in animals showing that tizanidine mediates gastric mucosal protection against anti-inflammatory drugs . More patients given tizanidine/ibuprofen suffered drowsiness and other central nervous system effects ( P = 0.025 ) . In patients with severe acute low-back pain , however , some sedation and bed rest is advantageous . This study shows that tizanidine/ibuprofen is more effective in the treatment of moderate or severe acute low-back pain than placebo and ibuprofen alone Two hundred and sixty patients with lumbago or sciatic pain participated in a multicenter observer-blind r and omized trial to compare the efficacy and tolerability of dipyrone 2.5 g , diclofenac 75 mg , and placebo administered as an intramuscular injection once daily for the duration of one to two days . The effectiveness of the test treatments in relieving sciatic pain was measured by a visual analog scale ( VAS ) before and 30 minutes , 1 , 2 , 3 , 6 and 24 hours after each injection . In addition , the patient 's general well-being was measured on a 5-point rating scale on day 0 , 1 and 2 . At the end of the trial , the patients evaluated the overall efficacy of the study drugs on a 5-point rating scale . Minimal finger-toe distance was measured every day of the trial . Pain intensity on VAS ( primary endpoint ) showed a significantly greater reduction with dipyrone than with diclofenac or placebo between 1 and 6 hours after application ( p < 0.01 ) and at the end of the trial ( after 48 hours ) . Improvement in general well-being and minimal finger-toe distance was greatest in the dipyrone group . 59 % of the patients with dipyrone assessed the overall efficacy as " excellent " or " very good " , compared with 30 % with diclofenac , and 18 % with placebo . Adverse reactions were reported in only 7 patients ( 3 % ) , 4 ( 5 % ) in the dipyrone , 1 ( 1 % ) in the diclofenac , and 2 ( 2 % ) in the placebo group A double-blind trial of azapropazone ( 300 mg . 4-times daily ) and ketoprofen ( 50 mg . 4-times daily ) was carried out in 50 patients with acute backache sufficiently severe to necessitate hospital admission . Of 39 patients who completed the full 3-weeks ' study period , 18 preferred azapropazone therapy , 10 preferred ketoprofen , and 11 showed either preference for the intermediate placebo period or no preference at all . Ten patients suffered from sufficiently severe side-effects with ketoprofen to necessitate their withdrawal from the trial . There were no similar episodes of withdrawal occurring during the azapropazone period The roles of bedrest , antiinflammatory medication , and analgesic medication in the treatment of acute back strain were objective ly analyzed to determine whether they have a measurable effect on the return of patients to full daily activities as well as on the relief of pain . Two hundred patients were studied prospect ively . Each patient had the diagnosis of acute back strain , which was defined as nonradiating low-back pain . The results of the patient 's neurologic examination , straight leg raising test , and lumbosacral spine roentgenograms had to be within normal limits for the patient to be included in the study . The results showed that bedrest , as compared with ambulation , will decrease the amount of time lost from work by 50 % . Bedrest will also decrease the amount of discomfort by 60 % . Analgesic medication , when combined with bedrest , will further decrease the amount of pain incurred , particularly when used in the first three days of the healing process . However , analgesic medication will not allow a more prompt return to work . Antiinflammatory medication , when added to bedrest in the treatment of lumbago , does not provide an advantage over bedrest alone BACKGROUND Acute low back pain is one of the most frequent complaints presented in general practice . This study compares acupuncture and antiphlogistica in the treatment of acute low back pain in general practice . MATERIAL AND METHODS Among 60 consecutively included patients with acute low back pain , 30 patients were r and omized to st and ardised acupuncture treatment for two weeks , and 30 patients to entero-soluble naproxen 500 mg twice daily for ten days . Effects were observed over six months , and observed for a further 12 months with regard to relapse of low back pain and number of days on sickness leave . RESULTS There were no differences in pain or stiffness ( VAS , physical tests ) at inclusion , nor in the reduction of pain or stiffness over a six month evaluation . However , patients receiving acupuncture used significantly less analgetic drugs during the first week after start of treatment than those receiving naproxen ( 2/28 versus 11/29 , p < 0.01 ) . Patients receiving acupuncture also reported fewer new episodes of low back pain ( 11/28 versus 30/29 , p < 0.05 ) during the 6 + 12 month follow-up . Side effects were frequent in the naproxen group , especially gastro-enteric side effects ( 0/28 versus 15/29 , p < 0.01 ) . INTERPRETATION St and ardised acupuncture treatment seems to be safe and effective in the treatment of acute low back pain in general practice Thirty-seven patients with chronic back pain were entered into a r and omised , 3-way , double-blind , cross-over comparison of naproxen sodium 550 mg twice daily , diflunisal 500 mg twice daily , and placebo . Each treatment was given for 14 days after a preadmission wash-out week during which only paracetamol was allowed . Patients were assessed on admission and at the end of each treatment with respect to global pain , night pain , pain on movement , and pain on st and ing . Both visual analogue scales and simple descriptive scales were used to measure pain . Side effects were elicited by a nonleading question . Both methods of pain measurement gave similar results and were highly correlated . Naproxen sodium was superior to placebo in relieving global pain and depending on the method of measurement , in relieving night pain and pain on movement . Diflunisal showed no significant differences from placebo . Side effects were similar on all 3 treatments . The final preference of the patients was significantly in favour of the active treatments Pain syndromes of the lumbar spine are one of the main problems in orthopedic practice . The therapeutic effect of NSAIDs is not subject to doubt in this connection . But considering that the application of NSAIDs is frequently associated with side effects , a reduction of dosage would be to the patient 's benefit . Clinical studies have shown that concomitant treatment with vitamins B1 , B6 , B12 and diclofenac leads to a more efficient pain relief than treatment using diclofenac alone and thus provides the possibility of saving NSAIDs . This clinical trial was carried out in order to determine whether these results can also be achieved when a reduced dosage of diclofenac ( 75 mg daily ) is used . 123 patients with acute pain syndromes of the lumbar spine were treated with either B-vitamins and diclofenac or diclofenac alone for a maximum of 7 days . There was the option to terminate therapy in the trial after 3 - 4 days in the case of total pain relief . 45 patients could stop the treatment due to remission of symptoms . 30 patients belonged to the combination therapy group , the other 15 took diclofenac alone ; this difference is statistically significant ( p less than 0.05 ) . All parameters concerning pain relief and movement of the vertebral column showed statistically significant differences in favour of the B-vitamin-diclofenac-combination , too . The results document the positive influence of B-vitamins on painful vertebral syndromes and indicate that B-vitamins contribute to saving of NSAIDs by shortening the treatment time and reducing daily NSAID-dosage A short-term double-blind sequential trial of indomethacin against placebo in the treatment of low back pain , with and without nerve root pain such as sciatica , showed that indomethacin was significantly more effective than placebo in the group with nerve root pain . On the other h and , no difference was found between the treatments in the patients with uncomplicated low back pain . This difference may result from an effect of indomethacin on the inflammatory process around the nerve root which has been shown to be present when this is compressed Thirty patients suffering from painful syndromes of the spine were admitted to a r and omized controlled clinical trial . They were divided into two groups and treated either with transcutaneous electrical nerve stimulation ( TENS ) , one application every other day , for 20 days or with TENS and an ointment containing etofenamate 10 % gel , 3 - 5 cm daily on the day of TENS therapy , and the same dose twice daily on the other days . The associated therapy achieved , when compared with TENS alone , a statistically significant better outcome . Furthermore a marked improvement of symptoms was observed in a shorter period of time . Therapy was well tolerated and in only four cases mild , self-limiting , skin reactions were observed . On the basis of these results the use of etofenamate and TENS could represent a viable alternative to systemic nonsteroidal antiinflammatory drug therapy Several clinical trials have shown that the duration of treatment of painful vertebral syndromes can be shortened by using a combination of vitamins B1 , B6 , B12 and diclofenac instead of diclofenac . In addition , a more efficient pain relief could be achieved by the combination therapy . In order to confirm these results , we compared the clinical efficacy of diclofenac ( 25 mg ) and a combination preparation with diclofenac ( 25 mg ) plus vitamins B1 ( thiamine nitrate 50 mg ) , B6 ( pyridoxine hydrochloride 50 mg ) and B12 ( cyanocobalamin 0.25 mg ) in a multicentric r and omized double-blind study including 418 patients . All patients received 3 x 2 capsules daily for a maximum of 2 weeks . In case of total pain relief , therapy should be discontinued after one week . Data of 376 patients could be evaluated . 53 out of 184 patients receiving the combination and 48 out of 192 patients treated with diclofenac alone could stop therapy due to sufficient pain relief after one week . The evaluation of the " Hoppe Pain Question naire " and the data concerning pain intensity also revealed better results for the combination preparation . The differences in favour of the B-vitamin-diclofenac-combination were statistically significant in patients with severe pain at the beginning of therapy . Considering undesirable side-effects ( symptoms in 70 out of 418 patients ) there were no significant differences between the two medications . This clinical trial provides further evidence that the combination therapy with diclofenac plus B-vitamins is more effective than diclofenac alone for the treatment of painful vertebral syndromes Study Design . A prospect i ve , r and omized double-blind comparative trial . Objectives . To evaluate the efficacy and tolerability of nimesulide , a cyclooxygenase (COX)-2–selective anti-inflammatory agent versus ibuprofen in patients with acute lumbosacral back pain . Summary of Background Data . Nonsteroidal anti-inflammatory drugs ( NSAIDs ) have been more effective than placebo in patients with uncomplicated acute low back pain in previous r and omized controlled trials . The efficacy and tolerability of a new COX-2–selective anti-inflammatory drug have not yet been established . Methods . One hundred four patients aged 18–65 years with acute low back pain were enrolled . The patients were r and omly allocated either to oral nimesulide ( 100 mg twice daily for 10 days ) or oral ibuprofen ( 600 mg three times daily for 10 days ) . Outcome measures on a visual analog scale were an average of the pain intensity and the pain relief , stiffness in the back , functional status , and the results of physical examinations . All side effects were recorded at each visit . Results . With both study therapies , there was a clear improvement in all measured parameters of the pain and back function parameters measured from the third day of treatment onward . The patients ’ capacity for daily tasks , showed improvement in both groups ( P < 0.001 ) , but a statistically significant difference was found between the two groups in favor of the nimesulide group ( P < 0.05 ) after 10 days . Nimesulide was more effective than ibuprofen in improved lateral bending measurements ( P = 0.026 ) . Nimesulide and ibuprofen provided similar degrees of improvement in the modified Schober tests and in the pain intensity and back stiffness scores . More gastrointestinal side effects were reported with ibuprofen than nimesulide , and the comparison showed a trend ( P = 0.067 ) . Ten side effects occurred in the nimesulide group in 7 ( 13 % ) patients and 13 in the ibuprofen group in 11 ( 21 % ) patients . Conclusions . The results confirmed that the COX-2–selective inhibitor nimesulide is an effective and well-tolerated agent for use in general practice s to treat acutelow back pain . The incidence of gastrointestinal side effects seems to be lower with nimesulide than with ibuprofen Patients ( 112 ) with acute low-back pain of recent onset were recruited to this double-blind , r and omized , placebo-controlled parallel group study in general practice to evaluate the efficacy and tolerability of the muscle relaxant , tizanidine . They were treated for 7 days with tizanidine ( 4 mg three times daily ) or matching placebo . Aspirin tablets ( 300 mg ) were taken as required as ‘ rescue ’ medication . Symptoms were assessed by the patient and doctor before treatment , and after 3 and 7 days . Patients recorded pain and aspirin consumption in a daily diary . Both treatments were effective . In patients who had taken no medication prior to entry , aspirin consumption was almost halved in the first 3 days of taking tizanidine compared with placebo ( P = 0.037 ) . Results for pain at rest , pain at night , restriction of movement and pain on movement suggest that tizanidine may give greater improvement , earlier . No serious drug-related adverse events or abnormal biochemistry or haematology were observed in either group . Drowsiness occurred in 22 % of patients taking tizanidine although , in patients with severe acute low-back pain , sedation , analgesia and bed rest might be beneficial and desired . Considerably more patients given aspirin/placebo had gastro-intestinal side-effects ( P = 0.018 ) . In conclusion , tizanidine may reduce the need for analgesics and be useful in the treatment of acute low-back pain The use of nonsteroidal anti-inflammatory drugs ( NSAID ) such as diclofenac for treatment of degenerative rheumatic disorders of the lumbar spine is of great significance in orthopedic practice . Clinical studies have shown that concomitant treatment with vitamins B1 , B6 , B12 and diclofenac provides more efficient pain relief than treatment using diclofenac alone . This study was undertaken in order to determine whether the duration of treatment with diclofenac for lower back pain can be shortened by adding B-vitamins to the therapeutic regimen . From September through December of 1986 , 256 patients participated in a multicenter , controlled , r and omized double-blind trial which compared the clinical efficacy of diclofenac ( 50 mg ) with a combined therapy of diclofenac ( 50 mg ) and vitamins B1 , B6 , and B12 ( thiamine nitrate , pyridoxine hydrochloride , and cyanocobalamine , resp . ; in dosages of 50 mg , 50 mg , and 0.25 mg , resp . ) . Patients were treated with 3 X 1 capsule daily for a maximum of two weeks , having the option to terminate participation in the trial after 1 week in the event of total pain relief . The data of 238 patients were able to be included in the evaluation . 29 patients opted to discontinue therapy due to remission on symptoms . Nineteen ( 65.6 % ) of these patients belonged to the combined therapy group , the other 10 ( 34.4 % ) having taken diclofenac alone ; this difference is statistically significant ( p less than 0.05 ) . An important aspect in the evaluation of therapy was the patient response regarding the improvement of painful symptoms which , in addition to their subjective feedback , was reflected in the test results of the " Hoppe Pain Question naire ( HPQ ) . " All parameters used as a measure of pain relief indicated superior results with the B-vitamin supplemented therapy when compared with results obtained with diclofenac alone . Moreover , after 3 days of therapy the " sensory " pain factor " sharpness " improved significantly . Undesirable side-effects were documented with 39 patients , 14 of them having discontinued therapy for this reason . No statistically significant difference could be determined within this group with regard to therapy . The study results document the positive influence of B-vitamins on painful symptoms and indicate that less NSAID is needed for pain relief when combined with B-vitamins Acute low back pain is a common problem in the emergency department ( ED ) . Effective management of acute pain enhances early rehabilitation and recovery . Given the importance of inflammatory mediators in pain generation and the adverse effects associated with opioids , it is logical to expect that a non-opioid agent with antiinflammatory and analgesic properties would provide excellent analgesia with fewer adverse effects . This double-blind , r and omized , multicenter clinical trial , performed in six university and community hospital EDs , compares the analgesic efficacy and adverse effects of ketorolac to those of acetaminophen-codeine in ED patients with acute musculoskeletal low back pain . Our hypothesis was that ketorolac would provide superior analgesia with fewer adverse effects . One hundred twenty-three patients with acute low back pain were r and omized to receive ketorolac ( KET , N = 63 ) or acetaminophen-codeine ( ACOD , N = 60 ) . Most ( 79 % ) were males , and the mean age was 34.5 years . After baseline clinical assessment , patients were treated with ketorolac ( 10 mg every 4 to 6 h as needed , up to four daily doses ) or acetaminophen-codeine ( 600 mg-60 mg , respectively , every 4 to 6 h as needed , up to six daily doses ) and followed for one week . Pain intensity was assessed on visual analogue and categorical scales . Functional capacity , overall pain relief , and overall medication rating were assessed on categorical scales . Adverse events were documented . Primary outcomes included : 1 ) Pain intensity differences , based on visual analogue scores , for the 0 to 6 h treatment phase . 2 ) Incidence of adverse events . Secondary outcomes included analgesic efficacy , functional capacity , and overall subjective drug evaluation at one week . Both drugs provided substantial pain relief , with maximal effect 2.2 h after oral dosing . There were no significant differences in analgesic efficacy , functional capacity , or overall pain relief between the two groups . Sixteen patients ( 10 KET vs. 6 ACOD , NS ) withdrew prematurely because of drug inefficacy . Patients in the ACOD group reported significantly more adverse drug events and serious adverse drug events . Seven patients --all in the ACOD group -- withdrew from the study because of adverse drug events . Based on comparable efficacy and a superior adverse event profile , ketorolac was preferable to acetaminophen with codeine for the treatment of acute low back pain in the ED Seventy out- patients with acute back pain participated in a double-blind comparative trial of the clinical efficacy and tolerance of orally administered meptazinol and diflunisal . Half of the patients received 200 mg meptazinol or 250 mg diflunisal 4-times daily for up to 3 weeks , depending on the duration of pain . Patients were examined 4 times at 1-week intervals for their capability to do daily tasks , for their capacity for forward bending , thoraco-lumbar torsion , straight leg raising , static hip flexion and sit-ups , and for subjective assessment of pain . Side-effects were recorded on a question naire . Both treatments produced marked improvement in most of the parameters assessed , often within the first week and , overall , the results were similar with the two drugs . Few side-effects were reported and those that were recorded were slight and similar in incidence apart from nausea in 5 meptazinol-treated patients and smarting and burning on urination in 2 patients receiving diflunisal Twenty-seven investigators participated in a double-blind , parallel placebo-controlled trial of piroxicam involving 278 patients with acute low back pain . Therapy commenced within 48 hours of the injury and continued for 7 days . The drug was given in the recommended regimen of 40 mg once daily for the first 2 days and 20 mg once daily thereafter . After 3 days of therapy , piroxicam patients showed a statistically greater amount of pain relief in the lying ( P<0.001 ) , sitting ( P<0.01 ) , and st and ing ( P<0.01 ) positions , but after 7 days the difference between treatments was no longer significant . After 1 week 's therapy , however , the requirement for additional analgesic was significantly lower in the piroxicam group ( P<0.05 ) , and more piroxicam than placebo patients ( 42 versus 28 ) had returned to work ( P<0.05 ) . Toleration was excellent in most patients , with only 13 % of the piroxicam and 17 % of the placebo group reporting adverse effects of mainly mild or moderate severity . The profile of the adverse effects was similar for both treatments . Piroxicam can provide effective relief of acute low-back pain with good toleration ; it should be considered for use in the initial treatment of this condition To study the natural history of acute sciatica , 208 patients with obvious symptoms and signs of a lumbar radiculopathy ( L5 and S1 ) were examined within 14 days of onset . A concomitant double-blind investigation of the effect of the nonsteroidal anti-inflammatory drug piroxicam was performed . The results measured by visual analog scale and Rol and 's functional tests showed a satisfactory improvement throughout the 4 weeks of observation . The piroxicam-treated group had same results as the control group . Based on question naires at months 3 and 12 approximately 30 % of the patients still complained about back trouble and 19.5 % were out of work after 1 year . Four patients underwent surgery during this period In a controlled multi-center single-blind study , the relative efficacy and tolerance of i.m . injectable preparations of etofenamat(e ) and diclofenac sodium were investigated in 96 patients with acute lumbago . Treatment result ed in obvious improvement in function and reduction in pain , no statistical difference being found between the two drugs . In 43 % of the patients treated with etofenamat(e ) and 27 % of those receiving diclofenac , the final medical report indicated very good therapeutic results . Under etofenamat(e ) i.m . therapy , no side effects occurred , and in no case did treatment have to be discontinued . Under diclofenac , two patients experienced adverse reactions , one allergic exanthema , and the other itching and a sensation of heat . A further patient experienced no improvement after the first injection and discontinued treatment The efficacy of an NSAID ( tenoxicam ) in the treatment of acute low back pain ( LBP ) was assessed in a double blind controlled study by using an objective functional evaluation . Seventy-three patients consulting for acute LBP were r and omized into two groups : Group I was treated with tenoxicam for 14 days and Group II was given a placebo . Trunk function was measured with a computerized isoinertial dynamometric trunk testing device ( Isostation B200 ) . Isometric and dynamic torques , range of motion and movement velocities were measured before treatment and after 14 days . Clinical evaluation was realized by the patient on a pain visual analogue scale ( VAS ) on days 1 , 8 and 15 and by the investigator on a five-point scale on days 8 and 15 . The functional evaluation showed significant differences in favour of the tenoxicam treatment for velocity and extension isometric torque . VAS and investigator evaluations showed a significant difference in favour of tenoxicam on day 8 but no difference on day 15 . This study shows that the use of tenoxicam in acute LBP is of interest . Tenoxicam has an effect on pain during the first part of the treatment and may help to restore full function even if the symptoms have disappeared The marketed formulations of 6 analgesic preparations were compared in the treatment of patients suffering from acute exacerbations of low back pain using a crossover trial of balanced incomplete block design . Sixty out- patients with symptoms result ing from a mechanical or degenerative condition were each prescribed 3 drugs which were administered consecutively for 1 week each . The medications ( and daily dosages ) were coded as A --aspirin ( 3600 mg ) , B --dextropropoxyphene plus paracetamol ( 260 mg plus 2600 mg ) , C --indomethacin ( 150 mg ) , D --mefenamic acid ( 1500 mg ) , E --paracetamol ( 4000 mg ) , and F --phenylbutazone ( 300 mg ) . Daily pain scores were significantly lower ( p less than 0.05 ) during treatment D than during treatments E and B , and significantly lower ( p less than 0.05 ) during treatment A than during treatment B. There were large and significant differences between treatments in the percentages of recommended doses acceptable to the patients and in the number of defaults from the prescribed regimens . The patients chose F and D significantly more ( p less than 0.05 ) often than A. Overall , there were consistently superior performances by mefenamic acid and phenylbutazone with little to choose between the two A total of 395 male infantry recruits were evaluated in a prospect i ve study of possible risk factors for overexertional back pain and the efficacy of drug treatment regimens for this syndrome . Recruits were classified into subgroups of lumbar or thoracic , and paraspinal or spinous process pain . Recruits were divided into three treatment groups : Ibuprofen , Paracetamol , and no drug treatment . Of the recruits , 18 % were diagnosed as having overexertional back pain during the course of 14 weeks of training . By multivariate analysis low body mass index was found to be a risk factor for overexertional lumbar pain ( p = 0.005 ) and increased lumbar lordosis a risk factor for overexertional thoracic pain ( p = 0.005 ) . Of recruits with overexertional back pain , 65 % were asymptomatic by the end of basic training . There was no statistically significant difference between cure rates according to treatment groups Two groups of 20 patients each , with mild to moderate acute low back pain with associated muscle spasm of ten days ' duration or less , were treated with a combination of cyclobenzaprine and naproxen or naproxen alone in a r and omized , 14-day open-label trial . Cyclobenzaprine was added to the naproxen regimen as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute , painful , musculoskeletal conditions . The clinical characteristics of each study group , including the number of worker 's compensation patients , were comparable . Combination therapy was associated with less objective muscle spasm and tenderness and greater motion of the lumbosacral spine ( P less than 0.05 ) . There were trends toward faster resolution of functional deficits and pain with combined therapy . Combination therapy was associated with more side effects , due primarily to drowsiness from the cyclobenzaprine . The results of this study demonstrated that patients with muscle spasm associated with acute low back strain benefited from the use of combination therapy consisting of a nonsteroidal anti-inflammatory agent ( naproxen ) and a muscle relaxant ( cyclobenzaprine ) In this controlled , single-blind parallel group study , the effect of ibuprofen 1200 mg daily was compared with diclofenac 75 mg daily . Thirty patients entered the study , r and omized into two groups , each group receiving one tablet three times daily for two weeks . A one-week wash-out period ( i.e. a drug-free period during which only physiotherapy was given ) , preceded and followed the treatment on active drug . Assessment s were made by the same clinician throughout who was unaware of the treatment of individual patients . Statistically significant improvement was shown by patients receiving ibuprofen for the degree of pain relief at rest and improvement was also shown for the degree of pain at rest and during exercise , for pain relief during exercise and for spinal flexion . Patients who received diclofenac showed stastistically significant improvement for forward flexion , together with improvement for the degree of pain on exercise . Side-effects were very few Two multicenter , double-blind , r and omized studies were performed to determine the antihypertensive efficacy and effects on laboratory values of a new , shorter-acting formulation of metolazone in patients with mild to moderate hypertension . After baseline placebo-control periods , 105 patients were r and omly assigned to receive single daily doses of either placebo or 0.5 , 1.0 , or 2.0 mg of the new formulation of metolazone for six weeks in one study , and 164 patients were r and omized to receive 0.5 , 1.0 , or 2.0 mg of the new formulation of metolazone or 2.5 mg of the older , long-acting metolazone in the other . Mean blood pressure reductions in all three metolazone groups were statistically and clinical ly significant . Blood pressures of 51 % to 58 % of patients in the 0.5-mg metolazone group were controlled ( diastolic blood pressure less than 90 or a fall of greater than or equal to 10 mmHg from baseline ) . Reductions in mean serum potassium levels were dose-related . We conclude that 0.5 mg of metolazone is safe and effective therapy for hypertension ; it will significantly reduce systolic and diastolic blood pressure and minimizes changes in laboratory test values The use of flurbiprofen as an analgesic and anti-inflammatory agent in patients with soft tissue trauma induced by sports injuries , lumbar disk syndrome , or surgery was considered in three clinical trials . In the first study , soft tissue injuries to the lower limb in 51 professional soccer players were treated for six days with 150 mg of flurbiprofen per day or 3.6 g of aspirin per day . The second study compared three weeks of treatment with daily doses of 200 mg of flurbiprofen and 4 g of acetaminophen in 50 patients with acute low back pain . In the third study , 100 postoperative patients were given 400 mg of flurbiprofen per day or 4 g of acetaminophen per day for seven days following total or partial meniscectomy . In all of these trials , flurbiprofen showed excellent analgesic efficacy in reducing pain and swelling , and enhanced the recovery of patients with soft tissue trauma Summary A double-blind , between-patient comparison of alclofenac and indomethacin was carried out in 60 patients with low back pain and sciatica . Pain , functional disability and signs of dural irritation ( Lasegue 's sign ) were rated by the clinician before and at the end of each 7-day treatment period , and an overall assessment of treatment effectiveness was made by both clinician and patients .Response to treatment in terms of patient improvement was considered satisfactory with both drugs , but more erratic in those patients with an acute condition . Analysis of pain scores showed a significant tendency for patients with acute or chronic low back pain to improve more with alclofenac than with indomethacin treatment . Overall assessment s by the clinician and patients also indicated signiJcantly greater improvement with alclofenac |
13,241 | 25,185,096 | RECOMMENDATIONS Endocrine therapy is preferable to chemotherapy as first-line treatment for patients with estrogen receptor-positive metastatic breast cancer unless improvement is medically necessary ( eg , immediately life-threatening disease ) .
Single agent is preferable to combination chemotherapy , and longer planned duration improves outcome but must be balanced against toxicity .
Other targeted therapies have not so far been shown to enhance chemotherapy outcome in HER2-negative breast cancer | PURPOSE To identify optimal chemo- and targeted therapy for women with human epidermal growth factor 2 (HER2)- negative ( or unknown ) advanced breast cancer . | PURPOSE To investigate whether sunitinib plus docetaxel improves clinical outcomes for patients with human epidermal growth factor receptor 2 (HER2)/neu-negative advanced breast cancer ( ABC ) versus docetaxel alone . PATIENTS AND METHODS In this phase III study , patients were r and omly assigned to open-label combination therapy ( sunitinib 37.5 mg/d , days 2 to 15 every 3 weeks ; and docetaxel 75 mg/m(2 ) , day 1 every 3 weeks ) or monotherapy ( docetaxel 100 mg/m(2 ) every 3 weeks ) . Progression-free survival ( PFS ) was the primary end point . RESULTS Two hundred ninety-six patients were r and omly assigned to combination therapy , and 297 patients were assigned to monotherapy . Median PFS times were 8.6 and 8.3 months with combination therapy and monotherapy , respectively ( hazard ratio , 0.92 ; one-sided P = .265 ) . The objective response rate ( ORR ) was significantly higher with the combination ( 55 % ) than with monotherapy ( 42 % ; one-sided P = .001 ) . Duration of response was similar in both arms ( 7.5 months with the combination v 7.2 months with monotherapy ) . Median overall survival ( OS ) times were 24.8 and 25.5 months with combination therapy and monotherapy , respectively ( one-sided P = .904 ) . There were 107 deaths with the combination and 91 deaths with monotherapy . The frequency of common adverse events ( AEs ) was higher with the combination , as were treatment discontinuations caused by AEs . CONCLUSION The combination of sunitinib plus docetaxel improved ORR but did not prolong either PFS or OS compared with docetaxel alone when given to an unselected HER2/neu-negative cohort as first-line treatment for ABC . Sunitinib combination therapy may also have result ed in AEs that yield an unfavorable risk-benefit ratio . The sunitinib-docetaxel regimen evaluated in this study is not recommended for further use in ABC BACKGROUND In a phase III trial , 3-weekly capecitabine ( 1250 mg/m(2 ) twice daily days 1 - 14 ) plus docetaxel ( 75 mg/m(2 ) day 1 ) demonstrated significantly superior overall survival to 3-weekly docetaxel ( 100 mg/m(2 ) day 1 ) . We report a retrospective analysis of the impact of capecitabine/docetaxel dose reduction on safety and efficacy . PATIENTS AND METHODS Safety and efficacy data were analyzed retrospectively according to the actual doses of capecitabine and docetaxel administered . RESULTS More patients receiving capecitabine/docetaxel ( 65 % ) had dose reductions for adverse events than docetaxel alone ( 35 % ) . In most patients requiring dose reduction with the combination ( 80 % ) , capecitabine and docetaxel were simultaneously reduced to 950 mg/m(2 ) and 55 mg/m(2 ) , respectively . Subsequently , there were fewer cycles ( 17 % ) with grade 3/4 adverse events than with the full doses ( 34 % ) . Time to progression and overall survival appeared to be similar in patients starting the second cycle with reduced doses of capecitabine/docetaxel and those who continued to receive full doses of capecitabine/docetaxel for at least the first four cycles . CONCLUSIONS Capecitabine/docetaxel dosing flexibility allows management of side-effects without compromising efficacy . This retrospective analysis , as well as multiple phase II studies of taxanes with reduced-dose capecitabine , shows that reducing the starting dose of capecitabine with docetaxel is a reasonable strategy for the treatment of patients with metastatic breast cancer . In addition , reducing the dose of both agents may be appropriate BACKGROUND The purpose of this study was to compare docetaxel plus epirubicin versus docetaxel plus capecitabine combinations as front-line treatment in women with advanced breast cancer ( ABC ) . PATIENTS AND METHODS Previously untreated patients with ABC were r and omly assigned to receive docetaxel 75 mg/m(2 ) plus epirubicin 75 mg/m(2 ) ( DE ) on day 1 or docetaxel 75 mg/m(2 ) on day 1 plus capecitabine 950 mg/m(2 ) orally twice daily on days 1 - 14 ( DC ) in 21-day cycles . Previous anthracycline-based (neo)-adjuvant chemotherapy was allowed if completed > 1 year before enrollment . The primary objective of the study was to compare time to disease progression ( TTP ) . RESULTS One hundred and thirty-six women were treated on each arm and median TTP was 10.6 versus 11.0 months ( P = 0.7 ) , for DE and DC , respectively . According to RECIST criteria we observed 15 ( 11 % ) versus 11 ( 8 % ) complete responses and 55 ( 40 % ) versus 61 ( 45 % ) partial responses ( P = 0.8 ) , with DE and DC , respectively . Severe toxicity included grade 3 - 4 neutropenia ( 57 % versus 46 % ; P = 0.07 ) , febrile neutropenia ( 11 % versus 8 % ; P = 0.4 ) , h and -foot syndrome ( 0 % versus 4 % ; P = 0.02 ) , grade 2 - 3 anemia ( 20 % versus 7 % ; P = 0.001 ) and asthenia ( 12 % versus 6 % ; P = 0.09 ) with DE and DC , respectively . CONCLUSIONS The DE and DC regimens have similar efficacy but different toxicity . Either regimen can be used as front-line treatment of ABC PURPOSE Dexrazoxane was found effective in reducing doxorubicin cardiotoxicity when given at a dose ratio ( dexrazoxane : doxorubicin ) of 20:1 . Pre clinical studies indicated that dexrazoxane at a dose ratio of 10 to 15:1 also protected against epirubicin-induced cardiotoxicity . The main objective of this study was to investigate the efficacy of dexrazoxane , given at a dose ratio of 10:1 against epirubicin cardiotoxicity . PATIENTS AND METHODS One hundred sixty-two advanced breast cancer patients were r and omized to receive epirubicin-based chemotherapy with or without dexrazoxane . Patients who had previously received adjuvant chemotherapy that contained anthracyclines were treated with cyclophosphamide 600 mg/m2 intravenously ( IV ) , epirubicin 60 mg/m2 IV , and fluorouracil 600 mg/m2 IV , on day 1 every 3 weeks . The other patients were treated with epirubicin 120 mg/m2 IV on day 1 every 3 weeks . Cardiac toxicity was defined as clinical signs of congestive heart failure , a decrease in resting left ventricular ejection fraction ( LVEF ) to < or = 45 % , or a decrease from baseline resting LVEF of > or = 20 EF units . RESULTS One hundred sixty patients were evaluated . Cardiotoxicity was recorded in 18 of 78 patients ( 23.1 % ) in the control arm and in six of 82 ( 7.3 % ) in the dexrazoxone arm . The cumulative probability of developing cardiotoxicity was significantly lower in dexrazoxane-treated patients than in control patients ( P = .006 ; odds ratio , 0.29 ; 95 % confidence limit [ CL ] , 0.09 to 0.78 ) . Noncardiac toxicity , objective response , progression-free survival , and overall survival were similar in both arms . CONCLUSION Dexrazoxane given at a dexrazoxane : epirubicin dose ratio of 10:1 protects against epirubicin-induced cardiotoxicity and does not affect the clinical activity and the noncardiac toxicity of epirubicin . The clinical use of dexrazoxane should be recommended in patients whose risk of developing cardiotoxicity could hamper the eventual use and possible benefit of epirubicin Our objective was to determine whether oral etoposide and cisplatin combination ( EoP ) is superior to paclitaxel in the treatment of advanced breast cancer ( ABC ) patients pretreated with anthracyclines . From December 1997 to August 2003 , 201 patients were r and omised , 100 to EoP and 101 to paclitaxel arms . Four patients in each arm were ineligible . The doses of etoposide and cisplatin were 50 mg p.o . twice a day for 7 days and 70 mg m−2 intravenously ( i.v . ) on day 1 , respectively , and it was 175 mg m−2 on day 1 for paclitaxel . Both treatments were repeated every 3 weeks . A median of four cycles of study treatment was given in both arms . The response rate obtained in the EoP arm was significantly higher ( 36.3 vs 22.2 % ; P=0.038 ) . Median response duration was longer for the EoP arm ( 7 vs 4 months ) ( P=0.132 ) . Also , time to progression was significantly in favour of the EoP arm ( 5.5 vs 3.9 months ; P=0.003 ) . Median overall survival was again significantly longer in the EoP arm ( 14 vs 9.5 months ; P=0.039 ) . Toxicity profile of both groups was similar . Two patients in each arm were lost due to febrile neutropenia . The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines PURPOSE An American Society of Clinical Oncology ( ASCO ) provisional clinical opinion ( PCO ) offers timely clinical direction to ASCO 's membership following publication or presentation of potentially practice -changing data from major studies . This PCO addresses the integration of palliative care services into st and ard oncology practice at the time a person is diagnosed with metastatic or advanced cancer . CLINICAL CONTEXT Palliative care is frequently misconstrued as synonymous with end-of-life care . Palliative care is focused on the relief of suffering , in all of its dimensions , throughout the course of a patient 's illness . Although the use of hospice and other palliative care services at the end of life has increased , many patients are enrolled in hospice less than 3 weeks before their death , which limits the benefit they may gain from these services . By potentially improving quality of life ( QOL ) , cost of care , and even survival in patients with metastatic cancer , palliative care has increasing relevance for the care of patients with cancer . Until recently , data from r and omized controlled trials ( RCTs ) demonstrating the benefits of palliative care in patients with metastatic cancer who are also receiving st and ard oncology care have not been available . RECENT DATA Seven published RCTs form the basis of this PCO . PROVISIONAL CLINICAL OPINION Based on strong evidence from a phase III RCT , patients with metastatic non-small-cell lung cancer should be offered concurrent palliative care and st and ard oncologic care at initial diagnosis . While a survival benefit from early involvement of palliative care has not yet been demonstrated in other oncology setting s , substantial evidence demonstrates that palliative care-when combined with st and ard cancer care or as the main focus of care-leads to better patient and caregiver outcomes . These include improvement in symptoms , QOL , and patient satisfaction , with reduced caregiver burden . Earlier involvement of palliative care also leads to more appropriate referral to and use of hospice , and reduced use of futile intensive care . While evidence clarifying optimal delivery of palliative care to improve patient outcomes is evolving , no trials to date have demonstrated harm to patients and caregivers , or excessive costs , from early involvement of palliative care . Therefore , it is the Panel 's expert consensus that combined st and ard oncology care and palliative care should be considered early in the course of illness for any patient with metastatic cancer and /or high symptom burden . Strategies to optimize concurrent palliative care and st and ard oncology care , with evaluation of its impact on important patient and caregiver outcomes ( eg , QOL , survival , health care services utilization , and costs ) and on society , should be an area of intense research . NOTE ASCO 's provisional clinical opinions ( PCOs ) reflect expert consensus based on clinical evidence and literature available at the time they are written and are intended to assist physicians in clinical decision making and identify questions and setting s for further research . Because of the rapid flow of scientific information in oncology , new evidence may have emerged since the time a PCO was su bmi tted for publication . PCOs are not continually up date d and may not reflect the most recent evidence . PCOs can not account for individual variation among patients and can not be considered inclusive of all proper methods of care or exclusive of other treatments . It is the responsibility of the treating physician or other health care provider , relying on independent experience and knowledge of the patient , to determine the best course of treatment for the patient . Accordingly , adherence to any PCO is voluntary , with the ultimate determination regarding its application to be made by the physician in light of each patient 's individual circumstances . ASCO PCOs describe the use of procedures and therapies in clinical trials and can not be assumed to apply to the use of these interventions in the context of clinical practice . ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of ASCO 's PCOs , or for any errors or omissions The EORTC Breast Cancer Cooperative Group carried out a r and omized trial to compare doxorubicin with epirubicin as second-line chemotherapy in patients with metastatic breast cancer . Two hundred and fifty-nine patients with at least one site of metastatic disease entered this trial , of whom 232 patients were eligible . Treatment consisted of doxorubicin 75 mg m(-2 ) or epirubicin 90 mg m(-2 ) i.v . every 3 weeks . The overall response rates for doxorubicin and epirubicin were 36 % and 28 % respectively ( P = 0.173 ) . The median time to progression was 23 weeks for doxorubicin and 19 weeks for epirubicin ( P = 0.063 ) and the median duration of response was 40 weeks for doxorubicin and 32 weeks for epirubicin ( P = 0.059 ) . The median survival was 47 weeks for doxorubicin and 44 weeks for epirubicin ( P = 0.196 ) . Leucocyte count on retreatment day ( P = 0.011 ) and platelet nadir ( P = 0.031 ) were significantly lower in the doxorubicin-treated group . Also mucositis ( P < 0.001 ) , diarrhoea ( P = 0.005 ) and haemorrhage ( P = 0.048 ) were significantly worse in the doxorubicin arm . Nine patients on doxorubicin and two patients on epirubicin experienced congestive heart failure ( CHF ) . At the dose levels used in this study , no statistical differences in response rate and survival were found between the two treatment arms . Treatment with doxorubicin tended to result in a slightly longer duration of response and time to progression but doxorubicin was more toxic than epirubicin Limited proven treatment options exist for patients with metastatic breast cancer ( MBC ) resistant to anthracycline and taxane treatment . Ixabepilone , a novel semisynthetic analog of epothilone B , has demonstrated single-agent activity in MBC resistant to anthracyclines and taxanes . In combination with capecitabine in a phase III trial ( CA163 - 046 ) in this setting , ixabepilone prolonged progression-free survival and increased objective response rate relative to capecitabine ( Thomas et al. J Clin Oncol 25:5210–5217 , 2007 ) . Here , we report the results of overall survival ( OS ) , a secondary efficacy endpoint from the CA163 - 046 trial . Seven hundred fifty-two patients with MBC resistant to anthracyclines and taxanes were r and omized to ixabepilone ( 40 mg/m2 intravenously on day 1 of a 21-day cycle ) plus capecitabine ( 2,000 mg/m2 orally on days 1 through 14 of a 21-day cycle ) or capecitabine alone ( 2,500 mg/m2 on the same schedule ) . Patients receiving ixabepilone plus capecitabine treatment had a median survival of 12.9 months compared to 11.1 months for patients receiving capecitabine alone ( HR = 0.9 ; 95%CI : 077–1.05 ; P = 0.19 ) . This observed increase in median OS favored the combination ; however , the difference was not statistically significant . Predefined subset analyses showed a clinical ly meaningful increase in OS in KPS 70–80 patients receiving ixabepilone plus capecitabine ( HR = 0.75 ; 95 % CI : 0.58–0.98 ) . Ixabepilone plus capecitabine did not show a significant improvement in survival compared to capecitabine alone in patients with MBC resistant to anthracyclines and taxanes . The observed differences in survival favored the combination arm . A clinical benefit was also seen in patients in the KPS 70–80 subgroup ( Clinical Trials.gov number , NCT000080301 ) The purpose of this article is to provide up date d recommendations for the treatment of patients with stage IV non-small-cell lung cancer . A literature search identified relevant r and omized trials published since 2002 . The scope of the guideline was narrowed to chemotherapy and biologic therapy . An Up date Committee review ed the literature and made up date d recommendations . One hundred sixty-two publications met the inclusion criteria . Recommendations were based on treatment strategies that improve overall survival . Treatments that improve only progression-free survival prompted scrutiny of toxicity and quality of life . For first-line therapy in patients with performance status of 0 or 1 , a platinum-based two-drug combination of cytotoxic drugs is recommended . Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy . For patients with performance status of 2 , a single cytotoxic drug is sufficient . Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment . Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy . The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor ( EGFR ) mutation ; for negative or unknown EGFR mutation status , cytotoxic chemotherapy is preferred . Bevacizumab is recommended with carboplatin-paclitaxel , except for patients with certain clinical characteristics . Cetuximab is recommended with cisplatin-vinorelbine for patients with EGFR-positive tumors by immunohistochemistry . Docetaxel , erlotinib , gefitinib , or pemetrexed is recommended as second-line therapy . Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib . Data are insufficient to recommend the routine third-line use of cytotoxic drugs . Data are insufficient to recommend routine use of molecular markers to select chemotherapy PURPOSE Docetaxel and capecitabine , a tumor-activated oral fluoropyrimidine , show high single-agent efficacy in metastatic breast cancer ( MBC ) and synergy in pre clinical studies . This international phase III trial compared efficacy and tolerability of capecitabine/docetaxel therapy with single-agent docetaxel in anthracycline-pretreated patients with MBC . PATIENTS AND METHODS Patients were r and omized to 21-day cycles of oral capecitabine 1,250 mg/m(2 ) twice daily on days 1 to 14 plus docetaxel 75 mg/m(2 ) on day 1 ( n = 255 ) or to docetaxel 100 mg/m(2 ) on day 1 ( n = 256 ) . RESULTS Capecitabine/docetaxel result ed in significantly superior efficacy in time to disease progression ( TTP ) ( hazard ratio , 0.652 ; 95 % confidence interval [ CI ] , 0.545 to 0.780 ; P = .0001 ; median , 6.1 v 4.2 months ) , overall survival ( hazard ratio , 0.775 ; 95 % CI , 0.634 to 0.947 ; P = .0126 ; median , 14.5 v 11.5 months ) , and objective tumor response rate ( 42 % v 30 % , P = .006 ) compared with docetaxel . Gastrointestinal side effects and h and -foot syndrome were more common with combination therapy , whereas myalgia , arthralgia , and neutropenic fever/sepsis were more common with single-agent docetaxel . More grade 3 adverse events occurred with combination therapy ( 71 % v 49 % , respectively ) , whereas grade 4 events were slightly more common with docetaxel ( 31 % v 25 % with combination ) . CONCLUSION The significantly superior TTP and survival achieved with the addition of capecitabine to docetaxel 75 mg/m(2 ) , with the manageable toxicity profile , indicate that this combination provides clear benefits over single-agent docetaxel 100 mg/m(2 ) . Docetaxel/capecitabine therapy is an important treatment option for women with anthracycline-pretreated MBC Background : Alternating administration of docetaxel and gemcitabine might result in improved time-to-treatment failure ( TTF ) and fewer adverse events compared with single-agent docetaxel as treatment of advanced breast cancer . Patients and methods : Women diagnosed with advanced breast cancer were r and omly allocated to receive 3-weekly docetaxel ( group D ) or 3-weekly docetaxel alternating with 3-weekly gemcitabine ( group D/G ) until treatment failure as first-line chemotherapy . The primary end point was TTF . Results : Two hundred and thirty-seven subjects were assigned to treatment ( group D , 115 ; group D/G , 122 ) . The median TTF was 5.6 and 6.2 months in groups D and D/G , respectively ( hazard ratio 0.85 , 95 % confidence interval 0.63–1.16 ; P = 0.31 ) . There was no significant difference in time-to-disease progression , survival , and response rate between the groups . When adverse events were evaluated for the worst toxicity encountered during treatment , there was little difference between the groups , but when they were assessed per cycle , alternating treatment was associated with fewer severe ( grade 3 or 4 ) adverse effects ( P = 0.013 ) , and the difference was highly significant for cycles when gemcitabine was administered in group D/G ( P < 0.001 ) . Conclusion : The alternating regimen was associated with a similar TTF as single-agent docetaxel but with fewer adverse effects during gemcitabine cycles In a large phase III trial of 511 patients with anthracycline-pretreated advanced/metastatic breast cancer , capecitabine/docetaxel combination therapy was shown to have significantly superior efficacy compared with single-agent docetaxel , including superior progression-free and overall survival and objective response rate . An up date d survival analysis with > /= 27 months follow-up shows that patients receiving combination therapy maintained significantly superior survival ( hazard ratio [ HR ] , 0.777 [ 95 % CI , 0.645 - 0.942 ] ; P < 0.01 ; median survival , 14.5 months vs. 11.5 months ) compared with those receiving single-agent docetaxel . Following the failure of docetaxel monotherapy , 35 % of patients did not receive additional cytotoxic chemotherapy . Among patients r and omized to single-agent docetaxel , only those given post study single-agent capecitabine had significantly prolonged survival compared with those given any other post study chemotherapy ( HR , 0.500 ; P = 0.0046 ; median survival , 21.0 months vs. 12.3 months , respectively ) . By contrast , post study vinorelbine-containing chemotherapy did not affect survival following progression on single-agent docetaxel compared with other post study chemotherapy regimens ( HR , 1.014 ; P = 0.94 ; median survival , 13.5 months vs. 12.6 months , respectively ) . Among patients r and omized to combination therapy , discontinuing docetaxel of capecitabine has a similar effect on survival ( HR , 0.720 ; P = 0.20 ; median survival , 15.8 months vs. 18.3 months , respectively ) . Median survival was 18.3 months in patients who discontinued docetaxel and continued to receive capecitabine versus 15.8 months in patients who discontinued capecitabine and continued to receive docetaxel , with a trend toward improved survival in patients continuing to receive capecitabine . Although this is a retrospective analysis , these data suggest that the sequential administration of docetaxel followed by capecitabine is associated with prolonged survival in patients who are c and i date s for sequential single-agent therapy INTRODUCTION A multicenter , open-label phase III study was conducted to test whether sunitinib plus paclitaxel prolongs progression-free survival ( PFS ) compared with bevacizumab plus paclitaxel as first-line treatment for patients with HER2(- ) advanced breast cancer . PATIENTS AND METHODS Patients with HER2(- ) advanced breast cancer who were disease free for ≥ 12 months after adjuvant taxane treatment were r and omized ( 1:1 ; planned enrollment 740 patients ) to receive intravenous ( I.V. ) paclitaxel 90 mg/m(2 ) every week for 3 weeks in 4-week cycles plus either sunitinib 25 to 37.5 mg every day or bevacizumab 10 mg/kg I.V. every 2 weeks . [ corrected ] RESULTS The trial was terminated early because of futility in reaching the primary endpoint as determined by the independent data monitoring committee during an interim futility analysis . At data cutoff , 242 patients had been r and omized to sunitinib-paclitaxel and 243 patients to bevacizumab-paclitaxel . Median PFS was shorter with sunitinib-paclitaxel ( 7.4 vs. 9.2 months ; hazard ratio [ HR ] 1.63 [ 95 % confidence interval ( CI ) , 1.18 - 2.25 ] ; 1-sided P = .999 ) . At a median follow-up of 8.1 months , with 79 % of sunitinib-paclitaxel and 87 % of bevacizumab-paclitaxel patients alive , overall survival analysis favored bevacizumab-paclitaxel ( HR 1.82 [ 95 % CI , 1.16 - 2.86 ] ; 1-sided P = .996 ) . The objective response rate was 32 % in both arms , but median duration of response was shorter with sunitinib-paclitaxel ( 6.3 vs. 14.8 months ) . Bevacizumab-paclitaxel was better tolerated than sunitinib-paclitaxel . This was primarily due to a high frequency of grade 3/4 , treatment-related neutropenia with sunitinib-paclitaxel ( 52 % ) precluding delivery of the prescribed doses of both drugs . CONCLUSION The sunitinib-paclitaxel regimen evaluated in this study was clinical ly inferior to the bevacizumab-paclitaxel regimen and is not a recommended treatment option for patients with advanced breast cancer PURPOSE This prospect i ve multicenter r and omized trial was performed to compare the effectiveness and safety of intravenous ( i.v . ) vinorelbine tartrate ( Navelbine [ NVB ] ; Burroughs Wellcome Co , Research Triangle Park , NC ) with i.v . melphalan ( Alkeran [ ALK ] ; Burroughs Wellcome Co ) in a heavily pretreated population of patients with anthracycline-refractory advanced breast cancer ( ABC ) . Efficacy end points included time to disease progression ( TDP ) , time to treatment failure ( TTF ) , survival , tumor response rates , and quality of life ( QL ) and relief of cancer-related symptoms . PATIENTS AND METHODS Between August 24 , 1990 , and December 1 , 1992 , 183 patients were r and omized ( 2:1 ) to treatment with NVB ( 30 mg/m2 weekly ) or ALK ( 25 mg/m2 every 4 weeks ) i.v . Patients were stratified by measurable or nonmeasurable-assessable disease and by treatment center . RESULTS Time to disease progression was significantly longer with NVB than with ALK , with a median 12 weeks versus 8 weeks , respectively ( P < .001 ) . NVB patients also had significantly longer time to treatment failure than ALK patients , with a median 12 weeks versus 8 weeks , respectively ( P < .001 ) . The effect of NVB on survival was also statistically significant ( P = .034 ) : 1-year survival rates were 35.7 % with NVB and 21.7 % with ALK and the median survival rate was 35 weeks and 31 weeks , respectively . In total , 46.5 % of NVB patients and 28.2 % of ALK patients achieved an objective response or stabilization of disease ( P = .06 ) . No intergroup differences were noted in patient-assessed QL and cancer-related symptoms . The most common toxicities were hematologic , including granulocytopenia with NVB and thrombocytopenia and granulocytopenia with ALK . Both drugs were generally well tolerated , and no septic deaths were reported . CONCLUSION This r and omized trial demonstrates a survival benefit in anthracycline-refractory ABC . NVB was well tolerated and demonstrated activity superior to ALK in anthracycline-refractory ABC , without compromising QL . Based on activity of single-agent NVB in this difficult-to-treat patient population , investigations of NVB in combination with other anticancer drugs are warranted |
13,242 | 25,931,672 | While there were few r and omized controlled trials with vali date d outcome measures , some discoveries about simulation can positively affect the design of the PT entry-to- practice curricula .
Using simulators to provide specific output feedback can help students learn specific skills .
Computer simulations can also augment students ' learning experience .
Human simulation experiences in managing the acute patient in the ICU are well received by students , positively influence their confidence , and decrease their anxiety .
There is evidence that simulated learning environments can replace a portion of a full-time 4-week clinical rotation without impairing learning .
CONCLUSIONS Simulation-based learning activities are being effectively incorporated into PT curricula . | PURPOSE To review the literature on simulation-based learning experiences and to examine their potential to have a positive impact on physiotherapy ( PT ) learners ' knowledge , skills , and attitudes in entry-to- practice curricula . | CONTEXT Education in simulated learning environments ( SLEs ) has grown rapidly across health care professions , yet no substantive r and omised controlled trial ( RCT ) has investigated whether SLEs can , in part , substitute for traditional clinical education . METHODS Participants were physiotherapy students ( RCT 1 , n = 192 ; RCT 2 , n = 178 ) from six Australian universities undertaking clinical education in an ambulatory care setting with patients with musculoskeletal disorders . A simulated learning programme was developed as a replica for clinical education in musculoskeletal practice to replace 1 week of a 4-week clinical education placement . Two SLE models were design ed . Model 1 provided 1 week in the SLE , followed by 3 weeks in clinical immersion ; Model 2 offered training in the SLE in parallel with clinical immersion during the first 2 weeks of the 4-week placement . Two single-blind , multicentre RCTs ( RCT 1 , Model 1 ; RCT 2 , Model 2 ) were conducted using a non-inferiority design to determine if the clinical competencies of students part-educated in SLEs would be any worse than those of students educated fully in traditional clinical immersion . The RCTs were conducted simultaneously , but independently . Within each RCT , students were stratified on academic score and r and omised to either the SLE group or the control ( ' Traditional ' ) group , which undertook 4 weeks of traditional clinical immersion . The primary outcome measure was a blinded assessment of student competency conducted over two clinical examinations at week 4 using the Assessment of Physiotherapy Practice ( APP ) tool . RESULTS Students ' achievement of clinical competencies was no worse in the SLE groups than in the Traditional groups in either RCT ( Margin [ Δ ] ≥ 0.4 difference on APP score ; RCT 1 : 95 % CI - 0.07 to 0.17 ; RCT 2 : 95 % CI - 0.11 to 0.16 ) . CONCLUSIONS These RCTs provide evidence that clinical education in an SLE can in part ( 25 % ) replace clinical time with real patients without compromising students ' attainment of the professional competencies required to practise OBJECTIVE The purpose of this study was to investigate a quantitative biomechanical evaluation method for contact forces exerted during a manual examination and treatment technique used in a learning environment . The evaluation was based on three-dimensional ( 3D ) force component data . METHODS A h and -/palm-held computerized 3D force component measuring system was used during a simple feedback experiment involving 20 second-year university students of physiotherapy who delivered 5 sets of grade d perpendicular manual push forces on the sensor part of the system , which was placed on the padded surface of an examination/treatment table . In an effect study with a multiple time-series design , a r and omly chosen subgroup of subjects received concurrent visual 3D kinetic/dynamic force-time feedback . RESULTS The students delivered grade d perpendicular forces with good intrasubject consistency ( intraclass correlation coefficient [ 3 , 1 ] : mean , 0.80 ; range , 0.76 - 0.88 ) but with poor intersubject consistency ( intraclass correlation coefficient [ 2 , 1 ] : mean , 0.38 ; range , 0.15 - 0.74 ) . A temporary performance improvement in forward-backward force direction deviations from the perpendicular in the subgroup given feedback indicates that students are sensitive to feedback training . CONCLUSION An evaluation tool using 3D contact force component measurement enables the assessment of the overall magnitude of the manual contact force as well as its directional aspect . Compared with existing evaluations based on 1-dimensional force components , this 3D system allows for a more complete and , at the same time , more specific quantitative evaluation of the manual contact forces . Three-dimensional dynamic/kinetic augmented feedback has the additional potential of helping students and practitioners to improve their palpation and force delivery skills This study was design ed to investigate whether concurrent quantitative feedback of performance could improve the learning of a joint mobilization technique . A group of 110 physical therapy students had been r and omly divided into two groups for teaching purpose s. All students had previously learned mobilization of peripheral joints and were currently learning spinal mobilization . From one of the groups , 22 students volunteered to comprise a control group , which was taught a spinal mobilization technique in the traditional way . Additional concurrent quantitative feedback of the level of force applied to the patient was given to 31 volunteers from the other group . These students formed the experimental group . A force plate was used for force measurement , and the feedback was given via an oscilloscope . The average force applied by the students ' instructors was taken as an " ideal " force . The oscilloscope showed both the applied force and the " ideal " force . Consistency was measured by the variance of the group 's performance . Accuracy was assessed by calculating the difference between the applied force and the " ideal " force . Results indicated that this feedback was associated with a significant improvement in accuracy and consistency in the application of the mobilizing force . This improvement was still present at a follow-up test conducted one week later . This result supports a greater use of such feedback in the teaching and practice of joint mobilization techniques , although the need for further research is emphasized Introduction Simulated learning environments ( SLEs ) are used worldwide in health professional education , including physiotherapy , to train certain attributes and skills . To date , no r and omized controlled trial ( RCT ) has evaluated whether education in SLEs can partly replace time in the clinical environment for physiotherapy cardiorespiratory practice . Methods Two independent single-blind multi-institutional RCTs were conducted in parallel using a noninferiority design . Participants were volunteer physiotherapy students ( RCT 1 , n = 176 ; RCT 2 , n = 173 ) entering acute care cardiorespiratory physiotherapy clinical placements . Two SLE models were investigated as follows : RCT 1 , 1 week in SLE before 3 weeks of clinical immersion ; RCT 2 , 2 weeks of interspersed SLE/ clinical immersion ( equivalent to 1 SLE week ) within the 4-week clinical placement . Students in each RCT were stratified on academic grade and r and omly allocated to an SLE plus clinical immersion or clinical immersion control group . The primary outcome was competency to practice measured in 2 clinical examinations using the Assessment of Physiotherapy Practice . Secondary outcomes were student perception of experience and clinical educator and patient rating of student performance . Results There were no significant differences in student competency between the SLE and control groups in either RCT , although students in the interspersed group ( RCT 2 ) achieved a higher score in 5 of 7 Assessment of Physiotherapy Practice st and ards ( all P < 0.05 ) . Students rated the SLE experience positively . Clinical educators and patients reported comparability between groups . Conclusions An SLE can replace clinical time in cardiorespiratory physiotherapy practice . Part education in the SLE satisfied clinical competency requirements , and all stakeholders were satisfied UNLABELLED The purpose of this study was to determine whether providing physical therapy ( PT ) students with instructions in proper ultrasound ( US ) pressure application would result in more optimal pressures compared with pressures obtained by students who were not instructed . Previous research determined that for transmission to be adequate , optimal pressure must be 600 g. A sample of convenience of PT students in our program participated in this study . Students were divided into two groups : 31 first-year students who were instructed ( group 1 ) and 34 third-year students who were not instructed ( group 2 ) in US pressure application . METHODS The students who were trained in this new parameter did so as part of the electromodalities course and were compared with untrained third-year students . Group 1 received specific verbal instructions during laboratory , and then performed the US to a gel pad placed on top of a digital scale while observing the digital pressure readout for feedback . This group was retested 7 months later to determine retention of skill acquisition . For data collection , all students applied US for 5 minutes with pressures recorded every 30 seconds and were blinded to the readout . The group without instructions had a mean pressure of 321.92 g ( SD , 257.82 ) , and the group with instructions had a mean of 607.29 g ( SD , 145.52 ) 4 weeks after training . The difference between means was significant ( t[60.4 ] = 8.54 , p < 0.000 ) . Follow-up scores 7 months later for group 1 showed a mean of 587.23 g ( SD , 284.17 ) , not significantly different from the first measurements ( p = 0.807 ) . The results showed a significant difference between groups , whereby students who received instructions outperformed those who did not , overall were more accurate in their perception of US pressure , and showed good retention skills , reaffirming that feedback is a valuable learning tool . For US to be effective , proper pressure must be exerted , and this should be a parameter instructed in schools where US is taught to improve treatment effectiveness Background and Purpose Joint mobilization is a complicated task to learn and to teach and is characterized by great intersubject variability . This study 's purpose was to investigate whether quantitatively augmented feedback could enhance the learning of joint mobilization and , more specifically , to compare the effects of training with concurrent or terminal feedback by using a joint translation simulator ( JTS ) . Subjects Thirty-six undergraduate physical therapist students were r and omly assigned to control ( no feedback ) , concurrent feedback , and terminal feedback groups . Methods The JTS was design ed to simulate tissue resistance based on load-displacement relationships of glenohumeral joint specimens . Subjects applied specific mobilization grade s of force on the JTS while quantitative feedback was given to the feedback groups either during a trial ( ie , concurrent feedback ) or after a trial ( ie , terminal feedback ) . The skill acquisition phase lasted a total of 40 minutes , and a total of 75 repetitions were performed for each grade of each joint model . Pretest and no-feedback retention tests were conducted . Results During acquisition and retention , both feedback groups performed more accurately than did the control group . No obviously superior performance was shown by the terminal feedback group compared with concurrent feedback group during retention testing . Discussion and Conclusion Subjects who trained with augmented feedback had less variability , and thus more consistency , than the control group subjects who received no feedback . Augmented feedback provides the student with a reference force and the status of his or her performance . The effectiveness of the JTS feedback compared with no feedback was clearly demonstrated . Skill acquisition in mobilization can be enhanced by either concurrent or terminal feedback Purpose To evaluate the effectiveness of a novel , simulation-based educational model rooted in scaffolding theory that capitalizes on a systematic progressive sequence of simulators that increase in realism ( i.e. , fidelity ) and information content . Method Forty-five medical students were r and omly assigned to practice intravenous catheterization using high-fidelity training , low-fidelity training , or progressive training from low to mid to high fidelity . One week later , participants completed a transfer test on a st and ardized patient simulation . Blinded expert raters assessed participants ' global clinical performance , communication , procedure documentation , and technical skills on the transfer test . Participants ' management of the re sources available during practice was also recorded . Data were analyzed using multivariate analysis of variance . The study was conducted in fall 2008 at the University of Toronto . Results The high-fidelity group scored higher ( P < .05 ) than the low-fidelity group on all measures except procedure documentation . The progressive group scored higher ( P < .05 ) than other groups for documentation and global clinical performance and was equivalent to the high-fidelity group for communication and technical skills . Total practice time was greatest for the progressive group ; however , this group required little practice time on the re source -intensive high-fidelity simulator . Conclusions Allowing students to progress in their practice on simulators of increasing fidelity led to superior transfer of a broad range of clinical skills . Further , this progressive group was re source -efficient , as participants concentrated on lower fidelity and lower re source -intensive simulators . It is suggested that clinical training curricula incorporate exposure to multiple simulators to maximize educational benefit and potentially save educator time |
13,243 | 20,591,088 | The available data indicate that compared to normotensive whites , normotensive black people have enhanced vascular reactivity to sympathetic stimulation , attenuated responses to vasodilators , and a relatively narrow vascular lumen diameter .
Of these mechanisms , the reduced vasodilation and reduced nitric oxide bioavailability in the vascular wall seem to form the most important distinction between resistance vessel properties of black and white participants | The risk of development of hypertension is greater in black people compared to white people through mechanisms that are poorly understood .
Several biological and environmental factors have been proposed .
Based on the role of an increased peripheral resistance in the pathogenesis of hypertension , the authors focus in this systematic review on ethnic differences in function and mechanical properties of resistance arteries in normotensive participants . | Blood pressure reactivity is enhanced in young black subjects through mechanisms that are poorly understood . We compared & agr;-adrenergic – mediated vasoconstrictor and & bgr;-adrenergic vasodilator sensitivity and their relation to sympathetic activity in blacks and whites . Ten healthy black ( age , 29.9±2.4 years ) and 10 white ( age , 28.3±1.9 years ) men were studied . Forearm blood flow was measured with strain-gauge plethysmography after the intrabrachial artery administration of phenylephrine ( 1.25 to 20 & mgr;g/min ) and isoproterenol ( 60 and 400 ng/min ) after application of lower-body negative pressure and after a cold pressor test . Forearm and systemic norepinephrine spillover were measured with a radioisotope dilution technique . & agr;-Adrenergic vasoconstriction was markedly increased ( ANOVA P = 0.008 ) and & bgr;-adrenergic vasodilation decreased ( ANOVA P = 0.02 ) in blacks . Phenylephrine ( 10 & mgr;g/min ) decreased forearm blood flow by 58.0±2.5 % in blacks but only by 26.6±6.0 % in whites ( P < 0.001 ) . Vasoconstrictor response to endogenous norepinephrine , stimulated by a cold pressor test , result ed in a higher forearm vascular resistance in blacks than in whites ( 107.3±13 versus 64.8±13 mm Hg · mL−1 · 100 mL−1 , P = 0.03 ) . There were no significant ethnic differences in basal or stimulated forearm or systemic norepinephrine spillover . Increased vasoconstrictor and decreased vasodilator responses in blacks were not correlated . Increased sympathetically mediated vascular tone caused by enhanced vasoconstriction and attenuated vasodilation , effects that would be additive , and not increased sympathetic activity could enhance vascular reactivity and may play a role in the pathogenesis of hypertension in blacks Presentation , response to therapy , and clinical outcome in hypertension differ according to race , and these observations could relate to differences in microvascular function . We examined forearm microvascular function in age-matched black ( n=56 ) and white subjects ( n=62 ) using intra-arterial agonist infusion and venous occlusion plethysmography . In normotensive subjects ( n=70 ; 34 black and 36 white normotensives ) , methacholine- , sodium nitroprusside- , and verapamil-induced vasodilation was equivalent in black and white subjects . In hypertensive subjects ( n=48 ; 22 black and 26 white hypertensives ) , the vasodilator response to methacholine was markedly lower in black subjects compared with white subjects ( P < 0.001 ) . The vasodilator responses to sodium nitroprusside and verapamil , however , were equivalent in black and white hypertensive subjects . Acute ascorbic acid infusion improved the methacholine response equally in black and white hypertensive patients , suggesting that a difference in a rapidly reversible form of oxidative stress does not explain these findings . Thus , the present study demonstrates important racial differences in vascular function and a marked impairment in endothelial vasomotor function in black patients with hypertension . Further studies will be required to eluci date the mechanisms and determine whether these insights will lead to more appropriately tailored management of hypertension and its complications In this prospect i ve investigation , all children enrolled in the public third- grade classrooms of an entire county ( n=474 ) had blood pressure measured both at rest and during a stressful television video game . Examinations were repeated in 4 subsequent years when cohort children as well as newly enrolled children were in grade s 4 , 5 , 7 , and 8 . Both crosssectional and longitudinal analyses indicated that black children demonstrated significantly greater systolic and diastolic pressor reactivity than white children . These data suggest that ethnic differences in children 's pressor reactivity presage ethnic differences in adulthood hypertension OBJECTIVES To determine arterial elasticity in normotensives and in treated and untreated hypertensive Black and White subjects . METHODS A prospect i ve multicenter , controlled clinical trial evaluated large ( C- ) and small ( C2 ) artery elasticity indices among 3 groups : 1 ) normotensive subjects with or without a family history of hypertension ; 2 ) controlled and treated hypertensive subjects ; and 3 ) untreated and uncontrolled hypertensive subjects . Blood pressure was measured using a mercury manometer and arterial compliance or elasticity was determined using a CVProfilor DO-2020 CardioVascular Profiling System ( Hypertension Diagnostics , Inc , Eagan , Minn ) . These parameters were measured in triplicate 3 minutes apart in a r and om sequence , with the patient in a supine position . Two-way ANOVA was used for statistical evaluation . RESULTS One hundred seventy eight subjects met stratification and enrollment criteria . The mean age was 46 years . 109 were White and 69 were Black . [ table : see text ] CONCLUSION Small and large arterial elasticity indices are reduced as hypertension status worsens . Age and height were important covariates of C1 and C2 . Race was not found to be a significant predictor of either C1 or C2 . Large and small artery elasticity indices do not differ between White and Black subjects with varying degrees of hypertension after adjusting for covariates . More studies with a larger number of subjects are required BACKGROUND Vasodilator reactivity is attenuated in normotensive blacks , and this may contribute to their enhanced susceptibility to hypertension and its complications . However , the mechanisms responsible for this phenomenon are unknown . We therefore studied nitric oxide (NO)-dependent and -independent vasorelaxation in healthy blacks and whites to investigate the nature of racial differences in vasodilator function . METHODS AND RESULTS Forearm flow responses to intra-arterial infusion of increasing doses of acetylcholine ( a vasodilator that stimulates endothelial release of NO ) , sodium nitroprusside ( an exogenous NO donor ) , and isoproterenol ( a beta-adrenergic agonist whose vasodilator effect stems from the combination of direct smooth muscle stimulation and endothelial NO release ) were studied in 18 normotensive whites and 18 blacks by use of strain-gauge plethysmography . A blunted vasodilator response to acetylcholine ( 7.2+/-1.1 versus 14.4+/-1.8 mL. min-1 . dL-1 ; P<0.001 ) and sodium nitroprusside ( 8.2+/-1.1 versus 12.1+/-1.3 mL. min-1 . dL-1 ; P<0.001 ) was observed in blacks compared with whites , suggesting decreased cGMP-mediated smooth muscle relaxation . The vasodilator effect of isoproterenol was lower in blacks than in whites both before ( 10.9+/-1.7 versus 14.9+/-1.5 mL. min-1 . dL-1 ; P=0.006 ) and after NG-monomethyl-L-arginine ( 6.1+/-1.2 versus 10 . 1+/-0.8 mL. min-1 . dL-1 ; P<0.001 ) , implying that cAMP-dependent vasodilator response to isoproterenol is diminished in blacks . No significant difference was observed in the hyperemic response to forearm ischemia . CONCLUSIONS Compared with whites , healthy blacks have reduced vasodilation in response to NO-dependent and -independent stimuli . This difference seems to be related to an attenuation in cyclic nucleotide-mediated vascular smooth muscle relaxation and may play a role in the increased prevalence of hypertension and its complications in blacks The health and life expectancy of Americans has dramatically improved during the past several decades , but racial and ethnic minorities have not benefited equally from this progress . Differences in health outcomes between majority and minority population s , commonly referred to as racial or ethnic disparities in health , are the result of several factors operating in complex sociologic , cultural , political , economic , and health care context s. Until recently , curricula addressing racial and ethnic health disparities focused on factors outside the health care system , including socioeconomic disadvantage and lack of health insurance ( 1 ) , but some publications ( 25 ) , culminating in 2002 with the Institute of Medicine report , Unequal Treatment : Confronting Racial and Ethnic Disparities in Health Care , have highlighted the fact that racial and ethnic minoritieseven those with equivalent access to the health care systemreceive lower- quality care than white patients for many medical conditions ( 6 ) . As a result , increased attention is now focused on addressing racial and ethnic disparities in health care ( hereafter referred to as health care disparities ) as a component of addressing racial and ethnic disparities in health ( hereafter referred to as health disparities ) ( 7 , 8) . Emerging consensus among national experts suggests that without new and more effective interventions , health disparities will be difficult to eliminate ( 9 ) , and they may become an even larger problem as racial and ethnic minorities become a larger proportion of the U.S. population ( 10 ) . Key stakeholders need to engage at many levels to eliminate disparities , including at the community and societal levels . However , considering the significance of the physicianpatient relationship in health care delivery , interventions by individual physicians will be an important component of an overall strategy to reduce health care disparities . Several surveys show that many physicians remain unaware of health care disparities nationally and in their own practice s ( 1113 ) . The Institute of Medicine 's report recommends that health professionals receive training to better underst and and address disparities ( 6 ) . However , few curricula on health disparities exist , and there are no well-accepted guidelines on what and how to teach about this complex topic . This report presents the work of the Society of General Internal Medicine Health Disparities Task Force to develop guidelines for medical education on disparities in health and health care . We provide learning objectives , suggested content , methods for teaching , and a set of current re sources . Although they were developed primarily for teaching medical students , residents , and practitioners in primary care , our general recommendations should apply to learners in any specialty . The Task Force has also developed recommendations for system-level and environment-of-care interventions to eliminate health care disparities , which are as important as recommendations for training individual practitioners but are beyond the scope of this report . Methods The Society of General Internal Medicine is an international organization that comprises internal medicine physicians and others who combine patient care with education and research in primary care internal medicine . The Task Force includes volunteers from the Society of General Internal Medicine membership , many of whom teach about ethics , health disparities , and cross-cultural care at their institutions . The Task Force convened a series of meetings from 2002 to 2005 , which included several conference calls , e-mail exchanges , and 4 face-to-face meetings . After the first meeting , Task Force teams completed a needs assessment and literature review . The entire Task Force then contributed to several versions of the recommendations . Subsequent meetings served to refine and tailor iterative versions of both the literature review and recommendations , which informed each other . Final recommendations were developed by a consensus , although various interpretations remain among members of the Task Force in the application of specific principles . Needs Assessment Few studies have formally assessed the need for health disparities training . Recent surveys on cross-cultural care demonstrate that resident physicians ' self-reported preparedness to deliver cross-cultural care lags well behind preparedness in other clinical and technical areas ( 14 , 15 ) . A national study on resident physicians reported that residents were receiving the message that health care disparities are important and that physicians should play a role in eliminating them , but they had not received guidance on how to do so . As a result , they developed coping behaviors rather than skills ( 16 ) . To supplement these studies , the Task Force conducted its own brief needs assessment survey with the assistance of the Institute for Ethics at the American Medical Association . The survey was sent to 60 r and omly selected internal medicine program directors nationwide , 22 of whom responded within the 1-month time frame ( 37 % response rate ) . Most of the 22 respondents ( 86 % ) reported teaching some information about health disparities , and none reported offering a lot of training . However , 77 % agreed that learning about health disparities was associated with better quality of care , and 73 % reported that a resident 's level of interest was not a barrier to teaching : health disparities . Rather , shortages of qualified faculty and lack of st and ardized curricula were often noted as barriers . Adding to the need for concrete guidance in this domain , the Liaison Committee on Medical Education , which sets st and ards for undergraduate medical education , required in 2004 that medical schools document objectives relating to the development of skills in cultural competence , indicate where in the curriculum students are exposed to such material , and demonstrate the extent to which the objectives are being achieved ( 17 ) . The Accreditation Council on Graduate Medical Education , which accredits residency training programs , has also included cultural sensitivity as a skill set in its core competencies for residency training : Programs must teach and monitor residents ' ability to demonstrate sensitivity and responsiveness to patients ' culture , age , gender , and disabilities ( 18 ) . The American Board of Medical Specialties and the Accreditation Council on Graduate Medical Education have created a toolbox of re sources for monitoring professionalism that includes useful material s for assessing residents in these domains ( 19 ) . Because these accreditation requirements have been implemented , new curricula ( 2022 ) and suggested st and ards for training programs ( 2325 ) have begun to emerge , although none are widely accepted yet . Literature Review Task Force members search ed for published curricula focused on health disparities but found very little documentation . We search ed MEDLINE ( 1966 to 2005 ) , EMBASE ( 1980 to 2005 ) , and the Cochrane Library of Systematic Review s ( all years ) and article bibliographies for curricula on health disparities or cross-cultural medical care by using various search terms . For example , by using the Medical Subject Headings and text terms health disparities and curriculum , our search yielded 39 articles . However , none of these reports on curricula explicitly focused on disparities by discussing the multifactorial causes of health disparities ; describing health care disparities as a component of health disparities ; targeting the elimination of health disparities as a professional goal for medicine ; or teaching learners how to help eliminate disparities . In contrast , several cross-cultural care curricula often prominently mentions the existence of health disparities and some root causes of disparities ( 26 ) . Various studies have summarized these curricula and evaluations of their effectiveness . A 1978 survey of medical school curricula concluded that courses on cross-cultural care in U.S. medical schools had substantial deficits ( 27 ) . A comprehensive review of U.S. and British medical school curricula in 1999 showed little apparent improvement ( 28 ) . At that time , only 13 criteria ; 11 were for first- or second-year medical students , 7 were part of core ( required ) curricula , and we only found 1 curriculum that reported any postteaching evaluation of learners . A survey of all U.S. and Canadian medical schools in 2000 concluded that most schools provided inadequate instruction about cultural issues ; separate courses addressing cultural issues were identified in only 8 % of U.S. schools and in no Canadian schools ( 29 ) . Good evidence indicated that cross-cultural care training can improve a professional 's knowledge , attitude , and skill , but there is little documented evidence of an effect on patient adherence and no evaluations of effects on patient health status ( 3032 ) . Recommendations Recommended Goals of a Curriculum The ultimate aim of a curriculum on disparities is that learners develop a professional commitment to eliminating inequities in health care quality and underst and and accept their role in eliminating racial and ethnic health care disparities . The curriculum should accomplish this by meeting 3 core teaching goals : 1 ) to help learners examine and underst and attitudes , such as mistrust , subconscious bias , and stereotyping , that practitioners and patients may bring to the clinical encounter ; 2 ) to impart knowledge of the existence and magnitude of health disparities , including the multifactorial causes of health disparities and the many solutions required to eliminate them ; and 3 ) to provide the learner with the skills required to effectively communicate and negotiate across cultures , language s , and literacy levels , including the use of key tools to improve communication . Attitudes Helping learners acquire knowledge and skills is commonly the primary goal of teaching ; however , teachers may give little explicit attention to the goal of |
13,244 | 15,106,207 | REVIEW ERS ' CONCLUSIONS We found only small , poor quality trials ; the evidence is therefore insufficient to determine whether the choice of dressing or topical agent affects the healing of surgical wounds healing by secondary intention .
Foam is best studied as an alternative for gauze and appears to be preferable as to pain reduction , patient satisfaction and nursing time | BACKGROUND Many different wound dressings and topical applications are used to cover surgical wounds healing by secondary intention .
It is not known whether these dressings heal wounds at different rates . | OBJECTIVE To assess the effect of a plaster cast socket on the healing of open wounds and on temporary prosthesis fitting after below-knee amputation because of arterial occlusive disease . DESIGN R and omized controlled trial . SETTING Rehabilitation center , university hospital . PATIENTS All included patients had undergone recent ( in the previous 3 months ) below-knee amputation because of arterial disease and initially had an open stump . Patients were r and omly assigned to two groups of 28 subjects each . The sizes of the amputation scars were 8 to 24 cm2 . Ischemia of the stump was eliminated as a probable cause of delayed wound healing by the inclusion criterion of transcutaneous oxygen tension ( TcPO2 ) of > 35 mmHg . The average age in group I ( the experimental group ) was 65.2 + /- 12.4 ( SD ) years and in group II ( the control group ) 66.8 + /- 10.8 years ( not significant ) . INTERVENTION A plaster cast ( supracondylar-type ) socket was fitted on the stumps of group I patients , interposed with a silicone sleeve . The patients were gradually trained to wear this cast for up to 5 hours a day . They were provided with elastic compression b and ages for the remainder of the time . Patients in group II wore elastic compression b and ages , which were only removed for dressing changes . MAIN OUTCOME MEASURES Time required for stump healing , length of time between amputation and ability to walk wearing a contact socket , and length of hospital stay . RESULTS Group I had a quicker average healing time ( 71.2 + /- 31.7 [ SD ] days compared to the control group 's 96.8 + /- 54.9 days ) and a shorter average length of hospital stay ( 99.8 + /- 22.4 days compared to the control group 's 129.9 + /- 48.3 days ) . CONCLUSION Use of a plaster cast socket leads to more rapid healing of the open stump and to a shorter hospitalization . If there is no stump ischemia , this plaster cast technique is safe To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrolment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results findings of impaired activity of aryl hydrocarbon hydroxylase in the liver and small bowel of patients with psoriasis . ' The salivary clearances indicate that the inducing effect of smoking on antipyrine metabolism is similar in patients and normal subjects . This contrasts with our observations in skin : so far we have been unable to show any difference in skin activity of aryl hydrocarbon hydroxylase between smokers and non-smokers , and in-vitro induction with benzanthracene of aryl hydrocarbon hydroxylase activity in lesion-free skin of patients with psoriasis is only about 50 % of normal . ' Clearly , in-vivo induction by smoking as measured by antipyrine clearance is not analogous to in-vitro induction by benzanthracene as measured by activity of aryl In this r and omised prospect i ve parallel-group controlled study , a modern cellulose-based fibre dressing was compared with a traditional ribbon gauze and proflavine dressing , used intra- and post-operatively . The study evaluates each treatment for the reduction in pain , improvement in the quality of treatment and patient satisfaction . Forty patients , with wounds left to heal by secondary intention , were studied . The results show several significant advantages for the cellulose-based fibre dressing . Pain levels on removal at the first dressing change were significantly reduced in the cellulose-based fibre dressing group ( p = 0.002 ) ; the ribbon gauze patients routinely required analgesia before removal of the first dressing . At one week , a significantly greater number of patients in the cellulose-based fibre dressing group stated that they would be happy to have their first dressing change carried out at home without analgesia compared to the ribbon gauze group . This would enable patients to be discharged earlier and could represent a considerable financial saving to the hospital A report of a study that examined some clinical characteristics of two commonly used wound PURPOSE The purpose of this study was to investigate the efficacy and safety of recombinant human platelet-derived growth factor ( rhPDGF-BB ) in a double-blind , placebo-controlled , multicenter study of patients with chronic diabetic ulcers . METHODS Patients with chronic , full-thickness , lower-extremity diabetic neurotrophic ulcers of at least 8 weeks ' duration , free of necrotic and infected tissue after debridement , and with transcutaneous oxygen tensions of 30 mm Hg or greater were studied . A total of 118 patients were r and omized to receive either topical rhPDGF-BB ( 2.2 micrograms/cm2 of ulcer area ) or placebo until the ulcer was completely resurfaced or for a maximum of 20 weeks , whichever occurred first . RESULTS Twenty-nine ( 48 % ) of 61 patients r and omized to the rhPDGF-BB group achieved complete wound healing during the study compared with only 14 ( 25 % ) of 57 patients r and omized to the placebo group ( p = 0.01 ) . The median reduction in wound area in the group given rhPDGF-BB was 98.8 % compared with 82.1 % in the group given placebo ( p = 0.09 ) . There were no significant differences in the incidence or severity of adverse events between the rhPDGF-BB and placebo groups . CONCLUSIONS Once-daily topical application of rhPDGF-BB is safe and effective in stimulating the healing of chronic , full-thickness , lower-extremity diabetic neurotrophic ulcers This prospect i ve r and omised trial compared the performance of three dressing protocol s in the management of 36 dehisced surgical abdominal wounds : a st and ard alginate ; a gauze moistened with sodium hypochlorite ( 0.05 % ) ; and a combine dressing pad . Outcomes assessed were : healing time ( cm2 per day and cm3 per day ) , patient comfort ( pain and satisfaction ) and cost . There were no statistically significant differences in healing rates between the three groups but there was a trend for the combine dressing pad protocol to produce a greater reduction in wound area . The combine dressing pad protocol performed well when compared with the calcium alginate in terms of healing time , patient comfort and cost . Maximum pain was significantly greater ( p = 0.011 ) and satisfaction significantly lower among patients who received the sodium hypochlorite protocol . Costs during the in-patient phase were also substantially higher for the sodium hypochlorite protocol . Trial results support the view that sodium hypochlorite dressing protocol s for surgical wounds should be ab and oned This trial was undertaken to examine the safety and efficacy of four-layer compared with short stretch compression b and ages for the treatment of venous leg ulcers within the confines of a prospect i ve , r and omised , ethically approved trial . Fifty-three patients were recruited from a dedicated venous ulcer assessment clinic and their individual ulcerated limbs were r and omised to receive either a four-layer b and age (FLB)(n = 32 ) or a short stretch b and age (SSB)(n = 32 ) . The endpoint was a completely healed ulcer . However , if after 12 weeks of compression therapy no healing had been achieved , that limb was withdrawn from the study and deemed to have failed to heal with the prescribed b and age . Leg volume was measured using the multiple disc model at the first b and aging visit , 4 weeks later , and on ulcer healing . Complications arising during the study were recorded . Data from all limbs were analysed on an intention to treat basis ; thus the three limbs not completing the protocol were included in the analysis . Of the 53 patients , 50 completed the protocol . At 1 year the healing rate was FLB 55 % and SSB 57 % ( chi 2 = 0.0 , df = 1 , P = 1.0 ) . Limbs in the FLB arm of the study sustained one minor complication , whereas SSB limbs sustained four significant complications . Leg volumes reduced significantly after 4 weeks of compression , but subsequent volume changes were insignificant . Ulcer healing rates were not influenced by the presence of deep venous reflux , post-thrombotic deep vein changes nor by ulcer duration . Although larger ulcers took longer to heal , the overall healing rates for large ( > 10 cm2 ) and small ( 10 cm2 or less ) ulcers were comparable . Four-layer and short stretch b and ages were equally efficacious in healing venous ulcers independent of pattern of venous reflux , ulcer area or duration . FLB limbs sustained fewer complications than SSB The treatment of established hidradenitis suppurativa dem and s complete excision of the apocrine gl and s in the affected area . Ten patients undergoing bilateral excision of the axillary skin , had one axilla grafted and the other allowed to heal by granulation utilising Silastic foam dressing , in order to compare the two methods . Split skin grafting result ed in more rapid healing of the excised area than healing by secondary intention . However , Silastic foam dressing result ed in certain healing with a good cosmetic result and avoided the need for immobilisation and a painful donor site . Most patients in this series preferred Silastic foam dressing to skin grafting After nail matrix ablation using phenolization , a medicated wound dressing ( 10 % povidone iodine ) , an amorphous hydrogel dressing ( Intrasite Gel ) , and a control dressing ( paraffin gauze ) were evaluated . Forty-two participants , r and omly divided into three dressing groups , were evaluated . Healing time did not differ between the 10 % povidone iodine ( 33 days ) , amorphous hydrogel ( 33 days ) , and the control dressing ( 34 days ) . For all groups , the clinical infection rate was lower than in previous studies , and there was no clinical difference between groups ( one infection in the povidone iodine and control groups ; none in the amorphous hydrogel group ) . However , in the amorphous hydrogel group , other complications , such as hypergranulation , were more likely . This investigation indicated that medicated or hydrogel dressings did not enhance the rate of healing or decrease infection rates Calcium alginate dressings have been used in the treatment of pressure ulcers and leg ulcers . This study analyzes the effectiveness of a calcium alginate dressing in wound exu date absorption , patient comfort , and ease of application OBJECTIVE We assessed in a r and omized prospect i ve trial the effectiveness of Graftskin , a living skin equivalent , in treating noninfected nonischemic chronic plantar diabetic foot ulcers . RESEARCH DESIGN AND METHODS In 24 centers in the U.S. , 208 patients were r and omly assigned to ulcer treatment either with Graftskin ( 112 patients ) or saline-moistened gauze ( 96 patients , control group ) . St and ard state-of-the-art adjunctive therapy , which included extensive surgical debridement and adequate foot off-loading , was provided in both groups . Graftskin was applied at the beginning of the study and weekly thereafter for a maximum of 4 weeks ( maximum of five applications ) or earlier if complete healing occurred . The major outcome of complete wound healing was assessed by intention to treat at the 12-week follow-up visit . RESULTS At the 12-week follow-up visit , 63 ( 56 % ) Graftskin-treated patients achieved complete wound healing compared with 36 ( 38 % ) in the control group ( P = 0.0042 ) . The Kaplan-Meier median time to complete closure was 65 days for Graftskin , significantly lower than the 90 days observed in the control group ( P = 0.0026 ) . The odds ratio for complete healing for a Graftskin-treated ulcer compared with a control-treated ulcer was 2.14 ( 95 % CI 1.23 - 3.74 ) . The rate of adverse reactions was similar between the two groups with the exception of osteomyelitis and lower-limb amputations , both of which were less frequent in the Graftskin group . CONCLUSIONS Application of Graftskin for a maximum of 4 weeks results in a higher healing rate when compared with state-of-the-art currently available treatment and is not associated with any significant side effects . Graftskin may be a very useful adjunct for the management of diabetic foot ulcers that are resistant to the currently available st and ard of care Many conventional dressings are painful when removed , and may be detrimental to healing . In a pilot study ten consecutive abscesses , requiring incision and drainage , were packed with a calcium alginate dressing : this was well tolerated , its removal causing minimal pain . No adverse effects were attributable to its use . A controlled trial was therefore carried out to compare calcium alginate with the more traditional saline-soaked gauze for packing abscess cavities , following incision and drainage . Patients were r and omized to receive either calcium alginate ( 16 patients ) or gauze dressing ( 18 patients ) . At the first dressing change the patient marked on a linear analogue scale the pain experienced ; the nurse noted similarly the ease of removal of the dressing . Calcium alginate was significantly less painful to remove after operation ( P less than 0.01 ) , and also easier to remove ( P less than 0.01 ) than gauze dressings . If abscess cavities are packed after incision and drainage , calcium alginate appears to be an improvement on conventional dressings Recent reports have suggested that polyurethane foam dressings provide a more rapid and comfortable healing of venous stasis cutaneous ulcerations than st and ard semirigid impregnated gauze dressings . This multi-institutional study consists of a r and omized , prospect i ve comparison of 36 consecutive patients who were treated with either polyurethane foam dressings ( group 1 , n = 17 ) or Unna 's boot ( group 2 , n = 19 ) for venous ulceration of the lower extremities . Ulcer size ranged from 6.0 to 270 cm2 ( mean , 32.2 cm2 ) for group 1 and 0.2 to 600 cm2 ( mean , 76.0 cm2 ) for group 2 . Nine ( 52.9 % ) of 17 group 1 patients withdrew from the study due to wound odor , while there was 100 % compliance in group 2 . Overall wound healing was superior in group 2 ( 18 [ 94.7 % ] of 19 ) as compared with group 1 ( 7 [ 41.2 % ] of 17 ) ( chi 2 = 8.2 ) . The rate of healing was also better in group 2 ( 0.5 cm2/d ) than in group 1 ( 0.07 cm2/d ) . Contrary to published European trials , impregnated gauze dressings exhibited superior treatment results when compared with polyurethane foam dressings in the current study Acticoat , a new silver-coated dressing , produces a moist healing environment along with the sustained release of ionic silver for improved microbial control . These properties suggest that Acticoat might be a useful donor site dressing . However , there are no human studies which assess Acticoat for this use . The purpose of this study was to compare the healing of human skin graft donor sites dressed with Acticoat , to the healing of those dressed with Allevyn , an occlusive moist-healing environment material , which is our st and ard donor site dressing . In burn patients who had undergone burn excision and grafting , identical side-by-side split thickness donor site wound pairs were dressed with Allevyn and Acticoat . Re-epithelialization was directly assessed daily by a single observer from post-operative day 6 onward , and by four independent observers who rated the extent of re-epithelialization by viewing st and ardized digital images of the wounds that had been obtained on post-operative days 6 , 8 , 10 , and 12 . Donor sites were swabbed for bacterial culture on days 3 , 6 , and 9 . Subsequently , each study donor site scar was rated by a blinded observer using the Vancouver Scar Scale at 1 , 2 , and 3 months . Sixteen paired sites in 15 patients ( 3 female , 12 male ) were studied . Donor sites dressed with Allevyn were > 90 % re-epithelialized at a mean of 9.1+/-1.6 days while donor sites dressed with Acticoat required a mean of 14.5+/-6.7 days to achieve > 90 % re-epithelialization ( P=0.004 ) . The Allevyn sites had significantly greater estimated re-epithelialization at days 6 , 8 , 10 and 12 than the Acticoat sites based on the observations of the digital images . There were no significant differences in the incidence of positive bacterial cultures with either dressing at days 3 , 6 , and 9 . Donor sites dressed with Acticoat had significantly worse scars at 1 and 2 months but this difference resolved by 3 months . Our findings do not support the use of Acticoat as a skin graft donor site dressing In this prospect i ve r and omized controlled trial of the cost benefits of the choice of dressings in acute surgical wounds left to heal by secondary intention , patients had their wounds dressed with either a traditional dressing ( ribbon gauze soaked in proflavine ) or a modern hydrofibre dressing . Results showed that the hydrofibre dressing , although more expensive than the ribbon gauze , facilitated an earlier discharge from hospital ( P = 0.001 ) . The total cost of the patient episode was less in the hydrofibre group ( P = 0.01 ) . In an average UK health authority of 300,000 population , 100 bed days a year could be saved releasing an overall potential saving of 55,000 Pounds . A modern hydrofibre dressing allows more effective use of scarce hospital beds and precious financial re sources , while still maintaining high quality patient care . It is important that clinical specialists and purchasers of health care should be aware of this clinical and cost-effective advance in the management of acute surgical wounds BACKGROUND Periodontal plastic surgery has increased the use of palatal wounds for donor tissue , with the most common complication being excessive bleeding from the palate after harvesting tissue . This study was conducted to evaluate the efficacy of 3 methods for achieving hemostasis on the palate after harvesting donor tissue for autogenous soft tissue grafts . METHODS Thirty sites were evaluated at surgery for hemostasis and followed over 21 days for healing and adverse events . Three treatment groups were r and omly selected and patients received either a test product or control comprising : 1 ) oxidized regenerated cellulose ; 2 ) absorbable gelatin sponge ; or 3 ) sterile gauze with external pressure as the control . All patients received a surgical stent for the palate . RESULTS The results were analyzed for smokers and non-smokers , and the median time to hemostasis was significantly shorter when a hemostatic agent was applied to the palatal wounds compared to controls in both groups . Pain assessment showed no differences across treatment groups . However , by 21 days , only the oxidized regenerated cellulose group had complete healing based on blinded clinical evaluation with all sites rated as normal to rapid healing , compared to the absorbable gelatin sponge group where 40 % of the sites were rated as slow healing . Adverse events , primarily bleeding episodes during the first 7 days after surgery , were found in 40 % of the oxidized regenerated cellulose and gauze control groups , while no sites in the absorbable gelatin sponge group had an adverse event . The patients were followed for an average of 10 months and demonstrated a mean shrinkage of their recipient grafts of 24 % in total surface area . CONCLUSIONS This study concluded that the use of hemostatic agents for palatal wounds is confirmed as the treatment of choice when performing free soft tissue grafts A prospect i ve r and omized controlled trial of dextranomer beads ( Debrisan ) and silicone foam elastomer ( Silastic ) dressings in open infected surgical wounds has been performed . The results indicate that the healing time for wounds treated by Debrisan ( n = 25 ) and elastomer ( n = 25 ) is similar , being 40.92 ± 3.98 and 36.90 ± 3.18 days respectively . The time taken for wounds to become pain‐free was similar in both treatment groups , as was the persistence of signs in the wounds of erythema , oedema and slough . Comparison of cost reveals the elastomer dressing to be considerably cheaper than Debrisan Previous studies have suggested that topically applied platelet-derived wound healing factors ( PDWHF ) accelerate wound healing by stimulating angiogenesis , fibroblast proliferation , and collagen synthesis . To assess the ability of platelet factors to facilitate healing of chronic cutaneous ulcers we performed a r and omized , prospect i ve , double-blind , placebo-controlled study of topical PDWHF in 18 patients with 26 lower extremity wounds refractory to conventional therapy . Wounds were present for at least 8 weeks ( mean , 5.5 + /- 4.3 months ) . They were extensively debrided initially and were measured and photographed at weekly intervals for 12 weeks . Eight patients with nine wounds were treated with placebo solution ( controls ) , and 10 patients with 17 wounds were treated with PDWHF ( treatment group ) . Seventy-eight percent of patients had diabetes mellitus , 72 % had occlusive peripheral vascular disease , and 28 % had venous disease ; distribution of these disorders was equivalent in both groups . Ankle-brachial indexes , which were often spuriously elevated , averaged 0.93 + /- 0.54 in controls and 1.04 + /- 0.56 in patients treated with PDWHF ( p greater than 0.5 ) . Mean transcutaneous oxygen tension was 37.8 + /- 11.9 mmHg in controls and 37.1 + /- 9.1 mmHg in patients treated with PDWHF . Initial wound area was larger in controls than in the patients treated with PDWHF ( 28.9 + /- 45.2 cm2 vs 13.0 + /- 4.4 cm2 ) , but this difference was not statistically significant ( p = 0.19 ) . Three ( 33 % ) wounds ( in two patients ) healed in controls , and four ( 24 % ) wounds ( in three patients ) healed in the PDWHF group ( p greater than 0.5 ) . The rate of healing in controls was 1.9 + /- 2.7 cm2/week . ( ABSTRACT TRUNCATED AT 250 WORDS The effect of Hyphecan ( 1 - 4,2-acetamide-deoxy-B-D-glucan ) on skin donor site healing was compared with the st and ard skin donor site dressing Kaltostat ( calcium sodium alginate ) in 35 burn patients with 70 skin donor sites prospect ively . The median time of wound healing for the Hyphecan group was 12 days with an average of 13.1+/-4.0 days ( ranged from 9 to 28 days ) while the Kaltostat group had a median healing time of 12 days ( ranged from 8 to 28 days ) with a mean of 13.0+/-4.1 days . The difference in healing time between these two groups was statistically insignificant with a P-value of 0.95 . The infection rate was 2.9 % for both Hyphecan and Kaltostat . These 35 patients had been followed up from 10 to 16 months and no difference in long-term donor site morbidity between Hyphecan and Kaltostat had been observed . This finding was encouraging because the cost of Hyphecan is less than 50 % of Kaltostat and it may be worthwhile to explore the clinical application of Hyphecan in other area of burns treatment OBJECTIVE The aim of this study was to assess the nutritional status of 374 surgical patients with gastrointestinal disease and hernias of the abdominal wall ; to identify risk factors associated with a poorer nutritional status in this group of patients and to assess awareness of the patient 's nutritional status by medical teams . SUMMARY BACKGROUND DATA Malnutrition is prevalent among surgical patients and is associated with higher surgical complication rates and mortality . The major causes of poor nutritional status are related to the underlying disease , socio-economic factors , age , and length of hospitalization . Despite its high prevalence , medical teams often overlook malnutrition , and screening of these patients is not routine . It is of utmost importance to identify patients at risk for malnutrition in order to prevent related complications . METHODS The 374 patients evaluated in this study were a subgroup of a larger multicenter , cross-sectional , r and omized study that was carried out in 1996 . Nutritional status was assessed by using Subjective Global Assessment . RESULTS Malnutrition was present in 55 % of the patients , with 19 % of the patients severely malnourished . The presence of cancer , infection , age over 60 years , upper gastrointestinal disease , and longer length of hospital stay all negatively influenced nutritional status . Despite the high prevalence of malnutrition , the medical teams only assessed the nutritional status of a few patients . CONCLUSION Malnutrition was highly prevalent in this setting of patients . Therefore , patients with the risk factors above presented should routinely undergo nutritional screening and /or assessment in order to be able to early diagnose or prevent malnutrition and its correlated morbidity and mortality Leg ulcers caused by chronic venous insufficiency plague an estimated 500,000 Americans , but there have been few improvements in conservative treatment in this century , and Unna 's boot continues to be a mainstay of therapy . A recent report suggests that Duoderm CGF dressing provides greater patient comfort and enhanced compliance , but Duoderm alone ( without compression ) result ed in slower healing compared with Unna 's boot . We enrolled 30 patients ( 30 ulcers ) in a clinical trial to compare Duoderm CGF plus compression ( Coban wrap ) to Unna 's boot . No significant difference was observed between the two groups with respect to age , sex , initial ulcer area , ulcer duration , or extent of venous insufficiency by duplex scan . Eight of 16 ulcers ( 50 % ) in the Duoderm group healed completely versus 6 of 14 ulcers ( 43 % ) in the Unna 's boot group ( p = 0.18 ) . Healing rates ( square centimeters per week ) correlated significantly with initial ulcer area and initial ulcer perimeter for both groups but best correlated with initial ulcer perimeter ( r = 0.88 with Duoderm , p less than 0.0001 ; r = 0.80 with Unna 's boot , p less than 0.002 ) . After adjusting for differences in initial ulcer perimeter , healing rates were significantly faster for patients on Duoderm than patients on Unna 's boot during the first 4 weeks of therapy ( 0.384 + /- 0.059 cm2/wk/cm perimeter for Duoderm versus 0.135 + /- 0.043 cm2/wk/cm perimeter for Unna 's boot ; p = 0.002 ) . At 12 weeks patients on Duoderm again appeared to heal faster than those on Unna 's boot , although the result did not reach statistical significance ( 0.049 + /- 0.007 cm2/wk/cm perimeter for Duoderm versus 0.020 + /- 0.017 for Unna 's boot , p = 0.11 ) . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE Traditionally , skin graft donor sites have been covered with fine-mesh gauze dressings , and a dry eschar has been allowed to form . Newer dressings that can provide a moist wound environment may facilitate reepithelialization . We compared a hydrophilic semipermeable absorbent polyurethane foam dressing that provides a moist wound environment with a petrolatum gauze dressing for donor sites . DESIGN Prospect i ve r and omized trial ; follow-up at 14 days . SETTING Department of head and neck surgery in a tertiary care center . PATIENTS Sixty-eight eligible patients received one of the two dressings . Harvested skin grafts were 0.375-mm ( 0.015-in ) thick ; donor site surface areas were recorded . At postoperative day 14 , the dressings were removed , and wound epithelialization was scored : 1 , none ; 2 , scattered or spotty ; and 3 , complete . Donor site and operative site pain intensities were assessed by a visual numeric scale : none ( 0 ) to the worst ( 100 ) experienced over the preceding 24-hour period . Pain scores were available for 58 patients . MAIN OUTCOME MEASURES Dressings were compared based on these criteria : healing at 14 days , infection , and donor site and operative site pain . RESULTS A healing score of 3 was seen in 37 % ( 14/38 ) of patients with hydrophilic semipermeable absorbent polyurethane foam dressings and in 17 % ( 5/30 ) of patients with petrolatum gauze dressings ( P = .06 ) by day 14 . Overall , however , mean healing scores were similar in both groups . Mean healing scores for the patients who received a hydrophilic semipermeable absorbent polyurethane foam dressing was 2.3 ( SD = 0.6 ) vs 2.2 ( SD = 0.6 ) for patients who received the petrolatum gauze dressing ( P = .20 ) . Numbers of days required for complete epithelialization in these groups were 20.6 ( SD = 10.1 ) and 19.3 ( SD = 5.1 ) , respectively ( P = .49 ) . One infection occurred in the group who received the petrolatum gauze dressing . The mean maximum pain intensity scores were lower for those who were given the hydrophilic semipermeable absorbent polyurethane foam dressing on postoperative days 1 through 3 ( P = .003 , .03 , and .04 , respectively ) . Pain increased with a larger donor site surface area for the patients with the petrolatum gauze dressing but not for the patients with the hydrophilic semipermeable absorbent polyurethane foam dressing . CONCLUSIONS The hydrophilic semipermeable absorbent polyurethane foam dressing appears to have potential advantages over the petrolatum gauze dressing ; it produces less initial patient donor site discomfort and tends to produce more complete donor site healing by postoperative day 14 Experimental studies in animals have demonstrated that the topical application of epidermal growth factor accelerates the rate of epidermal regeneration of partial-thickness wounds and second-degree burns . We conducted a prospect i ve , r and omized , double-blind clinical trial using skin-graft-donor sites to determine whether epidermal growth factor would accelerate the rate of epidermal regeneration in humans . Paired donor sites were created in 12 patients who required skin grafting for either burns or reconstructive surgery . One donor site from each patient was treated topically with silver sulfadiazine cream , and one was treated with silver sulfadiazine cream containing epidermal growth factor ( 10 micrograms per milliliter ) . The donor sites were photographed daily , and healing was measured with the use of planimetric analysis . The donor sites treated with silver sulfadiazine containing epidermal growth factor had an accelerated rate of epidermal regeneration in all 12 patients as compared with that in the paired donor sites treated with silver sulfadiazine alone . Treatment with epidermal growth factor significantly decreased the average length of time to 25 percent and 50 percent healing by approximately one day and that to 75 percent and 100 percent healing by approximately 1.5 days ( P less than 0.02 ) . Histologic evaluation of punch-biopsy specimens taken from the centers of donor sites three days after the onset of healing supported these results . We conclude that epidermal growth factor accelerates the rate of healing of partial-thickness skin wounds . Further studies are required to determine the clinical importance of this finding A prospect i ve controlled trial was carried out to assess the healing efficacy of calcium alginate and paraffin gauze on split skin graft donor sites . Thirty patients were r and omised to the calcium alginate group and 21 to the paraffin gauze group . The donor sites were assessed at 10 days post harvesting to determine if they were completely healed ( 100 % ) or not . Twenty one of the 30 patients dressed with calcium alginate were completely healed at day 10 , while only 7/21 in the paraffin gauze group were healed ( p < 0.05 ) . There were two infections in the study , both occurring in the alginate group while there was no difference in dressing slippage between the two groups . Calcium alginate dressings provide a significant improvement in healing split skin graft donor sites p < 0.01 ) and the median time to complete wound closure ( 7 vs. 15 weeks , p= 0.0021 , rank-sum test ) . There was no difference in the wound closure rate of meshed and unmeshed graft at 4 , 8 , 12 , or 24 weeks ( p > 0.05 ) . Three indolent localized wound infections in the tissue-engineered skin graft group were the only complication . Tissue-engineered skin grafting can be used safely in previously ischemic wounds after lower extremity revascularization . Treatment with this graft promotes healing more rapidly and in more patients than st and ard moist dressings . It obviates the risk , inconvenience , and expense of donor skin harvesting , anesthesia , and hospitalization associated with autologous skin grafting . This graft may represent an advance in the treatment of previously ischemic lower extremity foot wounds BACKGROUND Despite significant advancements in rectal surgery , poor perineal wound healing after abdominoperineal resection ( APR ) of the anorectum continues to be a potential complication of the procedure . The aim of this prospect i ve r and omized multicenter study was to investigate the efficacy of a new mode of local antibiotic administration . PATIENTS AND METHODS Ninety-seven patients who had to undergo APR for low rectal carcinoma either received sacral drainage plus primary wound closure ( control group , n = 48 ) or the same treatment and supplementary application of three resorbable gentamicin-impregnated collagen fleeces ( Septocoll ; Merck Bio material GmbH , Darmstadt , Germany ; Genta group , 49 ) . The following target criteria were investigated : bacteriologic efficacy with respect to the eradication of Enterobacteriaceae , Staphylococcus , and Pseudomonas organisms , and clinical efficacy with respect to perineal wound healing . RESULTS The Genta group showed a marked reduction in the investigated pathogens from the secretion obtained by sacral drainage on days 1 and 3 , as well as high gentamicin concentrations ( day 1 , median 126.2 microg/mL ; day 3 , median 97.6 microg/mL ) . In total , bacteriologic efficacy amounted to 83.7 % in the Genta group ( 41 of 49 patients ) versus 60.4 % ( 29 of 48 patients ) in controls ( P = 0.013 ) . In concurrence with these bacteriologic results , the postoperative infection rate was significantly higher in controls : 10 patients ( 20.83 % ) in the control group versus 3 ( 6.1 % ) in the Genta group developed perineal or sacral infection ( P < 0.05 ) . Postoperative complications in the recruited patients revealed no indication of gentamicin-induced adverse reactions . CONCLUSIONS The results of the study show that the specified dose of 3 Septocoll fleeces in patients with APR is liable to significantly eliminate enterobacteria , staphylococci , and pseudomonads . The clinical course is improved as a result of the bactericidal effect exerted by the gentamicin fleece . The use of Septocoll reduced the incidence of postoperative perineal and sacral infections . Local antibiotic carriers seem to be of great advantage in poorly perfused areas such as the sacral cavity or anatomically problematic regions as the rima ani . In locally contaminated or infected areas , local antibiotic carriers achieve greater concentrations of the active substance than those achieved with systemic antibiotics , even if the latter are administered by the parenteral route In a significant number of elderly patients , the healing of split skin donor sites can be delayed . The cultured allogenic epithelial graft ( CAG ) has been reported to heal leg ulcers . The mechanism of action may be to improve the healing environment and thus stimulate the host skin cells . A clinical trial was undertaken to compare the healing rate of the donor sites of elderly patients using CAGs and two commercially available dressings . Compared to Jelonet , CAGs ( p = 0.008 ) and OpSite ( p = 0.013 ) significantly reduced the number of patients with delayed healing . There was no significant difference between CAGs and the occlusive dressing , OpSite A prospect i ve trial of Biobrane versus scarlet red as a skin graft donor site dressing was done in 21 burn patients with mean total body surface area burns of 31.9 % . Corresponding body areas were r and omly selected on each patient to receive one of the dressings . Daily evaluations were made of subjective expression of pain , exu date formation and infection , and time of separation of the dressing from the wound . Biobrane was found to be superior in reducing donor site pain . However , with Biobrane there was a higher incidence of infection ( 57 % v 9.5 % ) and a significant delay in separation from the wound . Scarlet red was found to be more cost-effective . Occlusive dressings have previously been shown to have a high incidence of complications ( 30 % ) . In extensive burns , isolating the donor site from the wound is difficult and may lead to increased complications . Scarlet red appears to be superior to Biobrane for skin graft donor sites in this patient population Twenty patients with large area granulating wounds were selected for the study . On each patient , a small area of uniform appearance was divided into four sub areas , and each subarea was r and omly assigned treatment with a single 24 hour application of cadaver allograft , fresh porcine xenograft , formalinized xenograft , or " wet-to-dry " applications of coarse mesh gauze changed three times daily . At 24 hours , all four areas were uncovered . The sub areas were ranked in terms of appearance on a best , second best , third best , and worst scale by experienced paramedical personnel who were not told which area received which treatment . Contact sponge quantitative microbiology was performed on each subarea before and after treatment on seventeen of the twenty patients . The results of these rankings suggest that coarse mesh gauze , changed three times daily , was significantly better at improving wound appearance than any of the biologic dressings . Among the biologic dressings , formalinized xenograft was significantly the worst . There was no significant difference between cadaver allograft and porcine xenograft . Analysis of quantitative cultures was limited by the problems of applying statistical methods to series of paired cultures in which initial values are quite different . Within the framework of such limitations and our 24 hour study , there was not significant change in surface colonization when either coarse mesh gauze or biologic dressings were used Allowing selected full-thickness skin defects to heal by secondary intention offers the advantages of optimal cancer surveillance , simplified wound management , and avoidance of reconstructive procedures with their associated costs and potential complications . The topical use of bovine collagen has been suggested as a method of enhancing wound closure and final cosmetic appearance . This study evaluated the effect of bovine collagen on wound healing in patients undergoing facial Mohs surgery using the fresh-tissue technique . A total of 111 consecutive patients were assigned to a collagen or no-collagen group . Wound care was identical except for the weekly addition of bovine collagen to the wound of patients in the collagen group . Evaluation was at weekly intervals until the wound epithelialized , then bimonthly for at least 6 months . There was no difference in the rate of wound epithelialization or final cosmetic appearance . This study provides no evidence that the topical use of bovine collagen in a facial wound after Mohs surgery enhances wound epithelialization or the final cosmetic appearance In an attempt to improve the management of the perineal wound after abdominoperineal excision of the rectum we have assessed the value of foam elastomer , a catalysed silicone polymer dressing . This substance has already been used successfully in the treatment of open , granulating wounds at other sites ( 1 ) A prospect i ve clinical trial was conducted to evaluate the efficacy of a collagen-alginate wound dressing in the postoperative management of chemical matricectomies . The study involved 20 patients and 23 separate procedures . The collagen-alginate-dressing treatment group had an average healing time of 24.4 days , compared with 35.8 days for the control group , which received treatment consisting of soaks and daily dressing changes ( P < .05 ) . The authors suggest that using a collagen-alginate wound dressing in the postoperative management of chemical matricectomies will shorten healing time , thus reducing infection rates and increasing patient compliance and satisfaction The efficacy of factor-XIII concentrate in the improvement of postoperative wound healing disorders ( suture dehiscences , fistulae ) was examined in 61 patients . In an open , r and omised , and controlled trial the results ( decrease of wound area , signs of inflammation , wound secretion , drainage volume , contrast x-ray films , and colour photos ) were evaluated twice : open judgement by the clinicians themselves and blind judgement by an independent evaluation committee . The blind evaluation of the clinical data showed relevant general improvement in the patient groups treated with factor-XIII concentrate : 61.9 % ( dosage : 750 IU factor XIII for 3 days ) and 76.2 % ( dosage : 1500 IU factor XIII for 3 days ) as compared to 10.5 % in the control group without factor XIII substitution . The differences were significant ( Mann-Whitney-U-Test , p less than or equal to 0.001 ) . These results would suggest substituting factor XIII activity in plasma above 70 % of normal value in case of wound healing disorders A prospect i ve r and omised trial examining the effectiveness , comparative comfort and ease of care of two different split skin graft donor site dressings was performed . One of the dressings was an alginate ( Kaltostat ) , and the other an adhesive retention tape ( Mefix ) . Alginates are the st and ard plastic surgical dressing , whereas the use of adhesive retention tapes as a donor site dressing presents a novel use of a readily available product . A total of 30 consecutive patients requiring split skin grafts were r and omised to receive either alginate or retention donor site dressings . Dressings were assessed by interview and question naire at 24 h and 48 h and at 2 weeks , and by wound review at 2 weeks . Retention dressings were found to be more comfortable . They also required less nursing care and attention . The retention dressings allowed the patients easier mobility and a greater range of daily activities , especially washing . There was no significant difference in wound healing nor in complications . Adhesive retention tape applied directly to the split skin graft donor site wound is an effective , cheap and comfortable dressing requiring little postoperative care OBJECTIVE To assess the efficacy of hydrocolloid dressings in wound management after excision of pilonidal sinus . DESIGN Prospect i ve r and omised trial . SETTING District hospital , Spain . PATIENTS 38 patients with chronic pilonidal sinus . INTERVENTIONS Open excision with healing by second intention . Divided into three groups : conventional gauze dressing ( control , n = 15 ) , Comfeel ( n = 12 ) and Varihesive ( n = 11 ) . MAIN OUTCOME MEASURES Median healing time , infection rate , intolerance , pain , comfort , ease of management , leakage , and recurrence . RESULTS Median healing time was 68 days ( range 33 - 168 ) in the control group , compared with 65 days ( range 40 - 137 ) in the two hydrocolloid groups combined . There were no differences between the hydrocolloid groups . There were no recurrences during the 74 months of follow-up . A third of the postoperative cultures in the control group grew pathogens compared with 1/23 of the patients treated with hydrocolloid dressings ( p = 0.03 ) . This was of no clinical relevance . 14/23 in the hydrocolloid group developed leaks . Pain was significantly less in the first four postoperative weeks among the patients in the hydrocolloid group than in the control group ( p < 0.05 ) . CONCLUSIONS Hydrocolloid dressings lessen pain and increase comfort for patients after excision of pilonidal sinus , though time to healing is no shorten than when a conventional gauze dressing is used The excision of a pilonidal sinus with wound healing by second intention , often results in a long duration of treatment . On the other h and , primary suture after excision has a high rate of abscess formation . In a r and omized study we treated 40 patients with excision of pilonidal sinus , insertion of a collagen sponge containing Gentamicin and primary suture ( group 1 ) to prevent this abscess formation . Another 40 patients were treated in the same way but without applying the Gentamicin-collagen sponge ( group 2 ) . There had been no significant differences as to the history and duration of the disease , the wound size , the degree of inflammation , the weight of the patients or the amount of hair near the sinus . In group 1 only 7.5 % of the patients had a postoperative abscess formation , in contrast to group 2 , with an abscess rate of 52.5 % and consecutive surgery ( p less than 0.001 ) . One year after the operation the recurrence rate was 0 in both groups . Considering the results mentioned , surgical excision of the pilonidal sinus in combination with insertion of a resorbable antibiotic sponge we recommend this therapy Deep scalp donor sites can be difficult to manage because of the higher incidence of healing complications that can make daily wound care exquisitely painful . When faced with this problem , we prospect ively studied the Unna " cap " dressing on the scalp . Group 1 received our st and ard treatment -- Xeroform gauze ( Sherwood Medical , St Louis , Mo ) and daily wound care . Group 2 received the Unna cap -- Aquaphor gauze ( Beiersdorf , Norwalk , Conn ) and Dome Paste gauze ( Bayer Corp , West Haven , Conn ) with wound care every 3 days . Pain , healing time , and costs were compared . Twelve patients between the age of 1 and 54 years were studied . A significant number of patients in Group 1 developed wound complications after initial healing , result ing in a longer length of stay and higher costs . Group 2 reported significantly less procedural pain , comparable healing ( 11 days + /- 2 SD ) , and fewer dressing changes , result ing in an institutional savings of $ 5.51 to $ 16.25 per patient up to postoperative day 13 . This study supports use of the Unna cap as a less painful , safe , and cost-effective alternative to our st and ard deep scalp donor site dressing In a r and omised , double-blind , controlled trial , a comparison was made of the relative efficacy of using streptokinase/streptodornase ( Varidase ) in a hydrogel ( KY Jelly ) or the hydrogel alone in the debridement of Grade IV pressure sores . Seventeen subjects aged 57 - 94 years ( mean age 81 ) took part ; 21 sores were studied , 11 of which were r and omised to the enzyme treatment regime . Both treatments led to eschar removal ; fewer days were needed in the hydrogel-only group ( mean 8.1 days , sd 1.8 ) compared to the enzyme/hydrogel group ( mean 11.8 days , sd 2.9 ) , but this was not statistically significant . The results suggest that the use of hydrogel alone may be a cost-effective alternative to the use of streptokinase/streptodornase and hydrogel in the treatment of these wounds The clinical benefits of using the VENTEX Wound Dressing System ( VWDS ) ( The Kendall Co. ) in the management of donor site wounds were evaluated in this pilot study involving 10 informed and consenting patients . The study was a prospect i ve , r and omized , controlled study in which one donor site wound was managed with VWDS , and the other donor site wound on the same patient was managed by our st and ard of care , which involved the use of Xeroform gauze ( The Kendall Co. ) . Each donor site wound was independently assessed daily for pain , rate of reepithelialization , adverse reactions , and ease of dressing use while patients were hospitalized . Quality of scar was assessed during regularly scheduled follow-up visits . The use of VWDS eliminated donor site pain and accelerated reepithelialization compared with Xeroform gauze . There were no adverse reactions associated with the use of VWDS . In contrast , there were two cases of suspected infection at the donor sites treated with Xeroform gauze . The VWDS was more complicated to apply and use compared with Xeroform gauze . There were no differences observed in scar quality of donor sites treated with these dressings Twenty-eight patients with partial thickness skin loss of the limbs , mainly due to burns , were treated on an out-patient basis in an occupational health centre . Thirteen patients were treated with porcine skin graft and the other 15 by the conventional method with paraffin gauze . The results showed that the median healing time was 13 days in the porcine skin graft group and 28 days in the control group . Other than healing time , the effects of porcine xenograft in reducing pain , infection and sickenss absence were far greater than those with conventional treatment . From a comparison of total dressing costs , it was estimated that for lesions of comparable size the cost of treatment with porcine xenograft was approximately one-third of that using paraffin gauze The treatment of venous ulcers has remained largely unchanged for centuries . The application of properly applied graduated compression b and ages , the use of graduated compression stockings , and surgery have been shown to achieve healing . However , some ulcers persist despite appropriate management . A r and omized study was undertaken to compare two regimens of treatment for such patients . Both regimens included ulcer debridement , cleaning , nonadherent dressing , and graduated compression stockings . In one regimen , sequential gradient intermittent pneumatic compression was applied for 4 hours each day . Only one of 24 patients in the control group had complete healing of all ulcers compared with 10 of 21 patients healed in the intermittent pneumatic compression group . The median rate of ulcer healing in the control group was 2.1 % area per week compared to 19.8 % area per week in the intermittent pneumatic compression group . The results indicate that sequential gradient intermittent pneumatic compression is beneficial in the treatment of venous ulcers OBJECTIVE To assess the efficacy of topically applied CT-102 APST for treating diabetic neurotrophic foot ulcers . RESEARCH DESIGN AND METHODS Thirteen patients entered a r and omized , double-blind trial of topically applied CT-102 APST vs. placebo ( normal saline ) gauze dressings for the treatment of nonhealing diabetic neurotrophic foot ulcers . CT-102 APST ( Curative Technologies , Setauket , NY ) was prepared from homologous platelets and contained multiple growth factors including PDGF , PDAF , EGF , PF-4 , TGF-β , aFGF , and bFGF . Inclusion criteria for subjects included diabetes , ulcer of > 8 wk duration , peri-wound transcutaneous oxygen tension > 30 mmHg , platelet count > 100,000/mm3 , and no wound infection . Wounds were excised before entry and were > 700 mm3 but < 50,000 mm3 in volume , < 100 cm2 in area , and involved subcutaneous tissue . RESULTS In the CT-102 group , 5 of 7 ulcers were healed ( 100 % epithelialized ) by 15 wk , but only 1 of 6 ulcers was healed by 20 wk with placebo ( P < 0.05 ) . Average percent reduction in ulcer area at 20 wk was 94 % for CT-102 vs. 73 % for placebo . Daily reduction in ulcer volume was 73.8 ± 42.4 mm3/day ( mean ± SE ) for CT-102 vs. 21.8 ± 8.1 mm3/day for placebo ( P < 0.05 ) . Daily reduction in ulcer area was 6.2 ± 1.8 mm2/day for CT-102 vs. 1.8 ± 0.4 mm2/day for placebo ( P < 0.05 ) . CONCLUSIONS CT-102 significantly accelerated wound closure in diabetic leg ulcers when administered as part of a comprehensive program for the healing of chronic ulcers Two treatment protocol s for the management of patients with non-infected cavity wounds were studied , using data obtained from both the community and the out patients clinic . Patients were treated with either a polyurethane foam hydrophilic dressing ( Allevyn ) or a calcium sodium alginate dressing ( Kaltostat ) . Although alginate fibres were found to be incorporated in tissue , both dressing regimes were found to be easy to use , effective and acceptable to patients and clinicians |
13,245 | 30,720,698 | Studies with female sample s observed significantly greater benefits from dietary interventions , for symptoms of both depression and anxiety .
Conclusions Dietary interventions hold promise as a novel intervention for reducing symptoms of depression across the population . | Objective Poor diet can be detrimental to mental health .
However , the overall evidence for the effects of dietary interventions on mood and mental well-being has yet to be assessed .
We conducted a systematic review and meta- analysis examining effects of dietary interventions on symptoms of depression and anxiety . | Background Although lifestyle interventions targeting multiple lifestyle behaviors are more effective in preventing unhealthy weight gain and chronic diseases than intervening on a single behavior , few studies have compared individual and combined effects of diet and /or exercise interventions on health-related quality of life ( HRQOL ) . In addition , the mechanisms of how these lifestyle interventions affect HRQOL are unknown . The primary aim of this study was to examine the individual and combined effects of dietary weight loss and /or exercise interventions on HRQOL and psychosocial factors ( depression , anxiety , stress , social support ) . The secondary aim was to investigate predictors of changes in HRQOL . Methods This study was a r and omized controlled trial . Overweight/obese postmenopausal women were r and omly assigned to 12 months of dietary weight loss ( n = 118 ) , moderate-to-vigorous aerobic exercise ( 225 minutes/week , n = 117 ) , combined diet and exercise ( n = 117 ) , or control ( n = 87 ) . Demographic , health and anthropometric information , aerobic fitness , HRQOL ( SF-36 ) , stress ( Perceived Stress Scale ) , depression [ Brief Symptom Inventory (BSI)-18 ] , anxiety ( BSI-18 ) and social support ( Medical Outcome Study Social Support Survey ) were assessed at baseline and 12 months . The 12-month changes in HRQOL and psychosocial factors were compared using analysis of covariance , adjusting for baseline scores . Multiple regression was used to assess predictors of changes in HRQOL . Results Twelve-month changes in HRQOL and psychosocial factors differed by intervention group . The combined diet + exercise group improved 4 aspects of HRQOL ( physical functioning , role-physical , vitality , and mental health ) , and stress ( p ≤ 0.01 vs. controls ) . The diet group increased vitality score ( p < 0.01 vs. control ) , while HRQOL did not change differently in the exercise group compared with controls . However , regardless of intervention group , weight loss predicted increased physical functioning , role-physical , vitality , and mental health , while increased aerobic fitness predicted improved physical functioning . Positive changes in depression , stress , and social support were independently associated with increased HRQOL , after adjusting for changes in weight and aerobic fitness . Conclusions A combined diet and exercise intervention has positive effects on HRQOL and psychological health , which may be greater than that from exercise or diet alone . Improvements in weight , aerobic fitness and psychosocial factors may mediate intervention effects on HRQOL.Trial Registration Clinical Trials , Clinical Trials.gov register , Background : The impact of dietary flavonoid intakes on risk of depression is unclear . Objective : We prospect ively examined associations between estimated habitual intakes of dietary flavonoids and depression risk . Design : We followed 82,643 women without a previous history of depression at baseline from the Nurses ’ Health Study [ ( NHS ) aged 53–80 y ] and the Nurses ’ Health Study II [ ( NHSII ) aged 36–55 y ] . Intakes of total flavonoids and subclasses ( flavonols , flavones , flavanones , anthocyanins , flavan-3-ols , polymeric flavonoids , and proanthocyanidins ) were calculated from vali date d food-frequency question naires collected every 2–4 y. Depression was defined as physician- or clinician-diagnosed depression or antidepressant use and was self-reported in response to periodic question naires . Cox proportional hazards models were performed to examine associations . Results : A total of 10,752 incident depression cases occurred during a 10-y follow-up . Inverse associations between flavonol , flavone , and flavanone intakes and depression risk were observed . Pooled multivariable-adjusted HRs ( 95 % CIs ) were 0.93 ( 0.88 , 0.99 ) , 0.92 ( 0.86 , 0.98 ) , and 0.90 ( 0.85 , 0.96 ) when comparing the highest ( quintile 5 ) with the lowest ( quintile 1 ) quintiles , respectively , with evidence of linear trends across quintiles ( P-trend = 0.0004–0.08 ) . In flavonoid-rich food-based analyses , the HR was 0.82 ( 95 % CI : 0.74 , 0.91 ) among participants who consumed ≥2 servings citrus fruit or juices/d compared with < 1 serving/wk . In the NHS only , total flavonoids , polymers , and proanthocyanidin intakes showed significantly ( 9–12 % ) lower depression risks . In analyses among late-life NHS participants ( aged ≥65 y at baseline or during follow-up ) , for whom we were able to incorporate depressive symptoms into the outcome definition , higher intakes of all flavonoid subclasses except for flavan-3-ols were associated with significantly lower depression risk ; flavones and proanthocyanidins showed the strongest associations ( HR for both : 0.83 ; 95 % CI : 0.77 , 0.90 ) . Conclusions : Higher flavonoid intakes may be associated with lower depression risk , particularly among older women . Further studies are needed to confirm these associations Objectives : We investigated whether a Mediterranean-style diet ( MedDiet ) supplemented with fish oil can improve mental health in adults suffering depression . Methods : Adults with self-reported depression were r and omized to receive fortnightly food hampers and MedDiet cooking workshops for 3 months and fish oil supplements for 6 months , or attend social groups fortnightly for 3 months . Assessment s at baseline , 3 and 6 months included mental health , quality of life ( QoL ) and dietary question naires , and blood sample s for erythrocyte fatty acid analysis . Results : n = 152 eligible adults aged 18–65 were recruited ( n = 95 completed 3-month and n = 85 completed 6-month assessment s ) . At 3 months , the MedDiet group had a higher MedDiet score ( t = 3.95 , P < 0.01 ) , consumed more vegetables ( t = 3.95 , P < 0.01 ) , fruit ( t = 2.10 , P = 0.04 ) , nuts ( t = 2.29 , P = 0.02 ) , legumes ( t = 2.41 , P = 0.02 ) wholegrains ( t = 2.63 , P = 0.01 ) , and vegetable diversity ( t = 3.27 , P < 0.01 ) ; less unhealthy snacks ( t = −2.10 , P = 0.04 ) and red meat/chicken ( t = −2.13 , P = 0.04 ) . The MedDiet group had greater reduction in depression ( t = −2.24 , P = 0.03 ) and improved mental health QoL scores ( t = 2.10 , P = 0.04 ) at 3 months . Improved diet and mental health were sustained at 6 months . Reduced depression was correlated with an increased MedDiet score ( r = −0.298 , P = 0.01 ) , nuts ( r = −0.264 , P = 0.01 ) , and vegetable diversity ( r = −0.303 , P = 0.01 ) . Other mental health improvements had similar correlations , most notably for increased vegetable diversity and legumes . There were some correlations between increased omega-3 , decreased omega-6 and improved mental health . Discussion : This is one of the first r and omized controlled trials to show that healthy dietary changes are achievable and , supplemented with fish oil , can improve mental health in people with depression Older individuals with emotional distress and a history of psychologic trauma are at risk for post traumatic stress disorder ( PTSD ) and major depression . This study was an exploratory , secondary analysis of data from the study " Prevention of Depression in Older African Americans " . It examined whether Problem Solving Therapy- Primary Care ( PST-PC ) would lead to improvement in PTSD symptoms in patients with subsyndromal depression and a history of psychologic trauma . The control condition was dietary education ( DIET ) . Participants ( n=60 ) were age 50 or older with scores on the Center for Epidemiologic Studies -Depression scale of 11 or greater and history of psychologic trauma . Exclusions stipulated no major depression and substance dependence within a year . Participants were r and omized to 6 - 8 sessions of either PST-PC or DIET and followed 2 years with booster sessions every 6 months ; 29 participants were in the PST-PC group and 31 were in the DIET group . Mixed effects models showed that improvement of PTSD Check List scores was significantly greater in the DIET group over two years than in the PST-PC group ( based on a group time interaction ) . We observed no intervention⁎time interactions in Beck Depression Inventory or Brief Symptom Inventory-Anxiety subscale scores PURPOSE To conduct a clinical trial to determine if an educational intervention and a nutritional intervention could enhance physical and psychological functioning among younger women completing treatment for early-stage breast cancer . PATIENTS AND METHODS Younger women ( 50 years of age or younger , N = 252 ) , within 2 months of having completed active nonhormonal adjuvant therapy , diagnosed with stage 0 , I , or II breast cancer with 10 or fewer positive lymph nodes were r and omly assigned to a three-arm clinical trial . Women in the control arm of the trial received st and ard medical care . Women in the two active arms received either an educational intervention , design ed to provide information about their illness and enhance adjustment , or a nutritional intervention , design ed to promote a more healthy diet . Primary end points included mental functioning , physical functioning , and depressive symptoms . Women were assessed before r and om assignment , 4 months later ( immediately post-intervention ) , and 13 months later ( 9 months post-intervention ) . RESULTS Participants assigned to the two active treatment arms had significantly less depressive symptomatology and better physical functioning by 13-month follow-up ( differences between the two active arms were nonsignificant ) . These effects were primarily accounted for by changes in intrusive thoughts , concerns regarding cancer recurrence and mortality , self-concept perceptions , and self-efficacy expectations . CONCLUSION Tailored psychosocial interventions can be effectively design ed to enhance adjustment among younger women who are completing nonhormonal adjuvant therapy BACKGROUND Intensive dietary intervention programs may lead to benefits in vitality and other components of health quality . The Women 's Health Initiative Dietary Modification ( DM ) intervention includes a large r and omized controlled trial of an intensive intervention . OBJECTIVE To evaluate whether the intervention is associated with improved health-related quality of life ( HRQoL ) subscales , overall self-reported health , depression symptoms , cognitive functioning , and sleep quality . DESIGN This r and omized controlled trial was analyzed as intent to treat . PARTICIPANTS Between 1993 and 1998 , 48,835 women aged 50 to 79 years were recruited by 40 clinical centers across the United States . Eligibility included having fat intake at baseline ≥32 % of total calories , and excluded women with any prior colorectal or breast cancer , recent other cancers , type 1 diabetes , or medical conditions with predicted survival <3 years . INTERVENTION Goals were to reduce calories from fat to 20 % , increase vegetables and fruit to 5 + servings , and increase grain servings to 6 + servings a day . During the first year , 18 group sessions were held , with quarterly sessions thereafter . MAIN OUTCOME MEASURES The R AND 36-Item Health Survey was used to assess HRQoL at baseline , Year 1 , and close-out ( about 8 years postr and omization ) , and estimate differential HRQoL subscale change scores . STATISTICAL ANALYSES PERFORMED Mean change in HRQoL scores ( Year 1 minus baseline ) were compared by r and omization group using linear models . RESULTS At 1 year , there was a differential change between intervention and comparison group of 1.7 units ( 95 % CI 1.5 , 2.0 ) in general health associated with the intervention . DM intervention improved physical functioning by 2.0 units ( 95 % CI 1.7 , 2.3 ) , vitality by 1.9 units ( 95 % CI 1.6 , 2.2 ) , and global quality of life by 0.09 units ( 95 % CI 0.07 , 0.12 ) . With the exception of global quality of life , these effects were significantly modified by body mass index at baseline . CONCLUSIONS DM intervention was associated with small , but significant improvements in three HRQoL subscales : general health , physical functioning , and vitality at 1 year follow-up , with the largest improvements seen in the women with the greatest baseline body mass index Background The possible therapeutic impact of dietary changes on existing mental illness is largely unknown . Using a r and omised controlled trial design , we aim ed to investigate the efficacy of a dietary improvement program for the treatment of major depressive episodes . Methods ‘ SMILES ’ was a 12-week , parallel-group , single blind , r and omised controlled trial of an adjunctive dietary intervention in the treatment of moderate to severe depression . The intervention consisted of seven individual nutritional consulting sessions delivered by a clinical dietician . The control condition comprised a social support protocol to the same visit schedule and length . Depression symptomatology was the primary endpoint , assessed using the Montgomery – Åsberg Depression Rating Scale ( MADRS ) at 12 weeks . Secondary outcomes included remission and change of symptoms , mood and anxiety . Analyses utilised a likelihood-based mixed-effects model repeated measures ( MMRM ) approach . The robustness of estimates was investigated through sensitivity analyses . Results We assessed 166 individuals for eligibility , of whom 67 were enrolled ( diet intervention , n = 33 ; control , n = 34 ) . Of these , 55 were utilising some form of therapy : 21 were using psychotherapy and pharmacotherapy combined ; 9 were using exclusively psychotherapy ; and 25 were using only pharmacotherapy . There were 31 in the diet support group and 25 in the social support control group who had complete data at 12 weeks . The dietary support group demonstrated significantly greater improvement between baseline and 12 weeks on the MADRS than the social support control group , t(60.7 ) = 4.38 , p < 0.001 , Cohen ’s d = –1.16 . Remission , defined as a MADRS score < 10 , was achieved for 32.3 % ( n = 10 ) and 8.0 % ( n = 2 ) of the intervention and control groups , respectively ( χ2 ( 1 ) = 4.84 , p = 0.028 ) ; number needed to treat ( NNT ) based on remission scores was 4.1 ( 95 % CI of NNT 2.3–27.8 ) . A sensitivity analysis , testing departures from the missing at r and om ( MAR ) assumption for dropouts , indicated that the impact of the intervention was robust to violations of MAR assumptions . Conclusions These results indicate that dietary improvement may provide an efficacious and accessible treatment strategy for the management of this highly prevalent mental disorder , the benefits of which could extend to the management of common co-morbidities . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) : ACTRN12612000251820 . Registered on 29 February 2012 PURPOSE Epidemiological studies have suggested that cholesterol lowering could affect psychological functioning . This study was design ed to test whether cholesterol-lowering diets adversely affect mood and cognitive function.5.2 mM [ 198 mg/dL ] ) to either a low-fat diet , a Mediterranean diet , or a waiting-list control . Cholesterol levels , psychological well-being ( depression , anxiety , hostility ) , and cognitive function were assessed at baseline , 6 weeks , and 12 weeks . RESULTS Total serum cholesterol levels fell significantly more in the intervention groups ( 8.2 % reduction ) than in the control group ( P < 0.001 ) . All three groups showed a modest improvement in psychological well-being during the 12-week treatment period , but there were no differences among the groups . There were no between-group differences on three measures of cognitive function , but for a fourth measure , which involved the task with the greatest processing load , the two intervention groups did significantly worse ( P < 0.001 ) than the control group . The change in performance was correlated with the change in total serum cholesterol level ( r = 0 . 21 , P = 0.01 ) . CONCLUSIONS Two dietary interventions that successfully lowered serum cholesterol levels had no adverse effect on mood . There was some evidence for a relative impairment in cognitive function in the treated groups in one of four cognitive tests , but additional studies will be required to determine the relevance of this finding Background Clinical trials that have assessed the best approach for treating under-nutrition in old age are scarce . Objective To determine the impact of an intensive nutritional intervention program led by a dietitian on the health and nutritional status of malnourished community dwelling older adults . Methods Sixty-eight eligible participants ( age<75 ) were r and omly assigned to a Dietetic Intervention Treatment ( DIT ) , an intensive nutritional intervention led by a dietitian , or a Medical Treatment ( MT ) , a physician-led st and ard care group , with an educational booklet regarding dietary requirements and recommendations for older adults . An additional 59 eligible participants who were unable to participate in the r and omization were included as a non-r and omized “ untreated nutrition ” group ( UNG ) . Results Over the 6-month follow-up , the DIT group showed significant improvement in cognitive function ( from 25.8±4.5 to 26.8±4 , p=0.04 ) , and depression score ( from 7.3±3.9 to 5.4 ±3.9 , p=0.04 ) compared with the change in the other 2 groups . The DIT group showed a significant improvement in intake of carbohydrates ( + 15 % vs. + 1 % in the MT and + 3 % in the UNG ) , protein ( + 8 % vs. + 2 % in the MT and −3 % in the UNG ) , vitamin B6 ( + 20 % vs. + 7 % in the MT and + 8 % in the UNG ) , and vitamin B1 ( + 22 % vs. + 11 % in the MT and 0 % in the UNG ) . The DIT group had a significantly lower cost of physician visits than the other 2 groups ( $ 172.1±232.0 vs. $ 417.2±368.0 in the MT and $ 428.1±382.3 in the UNG , p=0.005 ) . Conclusion Intensive dietary intervention was moderately effective in lowering cost of services used and improving medical and nutritional status among community dwelling older adults OBJECTIVE Excess weight has been associated with numerous psychological problems , including depression and anxiety . This study examined the impact of intentional weight loss on the psychological well-being of adults participating in three clinical weight loss interventions . METHODS This population consisted of 588 overweight or obese individuals r and omized into one of three weight loss interventions of incremental intensity for 12 months . Psychological well-being was measured at baseline and 6 , and 12 months using the Psychological Well-Being Index . RESULTS Mean weight loss was 5.0 pounds at 12 months . Weight change at 12 months was associated with higher overall psychological well-being ( r = -.20 , p < .001 ) , lower levels of anxiety ( r = -.16 , p = .001 ) and depression ( r = -.13 , p = .004 ) , and higher positive well-being ( r = -.19 , p < .001 ) , self-control ( r = -.13 , p = .004 ) , and vitality ( r = -.22 , p < .001 ) . Vitality was found to be the best predictor of weight change at 12 months ( p < .001 ) . CONCLUSIONS Weight loss was associated with positive changes in psychological well-being . Increased vitality contributed the largest percentage of variance to this change Objective To determine whether dietary intervention or knee strengthening exercise , or both , can reduce knee pain and improve knee function in overweight and obese adults in the community . Design Pragmatic factorial r and omised controlled trial . Setting Five general practice s in Nottingham . Participants 389 men and women aged 45 and over with a body mass index ( BMI ) of ≥28.0 and self reported knee pain . Interventions Participants were r and omised to dietary intervention plus quadriceps strengthening exercises ; dietary intervention alone ; quadriceps strengthening exercises alone ; advice leaflet only ( control group ) . Dietary intervention consisted of individualised healthy eating advice that would reduce normal intake by 2.5 MJ ( 600 kcal ) a day . Interventions were delivered at home visits over a two year period . Main outcome measures The primary outcome was severity of knee pain scored with the Western Ontario McMaster ( WOMAC ) osteoarthritis index at 6 , 12 , and 24 months . Secondary outcomes ( all at 24 months ) included WOMAC knee physical function and stiffness scores and selected domains on the SF-36 and the hospital anxiety and depression index . Results 289 ( 74 % ) participants completed the trial . There was a significant reduction in knee pain in the knee exercise groups compared with those in the non-exercise groups at 24 months ( percentage risk difference 11.61 , 95 % confidence interval 1.81 % to 21.41 % ) . The absolute effect size ( 0.25 ) was moderate . The number needed to treat to benefit from a ≥30 % improvement in knee pain at 24 months was 9 ( 5 to 55 ) . In those r and omised to knee exercise improvement in function was evident at 24 months ( mean difference −3.64 , −6.01 to −1.27 ) . The mean difference in weight loss at 24 months in the dietary intervention group compared with no dietary intervention was 2.95 kg ( 1.44 to 4.46 ) ; for exercise versus no exercise the difference was 0.43 kg ( −0.82 to 1.68 ) . This difference in weight loss was not associated with improvement in knee pain or function but was associated with a reduction in depression ( absolute effect size 0.19 ) . Conclusions A home based , self managed programme of simple knee strengthening exercises over a two year period can significantly reduce knee pain and improve knee function in overweight and obese people with knee pain . A moderate sustained weight loss is achievable with dietary intervention and is associated with reduced depression but is without apparent influence on pain or function . Trial registration Current Controlled Trials IS RCT N 93206785 OBJECTIVE To estimate service utilization and social morbidity in the community associated with depressive symptoms . Estimates were made using an epidemiologic measure , population attributable risk . Population attributable risk is a compound measure reflecting both the morbid risk to an individual with a disorder and the prevalence of the disorder in the community . DESIGN Epidemiologic survey . PARTICIPANTS Eighteen thous and five hundred seventy-one adults in the Epidemiologic Catchment Area Study interviewed from a complex r and om sample in five US communities . OUTCOME MEASURES Suicide attempts , use of psychoactive medications , self-reported physical and emotional health , time lost from work , and general medical services or use of emergency departments for emotional problems . RESULTS Major depression-dysthymia ( lifetime prevalence , 6.1 % ) and depressive symptoms ( lifetime prevalence , 23.1 % ) were associated with increased service utilization and social morbidity as measured by the outcome variables . On a population basis , however , as much or more service burden and impairment was associated with depressive symptoms as with the clinical conditions of depression or dysthymia . The equal association results from the greater prevalence of depressive symptoms . Population attributable risk percentages associated with depressive symptoms ( not disorder ) were as follows : emergency department use ( 11.8 % ) or medical consultations for emotional problems ( 21.5 % ) ; use of tranquilizers ( 14.6 % ) , sleeping pills ( 21.0 % ) , or antidepressants ( 22.2 % ) ; fair or poor self-reported emotional health ( 15.3 % ) ; days lost from work ( 17.8 % ) ; and suicide attempts ( 25.0 % ) . CONCLUSIONS Estimates of population attributable risk indicated that physicians actually provided services to more persons with depressive symptoms than to persons with formally defined conditions of depressive disorders . Sub clinical depression , as a consequence of high prevalence , is a clinical and public health problem . Attention to diagnostic and treatment issues is indicated OBJECTIVES To determine the effect of a dietary intervention and micronutrient supplementation on self-reported infections in older adults . DESIGN A r and omized , placebo-controlled intervention trial . SETTING Community living older people in South Yorkshire , United Kingdom . PARTICIPANTS Two-hundred seventeen older adults aged 65 to 85 . INTERVENTION Participants were r and omized to a dietary intervention , a daily micronutrient supplement , or placebo for 3 months , with a 3-month follow-up . MEASUREMENTS Self-reported measures of infection were reported over the 6-month study period . Secondary outcome measures were nutritional status , dietary intake , quality of life , and depression . RESULTS Self-reported measures of infection over the 6-month duration of the study were significantly different between the treatment groups . The number of weeks in which illness affected life and the number of general practitioner and hospital visits were significantly lower in the food and micronutrient groups than in the placebo group . The number of weeks in which symptoms of an infection were described was significantly lower in the food group than the placebo and micronutrient groups . Significant improvements in biomarkers of micronutrient status were achieved in the food and micronutrient groups and showed significantly greater change than observed in the placebo group . Significant improvement in dietary intakes was observed in the food group only . CONCLUSION Improving dietary intake and micronutrient status reduces the clinical impact of self-reported infections in older adults Epidemiological and clinical studies have suggested that powerful cholesterol lowering may have adverse effects on mood and psychological well-being . Inhibition of cholesterol bio synthesis by simvastatin ( a hydroxymethyl glutaryl coenzyme A reductase inhibitor ) may also reduce steroid hormone bio synthesis . To explore if mood changes are related with steroid hormone levels , we design ed a r and omized double-blind placebo-controlled crossover trial . The separate and combined effects of a Mediterranean-type diet intervention and treatment with simvastatin 20 mg/day PO for 12 weeks were studied in 120 hypercholesterolemic but otherwise healthy middle-aged men . Psychological functioning was assessed with question naires , and steroid hormone levels in blood were assayed radioimmunologically before and after the treatments . Simvastatin result ed in a statistically significant increase of depression and somatization without changes in the anxiety , hostility or aggression scores . Mood changes seemed to be unrelated with the statistically significant but clinical ly insignificant decline in serum testosterone levels and unrelated with the increase in serum dehydroepi and rosterone levels OBJECTIVE We conducted a pilot study comparing problem solving therapy for primary care ( PST-PC ) to a dietary education control condition in middle-aged and older veterans with symptoms of emotional distress and subsyndromal depression . METHODS This was a two-site study at the VA Pittsburgh Healthcare System and Philadelphia VA Medical Center . Participants included veterans > 50 years of age referred from primary care clinics who were eligible if they obtained a pre-screen score > 11 on the Centers for Epidemiologic Studies Depression ( CES-D ) scale . Exclusions were a DSM-IV Major Depressive Episode within the past year , active substance abuse/dependence within 1 month , current antidepressant therapy , and a Mini mental status exam score < 24 . Participants were r and omized to receive one of two interventions --either PST-PC or an attention control condition consisting of dietary education (DIET)--each consisting of six to eight sessions within a 4-month period . RESULTS Of 45 individuals r and omized , 23 ( 11 PST-PC and 12 DIET ) completed treatment . Using regression models in completers that examined outcomes at end of treatment while controlling for baseline scores , there were significant differences between treatment groups in SF-36 mental health component scores but not in depressive symptoms ( as assessed with either the 17-item Hamilton Rating Scale for Depression or the Beck Depression Inventory ) , social problem solving skills , or physical health status ( SF-36 physical health component score ) . CONCLUSIONS These pilot study findings suggest that a six-to-eight session version of PST-PC may lead to improvements in mental health functioning in primary care veterans with subsyndromal depressive symptoms There are surprisingly few r and omised , controlled trials into the effects of dietary change on mood and cognition in healthy individuals . Here we examined the effects of 10 days of changing to a nutrient-rich diet on mood and cognitive performance . Young female adults ( N=25 ) were r and omised to a diet change ( DC ) , or a no change ( NC ) control group . Those in the DC condition adhered to the nutrient-dense Mediterranean diet . Mood and cognitive performance were assessed at baseline and on day 10 . Compared with the NC group , the DC group showed significant improvements in self-rated vigour , alertness and contentment . Changes in cognitive tasks were somewhat inconsistent . These preliminary findings require verification in larger trials but suggest that appropriate dietary change may benefit mood and some aspects of cognitive performance in healthy adults Background Recently , the efficacy of dietary improvement as a therapeutic intervention for moderate to severe depression was evaluated in a r and omised controlled trial . The SMILES trial demonstrated a significant improvement in Montgomery – Åsberg Depression Rating Scale scores favouring the dietary support group compared with a control group over 12 weeks . We used data collected within the trial to evaluate the cost-effectiveness of this novel intervention . Methods In this prospect i ve economic evaluation , sixty-seven adults meeting DSM-IV criteria for a major depressive episode and reporting poor dietary quality were r and omised to either seven sessions with a dietitian for dietary support or to an intensity matched social support ( befriending ) control condition . The primary outcome was Quality Adjusted Life Years ( QALYs ) as measured by the AQoL-8D , completed at baseline and 12 week follow-up ( endpoint ) assessment . Costs were evaluated from health sector and societal perspectives . The time required for intervention delivery was costed using hourly wage rates applied to the time in counselling sessions . Food and travel costs were also included in the societal perspective . Data on medications , medical services , workplace absenteeism and presenteesim ( paid and unpaid ) were collected from study participants using a re source -use question naire . St and ard Australian unit costs for 2013/2014 were applied . Incremental cost-effectiveness ratios ( ICERs ) were calculated as the difference in average costs between groups divided by the difference in average QALYs . Confidence intervals were calculated using a non-parametric bootstrap procedure . Results Compared with the social support condition , average total health sector costs were $ 856 lower ( 95 % CI -1247 to − 160 ) and average societal costs were $ 2591 lower ( 95 % CI -3591 to − 198 ) for those receiving dietary support . These differences were driven by lower costs arising from fewer allied and other health professional visits and lower costs of unpaid productivity . Significant differences in mean QALYs were not found between groups . However , 68 and 69 % of bootstrap iterations showed the dietary support intervention was dominant ( additional QALYs at less cost ) from the health sector and societal perspectives . Conclusions This novel dietary support intervention was found to be likely cost-effective as an adjunctive treatment for depression from both health sector and societal perspectives . Trial registration Australia and New Zeal and Clinical Trials Register ( ANZCTR ) : ACTRN12612000251820 . Registered on 29 February 2012 OBJECTIVE The effect of 12 weeks of exercise training ( five 45-minute walking sessions/week at 60 % to 75 % maximum heart rate ) and /or moderate energy restriction ( 4.19 to 5.44 MJ or 1200 to 1300 kcal/day ) on psychological general well-being ( GWB ) and profile of mood states ( POMS ) was studied in obese women ( n = 91 , age 45.6 + /- 1.1 years , body mass index 33.1 + /- 0.6 kg/m2 ) . METHODS Subjects were r and omized to one of four groups : control ( C ) ; exercise ( E ) ; diet ( D ) ; and exercise and diet ( ED ) . Psychological variables were measured in all subjects at three timepoints -- pre study , 3 weeks , and post study -- and analyzed using a 4 x 3 repeated measures design . RESULTS GWB but not POMS was improved in ED ( but not E or D ) relative to C post study , especially in four of six subscales : freedom from health concern or worry , life satisfaction ; cheerful versus depressed mood ; and relaxed versus tense feelings . CONCLUSION These data demonstrate that the combination of moderate energy restriction and exercise training during a 12-week period improves psychological general well-being scores but not mood states in obese subjects OBJECTIVE The purpose of this study is to investigate the long-term effects of participation in a cardiovascular screening program and of dietary counseling on self-reported psychosocial outcomes and health concerns . METHODS High-risk subjects ( n=563 ) with hyperlipidemia from the Oslo Diet and Antismoking Study ( 1972 - 1977 ) were reexamined after 25 years and r and omly assigned to a new 3-year prospect i ve 2x2 factorial placebo-controlled study in 1997 of n-3 polyunsaturated fatty acids and /or dietary counseling . Hospital Anxiety and Depression Scale ( HADS ) , Life Satisfaction Index ( LSI ) , and a new question naire on health concerns and behavior in response to risk information were collected at the 25-year follow-up . Hospital Anxiety and Depression Scale and LSI were evaluated at the end of the 3-year Diet and Omega-3 Intervention Trial on atherosclerosis ( DOIT ) in 505 subjects . RESULTS Twenty-five years after the screening program , HADS-anxiety was similar to the Norwegian norms ( 3.3 vs. 3.5 ) , while HADS-depression was significantly lower ( 3.6 vs. 4.1 , P<.01 ) . Patients reported that 25 years of awareness of hyperlipidemia had influenced health concerns through a moderate change in diet habits , some restriction in life conduct , but an improvement of the total life situation . After a novel 3-year intervention in DOIT , there was no difference between the dietary counseling and control group with regard to anxiety , depression , or life satisfaction , but HADS-anxiety increased significantly ( 4.0 vs. 3.3 , P<.001 ) in both groups . CONCLUSION Compared to the general population , screening-positive subjects did not have increased mental distress 25 years after screening , and beneficial health behavior persisted . Dietary counseling did not affect psychosocial outcomes OBJECTIVE Adding exercise to a comprehensive weight-loss program might not only attenuate any psychological distress associated with weight-loss attempts but also may provide psychological benefits . This study examined whether a diet-plus-exercise weight-loss program improved psychological outcomes more than a diet-only weight-loss program or an assessment -only control group . RESEARCH METHODS AND PROCEDURES This study was part of a larger 1-year r and omized weight-loss trial examining the effects of diet and exercise on cardiovascular disease risk factors in 264 overweight adults . Psychological measures specific to weight control ( e.g. , cognitive restraint , disinhibition , hunger , and body dissatisfaction ) as well as traditional measures of psychological distress ( e.g. , symptoms of depression , anxiety , and stress ) were obtained at baseline and 1 year . RESULTS Men and women in either weight-loss program reported greater restraint , less disinhibition , and less hunger at 1 year than those in no program . Men in the diet-plus-exercise program experienced additional increases in restraint and decreases in hunger than did men in the diet-only program . Women in the diet-plus-exercise program did not experience additional psychological benefits specific to weight control than those in the diet-only program , despite increases in aerobic capacity . DISCUSSION The pattern seen for overweight men in the diet-plus-exercise program at 1 year-greater restraint , less disinhibition , and less hunger-is similar to the pattern seen in successful weight maintainers . These results underscore the need for innovative strategies that will enhance and sustain the pattern of psychological benefits specific to weight control associated with successful weight loss , especially for overweight women |
13,246 | 30,817,618 | Conclusions : The findings of this systematic review may provide the existing evidence on the effectiveness and safety of VD for patients with IBS . | Background : Irritable bowel syndrome ( IBS ) is a prevalent and debilitating condition for patients who experience this disorder .
Clinical research es indicate that vitamin D ( VD ) can help relief the symptoms of IBS .
However , no systematic review has addressed this issue yet .
Thus , this systematic review aims to investigate the effectiveness and safety of VD for patients with IBS . | Importance Irritable bowel syndrome ( IBS ) is associated with significant morbidity in children and adolescents , and the therapeutic efficacy of available treatment options is limited . The role of vitamin D supplementation in pediatric IBS is unclear as the vitamin D status of pediatric patients with IBS is unknown . Equally , the relationship of vitamin D status with psychosomatic symptoms in children and adolescents is unclear . Aim To characterize the vitamin D status of pediatric patients with IBS using a case-control study design . Hypothesis Serum 25-hydroxyvitamin D [ 25(OH)D ] concentration will be similar between patients with IBS and controls . Subjects and methods A retrospective case-controlled study of 116 controls ( age 14.6 ± 4.3 y ) , female ( n = 67 ; 58 % ) and 55 subjects with IBS ( age 16.5 ± 3.1y ) , female ( n = 44 ; 80 % ) . Overweight was defined as BMI of ≥85th but < 95th percentile , and obesity as BMI ≥95th percentile . Vitamin D deficiency was defined as 25(OH)D of < 50 nmol/L , while seasons of vitamin D draw were categorized as summer , winter , spring , and fall . Major psychosomatic manifestations included in the analysis were depression , anxiety , and migraine . Results More than 50 % of IBS subjects had vitamin D deficiency at a cut-off point of < 50 nmol/L ( 53 % vs. 27 % , p = 0.001 ) ; and > 90 % of IBS subjects had vitamin D deficiency at a cut-off point of < 75 nmol/L ( 93 % vs. 75 % , p = 0.006 ) . IBS subjects had significantly lower mean 25(OH)D : 53.2 ± 15.8 nmol/L vs. 65.2 ± 28.0 nmol/L , p = 0.003 ; and albumin : 6.2 ± 0.6 vs. 6.5 ± 0.6 μmol/L , p = 0.0.01 . IBS subjects with migraine had significantly lower mean 25(OH)D concentration compared to controls ( p = 0.01 ) . BMI z-score was similar between the controls and IBS subjects ( 0.5 ± 1.4 vs. 1.2 ± 2.9 , p = 0.11 ) . Conclusions Pediatric patients with IBS had significantly lower 25(OH)D concentration compared to controls despite having similar mean BMI values as controls . Only 7 % of the children and adolescents with IBS were vitamin D sufficient , and > 50 % of the subjects with IBS had vitamin D deficiency . This is a much higher prevalence of vitamin D deficiency compared to IBD and other malabsorption syndromes . Monitoring for vitamin D deficiency should be part of the routine care for patients with IBS . R and omized control trials are warranted to determine the role of adjunctive vitamin D therapy in pediatric IBS Background / Aim : Vitamin D deficiency is common in irritable bowel syndrome ( IBS ) . There is growing interest in the role of vitamin D in pediatric IBS . We aim ed to evaluate the effect of vitamin D supplementation in adolescents with IBS and vitamin D deficiency . Patients and Methods : One hundred and twelve adolescents with IBS and vitamin D deficiency were r and omly divided into two groups of matched age and sex . The first group received oral vitamin D3 2000IU/day for 6 months and the second group received placebo for 6 months . Vitamin D status as well as different IBS score systems ( IBS-SSS , IBS-QoL , and total score ) were evaluated before and 6 months after treatment . Results : IBS patients who received vitamin D supplementation for 6 months showed significant improvement in IBS-SSS ( P < 0.001 ) , IBS-QoL ( P < 0.001 ) , and total score ( P = 0.02 ) compared to IBS placebo group . IBS patients treated with vitamin D showed two folds increase in their serum vitamin D levels ( from 17.2 ± 1.3 to 39 ± 3.3 ) ng/ml with P < 0.001 . While in the placebo group , their serum vitamin D levels were not significantly changed ( P = 0.66 ) . Vitamin D was tolerated well without any recorded adverse effects during the study period . Conclusion : Vitamin D supplementation can be effective in treating adolescents with IBS and vitamin D deficiency Background Vitamin D deficiency has been associated or implicated with the pathophysiology of the gastrointestinal conditions inflammatory bowel disease and colorectal cancer , as well as with depression . No trials or epidemiology studies to date have investigated a link with irritable bowel syndrome ( IBS ) . A single case report has suggested a benefit in IBS of vitamin D supplementation . We hypothesised that IBS participants with vitamin D insufficiency would benefit from repletion in terms of their IBS symptoms . We undertook a pilot trial to provide data to support a power calculation and to justify a full trial . Methods This was a r and omised , double blinded , three-arm parallel design trial of vitamin D , placebo or a combination of vitamin D and probiotics . Participants were further stratified according to whether they were vitamin D replete or insufficient . Vitamin D status was determined by blood test at baseline and exit ; IBS symptoms were assessed by vali date d question naire ; dietary intakes were assessed by food frequency question naire . Results A significant proportion of the IBS population were vitamin D deficient , such that the replete stratum could not be adequately recruited . There was a significant association in the baseline data between circulating vitamin D level and quality of life ( “ How much has IBS affected your life ? ” ) . Supplementation significantly improved vitamin D level versus placebo . IBS symptoms were not significantly improved in this pilot , although a power calculation was enabled from the intervention data . Conclusions The IBS population exhibits significant levels of vitamin D insufficiency and would benefit from screening and possible supplementation . The impact of IBS on quality of life may be reduced by vitamin D level . Future trials should have a sample size of over 97 . Trial registration number : ICTRN 6116003917 Background Low vitamin D status is associated with risk of colorectal cancer and has been implicated in inflammatory bowel disease . Irritable bowel syndrome ( IBS ) is a chronic , relapsing , functional bowel disorder . A nascent literature suggests a role for vitamin D in IBS , but this has not been collated or critiqued . To date , seven studies have been published : four observational studies and three r and omised controlled trials ( RCTs ) . All observational studies reported that a substantial proportion of the IBS population was vitamin D deficient . Two intervention studies reported improvement in IBS symptom severity scores and quality of life ( QoL ) with vitamin D supplementation . There are limited data around the role of vitamin D in IBS . Conclusions The available evidence suggests that low vitamin D status is common among the IBS population and merits assessment and rectification for general health reasons alone . An inverse correlation between serum vitamin D and IBS symptom severity is suggested and vitamin D interventions may benefit symptoms . However , the available RCTs do not provide strong , generalisable evidence ; larger and adequately powered interventions are needed to establish a case for therapeutic application of vitamin D in IBS BACKGROUND Low- grade mucosal inflammation and immune activation are involved in the pathogenesis of irritable bowel syndrome ( IBS ) . Furthermore , IBS symptoms are associated with a significantly higher prevalence of psychological distress , which in itself results into an impaired quality of life ( QoL ) . Vitamin D could ameliorate the symptoms of patients suffering from IBS through its beneficial effects on psychological factors and inflammation . METHODS A total of 90 IBS patients participated in this double-blind , r and omized , placebo-controlled study . Participants were r and omly selected to receive either 50 000 IU vitamin D3 or a placebo fortnightly for a period of 6 months . Patients reported their IBS symptoms at the baseline and monthly during intervention periods . The IBS severity score system ( IBSSS ) and IBS-specific QoL question naires were used at the baseline and postintervention . KEY RESULTS Over the 6-month intervention period , a significantly greater improvement in IBS symptoms such as abdominal pain and distention , flatulence , rumbling , and overall gastrointestinal ( GI ) symptoms ( except dissatisfaction with bowel habits ) was observed in the patients receiving vitamin D as compared to the placebo group . The IBSSS and the IBS-QoL scores in the vitamin D group significantly improved compared to the placebo group postintervention ( mean IBSSS score change : -53.82 ± 23.3 vs -16.85 ± 25.01 , p < 0.001 , respectively ; mean IBS-QoL score change : 14.26 ± 3 vs 11 ± 2.34 , p < 0.001 , respectively ) . CONCLUSIONS & INFERENCES Vitamin D seems to be an effective and safe option to improve QoL and symptoms of IBS . Clinical Trials.gov ( NCT02579902 ) |
13,247 | 30,941,745 | We were therefore unable to conclude with any confidence that , in people with chronic pain , TENS is harmful , or beneficial for pain control , disability , health‐related quality of life , use of pain relieving medicines , or global impression of change . | Abstract Background Chronic pain , considered to be pain lasting more than three months , is a common and often difficult to treat condition that can significantly impact upon function and quality of life .
Treatment typically includes pharmacological and non‐pharmacological approaches .
Transcutaneous electrical nerve stimulation ( TENS ) is an adjunct non‐pharmacological treatment commonly recommended by clinicians and often used by people with pain .
Objectives To provide an overview of evidence from Cochrane Review s of the effectiveness of TENS to reduce pain in adults with chronic pain ( excluding headache or migraine ) .
To provide an overview of evidence from Cochrane Review s of the safety of TENS when used to reduce pain in adults with chronic pain ( excluding headache or migraine ) .
To identify possible sources of inconsistency in the approaches taken to evaluating the evidence related to TENS for chronic pain ( excluding headache or migraine ) in the Cochrane Library with a view to recommending strategies to improve consistency in methodology and reporting .
To highlight areas of remaining uncertainty regarding the effectiveness of TENS for chronic pain ( excluding headache or migraine ) with a view to recommending strategies to reduce any uncertainty . | UNLABELLED Transcutaneous electrical nerve stimulation ( TENS ) is an electrophysical modality used for pain management . This study investigated the dose response of different TENS intensities on experimentally induced pressure pain . One hundred and thirty TENS naïve healthy individuals ( 18 - 64 years old ; 65 males , 65 females ) were r and omly allocated to 5 groups ( n = 26 per group ) : Strong Non Painful TENS ; Sensory Threshold TENS ; Below Sensory Threshold TENS ; No Current Placebo TENS ; and Transient Placebo TENS . Active TENS ( 80 Hz ) was applied to the forearm for 30 minutes . Transient Placebo TENS was applied for 42 seconds after which the current amplitude automatically reset to 0 mA. Pressure pain thresholds ( PPT ) were recorded from 2 points on the h and and forearm before and after TENS to measure hypoalgesia . There were significant differences between groups at both the h and and forearm ( ANOVA ; P = .005 and .002 ) . At 30 minutes , there was a significant hypoalgesic effect in the Strong Non Painful TENS group compared to : Below Sensory Threshold TENS , No Current Placebo TENS and Transient Placebo TENS groups ( P < .0001 ) at the forearm ; Transient Placebo TENS and No Current Placebo TENS groups at the h and ( P = .001 ) . There was no significant difference between Strong Non Painful TENS and Sensory Threshold TENS groups . The area under the curve for the changes in PPT significantly correlated with the current amplitude ( r(2 ) = .33 , P = .003 ) . These data therefore show that there is a dose-response effect of TENS with the largest effect occurring with the highest current amplitudes . PERSPECTIVE This study shows a dose response for the intensity of TENS for pain relief with the strongest intensities showing the greatest effect ; thus , we suggest that TENS intensity should be titrated to achieve the strongest possible intensity to achieve maximum pain relief Summary Pain and fatigue during movement , but not at rest , are reduced by a onetime 30‐m treatment with active transcutaneous electrical nerve stimulation ( TENS ) in individuals with fibromyalgia . Abstract Because transcutaneous electrical nerve stimulation ( TENS ) works by reducing central excitability and activating central inhibition pathways , we tested the hypothesis that TENS would reduce pain and fatigue and improve function and hyperalgesia in people with fibromyalgia who have enhanced central excitability and reduced inhibition . The current study used a double‐blinded r and omized , placebo‐controlled cross‐over design to test the effects of a single treatment of TENS with people with fibromyalgia . Three treatments were assessed in r and om order : active TENS , placebo TENS and no TENS . The following measures were assessed before and after each TENS treatment : pain and fatigue at rest and in movement ; pressure pain thresholds , 6‐m walk test , range of motion ; 5‐time sit‐to‐st and test , and single‐leg stance . Conditioned pain modulation was completed at the end of testing . There was a significant decrease in pain and fatigue with movement for active TENS compared to placebo and no TENS . Pressure pain thresholds increased at the site of TENS ( spine ) and outside the site of TENS ( leg ) when compared to placebo TENS or no TENS . During active TENS , conditioned pain modulation was significantly stronger compared to placebo TENS and no TENS . No changes in functional tasks were observed with TENS . Thus , the current study suggests TENS has short‐term efficacy in relieving symptoms of fibromyalgia while the stimulator is active . Future clinical trials should examine the effects of repeated daily delivery of TENS , similar to the way in which TENS is used clinical ly on pain , fatigue , function , and quality of life in individuals with fibromyalgia Objective . Pain is a patient-important outcome , but current reporting in r and omized controlled trials and systematic review s is often suboptimal , impeding clinical interpretation and decision making . Methods . A working group at the 2014 Outcome Measures in Rheumatology ( OMERACT 12 ) was convened to provide guidance for reporting treatment effects regarding pain for individual studies and systematic review s. Results For individual trials , authors should report , in addition to mean change , the proportion of patients achieving 1 or more thresholds of improvement from baseline pain ( e.g. , ≥ 20 % , ≥ 30 % , ≥ 50 % ) , achievement of a desirable pain state ( e.g. , no worse than mild pain ) , and /or a combination of change and state . Effects on pain should be accompanied by other patient-important outcomes to facilitate interpretation . When pooling data for meta analysis , authors should consider converting all continuous measures for pain to a 100 mm visual analog scale ( VAS ) for pain and use the established , minimally important difference ( MID ) of 10 mm , and the conventionally used , appreciably important differences of 20 mm , 30 mm , and 50 mm , to facilitate interpretation . Effects ≤ 0.5 units suggest a small or very small effect . To further increase interpretability , the pooled estimate on the VAS should also be transformed to a binary outcome and expressed as a relative risk and risk difference . This transformation can be achieved by calculating the probability of experiencing a treatment effect greater than the MID and the thresholds for appreciably important differences in pain reduction in the control and intervention groups . Conclusion . Presentation of relative effects regarding pain will facilitate interpretation of treatment effects & NA ; This study evaluated the effects of varying frequency , intensity and stimulation site , of transcutaneous electrical nerve stimulation ( TENS ) in an experimental model of pain . In a double‐blind design 240 volunteers were r and omised to one of six experimental TENS groups , a sham TENS or control ( n=30 per group ; gender balanced ) . Two TENS frequencies ( 110 or 4 Hz ) and two intensities ( strong but comfortable or highest tolerable ) at a fixed pulse duration ( 200 & mgr;s ) were applied at three sites relative to the measurement site ( segmentally , extrasegmentally or a combination of these ) , for 30 min . Pressure pain thresholds ( PPT ) were measured using a pressure algometer , in the first dorsal interosseous muscle , every 10 min , during stimulation and for a further 30 min . The high frequency , high intensity segmental , and combined stimulation groups , showed rapid onset and significant hypoalgesic effects . This effect was sustained for 20 min post‐stimulation in the high frequency segmental group . All other TENS intervention groups showed hypoalgesic responses similar to the sham TENS group , and none of these groups reached a clinical ly significant hypoalgesic level . Conclusions : The role of TENS frequency , intensity and site are pivotal to achieving optimal hypoalgesic effects , during and after stimulation . Clinical applications of these parameter combinations require further investigations & NA ; Transcutaneous electrical nerve stimulation ( TENS ) is a frequently applied therapy in chronic pain although evidence for effectiveness is inconclusive . Several types of TENS , based on different combinations of frequency , pulse duration and intensity , exist . The precise mechanism of action and the relevance of combinations of stimulus parameters are still unclear . To compare the effectiveness of three types of TENS we conducted a r and omized , single blinded crossover trial . Patients received two times a 2‐week period of daily TENS treatment , separated by a washout period of 2 weeks . In total , 180 chronic pain patients were r and omized into three groups . In group 1 , high frequency , low intensity TENS ( HFT ) was compared with high frequency , high intensity TENS ( HIT ) . In groups 2 and 3 , HFT and HIT were compared with a control TENS ( COT ) . The order of applying the different modalities of TENS in each group was also r and omized . Primary outcome was the patient 's overall assessment of effectiveness and pain reduction ( VAS ) . No differences were found in patient 's assessment or pain reducing effect between the three groups , indicating no superiority of one type of TENS . In total , 56 % continued TENS after the 2‐week treatment period . At 6 months , 42 % of all patients still used TENS . We concluded that there were no differences in effectiveness for the three types of TENS used in this study . Because no placebo group was included , no definite conclusions on effectiveness of TENS in general in the treatment of chronic pain could be made UNLABELLED This study compared a new transient sham transcutaneous electrical nerve stimulation ( TENS ) that delivers current for 45 seconds to an inactive sham and active TENS to determine the degree of blinding and influence on pain reduction . Pressure-pain thresholds ( PPT ) , heat-pain thresholds ( HPT ) , and pain intensities to tonic heat and pressure were measured in 69 healthy adults before and after r and omization . Allocation investigators and subjects were asked to identify the treatment administered . The transient sham blinded investigators 100 % of the time and 40 % of subjects compared to the inactive sham that blinded investigators 0 % of the time and 21 % of subjects . Investigators and subjects were blinded only 7 % and 13 % of the time , respectively , with active TENS . Neither placebo treatment result ed in significant changes in PPT , HPT , or pain intensities . Subjects using higher active TENS amplitudes ( > or = 17 mAs ) had significantly higher PPTs and lower pain intensities to tonic pressure than subjects using lower amplitudes ( < 17 mAs ) . HPTs and pain intensities to tonic heat were not significantly changed . The transient TENS completely blinds investigators to treatment and does not reduce pain , thereby providing a true placebo treatment . PERSPECTIVE This article presents the benefits of a new transient sham TENS device for use in prospect i ve , r and omized , clinical trials . This device facilitates blinding of subjects and investigators to eliminate expectation bias and determine the true efficacy of TENS for use in clinical population Objective : To investigate the hypoalgesic effects of transcutaneous electrical nerve stimulation ( TENS ) upon low back pain ( LBP ) in people with multiple sclerosis ( MS ) . Design : A r and omized double-blind placebo controlled clinical pilot study . Subjects and setting : Fifteen people with MS were recruited and r and omly allocated to one of the following groups under double blind conditions ( n = 5 per group ) : TENS 1 ( 4 Hz , 200 µs ) , TENS 2 ( 110 Hz , 200 µs ) , placebo TENS . Interventions : Treatment was applied for 45 minutes three times a week for six weeks with a four-week follow-up . Outcome measures : The following outcome measures were taken at weeks 1 , 6 , and 10 : visual analogue scale ( VAS ) ( for current LBP , right leg pain , left leg pain ) ; Leeds Multiple Sclerosis Quality of Life Question naire ; Rol and Morris Disability Question naire ; Short Form-36 ( SF-36 ) Version 1 ; and the McGill Pain Question naire ( MPQ ) . VAS for current LBP , right and left leg pain were also taken before and after treatment , and once a week during the follow-up period . Results : Analysis showed no statistically significant effects for any of the data . However , both active treatment groups showed a trend of improvement in the majority of the outcome measures . Conclusion : Active TENS was more effective than placebo TENS in decreasing VAS scores following each treatment although results were not statistically significant . Further work in this area is warranted and should include a larger number of participants in the form of a r and omized controlled clinical trial to determine the efficacy of this modality Incomplete and inadequate reporting is an avoidable waste that reduces the usefulness of research . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement is an evidence -based reporting guideline that aims to improve research transparency and reduce waste . In 2008 , the CONSORT Group developed an extension to the original statement that addressed method ological issues specific to trials of nonpharmacologic treatments ( NPTs ) , such as surgery , rehabilitation , or psychotherapy . This article describes an up date of that extension and presents an extension for reporting abstract s of NPT trials . To develop these material s , the authors review ed pertinent literature published up to July 2016 ; surveyed authors of NPT trials ; and conducted a consensus meeting with editors , trialists , and method ologists . Changes to the CONSORT Statement extension for NPT trials include wording modifications to improve readers ' underst and ing and the addition of 3 new items . These items address whether and how adherence of participants to interventions is assessed or enhanced , description of attempts to limit bias if blinding is not possible , and specification of the delay between r and omization and initiation of the intervention . The CONSORT extension for abstract s of NPT trials includes 2 new items that were not specified in the original CONSORT Statement for abstract s. The first addresses reporting of eligibility criteria for centers where the intervention is performed and for care providers . The second addresses reporting of important changes to the intervention versus what was planned . Both the up date d CONSORT extension for NPT trials and the CONSORT extension for NPT trial abstract s should help authors , editors , and peer review ers improve the transparency of NPT trial reports OBJECTIVES A preliminary examination of NMES and combined NMES/TENS for the management of chronic back pain . DESIGN Double-blind , placebo-controlled , r and omized repeated measures . SUBJECTS AND SETTING Consecutive sample of 24 chronic back pain patients ( 16 women and 8 men ) attending an outpatient pain clinic ( mean age 51.67 years , mean pain duration 3.83 years ) . All treatments were administered at home . INTERVENTIONS Subjects self-administered NMES , combined NMES/TENS , TENS , and placebo treatments . Each treatment had a duration of 5 consecutive hours per day over 2 consecutive days , with a 2-day hiatus between treatments to minimize carryover effects . MAIN OUTCOME MEASURES Pain reduction was assessed through pretreatment to posttreatment differences on the Present Pain Intensity ( PPI ) scale , and a visual analogue scale of Pain Intensity ( VAS-I ) . Posttreatment pain relief was assessed using a visual analogue scale of Pain Relief ( VAS-R ) . RESULTS Combined treatment , NMES , and TENS each produced significant pretreatment to posttreatment reductions in pain intensity as measured by both the PPI and VAS-I ( p < .05 ) . Combined treatment was superior to placebo on pain reduction ( p = .001 , p = .016 ) as well as pain relief ( p < .001 ) . Combined treatment was also superior to both TENS and NMES for pain reduction and pain relief ( p < .01 ) . NMES and TENS were superior only to placebo for pain relief ( p < .001 ) . CONCLUSIONS Combined NMES/TENS treatment consistently produced greater pain reduction and pain relief than placebo , TENS , or NMES . NMES alone , although less effective , did produce as much pain relief as TENS . Although preliminary , this pattern of results suggests that combined NMES/TENS may be a valuable adjunct in the management of chronic back pain . Further research investigating the effectiveness of both NMES and combined NMES/TENS seems warranted Introduction It is cl aim ed that transcutaneous electrical nerve stimulation ( TENS ) operates via a segmental mechanism by reducing ongoing transmission and sensitization of nociceptive dorsal horn neurons . Hence , TENS electrodes are usually placed at the site of pain . Objective This study compared TENS administered at the site of experimentally induced ischemic pain ( ipsilateral forearm ) with TENS administered at a location not related to pain ( contralateral lower leg ) . Methods Ten healthy , pain free volunteers took part in a cross-over study during which ischemic pain was induced in the nondominant arm using a modified version of submaximal effort tourniquet technique . Pain intensity was taken at 1-minute interval/s for 5 minutes while receiving TENS either at the ipsilateral arm or contralateral leg . Results There were no statistically significant differences in pain intensity or McGill Pain Question naire ratings between TENS given at the arm compared with the leg . Discussion Taken at face value , the findings suggest that TENS effects were nonspecific and that electrode location does not affect outcome . However , this study should be seen as a call for further research rather than a definitive conclusion Objective This study was design ed to investigate the hypoalgesic effects of self-applied transcutaneous electrical nerve stimulation ( TENS ) on chronic low-back pain ( LBP ) in a multiple sclerosis ( MS ) population . Methods Ninety participants with probable or definite MS ( aged 21 to 78 y ) presenting with chronic LBP were recruited and r and omized into 3 groups ( n=30 per group ) : ( 1 ) low-frequency TENS group ( 4 Hz , 200 μs ) ; ( 2 ) high-frequency TENS group ( 110 Hz , 200 μs ) ; and ( 3 ) placebo TENS . Participants self-applied TENS for 45 minutes , a minimum of twice daily , for 6 weeks . Outcome measures were recorded at weeks 1 , 6 , 10 , and 32 . Primary outcome measures included : Visual Analog Scale for average LBP and the McGill Pain Question naire . Secondary outcome measures included : Visual Analog Scale for worst and weekly LBP , back and leg spasm ; Rol and Morris Disability Question naire ; Barthel Index ; Rivermead Mobility Index ; Multiple Sclerosis Quality of Life-54 Instrument , and a daily logbook . Data were analyzed blind using parametric and nonparametric tests , as appropriate . Results Results indicated a statistically significant interactive effect between groups for average LBP ( P=0.008 ) ; 1-way analysis of covariance did not show any significant effects at any time point once a Bonferonni correction was applied ( P>0.05 ) . However , clinical ly important differences were observed in some of the outcome measures in both active treatment groups during the treatment and follow-up periods . Discussion Although not statistically significant , the observed effects may have implication s for the clinical prescription and the use of TENS within this population In 23 patients with pancreatitis , daily pain for at least 3 months , and no abuse of alcohol , the pain-relieving effect of electroacupuncture ( 13 patients ) or transcutaneous electric nerve stimulation ( TENS ) ( 16 patients ) was studied . In two prospect i ve studies with a cross-over design , active acupuncture was compared with sham acupuncture , and TENS of the segmental points of the pancreas with sham treatment . Neither electroacupuncture nor TENS brought about pain relief that could substitute for or supplement medical treatment |
13,248 | 21,328,295 | There is insufficient evidence supporting the effectiveness of educational interventions targeting nursing staff for preventing or reducing the use of physical restraints in geriatric long-term care | BACKGROUND Physical restraints ( PR ) are commonly used in geriatric long-term care .
Restraint-free care should be the aim of high quality nursing care .
OBJECTIVES To evaluate the effectiveness of interventions to prevent and reduce the use of physical restraints in older people who require long-term nursing care ( either in community nursing care or in residential care facilities ) . | Reports of cluster r and omised trials require additional information to allow readers to interpret them accurately The effective reporting of r and omised controlled trials has received useful attention in recent years . Many journals now require that reports conform to the guidelines in the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement , first published in 1996 and revised in 2001 . The statement includes a checklist of items that should be included in the trial report . These items are evidence based whenever possible and are regularly review ed . The statement also recommends including a flow diagram to show the flow of participants from group assignment through to the final analysis . The CONSORT statement focused on reporting parallel group r and omised trials in which individual participants are r and omly assigned to study groups . However , in some situations it is preferable to r and omly assign groups of individuals ( such as families or medical practice s ) rather than individuals . Reasons include the threat of contamination of some interventions ( such as dietary interventions ) if individual r and omisation is used . 5 Also , in certain setting s r and omisation by group may be the only feasible method of conducting a trial . Trials with this design are variously known as field trials , community based trials , place based trials , or ( as in this paper ) cluster r and omised trials . In an earlier discussion paper we considered the implication s of the CONSORT statement for the reporting of cluster r and omised trials . Here we present up date d guidance , based on the 2001 revision of the CONSORT statement OBJECTIVE To evaluate the efficacy of a dementia care program to reduce behavior disorders in nursing home patients with dementia . DESIGN R and omized controlled clinical trial with 6-month follow-up . SETTING A 250-bed community nursing home . PATIENTS The nursing home was screened to identify patients with dementia and behavior disorders . A total of 118 patients were eligible for r and omization . Of these , 89 ( 75.4 % ) were r and omized , and 81 of these ( 91.0 % ) completed the trial . INTERVENTION The A.G.E. dementia care program consisted of Activities , Guidelines for psychotropic medications , and Educational rounds . The control treatment was usual nursing home care . MEASUREMENTS Behavior disorders , antipsychotic drug and physical restraint use , patient activity levels , and cognitive and functional status . RESULTS After 6 months , 12 of 42 ( 28.6 % ) intervention patients exhibited behavior disorders compared with 20 of 39 ( 51.3 % ) controls ( OR = 0.38 ; 95 % CI [ 0.15 , 0.95 ] ; P = .037 ) . Controls were more than twice as likely to receive antipsychotics ( OR = 2.55 , 95 % CI [ 0.96 , 6.76 ] ; P < .056 ) , to be restrained during activity times ( OR = 2.98 , 95 % CI [ 1.10 , 8.04 ] ; P < .028 ) , and to be restrained on nursing units ( OR = 2.14 , 95 % CI [ 0.9 , 5.3 ] ; P < .10 ) . Intervention patients were much more likely to participate in activities ( OR = 13.71 ; 95 % CI [ 4.51 , 41.73 ] ; P = .001 ) . CONCLUSIONS The A.G.E. program reduces the prevalence of behavior disorders and the use of antipsychotic drugs and restraints . It is practical , feasible , and appears to improve the lives of patients with dementia in nursing homes At present , observational studies and expert opinion are the best evidence for the use of physical restraints . Large regional and national disparities are described in acute and long-term care . Epidemiological data demonstrate a prevalence of 3 - 5 % body-fixed or near body restraint devices . The hip fracture rate in Germany are approximately 50 per 1000 resident years . Between 40 - 50 % of the residents in nursing homes are treated with psycho-tropic medication potentially limiting their physical mobility . The presented study protocol was design ed to test the effectiveness of a multifactorial intervention to reduce physical restraints in long-term care ( LTC ) residents particularly with cognitive impairment . The intervention consists of an educational and an organizational part to empower staff members to improve their skills and practice in using restraints . Technical devices to reduce fall related injuries are additionally offered to the LTC facilities . The study population includes 200 LTC residents in 54 facilities in three states in Germany . The sample size calculation was based upon a 5 % prevalence rate in the control group and an expected reduction of 50 % in the intervention group . The protocol is a waiting-list control design . All waiting facilities will be offered to participate after their waiting period . Primary endpoints are the number of restrained residents and resident time ( hours ) of being restrained . The use of psychotropics , falls , fall-related injuries and the incidence of residents newly being restrained is being monitored . The study starts with a baseline documentation of all facilities followed by r and omization and a three month intervention . Change agents will be responsible for the intervention . Technical devices will include a newly developed soft hip protector and sensor mats which notice the intent of leaving the bed . The aim of the study is to develop an evidence -based model for a knowledge transfer project to implement minimum restraint environments in LTC BACKGROUND This paper shows patients ' enactment of choice in mixed methods , multidisciplinary study on the use of bedrails as restraints . APPROACH Under the pressure of the implementation of impending legislation , patients from a Canadian elderly care rehabilitation unit were recruited to be part of this study and assigned to either a study or control group . Study group patients were exposed to a new facility policy on restraints in which bedrails were not to be used on a patient 's bed except under specified conditions . Patients in the control group continued to have bedrails on a routine basis according to the facility 's old policy . Following group assignments , patients could choose to crossover to either the control or study group based on their opinions about bedrails . FINDINGS After patients crossed over into either the study or control group , findings for the new groups differed significantly . Participants in the rails-up group had lower admission Functional Independence Measure scores ( p = .001 ) and higher admission Cumulative Illness Rating scores ( p = .000 ) compared to those in the rails-down group . CONCLUSIONS Patients have specific concerns related to the use of bedrails that might affect implementing bedrail minimization policies . Additionally , the authors conclude that patients ' input into research design may increase patients ' support of the protocol and help maintain study integrity Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed to improve the reporting of r and omised controlled trials . It was initially published in 1996 and focused on the reporting of parallel group r and omised controlled trials . The statement was revised in 2001 , with a further up date in 2010 . A separate CONSORT statement for the reporting of abstract s was published in 2008 . In earlier papers we considered the implication s of the 2001 version of the CONSORT statement for the reporting of cluster r and omised trial . In this paper we provide up date d and extended guidance , based on the 2010 version of the CONSORT statement and the 2008 CONSORT statement for the reporting of abstract s. Background Physical restraints are still frequently used in nursing home residents despite growing evidence for the ineffectiveness and negative consequences of these methods . Therefore , reduction in the use of physical restraints in psycho-geriatric nursing home residents is very important . The aim of this study was to investigate the short-term effects of an educational intervention on the use of physical restraints in psycho-geriatric nursing home residents . Methods A cluster r and omized trial was applied to 5 psycho-geriatric nursing home wards ( n = 167 residents with dementia ) . The wards were assigned at r and om to either educational intervention ( 3 wards ) or control status ( 2 wards ) . The restraint status was observed and residents ' characteristics , such as cognitive status , were determined by using the Minimum Data Set ( MDS ) at baseline and 1 month after intervention . Results Restraint use did not change significantly over time in the experimental group ( 55%–56 % ) , compared to a significant increased use ( P < 0.05 ) in the control group ( 56%–70 % ) . The mean restraint intensity and mean multiple restraint use in residents increased in the control group but no changes were shown in the experimental group . Logistic regression analysis showed that residents in the control group were more likely to experience increased restraint use than residents in the experimental group . Conclusion An educational programme for nurses combined with consultation with a nurse specialist did not decrease the use of physical restraints in psycho-geriatric nursing home residents in the short term . However , the residents in the control group experienced more restraint use during the study period compared to the residents in the experimental group . Whether the intervention will reduce restraint use in the long term could not be inferred from these results . Further research is necessary to gain insight into the long-term effects of this educational intervention OBJECTIVES To investigate the effects of an educational intervention on the use of physical restraints with psychogeriatric nursing home residents . DESIGN Cluster-r and omized trial . SETTING Fifteen psychogeriatric nursing home wards in the Netherl and s. PARTICIPANTS In total , 432 psychogeriatric nursing home residents from 15 psychogeriatric nursing home wards in seven nursing homes were selected for participation ; 404 consented , and 371 of these were available at baseline . Two hundred forty-one from 14 wards had complete data and were included in the data analyses . INTERVENTION The nursing home wards were assigned at r and om to educational intervention or control status . The educational intervention consisted of an educational program for nursing staff combined with consultation with a nurse specialist ( registered nurse ( RN ) level ) . MEASUREMENTS Data were collected at baseline and 1 , 4 , and 8 months postintervention . At each measurement , the use of physical restraints was measured using observations of blinded , trained observers on four separate occasions over a 24-hour period . Other resident characteristics , such as cognitive status , were determined using the Minimum Data Set . RESULTS Logistic and linear regression analyses showed no treatment effect on restraint status , restraint intensity , or multiple restraint use in any of the three postintervention measurements . Furthermore , only small changes occurred in the types of restraints used with residents in the experimental group . CONCLUSION An educational program for nursing staff combined with consultation with a nurse specialist ( RN level ) had no effect on the use of physical restraints with psychogeriatric nursing home residents . In addition to restraint education and consultation , new measures to reduce the use of physical restraints with psychogeriatric nursing home residents should be developed Background Physical restraints are regularly applied in German nursing homes . Their frequency varies substantially between centres . Beneficial effects of physical restraints have not been proven , however , observational studies and case reports suggest various adverse effects . We developed an evidence -based guidance on this topic . The present study evaluates the clinical efficacy and safety of an intervention programme based on this guidance aim ed to reduce physical restraints and minimise centre variations . Methods / Design Cluster-r and omised controlled trial with nursing homes r and omised either to the intervention group or to the control group with st and ard information . The intervention comprises a structured information programme for nursing staff , information material s for legal guardians and residents ' relatives and a one-day training workshop for nominated nurses . A total of 36 nursing home clusters including approximately 3000 residents will be recruited . Each cluster has to fulfil the inclusion criteria of at least 20 % prevalence of physical restraints at baseline . The primary endpoint is the number of residents with at least one physical restraint at six months . Secondary outcome measures are the number of falls and fall-related fractures . Discussion If successful , the intervention should be implemented throughout Germany . In case the intervention does not succeed , a three-month pre-post- study with an optimised intervention programme within the control group will follow the r and omised trial . Trial registration IS RCT The prevention of injury associated with falls in older people is a public health target in many countries around the world . Although there is good evidence that interventions such as multifactorial fall prevention and individually prescribed exercise are effective in reducing falls , the effect on serious injury rates is unclear . Historically , trials have not been adequately powered to detect injury endpoints , and variations in case definition across trials have hindered meta- analysis . It is possible that fall-prevention strategies have limited effect on falls that result in injuries or are ineffective in population s who are at a higher risk of injury . Further research is required to determine whether fall-prevention interventions can reduce serious injuries . Prevention of Falls Network Europe ( ProFaNE ) is a collaborative project to reduce the burden of fall injury in older people through excellence in research and promotion of best practice ( www.profane.eu.org ) . The European Commission funds the network , which links clinicians , members of the public , and research ers worldwide . The aims are to identify major gaps in knowledge in fall injury prevention and to facilitate the collaboration necessary for large-scale clinical research activity , including clinical trials , comparative research , and prospect i ve meta- analysis . Work is being undertaken in a 4-year program . As a first step , the development of a common set of outcome definitions and measures for future trials or meta- analysis was considered OBJECTIVES To examine predictors of continued restraint use in nursing home residents following efforts aim ed at restraint reduction . DESIGN Secondary analysis of data from a clinical trial using a one-group , pre-test post-test design . SETTING Three nonprofit , religion-affiliated nursing homes in a metropolitan area . PARTICIPANTS The sample consisted of 201 physically restrained nursing home residents . Following restraint reduction efforts , 135 of the sample were still restrained . Mean age of participants was 83.9 years . MEASUREMENTS Physical restraint use was measured by observation and included any chest/vest , wrist , mitt , belt , crotch , suit , or harness restraint plus any sheet used as restraint or a geriatric chair with fixed tray table . Nursing home residents were subjected to any one of three conditions aim ed at restraint reduction , including adherence to the m and ate of the Omnibus Budget Reconciliation Act of 1987 ( OBRA ' 87 ) , staff education , and education with consultation from a gerontological clinical nurse specialist . Resident characteristics including dependency , health status , mental status , depression , behavior , fall risk ; presence of treatment devices and institutional factors were determined . RESULTS Physical dependency , lower cognitive status , behavior , presence of treatment devices , presence of psychiatric disorders , fall risk , and fall risk as staff rationale for restraint were associated ( P < .10 ) with continued restraint use . Nursing hours , staff mix , prevalence of restraint use by unit , and site were also associated ( P < .10 ) with continued use of physical restraints . Following bivariate analysis , associated resident characteristics were subjected to logistic regression . Lower cognitive status ( OR = 2.4 ( for every 7-point decrease in MMSE ) , 95 % CI , 1.7 , 3.3 ) and fall risk as staff rationale for restraint ( OR = 3.5 , 95 % CI . , 1.5 , 8.0 ) were predictive of continued restraint use . Adding nursing hours , staff mix , and prevalence of restraint use by unit to the logistic regression model was not statistically significant ( partial chi-square = 2.79 , df = 6 , P = .834 ) . Nursing home site was added to the model without changing the significance ( P < .05 ) of cognitive status or fall risk as a staff rationale for restraint use . CONCLUSION Continued restraint use in nursing home residents in this study most often occurred with severe cognitive impairment and /or when fall risk was considered by staff as a rationale for restraint . Efforts to reduce or eliminate physical restraint use with these groups will require greater efforts to educate staff in the assessment and analysis of fall risk , along with targeted interventions , particularly when cognition is also impaired BACKGROUND A recent question naire showed that different kinds of constraint such as physical restraint , electronic surveillance , use of force or pressure in medical treatment and in activities of daily living ( ADL ) are frequently used in Norwegian nursing homes . The study did not include information at patient level , and except for studies about physical restraints , we have not found any studies reporting the prevalence of various forms of constraint . AIM To describe the prevalence of various types of constraint in Norwegian nursing homes . MATERIAL S AND METHOD A structured interview was carried out with the primary carers of a r and om sample of 1501 patients from 222 nursing-home wards in 54 municipalities representing all five health regions in Norway . Data were collected from regular units ( RUs ) and special care units ( SCUs ) for persons with dementia . Episodes of constraint during 1 week were recorded . Five main groups of constraint were aggregated , mechanical restraint , nonmechanical restraint , electronic surveillance , force or pressure in medical examination or treatment and force or pressure in ADL . RESULTS Patients ( 36.7 % ) in RUs and 45.0 % of the patients in SCUs were subjected to any constraint . Most frequent was use of mechanical restraint ( 23.3 % in RUs ; 12.8 % in SCUs ) and use of force or pressure in ADL ( 20.9 % in SCUs ; 16.6 % in RUs ) . Use of force or pressure in medical examination or treatment was more frequent used in SCUs ( 19.1 % ) compared with RUs ( 13.5 % ) . Nonmechanical restraint was less frequently used ( 8.3 % in SCUs ; 3.0 % in RUs ) and electronic surveillance was seldom used ( 7.2 % in RUs ; 0.9 % in SCUs ) . CONCLUSION The use of constraint is a problem in Norwegian nursing homes . Studies are needed to learn more about why constraint is used , and if there is patient or ward characteristics that can explain the use of constraint OBJECTIVES To evaluate the effects of a restraint minimization education program on staff knowledge and attitudes and use of physical restraints . DESIGN Cluster-r and omized controlled trial with nursing units as the basis for r and omization . SETTING Forty group dwelling units for people with dementia . PARTICIPANTS At baseline , there were 184 staff and 191 residents in the intervention group and 162 staff and 162 residents in the control group . At the 6-month follow-up , there were 156 staff and 185 residents ( 36 newly admitted ) in the intervention group and 133 staff and 165 residents ( 26 newly admitted ) in the control group . INTERVENTION A 6-month education program for all nursing staff . MEASUREMENTS Staff knowledge and attitudes and physical restraint use were measured before and after the education program . RESULTS In the intervention group , staff knowledge about and attitudes toward restraint use changed , and the overall use of physical restraints decreased . A comparison including only residents present during the whole study period showed that the level of use was similar between the groups at baseline , whereas it was significantly lower in the intervention group at follow-up . Adjusted analyses showed that the odds of being restrained at follow-up were lower in the intervention group than in the control group . There was no significant change in the number of falls or use of psychoactive medication . CONCLUSION The results indicate that staff education can increase knowledge , change attitudes , and reduce the use of physical restraints without any change in the incidence of falls or use of psychoactive drugs BACKGROUND Approximately 80 % of nursing home residents who suffer from Alzheimer 's disease and related dementia develop behavioral symptoms of dementia . Given the deleterious side effects of pharmacologic therapy in this population there is an urgent need for clinical trials of nonpharmacologic interventions . OBJECTIVE To examine the effect of therapeutic touch on the frequency and intensity of behavioral symptoms of dementia . METHOD A r and omized , double-blind , three-group experimental study : experimental ( therapeutic touch ) , placebo ( placebo therapeutic touch ) , and control ( usual care ) . Fifty-seven residents , aged 67 to 93 years , exhibiting behavioral symptoms of dementia , were r and omized to one of the three groups within each of three Special Care Units within three Long-Term Care facilities in a western Canadian province . Behavioral observation was completed every 20 minutes from 8:00AM to 6:00PM for three days pre-intervention and for three days post-intervention by trained observers who were blind to group assignment . The intervention consisted of therapeutic touch given twice daily for 5 - 7 minutes for three days between 10:00AM and 11:30PM and between 3:00PM and 4:30PM ( N = 57 ) . The main outcome variable was overall behavioral symptoms of dementia , consisting of six categories of behaviors : manual manipulation ( restlessness ) , escape restraints , search ing and w and ering , tapping and banging , pacing and walking , and vocalization . RESULTS Analysis of variance ( ANOVA ) ( F = 3.331 , P = .033 ) and the Kruskal-Wallis test ( chi2 = 6.661 , P = .036 ) indicated a significant difference in overall behavioral symptoms of dementia , manual manipulation and vocalization when the experimental group was compared to the placebo and control groups . The experimental ( significant ) was more effective in decreasing behavioral symptoms of dementia than usual care , while the placebo group indicated a decreasing trend in behavioral symptoms of dementia compared to usual care . CONCLUSIONS Therapeutic touch offers a nonpharmacological , clinical ly relevant modality that could be used to decrease behavioral symptoms of dementia , specifically manual manipulation ( restlessness ) and vocalization , two prevalent behaviors OBJECTIVES This study was design ed to examine the impact of the Family Visit Education Program ( FVEP ) on family members , nursing staff , and nursing home residents with dementia . DESIGN The study employed a 2 x 3 single-blind , r and omized control group design with two study conditions , FVEP or usual care ( UC ) , and three times of measurement , baseline , 3-months , and 6-months . SETTING The study was conducted in five skilled-care nursing homes that ranged in size from 120 to 300 beds . PARTICIPANTS Sixty-six residents with dementia and their primary visitor were r and omly assigned to FVEP ( n = 32 ) or UC ( n = 34 ) . MEASUREMENTS Residents were assessed for ( 1 ) psychosocial functioning , ( 2 ) depression , ( 3 ) agitated behavior , and ( 4 ) degree of positive social interaction . Nursing staff were assessed for changes in the time and methods used to manage problem behaviors . Visitors were assessed for ( 1 ) dementia management skills , ( 2 ) extent of perceived caregiving hassles , and ( 3 ) visit satisfaction . RESULTS FVEP was effective for reducing residents ' problem behaviors and for decreasing their symptoms of depression and irritability . It was also effective for improving the way family members and other visitors communicated with residents , but , with the exception of reducing the use of mechanical restraints , it was not effective in changing nurses ' management of residents ' behavior problems . CONCLUSIONS It is possible to educate family members to communicate and interact more effectively with nursing home residents with dementia . This has beneficial effects on residents but not on nursing staff 's management of problem behaviors OBJECTIVE To investigate the relative effects of two experimental interventions on the use of physical restraints . DESIGN Prospect i ve 12-month clinical trial in which three nursing homes were r and omly assigned to restraint education ( RE ) , restraint education-with-consultation ( REC ) , or control ( C ) . SETTING Three voluntary nursing homes in the Philadelphia area providing both skilled and intermediate care . PARTICIPANTS A total of 643 nursing home residents over the age of 60 were enrolled at baseline , and 463 remained to completion ( 1 year ) . INTERVENTIONS Both RE and REC homes received intensive education by a masters-prepared gerontologic nurse to increase staff awareness of restraint hazards and knowledge about assessing and managing resident behaviors likely to lead to use of restraints . In addition , the REC home received 12 hours per week of unit-based nursing consultation to facilitate restraint reduction in residents with more complex conditions . MEASUREMENTS Restraint status was observed systematic ally at baseline , immediately after the 6-month intervention , and again at 9 and 12 months . Staff levels , psychoactive drug use , and injuries were also determined . RESULTS Compared with baseline , the REC home had a statistically significant reduction in restraint prevalence , whereas RE and C homes did not . At 9 months ( 3 months post-intervention ) , absolute decline in the percents restrained were 7 % RE , 7 % C , and 20 % REC ; at 12 months ( 6 months post-intervention ) declines were 4 % RE , 6 % C , and 18 % REC . However , relative to baseline , these declines represent an average reduction in restraint use of 23 % RE , 11 % C , and 56 % REC . The differences in changes over time were consistently significant ( P = .01 ) , whether considering survivors or those present at each time point , and also when controlling for differences between groups at baseline . Further , given any change in restraint use , REC-residents were between 25 % and 40 % more likely than either RE or C residents to experience decreased restraint use . Results were achieved without increased staff , psychoactive drugs , or serious fall-related injuries . CONCLUSION A 6-month-long educational program combined with unit-based , resident-centered consultation can reduce use of physical restraints in nursing homes effectively and safely . Whether extending the intervention will achieve greater reduction is not known from these results BACKGROUND The prevalence of psychological and behavioral disturbances among older adults living in residential care facilities is high , and it has been shown previously that people with such symptoms have poorer health outcomes . This study was design ed to assess the efficacy of an early psychiatric intervention on the 12-month health outcomes of older adults admitted to residential care facilities in Perth , Western Australia . We hypothesized that subjects in the intervention group would have better mental and physical health outcomes than controls . METHODS The study was design ed as a r and omized , single-blinded , controlled trial . All subjects aged 65 years or over admitted to one of the 22/26 participating residential care facilities of the Inner City area of Perth were approached to join the study and were allocated r and omly to the intervention or usual care group . Demographic and clinical information ( including medications and use of physical restraint ) was gathered systematic ally from all participants at baseline , and at 6 and 12 months . At each assessment , the Geriatric Depression Scale ( GDS ) , the Health of the Nation Outcome Scales for older adults ( HoNOS 65 + ) , the Mini-mental State Examination ( MMSE ) and the Neuropsychiatric Inventory ( NPI ) were administered . Subjects in the intervention group who screened positive at the baseline assessment for psychiatric morbidity were review ed within a 2-week period by the Inner City Mental Health Service of Older Adults ( ICMHSOA ) . If clinical ly appropriate , mental health services were introduced without the involvement of the research team . RESULTS One hundred and six subjects and their next of kin consented to participate in the study ( 53 in each group ) . Mental health screening and early referral to a psychogeriatric service did not significantly change the average number of medical contacts , self-rated health , use of psychotropic or PRN medication , use of physical restraint , 12-month mortality , or mental health outcomes , as measured by the GDS-15 , HoNOS 65 + and NPI ( p > 0.05 for all relevant outcomes ) . CONCLUSION Systematic mental health screening of older adults admitted to residential care facilities and early clinical intervention does not change 12-month health outcomes . More effective interventions to improve the health outcomes of older adults with psychological and behavioral disturbances admitted to residential care facilities are needed PURPOSE The purpose s of this study were to develop an educational program to reduce the use of physical restraints for caregivers in geriatric hospitals and to evaluate the effects of the program on caregivers ' knowledge , attitude and nursing practice related to the use of physical restraints . METHODS A quasi experimental study with a non-equivalent control group pretest-posttest design was used . Participants were recruited from two geriatric hospitals . Eighteen caregivers were assigned to the experimental group and 20 to the control group . The data were collected prior to the intervention and at 6 weeks after the intervention through the use of self-administered question naires . Descriptive statistics , X(2 ) test , Fisher 's exact probability test , and Mann-Whitney U test were used to analyze the data . RESULTS After the intervention , knowledge about physical restraints increased significantly in experimental group compared to the control group . However , there were no statistically significant differences between the groups for attitude and nursing practice involving physical restraints . CONCLUSION Findings indicate that it is necessary to apply knowledge acquired through educational programs to nursing practice to reduce the use of physical restraints . User friendly guidelines for physical restraints , administrative support of institutions , and multidisciplinary approaches are required to achieve this goal Design ing safe , appropriate , and nonmanpower-dependent alternatives to the physical restraint of confused and agitated patients is a significant nursing problem . An environmental intervention is proposed to reduce restraint use , improve patient outcomes , and use nursing re sources more effectively OBJECTIVES To describe the changes in psychoactive drug use in nursing homes after implementation of physical restraint reduction interventions and m and ates of the Omnibus Budget Reconciliation Act of 1987 ( OBRA ' 87 ) . METHODS A secondary analysis was conducted using data from a controlled clinical trial that took place in three nursing homes : a control home , one that received an educational intervention , and one that received an educational/consultation intervention . All three homes were influenced by the OBRA m and ates . Complete pre- and 6 months ' post-intervention data on use of psychoactive drugs and physical restraints were available for 446 resident subjects . Changes were first analyzed with the resident subjects as the unit of analysis and then using the nursing home ward ( n = 16 ) as the unit of analysis . RESULTS While physical restraint use declined in the home that received the educational/consultation intervention , neither neuroleptic nor benzodiazepine use increased in any of the homes after the interventions . The percentage of residents taking neuroleptics declined in the control home ( 18.6 % to 11.3 % , P = .014 ) . Benzodiazepine use , which was more prevalent than described previously in the literature , declined in all three homes ( P < .001 ) . Of those residents whose physical restraints were discontinued , only 2 % were started on neuroleptics . When the effect of OBRA m and ates on appropriateness of neuroleptic use was examined , the percentage of residents on neuroleptics who lacked an OBRA-approved indication declined from 21.3 % to 14.6 % in the total sample , and from 39.9 % to 8 % in the control home . CONCLUSIONS Interventions to reduce physical restraint did not lead to an increase in psychoactive drug use ; further , reduction in both can occur simultaneously . OBRA m and ates regarding psychoactive drug use were not uniformly effective , but appear , at minimum , to have increased awareness of the indications for neuroleptics BACKGROUND Although there is an urgent need for restraint-free care , the number of r and omized clinical trials on preventing or reducing physical restraints has been limited . OBJECTIVES To investigate the effectiveness of an educational intervention to prevent the use of physical restraints on residents newly admitted to psycho-geriatric nursing home wards . DESIGN Cluster-r and omized trial . SETTING Fourteen Dutch psycho-geriatric nursing home wards . PARTICIPANTS 138 residents admitted to 14 psycho-geriatric nursing home wards after baseline measurement of the trial were selected , out of which 33 residents died or informed consent had not been obtained . A total of 105 residents were included in the analyses . METHODS The nursing home wards were r and omly assigned to either educational intervention or control status . The educational intervention consisted of an educational programme for nurses combined with a nurse specialist 's consultation . The data were collected at 1 , 4 and 8 months post-intervention . The use of physical restraints was measured by blinded , trained observers on four separate occasions over a 24-h period . The Minimum Data Set was used to determine residents ' characteristics , such as their cognitive status . RESULTS During the study period , no statistically significant differences between the experimental group and the control group regarding restraint status , restraint intensity , multiple restraints and types of restraints were found . One month post-intervention , 38 % of the residents newly admitted to the experimental wards were restrained . Bilateral bedrails were the most frequently used restraints at Post-test 1 ( 24 % ) , Post-test 2 ( 23 % ) and Post-test 3 ( 28 % ) , followed by the use of infrared systems at Post-tests 2 and 3 . CONCLUSION An educational programme combined with the consultation of a nurse specialist does not prevent the use of physical restraints on residents newly admitted to psycho-geriatric nursing home wards . Although other studies have shown promising results with the effectiveness of these types of intervention on restraint reduction , the development of additional interventions to prevent restraint usage is recommended OBJECTIVE To evaluate a management system design ed to improve staff adherence to a federal regulation that stated restrained residents should be released , exercised , and repositioned every 2 hours . DESIGN A delayed intervention , controlled , cross-over design with three phases . During phase one , baseline , the length of intervals that residents remained in restraints was monitored . The intervention was implemented at site A in Phase two while site B remained in baseline . During Phase three , the intervention was replicated at site B. SETTING Two long-term care proprietary nursing facilities . PATIENTS Sixty-three physically restrained residents in the two facilities . INTERVENTION The intervention was a system of restraint release using colored pads corresponding to specific hours . The management rule was that the resident should be on a different colored pad every 2 hours . Staff had to lift residents to place the pad , and the colors made the system easy for supervisors to check . MAIN OUTCOME MEASURES Checks by research personnel by black light and invisible ink , to detect movement of the knot tying the restraints . RESULTS During the baseline phase , the majority of residents at both sites were inappropriately restrained longer than 2 hours ( site A : 54.1 % ; site B : 60.1 % ) . The percentage of residents restrained over 2 hours was significantly reduced during the intervention phase to 13.9 % ( site A ) and 19.4 % ( site B ) . Three weeks after the end of the intervention , inappropriate use of restraints remained low , 14.2 % , but rose to 47.7 % after another 3 weeks . CONCLUSION The management system is an effective way to increase the consistency with which nursing-home staff release and reposition restrained residents AIMS AND OBJECTIVES To investigate ( 1 ) the prevalence of physical restraints and psychoactive medication , ( 2 ) newly administered physical restraints , frequency of application of the devices and frequency of psychoactive medication on dem and during 12-month follow-up and ( 3 ) characteristics associated with restraint use in nursing homes . BACKGROUND High quality data on restraint use in German nursing homes are lacking so far . Such information is the basis for interventions to achieve a restraint-free care . DESIGN Cross-sectional study and prospect i ve cohort study . SETTING AND SUBJECTS Thirty nursing homes with 2367 residents in Hamburg , Germany . METHODS External investigators obtained prevalence of physical restraints by direct observation on three occasions on one day , psychoactive drugs were extracted from residents ' records and prospect i ve data were documented by nurses . RESULTS Residents ' mean age was 86 years , 81 % were female . Prevalence of residents with at least one physical restraint was 26.2 % [ 95 % confidence interval ( CI ) 21.3 - 31.1 ] . Centre prevalence ranged from 4.4 to 58.9 % . Bedrails were most often used ( in 24.5 % of residents ) , fixed tables , belts and other restraints were rare . Prevalence of residents with at least one psychoactive drug was 52.4 % ( 95 % CI 48.7 - 56.1 ) . The proportion of residents with at least one physical restraint after the first observation week of 26.3 % ( 21.3 - 31.3 ) cumulated to 39.5 % ( 33.3 - 45.7 ) at the end of follow-up ( 10.4 SD 3.3 months ) . The relative frequency of observation days with at least one device ranged from 4.9 - 64.8 % between centres . No characteristic was found to explain centre differences . CONCLUSIONS The frequency of physical restraints and psychoactive drugs in German nursing homes is substantial . Pronounced centre variation suggests that st and ard care is possible without restraints . RELEVANCE TO CLINICAL PRACTICE Effective restraint minimisation approaches are urgently warranted . An evidence -based guideline may overcome centre differences towards a restraint-free nursing home care INTRODUCTION Agitation is common in dementia and is associated with use of restraints and use of psychotropic drugs . The aim of this study was to determine whether an education and supervision intervention could reduce agitation and the use of restraints and antipsychotic drugs in nursing homes . METHOD Four Norwegian nursing homes were r and omly allocated to receive either treatment as usual or an intervention consisting of a 2-day educational seminar and monthly group guidance for 6 months . One hundred forty-five residents with dementia ( based on medical records and corroborated with a Functional Assessment Staging score > or= 4 ) completed baseline and 6-month intervention assessment s and were included in the analyses . The co- primary outcome measures were the proportion of residents subject to interactional restraint and the severity of agitation using the Cohen-Mansfield Agitation Inventory ( CMAI ) . Patients were assessed at baseline , immediately after completion of the intervention at 6 months , and 12 months after baseline . Comparison of change in the 2 groups was made using repeated- measures analysis of variance ( CMAI ) and Mann-Whitney test ( restraints ) . The study was conducted from 2003 to 2004 . RESULTS The proportion of residents starting new restraint was lower in the intervention than in the control group at 6-month evaluation ( P = .02 ) , but no statistically significant differences were found at 12-month assessment ( P = .57 ) . The total CMAI score declined from baseline to 6 and 12 months ' follow-up in the intervention homes compared to a small increase in the control homes ( F2,176 = 3.46 , P = .034 ) . There were no statistically significant differences in use of antipsychotic drugs . CONCLUSIONS A brief 2-day staff education program followed by continued monthly guidance was able both to improve quality of care by reducing the frequency of interactional restraints and to reduce severity of agitation BACKGROUND Use of restraint amongst institutionalised elderly with dementia and problem behaviour not only remains widespread , but also appears to be accepted as inevitable . OBJECTIVE The aim of this study was to reduce problem behaviour and the use of restraint in demented patients using a staff training program as intervention . METHODS The study was a r and omised single-blind controlled trial and took place in Stavanger , Norway . Four nursing homes were r and omised to a control or an intervention group after stratification for size . The intervention consisted of a full day seminar , followed by a one-hour session of guidance per month over six months . The content of the educational program focused on the decision making process in the use of restraint and alternatives to restraint consistent with professional practice and quality care . The primary outcome measures were number of restraints per patient in the nursing homes in one week and agitation as measured with the Brief Agitation Rating Scale ( BARS ) . These were rated before and immediately after the intervention was completed . The assessment s were performed blind to design and r and omisation group . RESULTS Clinical and demographic variables did not differ between the intervention and control groups at baseline . After the intervention period , the number of restraints had declined by 54 % in the treatment group , and increased by 18 % in the control group . The difference between the two groups was statistically significant ( p = 0.013 ) . There was a trend towards higher BARS score in the intervention compared to the control group at follow up ( p = 0.052 ) . CONCLUSION Although the level of agitated behaviour remained unchanged or increased slightly , the educational program led to a significant reduction of the use of restraint in institutionalised elderly with dementia . These results suggest that educational programs can improve the quality of care of people with dementia R and omised controlled trials are widely accepted as the most reliable method of determining effectiveness , but most trials have evaluated the effects of a single intervention such as a drug . Recognition is increasing that other , non-pharmacological interventions should also be rigorously evaluated.1 - 3 This paper examines the design and execution of research required to address the additional problems result ing from evaluation of complex interventions —that is , those “ made up of various interconnecting parts.”4 The issues dealt with are discussed in a longer Medical Research Council paper ( www.mrc.ac.uk/complex_packages.html ) . We focus on r and omised trials but believe that this approach could be adapted to other design s when they are more appropriate . # # # # Summary points Complex interventions are those that include several components The evaluation of complex interventions is difficult because of problems of developing , identifying , documenting , and reproducing the intervention A phased approach to the development and evaluation of complex interventions is proposed to help research ers define clearly where they are in the research process Evaluation of complex interventions requires use of qualitative and quantitative evidence There are specific difficulties in defining , developing , documenting , and reproducing complex interventions that are subject to more variation than a drug . A typical example would be the design of a trial to evaluate the benefits of specialist stroke units . Such a trial would have to consider the expertise of various health professionals as well as investigations , drugs , treatment guidelines , and arrangements for discharge and follow up . Stroke units may also vary in terms of organisation , management , and skill mix . The active components of the stroke unit may be difficult to specify , making it difficult to replicate the intervention . The box gives other examples of complex interventions . # # # # Examples of complex interventions Service delivery and organisation : Stroke units Hospital at home Interventions directed at health professionals ' behaviour : Strategies for implementing guidelines Computerised decision support Community interventions : Community OBJECTIVES To gain more knowledge of the application of physical restraints to restrict , restrain , or prevent movement by elderly people living at home . DESIGN Survey . SETTING Nursing staff in Dutch home care . PARTICIPANTS One hundred fifty-seven nursing staff in home care ( registered nurses and certified nursing assistants ) from a r and omly selected and nationally representative panel returned the question naire ( response rate 72 % ) . MEASUREMENTS A structured question naire on the use of physical restraints . RESULTS Four of every five nursing staff members have applied physical restraints . The use of bed rails , putting the client in a deep chair or using a chair with a table , and locking doors to prevent w and ering were most frequently applied , often at the request of the client or his or her family . Protection of the client is the reason most frequently given for these actions . Almost all respondents ( 94 % ) know of no alternatives , nor does consensus exist on what is considered to be a physical restraint . CONCLUSION Guidelines are necessary regarding the course of action to be taken when a client is in danger of hurting him- or herself . Further education on and due consideration of the use of physical restraints in home care are also required |
13,249 | 24,523,233 | The direction of results was confirmed by subgroup analyses for topiramate and partially for gabapentin and valproate . | BACKGROUND Alcohol dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications .
Besides psychosocial interventions , different pharmacological interventions have been or currently are under investigation through Cochrane systematic review s. OBJECTIVES The primary aim of the review is to assess the benefits /risks of anticonvulsants for the treatment of alcohol dependence . | CONTEXT Hypothetically , topiramate can improve drinking outcomes among alcohol-dependent individuals by reducing alcohol 's reinforcing effects through facilitation of gamma-aminobutyric acid function and inhibition of glutaminergic pathways in the corticomesolimbic system . OBJECTIVE To determine if topiramate is a safe and efficacious treatment for alcohol dependence . DESIGN , SETTING , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled , 14-week trial of 371 men and women aged 18 to 65 years diagnosed with alcohol dependence , conducted between January 27 , 2004 , and August 4 , 2006 , at 17 US sites . INTERVENTIONS Up to 300 mg/d of topiramate ( n = 183 ) or placebo ( n = 188 ) , along with a weekly compliance enhancement intervention . MAIN OUTCOME MEASURES Primary efficacy variable was self-reported percentage of heavy drinking days . Secondary outcomes included other self-reported drinking measures ( percentage of days abstinent and drinks per drinking day ) along with the laboratory measure of alcohol consumption ( plasma gamma-glutamyltransferase ) . RESULTS Treating all dropouts as relapse to baseline , topiramate was more efficacious than placebo at reducing the percentage of heavy drinking days from baseline to week 14 ( mean difference , 8.44 % ; 95 % confidence interval , 3.07%-13.80 % ; P = .002 ) . Prespecified mixed-model analysis also showed that topiramate compared with placebo decreased the percentage of heavy drinking days ( mean difference , 16.19 % ; 95 % confidence interval , 10.79%-21.60 % ; P < .001 ) and all other drinking outcomes ( P < .001 for all comparisons ) . Adverse events that were more common with topiramate vs placebo , respectively , included paresthesia ( 50.8 % vs 10.6 % ) , taste perversion ( 23.0 % vs 4.8 % ) , anorexia ( 19.7 % vs 6.9 % ) , and difficulty with concentration ( 14.8 % vs 3.2 % ) . CONCLUSION Topiramate is a promising treatment for alcohol dependence . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00210925 BACKGROUND Initiation of a relapse prevention medication is crucial at the end of alcohol detoxification . This study aim ed to examine the efficacy and safety of topiramate for alcoholism in patients receiving a residential treatment program of alcohol detoxification and post-acute treatment . METHODS This was a 12-week , r and omized , double-blind , placebo-controlled trial of topiramate for alcoholism in patients receiving a residential treatment program . Individuals with DSM-IV alcohol dependence with minimal withdrawal were enrolled . Participants were r and omly assigned to receive either 100 - 300 mg/day of topiramate or placebo . Primary outcomes were given as percentages of heavy drinking days and time to first day of heavy drinking . Other drinking outcomes , craving , and health-related quality of life were evaluated . RESULTS A total of 106 participants were r and omized to receive topiramate ( n=53 ) or placebo ( n=53 ) . Twenty-eight participants of the topiramate group ( 52.8 % ) and 25 participants of the placebo group ( 47.2 % ) completed the study . Averaged over the trial period , there was no significant difference between groups on the mean percentages of heavy drinking days [ 1.96 ( -1.62 to 5.54 ) , p=.28 ] . Log rank survival analysis found no difference of time to first day of heavy drinking between topiramate and placebo groups ( 61.8 vs. 57.5 days , respectively ; χ(2)=0.61 , d.f.=1 , p=.81 ) . Other secondary outcomes were not significantly different between groups . CONCLUSIONS By using a conservative model for data analysis , we could not detect the effectiveness of topiramate in this particular population . As the sensitivity analysis showed a trend of its benefit , further studies in larger sample sizes are still warranted BACKGROUND Topiramate , a sulphamate fructopyranose derivative , might antagonise alcohol 's rewarding effects associated with abuse liability by inhibiting mesocorticolimbic dopamine release via the contemporaneous facilitation of gamma-amino-butyric acid activity and inhibition of glutamate function . We aim ed to see whether topiramate was more effective than placebo as a treatment for alcohol dependence . METHODS We did a double-blind r and omised controlled 12-week clinical trial comparing oral topiramate and placebo for treatment of 150 individuals with alcohol dependence . Of these 150 individuals , 75 were assigned to receive topiramate ( escalating dose of 25 - 300 mg per day ) and 75 had placebo as an adjunct to weekly st and ardised medication compliance management . Primary efficacy variables were : self-reported drinking ( drinks per day , drinks per drinking day , percentage of heavy drinking days , percentage of days abstinent ) and plasma gamma-glutamyl transferase , an objective index of alcohol consumption . The secondary efficacy variable was self-reported craving . FINDINGS At study end , participants on topiramate , compared with those on placebo , had 2.88 ( 95 % CI -4.50 to -1.27 ) fewer drinks per day ( p=0.0006 ) , 3.10 ( -4.88 to -1.31 ) fewer drinks per drinking day ( p=0.0009 ) , 27.6 % fewer heavy drinking days ( p=0.0003 ) , 26.2 % more days abstinent ( p=0.0003 ) , and a log plasma gamma-glutamyl transferase ratio of 0.07 ( -0.11 to -0.02 ) less ( p=0.0046 ) . Topiramate-induced differences in craving were also significantly greater than those of placebo , of similar magnitude to the self-reported drinking changes , and highly correlated with them . INTERPRETATION Topiramate ( up to 300 mg per day ) is more efficacious than placebo as an adjunct to st and ardised medication compliance management in treatment of alcohol dependence CONTEXT The Consoli date d St and ards for Reporting of Trials ( CONSORT ) statement was developed to help improve the quality of reports of r and omized controlled trials ( RCTs ) . To date , a paucity of data exists regarding whether it has achieved this goal . OBJECTIVE To determine whether use of the CONSORT statement is associated with improvement in the quality of reports of RCTs . DESIGN AND SETTING Comparative before- and -after evaluation in which reports of RCTs published in 1994 ( pre-CONSORT ) were compared with RCT reports from the same journals published in 1998 ( post-CONSORT ) . We included 211 reports from BMJ , JAMA , and The Lancet ( journals that adopted CONSORT ) as well as The New Engl and Journal of Medicine ( a journal that did not adopt CONSORT and was used as a comparator ) . MAIN OUTCOME MEASURES Number of CONSORT items included in a report , frequency of unclear reporting of allocation concealment , and overall trial quality score based on the Jadad scale , a 5-point quality assessment instrument . RESULTS Compared with 1994 , the number of CONSORT checklist items in reports of RCTs increased in all 4 journals in 1998 , and this increase was statistically significant for the 3 adopter journals ( pre-CONSORT , 23.4 ; mean change , 3.7 ; 95 % confidence interval [ CI ] , 2.1 - 5.3 ) . The frequency of unclear reporting of allocation concealment decreased for each of the 4 journals , and this change was statistically significant for adopters ( pre-CONSORT , 61 % ; mean change , -22 % ; 95 % CI , -38 % to -6 % ) . Similarly , 3 of the 4 journals showed an improvement in the quality score for reports of RCTs , and this increase was statistically significant for adopter journals overall ( pre-CONSORT , 2.7 ; mean change , 0.4 ; 95 % CI , 0.1 - 0.8 ) . CONCLUSION Use of the CONSORT statement is associated with improvements in the quality of reports of RCTs BACKGROUND More than half of all individuals with bipolar disorder have a substance abuse problem at some point in their lifetime . Patients with comorbid substance abuse disorders often are excluded from clinical trials . Thus , treatments targeting this high-risk clinical population are lacking . OBJECTIVE To evaluate the efficacy of divalproex sodium ( hereafter referred to as valproate ) in decreasing alcohol use and stabilizing mood symptoms in acutely ill patients with bipolar disorder and alcoholism . DESIGN A 24-week , double-blind , placebo-controlled , r and omized parallel-group trial . SETTING A university hospital serving as a primary catchment-area hospital and tertiary-care facility . PARTICIPANTS Fifty-nine subjects with diagnoses of bipolar I disorder and alcohol dependence . Intervention All study subjects received treatment as usual , including lithium carbonate and psychosocial interventions , and were r and omized to receive valproate or placebo . MAIN OUTCOME MEASURES Primary alcohol use outcomes included changes in alcohol use as indicated by changes in proportion of heavy drinking days and number of drinks per heavy drinking day . Other alcohol use outcomes included proportion of any drinking days , number of drinks per drinking day , and relapse to sustained heavy drinking . Mood outcomes included changes in depressive and manic symptoms . We used the mixed model to analyze longitudinal data . The first model used time of assessment , bipolar subtype ( mixed , manic , or depressed ) , and treatment group ( placebo or valproate ) as covariates . The second nested model included the additional covariate of medication adherence . RESULTS The valproate group had a significantly lower proportion of heavy drinking days ( P = .02 ) and a trend toward fewer drinks per heavy drinking day ( P = .055 ) than the placebo group . When medication adherence was added as covariate , the valproate group had significantly fewer drinks per heavy drinking day ( P = .02 ) and fewer drinks per drinking day ( P = .02 ) . Higher valproate serum concentration significantly correlated with improved alcohol use outcomes . Manic and depressive symptoms improved equally in both groups . Level of gamma-glutamyl transpeptidase was significantly higher in the placebo group compared with the valproate group . CONCLUSIONS Valproate therapy decreases heavy drinking in patients with comorbid bipolar disorder and alcohol dependence . The results of this study indicate the potential clinical utility of the anticonvulsant mood stabilizer , valproate , in bipolar disorder with co-occurring alcohol dependence Although drinking urges and cravings are commonly reported by alcoholics , prospect i ve studies have found inconsistent associations between such urges and drinking relapses . Previous studies have measured drinking urges by use of single-item ratings of alcohol craving or other measures of unknown reliability and validity . To permit improved evaluation of hypotheses regarding alcohol craving , a 49-item question naire that reflects several urge-related domains was developed and pretested . Items assessed subjects ' desire for a drink , expectations of positive effects following drinking , relief of withdrawal and negative affect following drinking , and intention to drink . Exploratory and confirmatory factor analyses of the responses of 351 abstinent , treatment-seeking alcoholics indicated that alcohol urges are best described by a single factor . Based on these analyses , an internally consistent , reliable , and psychometrically valid 8-item scale , the Alcohol Urge Question naire ( AUQ ) , was developed . Data indicated that AUQ scores were strongly related to alcohol dependence severity and to cognitive preoccupation with alcohol , and that they declined with prolonged abstinence . The AUQ may be useful in alcoholism treatment research and in laboratory studies of reactivity to alcohol or other manipulations Pregabalin ( PRE ) acts as a presynaptic inhibitor of the release of excessive levels of excitatory neurotransmitters by selectively binding to the α2-δ subunit of voltage-gated calcium channels . In this r and omised , double-blind comparison trial with naltrexone ( NAL ) , we aim ed to investigate the efficacy of PRE on alcohol drinking indices . Craving reduction and improvement of psychiatric symptoms were the secondary endpoints . Seventy-one alcohol-dependent subjects were detoxified and subsequently r and omised into two groups , receiving 50 mg of NAL or 150—450 mg of PRE . Craving ( VAS ; OCDS ) , withdrawal ( CIWA-Ar ) and psychiatric symptoms ( SCL-90-R ) rating scales were applied . Alcohol drinking indices and craving scores were not significantly different between groups . Compared with NAL , PRE result ed in greater improvement of specific symptoms in the areas of anxiety , hostility and psychoticism , and survival function ( duration of abstinence from alcohol ) . PRE also result ed in better outcome in patients reporting a comorbid psychiatric disorder . Results from this study globally place PRE within the same range of efficacy as that of NAL . The mechanism involved in the efficacy of PRE in relapse prevention could be less related to alcohol craving and more associated with the treatment of the comorbid psychiatric symptomatology CONTEXT Alcohol dependence treatment may include medications , behavioral therapies , or both . It is unknown how combining these treatments may impact their effectiveness , especially in the context of primary care and other nonspecialty setting s. OBJECTIVES To evaluate the efficacy of medication , behavioral therapies , and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers ( median age , 44 years ) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , diagnoses of primary alcohol dependence . INTERVENTIONS Eight groups of patients received medical management with 16 weeks of naltrexone ( 100 mg/d ) or acamprosate ( 3 g/d ) , both , and /or both placebos , with or without a combined behavioral intervention ( CBI ) . A ninth group received CBI only ( no pills ) . Patients were also evaluated for up to 1 year after treatment . MAIN OUTCOME MEASURES Percent days abstinent from alcohol and time to first heavy drinking day . RESULTS All groups showed substantial reduction in drinking . During treatment , patients receiving naltrexone plus medical management ( n = 302 ) , CBI plus medical management and placebos ( n = 305 ) , or both naltrexone and CBI plus medical management ( n = 309 ) had higher percent days abstinent ( 80.6 , 79.2 , and 77.1 , respectively ) than the 75.1 in those receiving placebos and medical management only ( n = 305 ) , a significant naltrexone x behavioral intervention interaction ( P = .009 ) . Naltrexone also reduced risk of a heavy drinking day ( hazard ratio , 0.72 ; 97.5 % CI , 0.53 - 0.98 ; P = .02 ) over time , most evident in those receiving medical management but not CBI . Acamprosate showed no significant effect on drinking vs placebo , either by itself or with any combination of naltrexone , CBI , or both . During treatment , those receiving CBI without pills or medical management ( n = 157 ) had lower percent days abstinent ( 66.6 ) than those receiving placebo plus medical management alone ( n = 153 ) or placebo plus medical management and CBI ( n = 156 ) ( 73.8 and 79.8 , respectively ; P<.001 ) . One year after treatment , these between-group effects were similar but no longer significant . CONCLUSIONS Patients receiving medical management with naltrexone , CBI , or both fared better on drinking outcomes , whereas acamprosate showed no evidence of efficacy , with or without CBI . No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management . Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment . Naltrexone with medical management could be delivered in health care setting s , thus serving alcohol-dependent patients who might otherwise not receive treatment . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00006206 BACKGROUND Topiramate was recently reported to be efficacious in reducing drinking rates and craving among individuals with alcohol dependence in a r and omized controlled trial , but dose effects could not be determined . This laboratory study systematic ally examined the dose-dependent effects of topiramate on cue-elicited craving and other putative mechanisms of its pharmacotherapeutic effects on drinking . METHODS Male and female heavy drinkers ( n = 61 ) were r and omized to 1 of 3 medication conditions ( 200 mg/d ; 300 mg/d ; placebo ) in a double-blind study . Participants reached the target dose after a 32-day titration period , then were stabilized for approximately 1 week . All then participated in a laboratory assessment of alcohol cue reactivity and of the subjective effects of a moderate dose of alcohol . RESULTS Both doses of topiramate reduced the frequency of heavy drinking during the titration period as compared to placebo . However , topiramate did not affect self-reported craving for alcohol during the titration period , during the cue reactivity protocol , or in response to the alcohol challenge procedure . Topiramate reduced the stimulating effects of alcohol ingestion compared to placebo , but only in the 200 mg group . CONCLUSIONS The results of this study support previous findings that topiramate reduces drinking , but the behavioral mechanism underlying this effect does not appear to be attenuation of craving for alcohol as measured using the approaches employed in this study . Rather , the results tentatively suggest that topiramate may exert its beneficial effects by altering the subjective experiences of alcohol consumption . Limitations of the current study are discussed and complementary methods are recommended for future studies , such as the use of behavioral economic paradigms and ecological momentary assessment BACKGROUND Topiramate can improve drinking outcomes via a hypothesized mechanism of facilitating gamma-aminobutyric acid function and inhibiting glutaminergic pathways in the corticomesolimbic system . We sought to determine whether topiramate 's antidrinking effects are bolstered by improvements in physical and psychosocial well-being . METHODS In a 17-site , 14-week , double-blind , r and omized controlled trial , we compared the effects of topiramate ( up to 300 mg/d ) vs placebo on physical health , obsessional thoughts and compulsions about using alcohol , and psychosocial well-being among 371 alcohol-dependent subjects who received weekly adherence enhancement therapy . RESULTS Topiramate was more efficacious than placebo in reducing body mass index ( calculated as weight in kilograms divided by height in meters squared ) ( mean difference , 1.08 ; 95 % confidence interval [ CI ] , 0.81 - 1.34 ; P < .001 ) , all liver enzyme levels ( P < .01 for all comparisons ) , plasma cholesterol level ( mean difference , 13.30 mg/dL ; 95 % CI , 5.09 - 21.44 mg/dL ; P = .002 ) , and systolic ( mean difference , 9.70 mm Hg ; 95 % CI , 6.81 - 12.60 mm Hg ; P < .001 ) and diastolic ( mean difference , 6.74 mm Hg ; 95 % CI , 4.57 - 8.90 mm Hg ; P < .001 ) blood pressure to about prehypertension levels-effects that might lower the risk of fatty liver degeneration and cirrhosis as well as cardiovascular disease . Topiramate compared with placebo significantly ( P < .05 for all comparisons ) decreased obsessional thoughts and compulsions about using alcohol , increased subjects ' psychosocial well-being , and improved some aspects of quality of life , thereby diminishing the risk of relapse and longer-term negative outcomes . Paresthesia , taste perversion , anorexia , and difficulty with concentration were reported more frequently for topiramate than for placebo . CONCLUSION Topiramate appears to be generally effective at improving the drinking outcomes and physical and psychosocial well-being of alcoholic subjects BACKGROUND Subjective and objective measures of poor sleep in alcoholic insomniacs predict relapse to drinking . Nonalcoholic insomniacs underestimate their total sleep time ( TST ) and overestimate their sleep onset latency ( SOL ) and wake time after sleep onset ( WASO ) compared with polysomnography ( PSG ) . This study evaluated 3 hypotheses : ( 1 ) subjective SOL would predict frequency of future drinking ; ( 2 ) participants would overestimate SOL and WASO and underestimate TST ; and ( 3 ) higher amounts of over- and underestimates of sleep at baseline would predict worse drinking outcomes prospect ively . METHODS Participants ( N=18 ) , mean age 44.6 years ( + /-13.2 ) , underwent an adaptation night and then 2 nights of PSG 3 weeks apart . They also provided morning estimates of SOL , WASO , TST , and sleep efficiency ( SE ) . Following the baseline PSG , participants were followed over 12 weeks . A 2-way ANOVA ( night x method of measuring sleep ) compared results and regression analyses predicted drinking . Drinking outcomes were defined as number of days drinking ( DD ) and number of heavy-drinking days ( HDD ) during 2 consecutive 6-week follow-up periods . RESULTS Most participants ( 72 % ) overestimated SOL by a mean of 21.3 ( + /-36 ) minutes compared with PSG [ F(1 , 14)=7.1 , p<0.03 ] . Unexpectedly , 89 % underestimated WASO by a mean difference of 48.7 ( + /-49 ) minutes [ F(1 , 14)=15.6 , p<0.01 ] . Drinking during the first 6-week study period was predicted by both subjective estimates of WASO and their accuracy , whereas drinking during the second 6-week period was predicted by both subjective estimations of sleep and rapid eye movement sleep latency . CONCLUSION Greater subjective accuracy of wakefulness at night provided by the patient predicted drinking during the study . Unlike nonalcoholic insomniacs , this alcoholic sample significantly underestimated WASO compared with PSG values . The predictive ability of sleep parameters depended on the selected measure of drinking outcomes and when outcomes were measured . Subjective sleep measures were better predictors of future drinking than corresponding PSG measures Alcohol-dependent out patients with persisting insomnia were treated with either gabapentin or trazodone . Patients were assessed at baseline and after 4 - 6 weeks on medication using the Sleep Problems Question naire ( SPQ ) . Of 55 cases initially treated , 9 % dropped out due to morning drowsiness . Of the remaining 50 cases , 34 were treated with gabapentin ( mean dose + /- SD = 888 + /- 418 mg ) at bedtime and 16 were treated with trazodone ( 105 + /- 57 mg ) at bedtime . Both groups improved significantly on the SPQ but the gabapentin group improved significantly more than the trazodone group . Controlled studies are warranted to replicate these findings Objectives : The objectives of this study are to assess the tolerability and efficacy of the anticonvulsant zonisamide in an open label trial of the treatment of alcohol dependence . Methods : In this trial , zonisamide ( 400-mg daily ) was administered to alcohol-dependent subjects ( ADS ) ( n = 16 ) over 13 weeks . The mean daily consumption of st and ard alcoholic drinks and performance on a verbal fluency task , the COWAT , and on a measure of attention and visuomotor speed , the DSMT were assessed , and the occurrence of adverse events was monitored weekly . Results : The mean number of drinks consumed daily was significantly reduced from baseline levels during the treatment period . Performances on the COWAT and on the DSMT were not significantly reduced by zonisamide treatment . Overall , zonisamide was well tolerated by the study subjects . Conclusion : These results indicate that zonisamide administration may not impair verbal fluency in ADS , and are consistent with other studies that found zonisamide administration may reduce alcohol intake BACKGROUND Studies in experimental animals have implicated the mesolimbic dopaminergic projections into the ventral striatum in the neural processes underlying behavioral reinforcement and motivated behavior ; however , underst and ing the relationship between subjective emotional experience and ventral striatal dopamine ( DA ) release has awaited human studies . Using positron emission tomography ( PET ) , we correlated the change in endogenous dopamine concentrations following dextroamphetamine ( AMPH ) administration with the associated hedonic response in human subjects and compared the strength of this correlation across striatal subregions . METHODS We obtained PET measures of [(11)C]raclopride specific binding to DA D2/D3 receptors before and after AMPH injection ( 0.3 mg/kg IV ) in seven healthy subjects . The change in [(11)C]raclopride binding potential ( DeltaBP ) induced by AMPH pretreatment and the correlation between DeltaBP and the euphoric response to AMPH were compared between the anteroventral striatum ( AVS ; comprised of accumbens area , ventromedial cau date , and anteroventral putamen ) and the dorsal cau date ( DCA ) using an MRI-based region of interest analysis of the PET data . RESULTS The mean DeltaBP was greater in the AVS than in the DCA ( p < .05 ) . The AMPH-induced changes in euphoria analog scale scores correlated inversely with DeltaBP in the AVS ( r = -.95 ; p < .001 ) , but not in the DCA ( r = .30 , ns ) . Post hoc assessment s showed that changes in tension-anxiety ratings correlated positively with DeltaBP in the AVS ( r = .80 ; p [ uncorrected ] < .05 ) and that similar relationships may exist between DeltaBP and emotion ratings in the ventral putamen ( as were found in the AVS ) . CONCLUSIONS The preferential sensitivity of the ventral striatum to the DA releasing effects of AMPH previously demonstrated in experimental animals extends to humans . The magnitude of ventral striatal DA release correlates positively with the hedonic response to AMPH Rationale Many studies have reported medication effects on alcohol cue-elicited brain activation or associations between such activation and subsequent drinking . However , few have combined the method ological rigor of a r and omized clinical trial ( RCT ) with follow-up assessment s to determine whether cue-elicited activation predicts relapse during treatment , the crux of alcoholism . Objectives This study analyzed functional magnetic resonance imaging ( fMRI ) data from 48 alcohol-dependent subjects enrolled in a 6-week RCT of an investigational pharmacotherapy . Methods Subjects were r and omized , based on their level of alcohol withdrawal ( AW ) at study entry , to receive either a combination of gabapentin ( GBP ; up to 1,200 mg for 39 days ) and flumazenil ( FMZ ) infusions ( 2 days ) or two placebos . Midway through the RCT , subjects were administered an fMRI alcohol cue reactivity task . Results There were no main effects of medication or initial AW status on cue-elicited activation , but these factors interacted , such that the GBP/FMZ/higher AW and placebo/lower AW groups , which had previously been shown to have relatively reduced drinking , demonstrated greater dorsal anterior cingulate cortex ( dACC ) activation to alcohol cues . Further analysis suggested that this finding represented differences in task-related deactivation and was associated with greater control over alcohol-related thoughts . Among study completers , regardless of medication or AW status , greater left dorsolateral prefrontal cortex ( DLPFC ) activation predicted more post-scan heavy drinking . Conclusions These data suggest that alterations in task-related deactivation of dACC , a component of the default mode network , may predict better alcohol treatment response , while activation of DLPFC , an area associated with selective attention , may predict relapse drinking Background GABAergic anticonvulsants have been recommended for the treatment of alcohol dependence and the prevention of relapse . Several studies have demonstrated topiramate 's efficacy in improving drinking behaviour and maintaining abstinence . The objective of the present open-label controlled study was to assess efficacy and tolerability of low-dose topiramate as adjunctive treatment in alcohol dependence during the immediate post-detoxification period and during a 16-week follow-up period after alcohol withdrawal . Methods Following a 7 - 10 day inpatient alcohol detoxification protocol , 90 patients were assigned to receive either topiramate ( up to 75 mg per day ) in addition to psychotherapeutic treatment ( n = 30 ) or psychotherapy alone ( n = 60 ) . Symptoms of depression and anxiety , as well as craving , were monitored for 4 - 6 weeks immediately following detoxification on an inpatient basis . Thereafter , both groups were followed as out patients at a weekly basis for another 4 months in order to monitor their course and abstinence from alcohol . Results A marked improvement in depressive ( p < 0.01 ) , anxiety ( p < 0.01 ) , and obsessive-compulsive drinking symptoms ( p < 0.01 ) was observed over the consecutive assessment s in both study groups . However , individuals on topiramate fared better than controls ( p < 0.01 ) during inpatient treatment . Moreover , during the 4-month follow up period , relapse rate was lower among patients who received topiramate ( 66.7 % ) compared to those who received no adjunctive treatment ( 85.5 % ) , ( p = 0.043 ) . Time to relapse in the topiramate augmentation group was significantly longer compared to the control group ( log rank test , p = 0.008 ) . Thus , median duration of abstinence was 4 weeks for the non-medicated group whereas it reached 10 weeks for the topiramate group . No serious side effects of topiramate were recorded throughout the study . Conclusions Low-dose topiramate as an adjunct to psychotherapeutic treatment is well tolerated and effective in reducing alcohol craving , as well as symptoms of depression and anxiety , present during the early phase of alcohol withdrawal . Furthermore , topiramate considerably helps to abstain from drinking during the first 16-week post-detoxification period OBJECTIVE This study examined the efficacy of a 28-day gabapentin treatment in reducing alcohol consumption and craving . METHOD A r and omized , double-blind , placebo-controlled trial was performed in a Brazilian public outpatient drug treatment center , with 60 male alcohol-dependent subjects with a mean age of 44 years and an average of 27 years of alcohol use , who consumed 17 drinks per day ( 165 - 170 g/day ) over the past 90 days before baseline and had no other significant medical or psychiatric condition . Subjects were recruited between July 8 , 2004 , and February 24 , 2005 . Following screening , 60 subjects were selected and received diazepam and vitamins as treatment for acute withdrawal for at least 7 days . After the detoxification treatment , 30 subjects were r and omly assigned to receive gabapentin ( 300 mg twice daily ) for 4 weeks , and 30 subjects , with similar baseline characteristics , were r and omly assigned to receive matching placebo tablets for the same period . RESULTS After 28 days of treatment , the gabapentin group showed a significant reduction in both number of drinks per day and mean percentage of heavy drinking days ( p = .02 for both ) , and an increase in the percentage of days of abstinence ( p = .008 ) , compared to the placebo group . Additionally , some improvement in obsessive-compulsive symptoms was noted in both groups after the treatment , but it result ed in a more pronounced decrease in automaticity of drinking and aspects of craving in the gabapentin group than in the placebo group . CONCLUSION Gabapentin reduces alcohol consumption and craving , which may help patients to maintain abstinence . These results , together with the virtual absence of side effects and a favorable safety profile , support gabapentin as a potential drug for the treatment of alcohol withdrawal and dependence BACKGROUND Topiramate increases GABAergic activity and antagonizes the AMPA/kainate subtype of glutamate receptors . Through these mechanisms of action , topiramate may reduce alcohol and cocaine reward and may reduce alcohol and cocaine craving . Topiramate has been shown to reduce drinking in persons with alcohol dependence , and reduce relapse in stimulant-dependent patients . The current trial was intended to test the ability of topiramate to promote cocaine and alcohol abstinence among patients addicted to both drugs . METHODS The study was a double-blind , placebo-controlled , 13-week trial involving 170 cocaine and alcohol dependent subjects . After achieving a period of cocaine and alcohol abstinence , subjects were r and omized to topiramate , 300 mg daily , or identical placebo capsules . In addition , subjects received weekly individual psychotherapy . Primary outcome measures included self-reported alcohol and cocaine use , and thrice weekly urine drug screens . Secondary outcome measures included cocaine and alcohol craving , Addiction Severity Index results , cocaine withdrawal symptoms , and clinical global improvement ratings . RESULTS Topiramate was not better than placebo in reducing cocaine use on the a priori primary outcome measure , or in reducing alcohol use . Topiramate was not better than placebo in reducing cocaine craving . Topiramate-treated subjects , compared to placebo-treated subjects , were more likely to be retained in treatment and more likely to be abstinent from cocaine during the last three weeks of the trial . Subjects who entered treatment with more severe cocaine withdrawal symptoms responded better to topiramate . DISCUSSION Topiramate plus cognitive behavioral therapy may reduce cocaine use for some patients with comorbid cocaine and alcohol dependence BACKGROUND Despite advances in the development of medications to treat alcohol dependence , few medications have been approved by the U.S. Food and Drug Administration . The use of certain anticonvulsant medications has demonstrated potential efficacy in treating alcohol dependence . Previous research suggests that the anticonvulsant levetiracetam may be beneficial in an alcohol-dependent population of very heavy drinkers . METHODS In this double-blind , r and omized , placebo-controlled clinical trial , 130 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites . Patients received either levetiracetam extended-release ( XR ) or placebo and a Brief Behavioral Compliance Enhancement Treatment intervention . Levetiracetam XR was titrated during the first 4 weeks to 2,000 mg/d . This target dose was maintained during weeks 5 through 14 and was tapered during weeks 15 and 16 . RESULTS No significant differences were detected between the levetiracetam XR and placebo groups in either the primary outcomes ( percent heavy drinking days and percent subjects with no heavy drinking days ) or in other secondary drinking outcomes . Treatment groups did not differ on a number of nondrinking outcomes , including depression , anxiety , mood , and quality of life . The only difference observed was in alcohol-related consequences . The levetiracetam XR treatment group showed significantly fewer consequences than did the placebo group during the maintenance period ( p = 0.02 ) . Levetiracetam XR was well tolerated , with fatigue being the only significantly elevated adverse event , compared with placebo ( 53 % vs. 24 % , respectively ; p = 0.001 ) . CONCLUSIONS This multisite clinical trial showed no efficacy for levetiracetam XR compared with placebo in reducing alcohol consumption in heavy drinking alcohol-dependent patients Introduction : Zonisamide is an anticonvulsant medication with GABAergic , glutamatergic , and monoaminergic effects . Zonisamide has also been shown to reduce alcohol intake in rodents and in risky drinkers in the context of a laboratory study . This pilot clinical trial evaluated the safety , tolerability , and efficacy of zonisamide for the treatment of alcohol dependence . Methods : Forty alcohol-dependent subjects ( 23 men ) were r and omly assigned to receive treatment with either placebo or zonisamide in a 12-week double-blind trial . Zonisamide was initiated at a dosage of 100 mg/d , which was increased by 100 mg/d every 2 weeks for 8 weeks to a maximum dosage of 500 mg/d . The medication was continued for 4 weeks at the target dosage and then tapered and discontinued . The primary outcomes were drinks per week , heavy drinking days per week , and abstinent days per week , which were measured using the Timeline Follow-Back method . Results : There was a significant medication by treatment week interaction effect favoring the zonisamide group for heavy drinking days ( HDD ; P = 0.012 ) , drinks per week ( P = 0.004 ) , and alcohol urge scores ( P = 0.006 ) . There was not a significant effect on the number or rate of increase in abstinent days . There were no serious adverse events reported and zonisamide treatment was well tolerated . Conclusion : The findings provide preliminary support for the use of zonisamide to treat alcohol dependence . Efforts to replicate and extend these findings are warranted Background : Insomnia is a prevalent health complaint that is often difficult to evaluate reliably . There is an important need for brief and valid assessment tools to assist practitioners in the clinical evaluation of insomnia complaints . Objective : This paper reports on the clinical validation of the Insomnia Severity Index ( ISI ) as a brief screening measure of insomnia and as an outcome measure in treatment research . The psychometric properties ( internal consistency , concurrent validity , factor structure ) of the ISI were evaluated in two sample s of insomnia patients . Methods : The first study examined the internal consistency and concurrent validity of the ISI in 145 patients evaluated for insomnia at a sleep disorders clinic . Data from the ISI were compared to those of a sleep diary measure . In the second study , the concurrent validity of the ISI was evaluated in a sample of 78 older patients who participated in a r and omized-controlled trial of behavioral and pharmacological therapies for insomnia . Change scores on the ISI over time were compared with those obtained from sleep diaries and polysomnography . Comparisons were also made between ISI scores obtained from patients , significant others , and clinicians . Results : The results of Study 1 showed that the ISI has adequate internal consistency and is a reliable self-report measure to evaluate perceived sleep difficulties . The results from Study 2 also indicated that the ISI is a valid and sensitive measure to detect changes in perceived sleep difficulties with treatment . In addition , there is a close convergence between scores obtained from the ISI patient 's version and those from the clinician 's and significant other 's versions . Conclusions : The present findings indicate that the ISI is a reliable and valid instrument to quantify perceived insomnia severity . The ISI is likely to be a clinical ly useful tool as a screening device or as an outcome measure in insomnia treatment research Background Antiepileptics have been shown to reduce alcohol intake or to prevent relapse in patients with alcoholism . Goal To investigate if the new antiepileptic levetiracetam ( LEV ) prevents relapse after detoxification compared with placebo in patients with alcohol dependence . Methods Two hundred one patients were included in the prospect i ve , r and omized , double-blind , multicenter , placebo-controlled trial . After detoxification treatment and a screening period of 7 days , patients were r and omized to treatment with LEV or placebo . Medication was administered in a fixed-dose schedule for 16 weeks . Primary outcome parameters were the overall rate and time to relapse with heavy drinking . Secondary outcome parameters were time to the first drink , craving , adherence , tolerability , and safety data ( mean corpuscular volume , serum alanine aminotransferase , serum aspartate aminotransferase , & ggr;-glutamyltransferase ) . Results The rate of relapse and the time to relapse did not differ significantly between both groups , but less patients treated with LEV terminated treatment early compared with patients receiving placebo . Tolerability and safety data were similar in the LEV group compared with placebo . Conclusions Our data do not support a significant effect of LEV on relapse prevention in patients with alcohol dependence during the first 16 weeks of abstinence INTRODUCTION Oxcarbazepine ( OXC ) reduces high-voltage-activated calcium currents , thus reducing glutamatergic transmission at corticostriatal synapses . This effect on NMDA glutamatergic transmission may play a role against the increased glutamatergic transmission determined by alcohol withdrawal . To investigate the efficacy and safety of OXC in relapse prevention we compared OXC at different dosages with Naltrexone ( NAL ) in a 90 days r and omised open-label trial . Craving and psychiatric symptoms improvements were the secondary endpoints . METHODS Eighty-four detoxified alcohol dependent subjects currently meeting clinical criteria for alcohol dependence were r and omised into three groups : 27 patients received 50 mg of naltrexone , 29 received 1500 - 1800 mg of oxcarbazepine ( OXC high ) , 28 patients 600 - 900 mg of oxcarbazepine ( OXC low ) . Craving ( VAS ; OCDS ) and withdrawal ( AWRS ) rating scales were applied ; psychiatric symptoms were evaluated through the SCL-90-R. RESULTS A significantly larger number of subjects remained alcohol free in the OXC high group ( 58.6 % ) with respect to both the OXC low ( 42.8 % ) and the NAL groups ( 40.7 % ) . Comparing the OCDS total scores at the end of the treatment , the improvement was significantly greater for the NAL group with respect to the OXC low group . The reduction of the Hostility-Aggression subscore of the SCL-90-R was significantly greater in the OXC high group than that of the other groups . Dual diagnosis patients had a better outcome when treated with OXC high . DISCUSSION OXC at a dosage of 1500 - 1800 mg/day might be beneficial in terms of alcohol relapse prevention . The low dosage formulation did not show the same trend , but it still remain in the same range as NAL . The mechanism involved in the efficacy of oxcarbazepine in relapse prevention could be less related to craving and more connected to the treatment of the comorbid psychiatric symptomatology and the alcohol protracted withdrawal syndrome It has been suggested that a crucial dimension of alcohol " craving " includes the concept of both obsessive thoughts about alcohol use and compulsive behaviors toward drinking . An interview-based rating scale , the Yale-Brown Obsessive Compulsive Scale-heavy drinkers ( YBOCS-hd ) , has been found useful in quantifying this concept in alcohol-dependent individuals . A self-rating scale , the Obsessive Compulsive Drinking Scale ( OCDS ) has been developed by us as a modification of the YBOCS-hd . The YBOCS-hd showed excellent interrater reliability in our h and s. The correlation between the YBOCS-hd and the OCDS total scores obtained on 60 alcohol-dependent individuals was 0.83 . The test-retest correlation for the OCDS total score was 0.96 , and the obsessive and compulsive subscales test-retest correlations were 0.94 and 0.86 , respectively . The internal consistency of the items in the OCDS was high ( 0.86 ) and did not improve significantly with removal of individual items . The shared variance between the OCDS scores and alcohol consumption during the period of evaluation was only approximately 20 % , indicating that the dimension measured by the scale was somewhat independent of actual drinking . As such , it might act as an independent measure of the " state of illness " for alcohol-dependent individuals . When used during a prospect i ve 12-week treatment research study , initial results indicate that the OCDS seems to validly measure a dimension of alcohol dependence , because it decreased from baseline during alcohol reduction and increased in relationship to relapse drinking . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Insomnia and other sleep disturbances are common , persistent , and associated with relapse in alcohol-dependent patients . The purpose of this pilot study was to compare gabapentin versus placebo for the treatment of insomnia and prevention of relapse in alcohol-dependent patients . METHODS Twenty-one subjects , including 10 women who met study criteria for alcohol dependence and insomnia and expressed a desire to abstain from alcohol , were recruited to the study . During a 1 to 2 week placebo lead-in and screening phase , a complete medical history , physical exam , blood tests , urine drug test , and structured interviews were performed to determine eligibility and patterns of alcohol use and sleep . Insomnia due to intoxication or acute withdrawal , psychiatric or medical illness , medications , and other sleep disorders were ruled out . Subjects were then r and omized to either placebo ( n = 11 ) or gabapentin ( n = 10 ) for 6 weeks and titrated over a 10-day period to 1,500 mg or 5 pills at bedtime . After a 4-day taper , subjects were reassessed 6 weeks after ending treatment . RESULTS Gabapentin significantly delayed the onset to heavy drinking , an effect which persisted for 6 weeks after treatment ended . Insomnia improved in both treatment groups during the medication phase , but gabapentin had no differential effects on sleep as measured by either subjective report or polysomnography . CONCLUSION Because gabapentin is a short-acting medication that was taken only at nighttime in this study , it may possibly exert a nocturnal effect that prevents relapse to heavy drinking by a physiological mechanism not measured in this pilot study BACKGROUND To compare topiramate versus naltrexone in the treatment of alcohol dependence . METHODS A 6-month naturalistic , r and omized and open-label , trial of topiramate versus naltrexone , with assessment s at enrollment and after 3 and 6 months of treatment . The setting was an outpatient alcohol clinic . One hundred and two alcohol-dependent patients who had been drinking heavily during the past month were included . Two r and omized groups were created . In one , naltrexone was used as the therapeutic agent and , in the other , topiramate was chosen as the therapeutic agent . Both groups received psychological relapse prevention therapy . Outcome was measured using tools that assessed alcohol intake , cravings , disability , and quality of life ; changes in biomarkers of alcohol intake were also used . With all the data , a secondary composite measure was created in order to assess each patient 's global alcohol intake and its consequences . RESULTS Both groups showed substantial reduction in their drinking . Naltrexone patients had higher nicotine consumption throughout the study . Topiramate was better at reducing alcohol-related cravings throughout the study . Both treatments had a similar mean cost throughout the study . CONCLUSIONS Both topiramate and naltrexone were efficacious in the treatment of alcohol dependence , and the treatment costs were similar . There is a trend for topiramate to be superior to naltrexone on critical measures of drinking ; however , the study did not have adequate statistical power to establish this fact BACKGROUND One of the aims of the World Health Organization/Alcohol , Drug Abuse , and Mental Health Administration joint program on psychiatric diagnosis and classification is the development and st and ardization of diagnostic assessment instruments for use in clinical research worldwide . The International Personality Disorder Examination ( IPDE ) is a semistructured clinical interview compatible with the International Classification of Diseases , Tenth Revision , and the DMS-III-R classification systems . This is the first report of the results of a field trial to investigate the feasibility of using the IPDE to assess personality disorders worldwide . METHODS The IPDE was administered by 58 psychiatrists and clinical psychologists to 716 patients enrolled in clinical facilities at 14 participating centers in 11 countries in North America , Europe , Africa , and Asia . To determine interrater reliability , 141 of the IPDEs ( 20 % ) were independently rated by a silent observer . To determine temporal stability , 243 patients ( 34 % ) were reexamined after an average interval of 6 months . RESULTS The IPDE proved acceptable to clinicians and demonstrated an interrater reliability and temporal stability roughly similar to instruments used to diagnose the psychoses , mood , anxiety , and substance use disorders . CONCLUSION It is possible to assess personality disorders with reasonably good reliability in different nations , language s , and cultures using a semistructured clinical interview that experienced clinicians find relevant , meaningful , and user-friendly Improved treatment of alcohol dependence is a high priority , including defining subtypes that might respond differently . We evaluated a medication combination of intravenous flumazenil ( FMZ ) and oral gabapentin ( GBP ) in alcoholics who did and did not exhibit pretreatment alcohol withdrawal ( AW ) symptoms . Sixty alcohol-dependent individuals ( 44 with low AW and 16 with high AW ) were r and omized to receive FMZ ( 2 mg of incremental bolus for 20 minutes for 2 consecutive days ) and GBP ( up to 1200 mg nightly for 39 days ) or their inactive placebos . Alcohol withdrawal was measured for the first 2 days , and drinking , sleep parameters , and adverse events were monitored during weekly evaluations , along with behavioral counseling sessions . Percent days abstinent ( PDA ) during treatment and time to first heavy drinking ( TFHD ) day were primary outcome variables . There was an interaction between the pretreatment AW status and the medication group on PDA ( P = 0.0006 ) and TFHD ( P = 0.06 ) . Those in the high AW group had more PDA and more TFHD if treated with active medications , whereas those in the low AW group had more PDA and more TFHD if treated with placebo . This interaction remained for those totally abstinent ( P = 0.03 ) and was confirmed by percent carbohydrate-deficient transferrin values . In addition , the pattern of response remained up to 8 weeks after treatment . In addition , in those with high AW , greater improvement in AW symptoms was observed in the active medication group compared with the placebo group . These results suggest a differential response to FMZ/GBP treatment , depending on pretreatment AW status that should be taken into account during future treatment trials This study compared the efficacy of disulfiram ( DSF ) and topiramate ( TPM ) for preventing alcoholic relapse in an open study of routine clinical practice in India . One hundred alcohol-dependent men with family members who agreed to encourage medical compliance and to accompany them for follow-up were r and omly allocated to 9 months of treatment with DSF or TPM . Weekly psychotherapy was also provided . There was no blinding of conditions for the psychiatrist , patient , or family members . Supervision and support of the family member were used in the maintenance of compliance among the patients . Alcohol consumption , craving , and adverse events were recorded weekly for 3 months and then biweekly . Serum gamma glutamyl transferase was measured at the start and at the end of the study . At the end of the trial , 92 patients were still in contact . Relapse occurred at a mean of 133 days for DSF as compared with 79 days for TPM . At 9 months , 90 % of DSF patients , as compared with 56 % of TPM patients , remained abstinent . TPM-treated patients did show less craving than DSF patients did . Further comparisons between these drugs in different treatment setting s and patient population s are warranted BACKGROUND the 14-item Obsessive Compulsive Drinking Scale ( OCDS ) is a quick and reliable self-rating instrument that provides a total and two subscale scores that measure some cognitive aspects of alcohol " craving " . This study vali date d further its utility as an alcoholism severity and treatment outcome instrument . METHODS Alcoholism severity and analogue craving scales were administered at baseline , and the OCDS was given at baseline and weekly to 41 alcohol-dependent individuals who participated in a 12-week pharmacologic and cognitive-behavioral treatment trial . Repeated- measures analysis of variance was used to examine group differences in the OCDS scores of those individuals who remained abstinent or drank during the trial . RESULTS At baseline , the OCDS was correlated with the alcohol composite score of the addiction severity index ( r=.48 ) , the alcohol dependence scale ( r=.42 ) , the analogue craving measures ( range r=.40 to .57 ) , and pre study alcohol consumption ( r=.60 ) . Most importantly the OCDS total and subscale scores were significantly different between individuals who had relapse drinking , who had " slip " drinking , and who remained abstinent , with relapsers showing the highest scores . CONCLUSIONS The OCDS scores appear to be sensitive to alcoholism severity and change during abstinence and relapse drinking . Since the shared variance with analogue craving measures is only about 20 % to 30 % , it appears to be measuring a largely independent dimension of alcohol dependence . Its ease of use ( 5 minutes per self-rating ) , reliability , validity , and analytic capabilities support its utility as a tool to measure severity and improvement during alcoholism treatment trials Topiramate ( TP ) , an anticonvulsant drug , has been widely used in the treatment of disorders characterized by impulsivity symptoms , so it goes to reason that it might be useful in addictive disorders . Recently , TP has been used to treat alcohol dependence , but it is still not known whether the effects of TP on alcohol consumption are related with its action on impulsivity . The aim of this preliminary study was to investigate which dimension of behavioral impulsivity is associated with the effects of TP . A 12-week , double-blind , placebo-controlled pilot study of TP for the treatment of alcohol dependence was conducted . Subjects were men recruited from alcoholism treatment units ( TP = 31 ; placebo = 32 ) . Diagnoses were made using the Structured Interview for Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) . Behavioral inhibition was assessed using the continuous performance test ( CPT ) and the stop-signal task . Differential reinforcement for low-rate responding ( DRLR ) was used to evaluate the delay-discounting dimension . Alcohol craving and alcohol consumption during the study were evaluated . Patients treated with TP presented lower rates of alcohol consumption in the number of drinks per drinking day ( P < 0.05 ) and the number of heavy drinking days ( P < 0.001 ) . Scores on alcohol craving scales decreased significantly , and there was more improvement on the continuous performance test ( total omissions and total commissions ) and on the stop-signal task in the TP group than in the control group . Improved alcohol consumption behavior was associated with performance on the behavioral inhibition paradigm . The results of this study indicate that TP reduces drinking and that the mechanisms underlying this effect may involve , at least in part , modulation of the behavioral inhibition paradigm AIM To compare the efficacy of topiramate with naltrexone in the treatment of alcohol dependence . DESIGN The investigation was a double-blind , placebo-controlled , 12-week study carried out at the University of São Paulo , Brazil . SAMPLE A total of 155 patients , 18 - 60 years of age , with an International Classification of Diseases ( ICD-10 ) diagnosis of alcohol dependence . METHODS After a 1-week detoxification period , patients were assigned r and omly to receive topiramate ( induction to 300 mg/day ) , naltrexone ( 50 mg/day ) or placebo . MEASUREMENTS Time to first relapse ( consumption of > 60 g ethyl alcohol ) , cumulative abstinence duration and weeks of heavy drinking . FINDINGS In intention-to-treat analyses , topiramate was statistically superior to placebo on a number of measures including time to first relapse ( 7.8 versus 5.0 weeks ) , cumulative abstinence duration ( 8.2 versus 5.6 weeks ) , weeks of heavy drinking ( 3.4 versus 5.9 ) and percentage of subjects abstinent at 4 weeks ( 67.3 versus 42.6 ) and 8 weeks ( 61.5 versus 31.5 ) , but not 12 weeks ( 46.2 versus 27.8 ) . RESULTS remained significant after controlling for Alcoholics Anonymous attendance , which was higher in topiramate than in other groups . There were no significant differences between naltrexone versus placebo or naltrexone versus topiramate groups , but naltrexone showed trends toward inferior outcomes when compared to topiramate . CONCLUSIONS The results of this study support the efficacy of topiramate in the relapse prevention of alcoholism . Suggestive evidence was also obtained for superiority of topiramate versus naltrexone , but this needs to be verified in future research with larger sample sizes BACKGROUND Topiramate , a fructopyranose derivative , was superior to placebo at improving the drinking outcomes of alcohol-dependent individuals . OBJECTIVES To determine whether topiramate , compared with placebo , improves psychosocial functioning in alcohol-dependent individuals and to discover how this improvement is related to heavy drinking behavior . DESIGN Double-blind , r and omized , controlled , 12-week clinical trial comparing topiramate vs placebo for treating alcohol dependence ( 1998 - 2001 ) . PARTICIPANTS One hundred fifty alcohol-dependent individuals , diagnosed using the DSM-IV . INTERVENTIONS Seventy-five participants received topiramate ( escalating dose of 25 mg/d to 300 mg/d ) , and 75 had placebo and weekly st and ardized medication compliance management . MAIN OUTCOME MEASURES Three elements of psychosocial functioning were measured : clinical ratings of overall well-being and alcohol-dependence severity , quality of life , and harmful drinking consequences . Overall well-being and dependence severity and quality of life were analyzed as binary responses with a generalized estimating equation approach ; harmful drinking consequences were analyzed as a continuous response using a mixed-effects , repeated- measures model . RESULTS Averaged over the course of double-blind treatment , topiramate , compared with placebo , improved the odds of overall well-being ( odds ratio [ OR ] = 2.17 ; 95 % confidence interval [ CI ] , 1.16 - 2.60 ; P = .01 ) ; reported abstinence and not seeking alcohol ( OR = 2.63 ; 95 % CI , 1.52 - 4.53 ; P = .001 ) ; overall life satisfaction ( OR = 2.28 ; 95 % CI , 1.21 - 4.29 ; P = .01 ) ; and reduced harmful drinking consequences ( OR = -0.07 ; 95 % CI , -0.12 to -0.02 , P = .01 ) . There was a significant shift from higher to lower drinking quartiles on percentage of heavy drinking days , which was associated with improvements on all measures of psychosocial functioning . CONCLUSIONS As an adjunct to medication compliance enhancement treatment , topiramate ( up to 300 mg/d ) was superior to placebo at not only improving drinking outcomes but increasing overall well-being and quality of life and lessening dependence severity and its harmful consequences BACKGROUND The Drinker Inventory of Consequences ( DrInC ) measures overall consequences of drinking and yields five subscale scores . A short form of the DrInC , the Short Index of Problems ( SIP ) , was developed for use when time does not permit completion of the DrInC. This study investigates the psychometric properties of the SIP . METHODS The study sample consisted of 153 problem drinkers who were participants in a placebo-controlled trial of naltrexone and brief counseling . RESULTS The SIP showed good internal consistency , good concurrent validity , and adequate stability . Four of the five SIP subscales contributed unique variance beyond general drinking consequences . CONCLUSIONS The SIP is useful for measuring drinking consequences in a sample of problem drinkers , and the subscale scores can be interpreted clinical ly . Further research on the SIP in other population s is warranted True intention-to-treat analyses are rare in reports of r and omized clinical trials . To highlight the complex issues that arise in conducting and interpreting data from intention-to-treat analyses in studies with substantial levels of protocol violation ( e.g. attrition , noncompliance , or withdrawal of participants ) , data from a clinical trial of treatment for cocaine dependence were analyzed using three strategies to manage missing data : Strategy 1 addressed the effectiveness of treatments based on data collected from participants up to the point of dropout . Strategy 2 addressed the effectiveness of treatments based on data from the full intended duration of the protocol including data collected after participant dropout . The third strategy used a more novel approach , which used an intention-to-treat strategy for the full duration of the trial and the full sample , but also evaluated the effect of treatment retention outcomes by including an independent variable to reflect active treatment retention as a time-varying covariate . Conclusions about the relative efficacy of the study treatments varied to some extent depending on the analytic strategy used . These findings suggest that investigators should make every effort to conduct intent-to-treat analyses , but also to make use of multiple analytic strategies to fully underst and the effects of the treatments studied . Moreover , regardless of the strategy used , investigators should clearly describe their h and ling of data from participants who violate the protocol OBJECTIVES This pilot study has been design ed to collect preliminary data on the use of a new antiepileptic drug in the management of alcoholic patients . Oxcarbazepine ( OXC ) blocks voltage-sensitive sodium channels . Its metabolite reduces high-voltage-activated calcium currents in striatal and cortical neurons , thus reducing glutamatergic transmission at corticostriatal synapses . This reduction is of interest in the treatment of alcohol dependence , as acamprosate ( ACP ) modulates NMDA receptors , result ing in an inhibition of glutamatergic transmission . Furthermore , OXC has revealed a mood-stabilizing effect in bipolar affective disorders . We have compared OXC with ACP in relapse prevention in recently withdrawn alcohol-dependent patients . METHODS We investigated the efficacy and safety of OXC ( vs ACP ) by conducting a 24-week r and omized , parallel-group , open-label , clinical trial on 30 acutely detoxified alcoholic patients . Survival analyses ( Kaplan-Meier ) were performed to look for evidence of a longer " survival " of patients receiving OXC . We assessed time to first severe relapse and additional secondary endpoints . RESULTS After withdrawal , time to severe relapse and time to first consumption of any ethanol by OXC patients were not longer than for ACP patients . Abstinent patients in both study groups showed a significantly lower obsessive compulsive drinking scale-German version ( OCDS-G ) than relapsed patients . No undesired effects occurred when OXC patients consumed alcohol . CONCLUSION Our findings indicate that it could be worthwhile to test relapse prevention using OXC in an adequate sample . While the current sample size clearly limits further conclusions from this pilot study , it is noteworthy that OXC is well tolerated , even when alcohol is on board . Thus , in medication-based relapse prevention , OXC could be a promising alternative for alcoholic patients unable to benefit from ACP or naltrexone or those who have affective liability . OXC certainly merits a larger placebo-controlled trial BACKGROUND In a search for an effective ' anti-alcohol pill ' , three modern anti-craving agents have been studied in alcoholics of Army/ DSC , Air Force , Navy and Coast Guard . METHODS 129 patients of alcohol dependence syndrome were r and omly assigned to three groups where topiramate , acamprosate and naltrexone were used as anti-craving agents in a year long prospect i ve study . Of these 92 patients completed the study . RESULT AND CONCLUSION Topiramate ( 76.3 % ) appears to be significantly more effective ( p<0.01 ) in sustaining abstinence , though naltrexone ( 57.7 % ) and acamprosate ( 60.70 % ) offer moderate relapse-prevention efficacy . Side effects of all the three agents have been mild , transient and self-limiting . We recommend a trial of topiramate , before invaliding out of any alcoholic soldier AIMS Having demonstrated previously the efficacy of topiramate -- a sulfamate-substituted fructopyranose derivative-as pharmacotherapy for treating alcohol dependence , promoting abstinence and reducing the harmful psychosocial consequences of drinking , we investigated whether topiramate also promoted ' safe ' levels of drinking : < or = 1 and < or = 2 st and ard drinks/day for women and men , respectively , among alcohol-dependent individuals . DESIGN , SETTING AND PARTICIPANTS In a double-blind , r and omized , controlled , 12-week clinical trial conducted in San Antonio , Texas , 75 alcohol-dependent adults received topiramate and 75 received placebo as an adjunct to weekly st and ardized medication compliance management . MEASUREMENTS For this secondary analysis of data from that trial , we calculated , based on self-reports , specific intervals of up to 30 days of continuous ' safe ' drinking for each subject . FINDINGS The average longest ' safe ' drinking period was 16.7 days for topiramate recipients versus 8.9 days for placebo recipients . By day 50 of treatment , 44 % versus 26.4 % had achieved > or = 7 and 30.8 % versus 10 % had achieved > or = 14 continuous ' safe ' drinking days . Similarly , topiramate increased the relative likelihood of continuous ' safe ' drinking from 77 % for > or = 7 days [ relative risk ( RR ) for achieving continuous ' safe ' drinking = 1.77 ] to threefold for > or = 14 days ( RR = 3.37 ) and fourfold for > or = 28 days ( RR = 4.07 ) . Thus , participants who received topiramate were more likely to achieve longer periods of ' safe ' drinking compared with those who received placebo . CONCLUSIONS For alcohol-dependent individuals who drank within an abstinence-oriented treatment program , topiramate promoted ' safe ' drinking . Topiramate 's potential to decrease the public health consequences of hazardous drinking needs to be established in future long-term studies There is evidence that GABAergic anticonvulsants can be efficacious in the treatment of alcohol dependence and in the prevention of alcohol relapse because these agents act on the substrate that is involved in alcoholism . Tiagabine , a selective GABA transporter1 reuptake inhibitor , may be a promising c and i date for the treatment of alcohol-dependent individuals . In this r and omized , open pilot study , we aim ed to investigate the efficacy and tolerability of tiagabine as adjunctive treatment of alcohol-dependent individuals ( N = 60 ) during the immediate post-detoxification period and during a 6-month follow-up period following alcohol withdrawal . A control non-medicated group of alcohol-dependent individuals ( N = 60 ) was used for comparisons in terms of anxiety and depressive symptoms , craving and drinking outcome . Although a steady improvement in terms of psychopathology , craving and global functioning was observed in both groups throughout the study , subjects on tiagabine improved significantly more compared to the control subjects ( P < 0.001 ) . Furthermore , the relapse rate in the tiagabine group was lower than in the control group ( 7 vs 14.3 % ) . Tiagabine was well tolerated and only a minority of the participants reported some adverse effects in the beginning of tiagabine treatment . Results from this study suggest that tiagabine is a safe and effective medication for the management of alcohol dependence when given adjunctively to a st and ard psychotherapy treatment . Further studies are warranted before definite conclusions can be reached OBJECTIVE Naltrexone , an efficacious medication for alcohol dependence , does not work for everyone . Symptoms such as insomnia and mood instability that are most evident during early abstinence might respond better to a different pharmacotherapy . Gabapentin may reduce these symptoms and help prevent early relapse . This clinical trial evaluated whether the combination of naltrexone and gabapentin was better than naltrexone alone and /or placebo during the early drinking cessation phase ( first 6 weeks ) , and if so , whether this effect persisted . METHOD A total of 150 alcohol-dependent individuals were r and omly assigned to a 16-week course of naltrexone alone ( 50 mg/day [ N=50 ] ) , naltrexone ( 50 mg/day ) with gabapentin ( up to 1,200 mg/day [ N=50 ] ) added for the first 6 weeks , or double placebo ( N=50 ) . All participants received medical management . RESULTS During the first 6 weeks , the naltrexone-gabapentin group had a longer interval to heavy drinking than the naltrexone-alone group , which had an interval similar to that of the placebo group ; had fewer heavy drinking days than the naltrexone-alone group , which in turn had more than the placebo group ; and had fewer drinks per drinking day than the naltrexone-alone group and the placebo group . These differences faded over the remaining weeks of the study . Poor sleep was associated with more drinking in the naltrexone-alone group but not in the naltrexone-gabapentin group , while a history of alcohol withdrawal was associated with better response in the naltrexone-gabapentin group . CONCLUSIONS The addition of gabapentin to naltrexone improved drinking outcomes over naltrexone alone during the first 6 weeks after cessation of drinking . This effect did not endure after gabapentin was discontinued OBJECTIVE Regular measurement of craving during treatment for cocaine dependence can monitor patients ' clinical status and potentially assess their risk for drug use in the near future . Effective treatment can reduce the correlation between craving and subsequent drug use by helping patients abstain despite high craving . This study examined the relationship between cocaine craving , psychosocial treatment , and cocaine use in the ensuing week . METHOD In the National Institute on Drug Abuse Collaborative Cocaine Treatment Study , which compared four psychosocial treatments for cocaine dependence , a three-item craving question naire was administered weekly to 449 patients to see whether it predicted cocaine use in the ensuing week . Cocaine use was assessed with self-reports and urine screening . RESULTS With control for the previous week 's cocaine use , a higher composite score on the craving question naire was associated with greater likelihood of cocaine use in the subsequent week ; each 1-point increase on the composite score of the craving question naire increased the likelihood of cocaine use in the ensuing week by 10 % . However , among patients who received individual plus group drug counseling , the treatment condition with the best overall cocaine use outcome , increased craving scores were not associated with greater likelihood of cocaine use in the subsequent week . CONCLUSIONS A three-item cocaine craving question naire predicted the relative likelihood of cocaine use during the subsequent week . Moreover , the relationship between craving and subsequent cocaine use varied by treatment condition , suggesting that the most effective treatment in the study might have weakened the link between craving and subsequent use Background Levetiracetam ( Keppra ) is a commonly prescribed anticonvulsant that has been shown to attenuate alcohol consumption in an open-label study of treatment-seeking , alcohol-dependent subjects . Methods Here we performed a 42-day placebo-controlled , double-blind , r and omized crossover trial to evaluate the effects of levetiracetam on moderate to heavy drinkers receiving either a low ( 500–1000 g/d ) or a moderate ( 1000–2000 g/d ) dose . Electronic diaries were used to monitor daily ethanol intake . Results Across the entire group , there was no effect of levetiracetam on drinking irrespective of dose , treatment order , family history , ethnicity , sex , or adverse effects . However , a median split of the data based on the number of drinks consumed while taking placebo revealed that levetiracetam significantly increased drinking in the lower drinking subjects ( n = 23 , P = 0.05 , t = 2.07 ) while having no effect on drinking in the higher half ( n = 23 , P = 0.75 , t = 0.32 ) . Preliminary stratification based on common polymorphisms associated with alcoholism and impulsivity indicated that subjects with alcoholism-associated alleles may drink even more while taking levetiracetam . Conclusions Our data suggest that levetiracetam is not an appropriate treatment for non-treatment seeking alcohol abusers and can , in fact , increase their consumption of alcohol Anticonvulsant agents show promise in the treatment of the acute symptoms of alcohol withdrawal and may also treat some symptoms associated with the protracted abstinence syndrome . Impulsivity , hostility and irritability are common characteristics of alcohol-dependent individuals , and there is some evidence that anticonvulsant agents decrease these traits in individuals with a number of different psychiatric disorders . This pilot study is a 12-week , double-blind , placebo-controlled trial of an anticonvulsant agent , divalproex ( DVPX ) , in alcohol-dependent individuals . Alcohol use ( Timeline Follow Back ) , impulsivity ( Barratt Impulsivity Scale ) , irritability and aggression ( Buss-Durkee Hostility Index ; and Anger , Irritability , Aggression Scale ) were measured at baseline and throughout the 12-week treatment period . Drinking decreased significantly in both the placebo and the DVPX-treated groups . In the DVPX group , a significantly smaller percentage of individuals relapsed to heavy drinking , but there were no significant differences in other alcohol-related outcomes . There were significantly greater decreases in irritability in the DVPX-treated group and a trend towards greater decreases on measures of lability and verbal assault . There were no significant between-group differences on measures of impulsivity . While DVPX did not have a robust effect on alcohol-related outcomes , it did have modest impact on a measure of irritability . This is consistent with the findings of other investigators exploring the use of DVPX in schizophrenia , personality disorder and a number of other psychiatric disorders In comparative or matching research involving two or more treatments , the equivalence of the patient groups is of critical importance . In the past , equivalence has either been imposed by matching or balancing , or has been assured statistically by r and omization . Matching and balancing , while useful in many context s , nonetheless have important limitations , as does simple r and omization . In recent years , a new tool has been developed that represents a compromise between balancing and r and omization . This method , urn r and omization , gives clinical investigators new options for improving the credibility of studies at a relatively modest cost . Urn r and omization is r and omization that is systematic ally based in favor of balancing . It can be used with several covariates , both marginally and jointly , producing optimal multivariate equivalence of treatment groups for large sample sizes . It preserves r and omization as the primary basis for assignment to treatment and is less susceptible to experimenter bias or manipulation of the allocation process by staff than is balancing . Disadvantages include the fact that it is more difficult to implement , and that it violates the simple probability model of simple r and omization . A number of research studies on addictions , including client-treatment matching trials , have used urn r and omization . A summary of the mechanics of urn r and omization is presented , and guidelines for its use in treatment studies are discussed BACKGROUND The Obsessive Compulsive Drinking Scale ( OCDS ) is a 14-item , self-report instrument developed to measure obsessive thoughts about alcohol use and compulsive behaviors toward drinking . The objective of this study was to ascertain the factor structure underlying responses to the OCDS , and to further assess whether subscale scores derived from this structure were distinctive , internally consistent , predictive of future drinking , and able to differentiate between patients receiving naltrexone versus placebo in a controlled alcoholism treatment trial . METHODS OCDS data were collected from a total of 132 alcohol-dependent subjects at up to 15 assessment points during the study . Interitem correlations were pooled across assessment periods , and an iterated principal axis factor analysis with oblique promax rotation was performed . The factor analysis suggested that three primary factors could parsimoniously account for the common variance in item responses . Subscale scores were formed by summing responses to the most salient items on each factor . RESULTS The three common factors were interpreted as " resistance/control impairment , " " obsession , " and " interference . " The subscale scores corresponding to these three factors were internally consistent , and their correlation with other baseline measures of alcohol use and severity suggested that they were distinct . Scores on each subscale reliably distinguished between subjects who remained abstinent , exhibited " slip " drinking , or relapsed to heavy drinking during the 12 weeks of active treatment . Additionally , scores on the resistance/control impairment subscale distinguished between those patients receiving treatment with naltrexone or placebo . Scores from each subscale also were able to predict the hazard for heavy drinking in the following week of treatment . CONCLUSIONS The three OCDS factors are easily estimated with the summated scoring approach , and the result ing subscales appear to be internally consistent and distinctive . Moreover , the group differentiation capability and predictive utility of the subscale scores suggest that they might be useful as either predictor or outcome variables in alcoholism treatment trials . The duration of time for which a given OCDS assessment maintains its predictive utility awaits further confirmation Background : A 6-month naturalistic , r and omized and open-label , trial of topiramate versus naltrexone was conducted , with assessment s at enrollment and after 3 and 6 months of treatment . 182 alcohol-dependent patients who had been drinking heavily during the past month were included . Methods : Outcome was measured using tools that assessed alcohol intake , cravings , disability , and quality of life ; changes in biomarkers of alcohol intake were also used . Results : At the 6-month evaluation , patients taking topiramate had significantly lower scores on the OCDS ( all subscales ) , the EuropASI ( medical , alcohol , family/social , and psychiatric ) and the WHO/DAS ( employment/social ) . More patients taking topiramate remained in the abstinence group and the moderate drinking without problems group . Conclusions : Topiramate at a mean dose of 200 mg/day was better than naltrexone at a mean dose of 50 mg/day at reducing alcohol intake and cravings throughout the study Carbamazepine , chemically related to the tricyclic antidepressants , has multiple clinical actions . It is a potent anticonvulsant , mild sedative , and mood stabilizer . It is nonaddictive and has little toxicity when clinical and laboratory monitoring is performed . It has proven efficacy in the treatment of acute alcohol withdrawal . Kindling and protracted withdrawal are the theoretical rationale for the mechanism of its action in the treatment of alcohol dependence . This 12-month double-blind placebo-controlled pilot study of 29 subjects evaluated the efficacy of carbamazepine for the treatment of alcohol dependence . Subjects were r and omly assigned to either placebo or carbamazepine . A baseline assessment and bimonthly follow-up for 12 months assessed demographic variables , mood and functioning , treatment compliance , drinking behaviors , biological markers of drinking , and medication toxicity . Despite the small sample size , compliance difficulties after 4 months and a sizable drop-out rate , there were treatment effects favoring carbamazepine . Univariate analyses showed a decrease in drinks per drinking day and maximum number of heavy drinking days in a row at 2 and 4 months of follow-up . Survival analysis revealed a significant delay in time to first episode of heavy drinking , and close to a trend level of significance for time to first drink . There were significant time , but not time by treatment group , effects on multiple measures of mood . These pilot results are encouraging and support carbamazepine as a possible pharmacologic tool in the treatment of alcohol dependence To comprehend the results of a r and omised controlled trial ( RCT ) , readers must underst and its design , conduct , analysis , and interpretation . That goal can be achieved only through total transparency from authors . Despite several decades of educational efforts , the reporting of RCTs needs improvement . Investigators and editors developed the original CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to help authors improve reporting by use of a checklist and flow diagram . The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement . The checklist items pertain to the content of the Title , Abstract , Introduction , Methods , Results , and Discussion . The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect , or because the information is essential to judge the reliability or relevance of the findings . We intended the flow diagram to depict the passage of participants through an RCT . The revised flow diagram depicts information from four stages of a trial ( enrollment , intervention allocation , follow- up , and analysis ) . The diagram explicitly shows the number of participants , for each intervention group , included in the primary data analysis . Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis . In sum , the CONSORT statement is intended to improve the reporting of an RCT , enabling readers to underst and a trial 's conduct and to assess the validity of its results |
13,250 | 27,465,509 | Under current NOGG guidelines , based on age-dependent probability thresholds , inequalities in access to therapy arise especially at older ages ( ≥70 years ) depending on the presence or absence of a prior fracture .
An alternative threshold using a hybrid model reduces this disparity .
Conclusion The use of FRAX ( fixed or age-dependent thresholds ) as the gateway to assessment identifies individuals at high risk more effectively than the use of BMD . | Introduction In most assessment guidelines , treatment for osteoporosis is recommended in individuals with prior fragility fractures , especially fractures at spine and hip .
However , for those without prior fractures , the intervention thresholds can be derived using different methods .
The aim of this report was to undertake a systematic review of the available information on the use of FRAX ® in assessment guidelines , in particular the setting of thresholds and their validation .
Age-dependent intervention thresholds , first developed by the National Osteoporosis Guideline Group ( NOGG ) , are based on the rationale that if a woman with a prior fragility fracture is eligible for treatment , then , at any given age , a man or woman with the same fracture probability but in the absence of a previous fracture ( i.e. at the ‘ fracture threshold ’ ) should also be eligible . | The National Institutes of Health 's consensus conference ( 1 ) defined osteoporosis as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk for fracture . Bone strength reflects the integration of two main features : bone density and bone quality .Bone quality refers to architecture , turnover , damage accumulation ( e.g. , microfractures ) , and mineralization . Although osteoporosis can affect any bone , the hip , spine , and wrist are most likely to be affected . Osteoporosis affects an estimated 44 million Americans or 55 % of people 50 years of age or older . Another 34 million Americans are estimated to have low bone mass , meaning that they are at an increased risk for osteoporosis . Osteoporosis can be diagnosed by the occurrence of fragility fracture . In patients without fragility fracture , osteoporosis is often diagnosed by low bone density . Dual x-ray absorptiometry ( DXA ) is the current gold st and ard test for diagnosing osteoporosis in people without an osteoporotic fracture . Dual x-ray absorptiometry results are scored as st and ard deviations ( SDs ) from a young healthy norm ( usually female ) and reported as T-scores . For example , a T-score of 2 indicates a bone mineral density that is 2 SDs below the comparative norm . The international reference st and ard for the description of osteoporosis in postmenopausal women and in men age 50 years or older is a femoral neck bone mineral density of 2.5 SD or more below the young female adult mean ( 2 ) . Low bone density , as measured by DXA , is an imperfect predictor of fracture risk , identifying fewer than half the people who go on to have an osteoporotic fracture . Screening guidelines for women are well established ( 3 ) , and the American College of Physicians ( ACP ) recently published guidelines on screening for men ( 4 ) . This guideline presents the available evidence on various pharmacologic treatments to prevent fractures in men and women with low bone density or osteoporosis . Medications used to treat osteoporosis may affect different parts of the skeletal system differently , and efficacy for vertebral fractures does not necessarily imply efficacy for nonvertebral fractures . The target audience for this guideline is all clinicians and the target patient population is all adult men and women with low bone density or osteoporosis . These recommendations are based on the systematic evidence review by MacLean and colleagues ( 5 ) and the Agency for Healthcare Research and Quality sponsored Southern California Evidence -Based Practice Center evidence report ( 6 ) . The drugs currently approved for prevention of osteoporosis include alendronate , ib and ronate , risedronate , zoledronic acid , estrogen , and raloxifene . The drugs currently approved for treatment of osteoporosis include alendronate , ib and ronate , risedronate , calcitonin , teriparatide , zoledronic acid ( in postmenopausal women ) , and raloxifene . Testosterone , pamidronate , and etidronate are not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Methods The literature search done by MacLean and colleagues for the systematic review ( 5 ) included studies from MEDLINE ( 1966 to December 2006 ) , the ACP Journal Club data base , the Cochrane Central Register of Controlled Trials ( no date limits ) , the Cochrane Data base of Systematic Review s ( no date limits ) , Web sites of the United Kingdom National Institute of Health and Clinical Excellence ( no date limits ) , and the United Kingdom Health Technology Assessment Program ( January 1998 to December 2006 ) . The review ers limited their search to English- language publications and human studies . They derived evidence for comparative benefits of various treatments exclusively from r and omized , controlled trials , whereas they included evidence from other types of studies for short- and long-term harms . Two physicians independently abstract ed data about study population s , interventions , follow-up , and outcome ascertainment by using a structured form . For each group within a r and omized trial , a statistician extracted the sample size and number of persons reporting fractures . Two review ers , under the supervision of the statistician , independently abstract ed information about adverse events . The statistician or the principal investigator resolved disagreements . This guideline is based on an evaluation of 76 r and omized , controlled trials , 4 of which were identified in the up date d search , and 24 meta-analyses that were included in the efficacy analyses . The analyses of adverse events included 491 articles , representing 417 r and omized trials , 25 other controlled clinical trials , 11 open-label trials , 31 large observational studies , and 9 case reports of osteonecrosis among bisphosphonate users . MacLean and colleagues ' background article ( 5 ) includes details about the methods used for the systematic evidence review . The ACP rates the evidence and recommendations by using the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) system with minor modifications ( Table 1 ) . In addition , the evidence review ers used predefined criteria to assess the quality of systematic review s and r and omized trials , based on internal and external validity assessment s detailed in the Quality of Reporting of Meta-Analyses ( QUOROM ) statement ( 7 ) . Table 1 . The American College of Physicians ' Guideline Grading System The objective of this guideline is to synthesize the evidence for the following questions : What are the comparative benefits in fracture reduction among and also within the following treatments for low bone density : bisphosphonates , specifically alendronate , risedronate , etidronate , ib and ronate , pamidronate , and zoledronic acid ; calcitonin ; estrogen for women ; teriparatide ; selective estrogen receptor modulators ( SERMs ) , specifically raloxifene and tamoxifen ; testosterone for men ; vitamins and minerals , specifically vitamin D and calcium ; and the combination of calcium plus vitamin D ? How does fracture reduction result ing from treatments vary among individuals with different risks for fracture as determined by bone mineral density ( borderline , low , or severe ) , previous fractures ( prevention vs. treatment ) , age , sex , glucocorticoid use , and other factors ( such as community-dwelling vs. institutionalized or vitamin Ddeficient vs. not ) ? What are the short- and long-term harms ( adverse effects ) of these therapies , and do these vary by specific sub population s ? Comparative Benefits of Drugs versus Placebo in Fracture Reduction Evidence from 24 meta-analyses ( 830 ) and 35 additional r and omized trials published after the meta-analyses ( 3165 ) described the effect of 9 of the 14 agents ( alendronate , etidronate , risedronate , calcitonin , estrogen , teriparatide , raloxifene , calcium , and vitamin D ) on fracture incidence . For 4 agents ( ib and ronate , pamidronate , zoledronic acid , and tamoxifen ) , the review ers found no meta-analyses and instead gathered the evidence from 14 r and omized trials ( 6679 ) . No studies were found that reported fracture rates for testosterone . Three r and omized trials ( 35 , 80 , 81 ) and 1 meta- analysis ( 82 ) evaluated the combination of calcium plus vitamin D on fractures . Bisphosphonates Good- quality evidence showed that alendronate , etidronate , ib and ronate , and risedronate prevent vertebral fractures . In addition , evidence from good- quality studies demonstrated that both alendronate and risedronate prevent nonvertebral and hip fractures . Two large r and omized trials showed that zoledronic acid prevents vertebral and nonvertebral fractures in high-risk population s and reduces the risk for hip fracture ( 67 , 74 ) . Ib and ronate has not been shown to reduce nonvertebral fractures ( 68 ) . Of the 6 fairly small trials that looked at vertebral fractures , 1 demonstrated a statistically significant reduction in fractures with pamidronate relative to placebo ( 0.14 [ 95 % CI , 0.03 to 0.72 ] ) ( 73 ) . However , after these data were pooled , the pooled risk estimate for fractures for pamidronate relative to placebo was not significant ( 0.52 [ CI , 0.21 to 1.24 ] ) ( 6 ) . Calcitonin Fair- quality evidence shows that calcitonin reduces vertebral fractures ( 83 , 84 ) . Good- quality evidence indicates that calcitonin does not reduce nonvertebral fractures ( 13 , 16 ) . Estrogen Good- quality evidence shows that estrogen reduces the incidence of vertebral ( 29 , 85 ) , nonvertebral ( 86 ) , and hip fractures ( 85 ) . Teriparatide Good- quality evidence shows that teriparatide prevents vertebral fractures . The evidence related to teriparatide preventing nonvertebral fractures is mixed ; 1 large r and omized trial showed a reduction in nonvertebral fractures ( 34 ) but 2 small trials did not ( 87 , 88 ) . SERMs Good- quality evidence shows that raloxifene prevents vertebral fractures , but that tamoxifen has no effect on vertebral fractures ( 8991 ) . In addition , both raloxifene and tamoxifen had no effect on hip fractures ( 91 ) . Tamoxifen is not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Testosterone No studies reported fracture rates for testosterone . Calcium and Vitamin D In the studies evaluated by MacLean and colleagues ( 5 ) , the evidence for the effect of calcium alone on reduction of fractures is complex . Most studies of pharmacologic agents for osteoporosis include calcium and vitamin D as part of the treatment regimen . Evidence from 1 meta- analysis ( 27 ) and several r and omized trials ( 35 , 48 , 51 , 92 ) showed no significant difference between calcium and placebo in preventing vertebral , nonvertebral , and hip fractures in postmenopausal women . However , nonadherence to therapy may influence this result , and 1 trial with a prespecified analysis of adherent patients found a reduction in fracture risk ( 48 ) . A recent meta- analysis ( 82 ) concluded that the relative risk ( RR ) for fracture with calcium alone was 0.90 ( CI , 0.80 to 1.00 ) , but it did not include a modestly large trial with negative results ( 35 ) . MacLean and colleagues ( 5 ) Objective To evaluate the performance of the QFractureScores for predicting the 10 year risk of osteoporotic and hip fractures in an independent UK cohort of patients from general practice records . Design Prospect i ve cohort study . Setting 364 UK general practice s contributing to The Health Improvement Network ( THIN ) data base . Participants 2.2 million adults registered with a general practice between 27 June 1994 and 30 June 2008 , aged 30 - 85 ( 13 million person years ) , with 25 208 osteoporotic fractures and 12 188 hip fractures . Main outcome measures First ( incident ) diagnosis of osteoporotic fracture ( vertebra , distal radius , or hip ) and incident hip fracture recorded in general practice records . Results Results from this independent and external validation of QFractureScores indicated good performance data for both osteoporotic and hip fracture end points . Discrimination and calibration statistics were comparable to those reported in the internal validation of QFractureScores . The hip fracture score had better performance data for both women and men . It explained 63 % of the variation in women and 60 % of the variation in men , with areas under the receiver operating characteristic curve of 0.89 and 0.86 , respectively . The risk score for osteoporotic fracture explained 49 % of the variation in women and 38 % of the variation in men , with corresponding areas under the receiver operating characteristic curve of 0.82 and 0.74 . QFractureScores were well calibrated , with predicted risks closely matching those across all 10ths of risk and for all age groups . Conclusion QFractureScores are useful tools for predicting the 10 year risk of osteoporotic and hip fractures in patients in the United Kingdom Summary Using FRAX ® , this study aim ed at estimating 10-years probability of osteoporosis (OP)-related fractures and identifies those in need of OP treatment among primary care attendees in Saudi Arabia . Of those aged ≥ 60 years , 14.4 and 18.4 % scored probabilities for major and hip fractures respectively suggesting OP treatment . Predictors for receiving OP screening included the presence of multiple clinical risk factors , occurrence of fragility fractures and physicians recommendation . Purpose This study aim ed at estimating the 10-years probability of osteoporosis (OP)-related fractures and identifying those in need of OP treatment among Saudi adults attending primary care centers ( PHCs ) in Al Hassa , Saudi Arabia , using FRAX ® calculator and to determine factors possibly influence receiving of OP screening among them . Subjects and Methods A total of 1,251 Saudi aged ≥ 40 years , of both genders , were recruited from four urban and three rural r and omly selected PHCs . All were subjected to anthropometric measurements followed by a personal interview with structured question naire to asses OP clinical risk factors ( CRFs ) and possible correlates for receiving OP screening . Ten-year probabilities for major osteoporotic and hip fractures were calculated using the Lebanese version of FRAX ® calculator . Results Of participants aged ≥ 60 years , 14.4 and 18.4 % were identified with probability scores for major osteoporotic and hip fractures respectively , suggesting OP treatment . Out of sample d population , 16.1 % received OP screening . The presence of ≥two OP CRFs ( odds ratio OR = 4.45 ) , being aware of OP ( OR = 2.89 ) , physician recommendation of OP screening ( OR = 2.01 ) , and history of fragility fracture ( OR = 1.92 ) were all possible positive predictors for receiving OP screening . Conclusion A sizable portion of the sample d older Saudis especially those aged ≥ 60 years are at high risk for OP-related fractures indicative to receive OP treatment . Occurrence of fragility fractures , multiplicity of CRFs and physician ’s recommendations are significant positive predictors to receive OP screening among them Summary A new Canadian WHO fracture risk assessment ( FRAX ® ) tool to predict 10-year fracture probability was compared with observed 10-year fracture outcomes in a large Canadian population -based study ( CaMos ) . The Canadian FRAX tool showed good calibration and discrimination for both hip and major osteoporotic fractures . Introduction The purpose of this study was to vali date a new Canadian WHO fracture risk assessment ( FRAX ® ) tool in a prospect i ve , population -based cohort , the Canadian Multicentre Osteoporosis Study ( CaMos ) . Methods A FRAX tool calibrated to the Canadian population was developed by the WHO Collaborating Centre for Metabolic Bone Diseases using national hip fracture and mortality data . Ten-year FRAX probabilities with and without bone mineral density ( BMD ) were derived for CaMos women ( N = 4,778 ) and men ( N = 1,919 ) and compared with observed fracture outcomes to 10 years ( Kaplan – Meier method ) . Cox proportional hazard models were used to investigate the contribution of individual FRAX variables . Results Mean overall 10-year FRAX probability with BMD for major osteoporotic fractures was not significantly different from the observed value in men [ predicted 5.4 % vs. observed 6.4 % ( 95%CI 5.2–7.5 % ) ] and only slightly lower in women [ predicted 10.8 % vs. observed 12.0 % ( 95%CI 11.0–12.9 % ) ] . FRAX was well calibrated for hip fracture assessment in women [ predicted 2.7 % vs. observed 2.7 % ( 95%CI 2.2–3.2 % ) ] but underestimated risk in men [ predicted 1.3 % vs. observed 2.4 % ( 95%CI 1.7–3.1 % ) ] . FRAX with BMD showed better fracture discrimination than FRAX without BMD or BMD alone . Age , body mass index , prior fragility fracture and femoral neck BMD were significant independent predictors of major osteoporotic fractures ; sex , age , prior fragility fracture and femoral neck BMD were significant independent predictors of hip fractures . Conclusion The Canadian FRAX tool provides predictions consistent with observed fracture rates in Canadian women and men , thereby providing a valuable tool for Canadian clinicians assessing patients at risk of fracture INTRODUCTION The aim of this study was to develop a methodology to optimize the role of BMD measurements in a case finding strategy . We studied 2113 women > or = 75 years of age r and omly selected from Sheffield , UK , and adjacent regions . Baseline assessment included hip BMD and clinical risk factors . Outcomes included death and fracture in women followed for 6723 person-years . MATERIAL S AND METHODS Poisson models were used to identify significant risk factors for all fractures and for death with and without BMD and the hazard functions were used to compute fracture probabilities . Women were categorized by fracture probability with and without a BMD assessment . A 10-year fracture probability threshold of 35 % was taken as an intervention threshold . Discordance in categorization of risk ( i.e. , above or below the threshold probability ) between assessment with and without BMD was examined by logistic regression as probabilities of re-classification . Age , prior fracture , use of corticosteroids , and low body mass index were identified as significant clinical risk factors . RESULTS A total of 16.8 % of women were classified as high risk based on these clinical risk factors . The average BMD in these patients was approximately 1 SD lower than in low-risk women ; 21.5 % of women were design ated to be at high risk with the addition of BMD . Fifteen percent of all women were reclassified after adding BMD to clinical risk factors , most of whom lay near the intervention threshold . When a high probability of reclassification was accepted ( without a BMD test ) for high risk to low risk ( p1 < or = 0.8 ) and a low probability accepted for low to high risk ( P2 < or = 0.2 ) , BMD tests would be required in only 21 % of the population . CONCLUSION We conclude that the use of clinical risk factors can identify elderly women at high fracture risk and that such patients have a low average BMD . BMD testing is required , however , in a minority of women -- a fraction that depends on the probabilities accepted for classification and the thresholds of risk chosen . These findings need to be vali date d in other cohorts at different ages and from different regions of the world Summary SCOOP is a UK seven-centre , pragmatic , r and omised controlled trial with 5-year follow-up , including 11,580 women aged 70 to 85 years , to assess the effectiveness and cost-effectiveness of a community-based screening programme to reduce fractures . It utilises the FRAX algorithm and DXA to assess the 10-year probability of fracture . Introduction Osteoporotic , or low-trauma , fractures present a considerable burden to the National Health Service and have major adverse effects on quality of life , disability and mortality for the individual . Methods Given the availability of efficacious treatments and a risk assessment tool based upon clinical risk factors and bone mineral density , a case exists to undertake a community-based controlled evaluation of screening for subjects at high risk of fracture , under the hypothesis that such a screening programme would reduce fractures in this population . Results This study is a UK seven-centre , unblinded , pragmatic , r and omised controlled trial with a 5-year follow-up period . A total of 11,580 women , aged 70 to 85 years and not on prescribed bone protective therapy will be consented to the trial by post via primary care providing 90 % power to detect an 18 % decrease in fractures . Conclusions Participants will be r and omised to either a screening arm or control . Those undergoing screening will have a 10-year fracture probability computed from baseline risk factors together with bone mineral density measured by DXA in selected subjects . Individuals above an age-dependent threshold of fracture probability will be recommended for treatment for the duration of the trial . Subjects in the control arm will receive ‘ usual care ’ . Participants will be followed up 6 months after r and omisation and annually by postal question naires with independent checking of hospital and primary care records . The primary outcome will be the proportion of individuals sustaining fractures in each group . An economic analysis will be carried out to assess cost-effectiveness of screening . A qualitative evaluation will be conducted to examine the acceptability of the process to participants OBJECTIVE To provide guidelines for the health care provider on the prevention , diagnosis , and clinical management of postmenopausal osteoporosis . OUTCOMES Strategies for identifying and evaluating high-risk individuals , the use of bone mineral density ( BMD ) and bone turnover markers in assessing diagnosis and response to management , and recommendations regarding nutrition , physical activity , and the selection of pharmacologic therapy to prevent and manage osteoporosis . EVIDENCE Published literature was retrieved through search es of PubMed and The Cochrane Library on August 30 and September 18 , 2012 , respectively . The strategy included the use of appropriate controlled vocabulary ( e.g. , oteoporosis , bone density , menopause ) and key words ( e.g. , bone health , bone loss , BMD ) . Results were restricted to systematic review s , practice guidelines , r and omized and controlled clinical trials , and observational studies published in English or French . The search was limited to the publication years 2009 and following , and up date s were incorporated into the guideline to March 2013 . Grey ( unpublished ) literature was identified through search ing the websites of health technology assessment and health technology assessment -related agencies , clinical practice guideline collection s , clinical trial registries , and national and international medical specialty societies CONTEXT Type 2 diabetes mellitus ( DM ) is associated with higher bone mineral density ( BMD ) and paradoxically with increased fracture risk . It is not known if low BMD , central to fracture prediction in older adults , identifies fracture risk in patients with DM . OBJECTIVE To determine if femoral neck BMD T score and the World Health Organization Fracture Risk Algorithm ( FRAX ) score are associated with hip and nonspine fracture risk in older adults with type 2 DM . DESIGN , SETTING , AND PARTICIPANTS Data from 3 prospect i ve observational studies with adjudicated fracture outcomes ( Study of Osteoporotic Fractures [ December 1998-July 2008 ] ; Osteoporotic Fractures in Men Study [ March 2000-March 2009 ] ; and Health , Aging , and Body Composition study [ April 1997-June 2007 ] ) were analyzed in older community-dwelling adults ( 9449 women and 7436 men ) in the United States . MAIN OUTCOME MEASURE Self-reported incident fractures , which were verified by radiology reports . RESULTS Of 770 women with DM , 84 experienced a hip fracture and 262 a nonspine fracture during a mean ( SD ) follow-up of 12.6 ( 5.3 ) years . Of 1199 men with DM , 32 experienced a hip fracture and 133 a nonspine fracture during a mean ( SD ) follow-up of 7.5 ( 2.0 ) years . Age-adjusted hazard ratios ( HRs ) for 1-unit decrease in femoral neck BMD T score in women with DM were 1.88 ( 95 % confidence interval [ CI ] , 1.43 - 2.48 ) for hip fracture and 1.52 ( 95 % CI , 1.31 - 1.75 ) for nonspine fracture , and in men with DM were 5.71 ( 95 % CI , 3.42 - 9.53 ) for hip fracture and 2.17 ( 95 % CI , 1.75 - 2.69 ) for nonspine fracture . The FRAX score was also associated with fracture risk in participants with DM ( HRs for 1-unit increase in FRAX hip fracture score , 1.05 ; 95 % CI , 1.03 - 1.07 , for women with DM and 1.16 ; 95 % CI , 1.07 - 1.27 , for men with DM ; HRs for 1-unit increase in FRAX osteoporotic fracture score , 1.04 ; 95 % CI , 1.02 - 1.05 , for women with DM and 1.09 ; 95 % CI , 1.04 - 1.14 , for men with DM ) . However , for a given T score and age or for a given FRAX score , participants with DM had a higher fracture risk than those without DM . For a similar fracture risk , participants with DM had a higher T score than participants without DM . For hip fracture , the estimated mean difference in T score for women was 0.59 ( 95 % CI , 0.31 - 0.87 ) and for men was 0.38 ( 95 % CI , 0.09 - 0.66 ) . CONCLUSIONS Among older adults with type 2 DM , femoral neck BMD T score and FRAX score were associated with hip and nonspine fracture risk ; however , in these patients compared with participants without DM , the fracture risk was higher for a given T score and age or for a given FRAX score Background The WHO has recently published the FRAX ® tool to determine the absolute risk of osteoporotic fracture at 10 years . This tool has not yet been vali date d in Spain . Methods / design A prospect i ve observational study was undertaken in women in the FRIDEX cohort ( Barcelona ) not receiving bone active drugs at baseline . Baseline measurements : known risk factors including those of FRAX ® and a DXA . Follow up data on self-reported incident major fractures ( hip , spine , humerus and wrist ) and verified against patient records . The calculation of absolute risk of major fracture and hip fracture was by FRAX ® website . This work follows the guidelines of the STROBE initiative for cohort studies . The discriminative capacity of FRAX ® was analyzed by the Area Under Curve ( AUC ) , Receiver Operating Characteristics ( ROC ) and the Hosmer-Lemeshow goodness-of-fit test . The predictive capacity was determined using the ratio of observed fractures/expected fractures by FRAX ® ( ObsFx/ExpFx ) . Results The study subjects were 770 women from 40 to 90 years of age in the FRIDEX cohort . The mean age was 56.8 ± 8 years . The fractures were determined by structured telephone question naire and subsequent testing in medical records at 10 years . Sixty-five ( 8.4 % ) women presented major fractures ( 17 hip fractures ) . Women with fractures were older , had more previous fractures , more cases of rheumatoid arthritis and also more osteoporosis on the baseline DXA . The AUC ROC of FRAX ® for major fracture without bone mineral density ( BMD ) was 0.693 ( CI 95 % ; 0.622 - 0.763 ) , with T-score of femoral neck ( FN ) 0.716 ( CI 95 % ; 0.646 - 0.786 ) , being 0.888 ( CI 95 % ; 0.824 - 0.952 ) and 0.849 ( CI 95 % ; 0.737 - 0.962 ) , respectively for hip fracture . In the model with BMD alone was 0.661 ( CI 95 % ; 0.583 - 0.739 ) and 0.779 ( CI 95 % ; 0.631 - 0.929 ) . In the model with age alone was 0.668 ( CI 95 % ; 0.603 - 0.733 ) and 0.882 ( CI 95 % ; 0.832 - 0.936 ) . In both cases there are not significant differences against FRAX ® model . The overall predictive value for major fracture by ObsFx/ExpFx ratio was 2.4 and 2.8 for hip fracture without BMD . With BMD was 2.2 and 2.3 respectively . Sensitivity of the four was always less than 50 % . The Hosmer-Lemeshow test showed a good correlation only after calibration with ObsFx/ExpFx ratio . Conclusions The current version of FRAX ® for Spanish women without BMD analzsed by the AUC ROC demonstrate a poor discriminative capacity to predict major fractures but a good discriminative capacity for hip fractures . Its predictive capacity does not adjust well because leading to underdiagnosis for both predictions major and hip fractures . Simple models based only on age or BMD alone similarly predicted that more complex FRAX ® models Summary This study examined the effects of the use of clinical risk factors ( CRFs ) alone , BMD alone or the combination using the FRAX ® tool for the detection of women at risk of hip fracture . BMD tests alone selected women at higher risk and a greater number of hip fracture cases were identified compared to the use of CRFs alone . The combined use of CRFs and BMD identified fewer women above a threshold risk than the use of BMD alone , but with a higher hip fracture risk and thus had the more favourable positive predictive value ( PPV ) and number needed to treat ( NNT ) . Introduction Algorithms have recently become available for the calculation of hip fracture probability from CRFs with and without information on femoral neck BMD . The aim of this study was to examine the effects of the use of CRFs alone , BMD alone or their combination using the FRAX ® tool for the detection of women at risk of hip fracture . Methods Data from 10 prospect i ve population based cohorts , in which BMD and CRFs were documented , were used to compute the 10-year probabilities of hip fracture calibrated to the fracture and death hazards of the UK . The effects of the use of BMD tests were examined in simulations where BMD tests were used alone , CRFs alone or their combined use . The base case examined the effects in women at the age of 65 years . The principal outcome measures were the number of women identified above an intervention threshold , the number of hip fracture cases that would be identified , the positive predicted value and the NNT to prevent a hip fracture during a hypothetical treatment with an effectiveness of 35 % targeted to those above the threshold fracture risk . We also examined BMD values in women selected for treatment . Sensitivity analysis examined the effect of age and limited use of BMD re sources . Results BMD tests alone selected women at higher risk of hip fracture than the use of CRFs alone ( 6.1 % versus 5.3 % ) . BMD tests alone also identified a greater number of hip fracture cases ( 219/1,000 ) compared to the use of CRFs alone ( 140/1,000 ) . The combined use of CRFs and BMD identified fewer women above a threshold risk than the use of BMD alone ( 168/1,000 versus 219/1,000 , respectively ) , but with a higher hip fracture risk ( PPV , 8.6 % versus 6.1 % ) , and consequently a lower number needed to treat ( NNT ) ( 33 versus 47 ) . In sensitivity analyses , the PPV and NNT were always better for the combination than either BMD or CRFs alone across all ages studied ( 50–70 years ) . Conclusions The use of FRAX ® in combination with BMD increases the performance characteristics of fracture risk assessment Objective To develop and vali date two new fracture risk algorithms ( QFractureScores ) for estimating the individual risk of osteoporotic fracture or hip fracture over 10 years . Design Prospect i ve open cohort study with routinely collected data from 357 general practice s to develop the scores and from 178 practice s to vali date the scores . Setting General practice s in Engl and and Wales . Participants 1 183 663 women and 1 174 232 men aged 30 - 85 in the derivation cohort , who contributed 7 898 208 and 8 049 306 person years of observation , respectively . There were 24 350 incident diagnoses of osteoporotic fracture in women and 7934 in men , and 9302 incident diagnoses of hip fracture in women and 5424 in men . Main outcome measures First ( incident ) diagnosis of osteoporotic fracture ( vertebral , distal radius , or hip ) and incident hip fracture recorded in general practice records . Results Use of hormone replacement therapy ( HRT ) , age , body mass index ( BMI ) , smoking status , recorded alcohol use , parental history of osteoporosis , rheumatoid arthritis , cardiovascular disease , type 2 diabetes , asthma , tricyclic antidepressants , corticosteroids , history of falls , menopausal symptoms , chronic liver disease , gastrointestinal malabsorption , and other endocrine disorders were significantly and independently associated with risk of osteoporotic fracture in women . Some variables were significantly associated with risk of osteoporotic fracture but not with risk of hip fracture . The predictors for men for osteoporotic and hip fracture were age , BMI , smoking status , recorded alcohol use , rheumatoid arthritis , cardiovascular disease , type 2 diabetes , asthma , tricyclic antidepressants , corticosteroids , history of falls , and liver disease . The hip fracture algorithm had the best performance among men and women . It explained 63.94 % of the variation in women and 63.19 % of the variation in men . The D statistic values for discrimination were highest for hip fracture in women ( 2.73 ) and men ( 2.68 ) and were over twice the magnitude of the corresponding values for osteoporotic fracture . The ROC statistics for hip fracture were also high : 0.89 in women and 0.86 for men versus 0.79 and 0.69 , respectively , for the osteoporotic fracture outcome . The algorithms were well calibrated with predicted risks closely matching observed risks . The QFractureScore for hip fracture also had good performance for discrimination and calibration compared with the FRAX ( fracture risk assessment ) algorithm . Conclusions These new algorithms can predict risk of fracture in primary care population s in the UK without laboratory measurements and are therefore suitable for use in both clinical setting s and for self assessment ( www.qfracture.org ) . QFractureScores could be used to identify patients at high risk of fracture who might benefit from interventions to reduce their risk BACKGROUND A Web-based risk assessment tool ( FRAX ) using clinical risk factors with and without femoral neck bone mineral density ( BMD ) has been incorporated into clinical guidelines regarding treatment to prevent fractures . However , it is uncertain whether prediction with FRAX models is superior to that based on parsimonious models . METHODS We conducted a prospect i ve cohort study in 6252 women 65 years or older to compare the value of FRAX models that include BMD with that of parsimonious models based on age and BMD alone for prediction of fractures . We also compared FRAX models without BMD with simple models based on age and fracture history alone . Fractures ( hip , major osteoporotic [ hip , clinical vertebral , wrist , or humerus ] , and any clinical fracture ) were ascertained during 10 years of follow-up . Area under the curve ( AUC ) statistics from receiver operating characteristic curve analysis were compared between FRAX models and simple models . RESULTS The AUC comparisons showed no differences between FRAX models with BMD and simple models with age and BMD alone in discriminating hip ( AUC , 0.75 for the FRAX model and 0.76 for the simple model ; P = .26 ) , major osteoporotic ( AUC , 0.68 for the FRAX model and 0.69 for the simple model ; P = .51 ) , and clinical fracture ( AUC , 0.64 for the FRAX model and 0.63 for the simple model ; P = .16 ) . Similarly , performance of parsimonious models containing age and fracture history alone was nearly identical to that of FRAX models without BMD . The proportion of women in each quartile of predicted risk who actually experienced a fracture outcome did not differ between FRAX and simple models ( P > or = .16 ) . CONCLUSION Simple models based on age and BMD alone or age and fracture history alone predicted 10-year risk of hip , major osteoporotic , and clinical fracture as well as more complex FRAX models To assess the number of anti-osteoporosis treatments that would be reimbursed by the Belgian social security if either FRAX ® or the current criteria were used to determine access to reimbursement . This is a retrospective study based on data from 1,000 women r and omly selected from an outpatient hospital specialized in bone metabolism in Belgium . Proportions of potentially refunded treatments between FRAX ® and current criteria were compared . Out of the 1,000 women files , 890 have sufficient information to assess FRAX ® . In Belgium , current criteria include a bone mineral density ( BMD ) T score below −2.5 at the lumbar spine , the femoral neck or the total hip and /or at least a prevalent vertebral fracture . Using these criteria , 167 women ( 18.8 % ) would have access to reimbursement . Using the criteria based on the vali date d Belgian FRAX ® tool , only 116 women ( 13.0 % ) would have access to reimbursement , meaning that access to reimbursement based on FRAX ® criteria would reduce by 30 % the anti-osteoporosis drug expenses covered by the national social security . Interestingly , only 65 women out of the 116 ( 56.0 % ) selected with the FRAX ® criteria were also selected with the current criteria of the national social security . A substantial proportion of individuals that would potentially receive a reimbursement for their treatment using the FRAX ® criteria do not have access to any refund for their treatment with the current criteria . Since patients identified with the FRAX ® tool are those with the highest risk profile for future fractures , re appraisal s of treatment reimbursement guidelines are expected in Belgium BACKGROUND The 2007 WHO guidelines for the treatment of osteoporosis require that we know the population risk of an osteoporotic fracture for each country to classify patients requiring treatment . MATERIAL AND METHODS Studies have been carried out among a r and om cohort of 1,608 women over the age of 40 to assess a ten-year absolute risk of main osteoporotic fractures ( AR-10 m.o.fx . ) and hip fractures ( AR-10 h.fx . ) by using FRAX ® BMI and FRAX ® BMD based on the epidemiology of fractures in Engl and . RESULTS Both methods gave similar results in assessing the probability of fracture , showing the increase of AR-10 m.o.fx . in subsequent life decades to rise from 5 % in the fifth decade to 25 % in the ninth , mean result 11 % , and AR-10 h.fx . to rise over the same period from 0.5 % to 13 % , mean result 3 % . The number of fractures increases up to the seventh and eighth decades , and decreases according to the number of patients in the age group . The commonest fracture risks reported , other than old age and low BMI , were a prior fracture , a family history of hip fracture and smoking . CONCLUSIONS Comparative analysis of examined parameters of FRAX between people with and without fractures showed considerable differences only in age and AR-10 m.o.fx . This doubled in people with previous fractures ( ca . 18 % vs. 9 % ) and AR-10 h.fx . ( ca . 5 % vs. 2.5 % ) . The " middle " area between the average population risks ( AR-10 m.o.fx . 11 % and AR-10 h.fx . 3 % ) and the risks in patients with fractures ( AR-10 m.o.fx . 18 % and AR-10 h.fx . 9 % ) could work as an indicator : below those values the risk is low and no treatment is required ; above those values , the risk is high , and intervention is necessary ; the middle area implies a BMD examination and re assessment of the fracture risk Purpose : To evaluate the performance of the Swedish version of Fracture Risk Assessment Tool ( FRAX ) ) without bone mass density ( BMD ) in a Danish population to examine the possibility of applying this version to Danish women . Methods : From the Danish National Register of social security numbers , we r and omly selected 5000 women living in the region of Southern Denmark aged 40—90 years to receive a mailed question naire concerning risk factors for osteoporosis based on FRAX . The predicted 10-year probability of hip fractures was calculated for each woman returning a complete question naire using the Swedish version of FRAX . The observed 10-year hip fracture risk was also calculated for each woman using age-specific hip fracture rates from the National Hospital Discharge Register and National survival tables . Results : A total of 4194 ( 84 % ) women responded to the question naire and 3636 ( 73 % ) gave complete information and were included in the analysis . Using FRAX , the predicted 10-year fracture risk was 7.6 % , ranging from 0.3 to 25.0 % at the age of 41—50 and 81—90 , respectively , while the corresponding observed fracture risk was 7.6 % , ranging from 0.4 to 24.0 % , respectively and not significantly different from the predicted risk ( p = 0.92 ) . Conclusions : The Swedish version of FRAX without BMD is applicable to Danish women Objective To develop and vali date an up date d version of the QFracture algorithm for estimating the risk of a patient sustaining an osteoporotic fracture or hip fracture in a primary care population . Design Prospect i ve open cohort study using routinely collected data from 420 general practice s in the United Kingdom to develop up date d QFracture scores and 207 practice s to vali date scores . Cox ’s proportional hazards model was used in the derivation cohort to derive risk equations using several explanatory variables . We calculated measures of calibration and discrimination using the validation cohort . Participants 3 142 673 patients in derivation cohort and 1 583 373 in validation cohort , aged 30 - 100 years , who contributed 23 608 337 and 11 732 106 person years of observation , respectively . We identified 59 772 incident diagnoses of osteoporotic fracture in the derivation cohort and 28 685 in the validation cohort . Outcomes Incident diagnosis of osteoporotic fracture ( vertebral , distal radius , proximal humerus , or hip ) and incident hip fracture recorded in general practice records or linked cause of death records . Results We found significant independent associations with overall fracture risk in women for age , body mass index , ethnic origin , alcohol intake , smoking status , chronic obstructive pulmonary disease or asthma , any cancer , cardiovascular disease , dementia , diagnosis or treatment for epilepsy , history of falls , chronic liver disease , Parkinson ’s disease , rheumatoid arthritis or systemic lupus erythematosus , chronic renal disease , type 1 diabetes , type 2 diabetes , previous fracture , endocrine disorders , gastrointestinal malabsorption , any antidepressants , corticosteroids , unopposed hormone replacement therapy , and parental history of osteoporosis . Risk factors for hip fracture in women were similar except for gastrointestinal malabsorption and parental history of hip fracture . Risk factors for men were largely the same as those for women but also included care home residence . The up date d hip fracture algorithm explained 71.7 % ( 95 % confidence interval 71.1 % to 72.3 % ) of the variation in women and 70.4 % ( 69.3 % to 71.5 % ) in men . D statistic values for hip fracture were high for women ( 3.26 , 3.21 to 3.31 ) and men ( 3.15 , 3.06 to 3.24 ) , and higher than for osteoporotic fracture . Values for the area under the receiver operating characteristics curves for hip fracture were 0.89 for women and 0.88 for men , compared with 0.79 and 0.71 for osteoporotic fracture , respectively . The up date d algorithms performed better than the 2009 algorithms . Conclusions Two QFracture algorithms were up date d to predict risk of osteoporotic and hip fracture in primary care population s to include ethnic origin , all classes of antidepressants , chronic obstructive pulmonary disease , epilepsy , dementia , Parkinson ’s disease , cancer , systemic lupus erythematosus , chronic renal disease , type 1 diabetes , previous fragility fracture , and care home residence . These up date d algorithms showed improved performance compared with previous QFracture algorithms reported in 2009 Vertebral fractures are the most common osteoporotic fracture , and patients with prevalent vertebral fractures have a greater risk of future fractures . However , radiographically determined vertebral fractures are not identified as a distinct risk factor in the World Health Organization ( WHO ) fracture risk assessment tool . The objective of this study was to evaluate and compare potential risk factors including morphometric spine fracture status and the WHO risk factors for predicting 5-yr fracture risk . We hypothesized that spine fracture status provides prognostic information in addition to consideration of the WHO risk factors alone . A r and omly selected , population -based community cohort of 2761 noninstitutionalized men and women > or = 50 yr of age living within 50 km of one of nine regional centers was enrolled in the Canadian Multicentre Osteoporosis Study ( CaMOS ) , a prospect i ve and longitudinal cohort study following subjects for 5 yr . Prevalent and incident spine fractures were identified from lateral spine radiographs . Incident nonvertebral fragility fractures were determined by an annual , mailed fracture question naire with validation , and nonvertebral fragility fracture was defined by investigators as a fracture with minimal trauma . A model considering the WHO risk factors plus spine fracture status provided greater prognostic information regarding future fracture risk than a model considering the WHO risk factors alone . In univariate analyses , age , BMD , and spine fracture status had the highest gradient of risk . A model considering these three risk factors captured almost all of the predictive information provided by a model considering spine fracture status plus the WHO risk factors and provided greater predictive information than a model considering the WHO risk factors alone . The use of spine fracture status along with age and BMD predicted future fracture risk with greater simplicity and higher prognostic accuracy than consideration of the risk factors included in the WHO tool |
13,251 | 22,071,859 | The qualitative analyses found no evidence of an effect of antidepressants on pain intensity or depression in the short-term ( less than one week ) , and conflicting evidence of a medium- ( one to six weeks ) or long-term ( more than six weeks ) benefit .
The use of these agents may be associated with adverse events which are generally mild and do not lead to cessation of treatment . | BACKGROUND Pain management is a high priority for patients with rheumatoid arthritis ( RA ) .
Antidepressants are sometimes used as adjuvant agents to enhance pain relief , help with sleep and reduce depression .
Such antidepressants include tricyclic antidepressants ( TCAs ) , monoamine oxidase inhibitors ( MAOIs ) , selective serotonin reuptake inhibitors ( SSRIs ) , selective serotonin noradrenaline reuptake inhibitors ( SNRIs ) and norepinephrine reuptake inhibitors ( NRIs ) .
However , the prescription of antidepressants in this population remains controversial because of conflicting scientific evidence .
OBJECTIVES The aim of this review was to determine the efficacy and safety of antidepressants in pain management in patients with RA . | OBJECTIVE To compare the efficacy and tolerability of paroxetine ( a selective serotonin reuptake inhibitor ) with that of amitriptyline ( a tricyclic antidepressant ) in the treatment of depression in 191 patients with rheumatoid arthritis ( RA ) . METHODS A r and omized , double blind , double dummy , parallel group study . A placebo washout period of 3 - 7 days was followed by an 8 week active treatment phase during which patients received either paroxetine ( 20 - 40 mg daily ) or amitriptyline ( 75 - 150 mg daily ) . The primary efficacy variable was the change from baseline in Montgomery Asberg Depression Rating Scale score at endpoint . RESULTS Paroxetine was as effective as amitriptyline for the treatment of depression , with similar improvements in RA associated pain and disability also seen in both groups . However , paroxetine was better tolerated than amitriptyline , with an overall frequency of adverse experiences of 56.4 % and 67.7 % in the 2 groups , respectively . The frequency of anticholinergic adverse experiences was much lower in the paroxetine treatment group ( 18.1 % vs 43.8 % taking amitriptyline ) and paroxetine treated patients also experienced fewer severe ( 16.0 % vs 21.9 % ) , serious nonfatal ( 0 % vs 4.2 % ) , and drug related adverse experiences ( 12.8 % vs 29.2 % ) . CONCLUSION Tolerability is an important consideration in this patient population , which is largely composed of elderly patients who are taking additional medications for RA . Paroxetine shows a number of advantages in the management of depression comorbid with RA Thirty-six patients with definite or classical rheumatoid arthritis participated in a double-blind , r and omized , placebo-controlled trial to assess the effectiveness of adding amitriptyline to the treatment regimen for the relief of pain not adequately controlled by non-steroidal anti-inflammatory drugs . Dosage of amitriptyline was increased gradually up to 25 mg 3-times daily and patients were followed up for 12 weeks . Assessment s were made of joint pain and tenderness every 4 weeks . The results showed no difference between the amitriptyline and placebo-treated patients for either parameter The effectiveness of dothiepin ( a tricyclic anti-depressant ) at a dose of 75 mg given orally at night was compared with placebo for 4 weeks in alleviating pain in 60 patients with classical or definite active rheumatoid arthritis . Patients were classified as either ‘ depressed ’ or ‘ not depressed ’ . The week before , during and 2 weeks after the study , 600 mg ibuprofen was given orally three times daily to all patients . Compared with placebo , dothiepin produced a significant reduction in daytime pain by the end of the treatment period . The Hamilton rating scale in ‘ depressed ’ patients was significantly improved in patients given dothiepin . The Cassano – Castrogiovanni self-evaluation rating scale in both ‘ depressed ’ and ‘ not depressed ’ patients showed a tendency ( not significant ) to be improved following dothiepin treatment compared with placebo . These results suggest that patients with rheumatoid arthritis may experience an increase in pain symptoms due to an alteration of mood . Therapy with tricyclic anti-depressants , such as dothiepin , therefore , may determine an improvement of pain indexes besides having an anti-depressant effect We report an open-label trial of sertraline in the treatment of major depression in 54 consecutive rheumatoid arthritis ( RA ) patients meeting DSM-IV criteria for major depressive disorder . We initially surveyed 628 RA out patients with the Center for Epidemiologic Studies Depression Scale ( CES-D ) and invited those with depression to be evaluated further and treated . Eighty-four RA patients reporting depressive symptoms agreed to participate in person , and 56 met the criteria for major depressive disorder . Of these 56 patients , 54 agreed to medication treatment and were enrolled in the study . Patients were also r and omized to one of three psychological treatment conditions , but for this study , conditions were collapsed because previous research on this sample indicated no significant between-group differences in depression after treatment . Patients were assessed with the CES-D and the Hamilton Rating Scale for Depression after the intervention , at 6-month follow-up , and at 15-month follow-up . At the last follow-up , 41 patients remained for assessment . In this study , sertraline was found to be a safe and efficacious treatment of depression complicating RA Actions on performance of dextropropoxyphene ( DXP ) alone and in combination with amitriptyline ( AMI ) , indomethacin ( IN ) , and placebo were compared in 15 patients with rheumatoid arthritis . The patients were on their prescribed maintenance regimen excluding analgesics . In four r and omized test sessions at two-week intervals , they received double blind and crossover single oral doses of DXP 130 mg , IN 50 mg , DXP 65 mg + AMI 25 mg or placebo , each after two days ' pretreatment with the same drug . Objective and subjective effects were measured at baseline and 2 and 4 hours after drug administration . DXP impaired critical flicker discrimination , symbol copying and body balance without modifying tracking , choice reactions or attention . It rendered the subjects elated , muzzy , mentally slow and calm . Actions of AMI + DXP were about the same . IN impaired body balance and critical flicker recognition . Plasma concentrations of DXP were moderate to high whilst those of IN and AMI were fairly low . We conclude that therapeutic doses of DXP and IN are relatively safe in regard to driving skills . Small doses of AMI may not enhance the mild psychomotor effects of DXP . Earlier single dose studies carried out with healthy volunteers might have overestimated the decremental effects of analgesics on psychomotor performance OBJECTIVE To examine the effectiveness of cognitive-behavioral and pharmacologic treatment of depression in rheumatoid arthritis ( RA ) . METHODS Subjects ( n = 54 ) with confirmed diagnoses of both major depression and RA were r and omly assigned to 1 of 3 groups : 1 ) cognitive-behavioral/pharmacologic group ( CB-PHARM ) , 2 ) attention-control/pharmacologic group , or 3 ) pharmacologic control group . Measures of depression , psychosocial status , health status , pain , and disease activity were collected at baseline , posttreatment ( 10 weeks ) , 6-month followup , and 15-month followup . Data were analyzed to compare the treatment effectiveness of the groups ; data also were aggregated to examine the effects of antidepressive medication over time . Lastly , a no-treatment control group was defined from a cohort of persons who declined participation . RESULTS Baseline comparisons on demographic and dependent measures revealed a need to assess covariates on age and education ; baseline scores on dependent measures also were entered as covariates . Analyses of covariance revealed no statistically significant group differences at postintervention , 6-month followup , or 15-month followup , except higher state and trait anxiety scores for the CB-PHARM group at the 15-month followup . In the longitudinal analyses of the effects of antidepressive medication , significant improvement in psychological status and health status were found at posttreatment , 6-month followup , and 15-month followup , but no significant improvements were shown for pain or disease activity . In addition , the comparison of the aggregated pharmacologic group with a no-treatment group revealed a statistically significant benefit for the 3 groups that received the antidepressive medication . CONCLUSION In persons with RA , cognitive-behavioral approaches to the management of depression were not found to be additive to antidepressant medication alone , but antidepressant intervention was superior to no treatment Summary A double-blind placebo-controlled trial was carried out in 20 patients with classical rheumatoid arthritis to study the effect of imipramine on rheumatoid factor titres . Patients were allocated at r and om to receive 6-weeks treatment with imipramine , in low dosage , or placebo in addition to their antirheumatic medication . They were then followed up for a further 4 weeks during which only their antirheumatic medication was continued . Assessment s were made , at entry and after 3,6 and 10 weeks , of rheumatoid factor titres , pain scores , articular index , PIP joint size , grip strength , erythrocyte sedimentation rate and depression index . The results showed that changes in rheumatoid factor titre in the placebo and post-treatment groups were similar to changes occurring during the administration of imipramine . There was , however , a significant correlation between the changes in depression rating score and articular index A r and omised , double‐blind , multiple dose , crossover study with three 3‐week treatment periods was set up to compare the analgesic efficacy and adverse effects of amitriptyline in oral doses of 25 , 50 or 75 mg . Patients used diaries to assess their pain , and clinic assessment s were made at the end of each treatment period . It was found that in 29 patients with chronic ( more than 2 months ) pain , amitriptyline 75 mg provided significantly greater efficacy than amitriptyline 25 or 50 mg . There was no significant difference in mood scores between the different doses of amitriptyline , but sleep was judged significantly better with 75 mg compared with 25 mg . The incidence of adverse effects was significantly higher with the 75 mg dose , and the principal adverse effects were dry mouth and drowsiness . In the context of chronic pain , the analgesic effect of amitriptyline was shown to have a dose‐response unrelated to mood elevation , but there was a dose‐response for the incidence of adverse effects The effect of low-dose trimipramine ( 25 to 75 mg/day ) on joint pain and tenderness in 36 patients with rheumatoid arthritis was studied in a r and omized double-blind trial carried out over a period of 12 weeks . The patients were pre-selected to include only patients who were depressed on a ' self-rating depression scale ' but had no evidence of fibrositic ' trigger-points ' . The results showed that joint pain and tenderness were significantly reduced with trimipramine , but depression scores remained unchanged & NA ; The aim of this study was to examine the impact of pain on quality of life and its components in a representative sample of 320 well people , and patients selected from all major categories of illness . Quality of life was assessed using a new , multidimensional , multilingual , generic profile design ed for cross‐cultural use in health care , i.e. the WHOQOL . Within the WHOQOL , pain and discomfort is one of 29 areas or facets of quality of life , grouped into six domains . It was found that pain and discomfort made a significant impact on perceptions of general quality of life related to health . Furthermore , the presence of pain affected perceptions of five of the six domains of quality of life ; the domain of spirituality , religion and personal beliefs being the exception . When quality of life is assessed , negative feelings are most closely associated with reports of pain and discomfort than any other facet . But quality of life surrounding pain and discomfort is more fully explained by the inclusion of six additional facets ; the availability of social care , mobility , activities of daily living , positive mood and to a lesser extent , sleep and dependence on medication . Together , these seven facets represent criteria against which the success of pain treatments may be evaluated . As predicted , those who were pain‐free had significantly better quality of life than those in pain . A longer duration of pain is associated with increasingly poorer quality of life . Intense affective pain is particularly detrimental to a good quality of life . The psychometric properties of the pain and discomfort facet of the WHOQOL and WHOQOL‐100 were assessed . Internal consistency ( reliability ) , discriminant and criterion/concurrent validity were found to be good to excellent , justifying the use of this instrument with a range of chronic and acute pain patients A long-term ( two years ) double-blind , comparative trial of diftalone ( Aladione ® ) 500 mg versus indomethacin 75 mg per day , in rheumatoid arthritis ( thirty-two patients ) , has shown a similar effectiveness for both anti-inflammatory agents on various clinical parameters of disease activity , some better results being obtained for diftalone as regards the capacity of reducing erythrocyte sedimentation rate . The tolerability of diftalone proved to be somewhat superior , as is shown by the lower number of patients complaining of side-effects or being dropped out for intolerance , and by the lower frequency of central nervous system disturbances In a r and omized , double-blind , parallel study , fluoxetine and amitriptyline were compared with placebo in the treatment of chronic rheumatic pain . A total of 59 patients were evaluated during 4 wk of treatment and received 20 mg fluoxetine , 25 mg amitriptyline , or placebo daily . Pain intensity , pain relief , vital variables , and global evaluation were used to assess efficacy . To evaluate safety variables , the incidence of side effects was noted . Both amitriptyline and fluoxetine significantly reduced pain intensity compared with placebo . Similarly , pain relief was greater with both amitriptyline and fluoxetine than with placebo . At the end of the fourth week , fluoxetine was superior in efficacy to amitriptyline . The incidence of adverse effects was significantly greater with amitriptyline ; dryness of the mouth was the most predominant side effect . We conclude that fluoxetine is an effective analgesic with fewer side effects . ( Anesth Analg 1996;83:371 - 5 Forty-seven patients with definite rheumatoid arthritis ( RA ) were treated in a 32 week , double blind , crossover trial of amitriptyline , desipramine , trazodone , and placebo . All drug regimens produced significant changes on pain measures relative to baseline , but only amitriptyline exceeded placebo . Amitriptyline was associated with a significant reduction in the number of painful/tender joints . Our study supports the efficacy of a moderate dose of amitriptyline as an adjunct drug for the treatment of pain in both depressed and nondepressed patients with RA A multicentre double-blind clinical trial was conducted in general practice in which imipramine ( Tofranil ) was added to existing st and ard analgesic anti-rheumatic therapy in patients suffering from osteo-arthritis , rheumatoidtero-arthritis , rheumatoid arthritis or ankylosing spondylitis . Twelve doctors admitted sixty-five patients to the trial . Fifty-five patients completed an eitht-week treatment period . According to clinical assessment s imipramine brough about statistically significant improvements in pain , stiffness and grip strength and , according to patient self-rating , significant improvement in pain and stiffness . On the basis of a global assessment patients showed a highly significant preference for imipramine compared with placebo as adjunctive therapy BACKGROUND The relative importance of direct analgesic and antidepressant effects of antidepressant drugs in rheumatoid arthritis ( RA ) is not clear . METHOD Forty-eight female out- patients with RA , with depression and /or anxiety , were entered into a double-blind , placebo-controlled study of dothiepin in doses up to 150 mg daily to assess the effects on mood [ Hospital Anxiety and Depression ( HAD ) scale and Hamilton Rating Scale ( HRS ) for Depression ] , pain [ visual analogue scale ( VAS ) ] and disability [ Health Assessment Question naire ( HAQ ) ] . RESULTS Repeated measures multivariate analysis of variance revealed that treatment had a significant effect on pain ( F(d.f . 1,39 ) = 5.7 , P=0.02 ) . There were further interaction effects between treatment and time on pain ( F(d . f. 3,117 ) = 3.3 , P=0.03 ) , disability ( F(d.f . 3,117)=4.2 , P=0.008 ) and duration of early morning stiffness ( F(d.f . 3,117 ) = 3.3 , P=0.03 ) . Depression ( HRS ) was considerably reduced in both the dothiepin and placebo groups , and there was no significant difference between groups . Post hoc analyses using analysis of covariance revealed that , in the dothiepin group , pain was significantly reduced by week 4 and remained so at week 12 . Disability scores and duration of early morning stiffness were consistently lower in the dothiepin group , although differences failed to reach statistical significance at any follow-up assessment . In the group as a whole , reductions in pain were highly significantly correlated with reductions in HAD depression ( r = 0.63 , P<0.0005 ) , HAD anxiety ( r=0.46 , P=0.001 ) and HRS depression ( r=0.37 , P=0.01 ) . CONCLUSION Dothiepin is effective in relieving pain , disability and reducing the duration of early morning stiffness in out- patients with RA . Although there is a general association between pain reduction and improved anxiety and depression , the analgesic effect of dothiepin is independent of its antidepressant effect . Individual variation is considerable and further research should try to identify mechanisms of interaction between the antidepressant and analgesic effects of treatment in different patient groups |
13,252 | 22,566,015 | RESULTS Smoking decreases tissue oxygenation and aerobe metabolism temporarily .
The inflammatory healing response is attenuated by a reduced inflammatory cell chemotactic responsiveness , migratory function , and oxidative bactericidal mechanisms .
In addition , the release of proteolytic enzymes and inhibitors is imbalanced .
The proliferative response is impaired by a reduced fibroblast migration and proliferation in addition to a downregulated collagen synthesis and deposition .
Smoking cessation restores tissue oxygenation and metabolism rapidly .
Inflammatory cell response is reversed in part within 4 weeks , whereas the proliferative response remains impaired .
Nicotine does not affect tissue microenvironment , but appears to impair inflammation and stimulate proliferation .
CONCLUSIONS Smoking has a transient effect on the tissue microenvironment and a prolonged effect on inflammatory and reparative cell functions leading to delayed healing and complications .
Smoking cessation restores the tissue microenvironment rapidly and the inflammatory cellular functions within 4 weeks , but the proliferative response remain impaired .
Nicotine and nicotine replacement drugs seem to attenuate inflammation and enhance proliferation but the effect appears to be marginal | OBJECTIVE The aim was to clarify how smoking and nicotine affects wound healing processes and to establish if smoking cessation and nicotine replacement therapy reverse the mechanisms involved .
BACKGROUND Smoking is a recognized risk factor for healing complications after surgery , but the pathophysiological mechanisms remain largely unknown . | BACKGROUND It is generally accepted that smoking increases blood pressure and inhibits muscle sympathetic nerve activity ( SNA ) . The decrease in muscle SNA with cigarette smoking might be secondary to baroreflex responses to the pressor effect of smoking , thus obscuring a sympathetic excitatory effect of smoking . We tested the hypothesis that smoking increases sympathetic outflow . METHODS AND RESULTS We examined the effects of sham smoking , cigarette smoking , and cigarette smoking in combination with nitroprusside on muscle ( baroreflex-dependent ) SNA in 10 healthy habitual smokers . The 3 sessions were performed in r and om order , each study on a separate day . In an additional study , we also investigated the effects of sham smoking and cigarette smoking on skin ( baroreflex-independent ) SNA in 9 subjects . Compared with sham smoking , cigarette smoking alone increased blood pressure and decreased muscle SNA . When the blood pressure increase in response to smoking was blunted by nitroprusside infusion , there was a striking increase in muscle SNA . Muscle SNA increased up to 3-fold the levels seen before smoking ( P<0.001 ) , accompanied by an increase in heart rate of up to 37+/-4 bpm . Cigarette smoking also induced a 102+/-22 % increase in skin SNA ( P=0.03 ) . CONCLUSIONS These data provide the first direct evidence that cigarette smoking increases sympathetic outflow Cigarette smoking is associated with impaired endothelium‐dependent dilatation in human veins and arteries . An in vivo study in animals suggests that nicotine may contribute to this abnormality . We tested the hypothesis that local administration of nicotine at a dose reproducing the plasma concentration observed during smoking would impair endothelium‐dependent vasodilatation in human veins in vivo Using a reliable , newly developed assay for ascorbic acid ( reduced form ) and dehydroascorbic acid ( DHAA ; the oxidized form ) in plasma , we studied the influence of age , sex , and smoking on 219 healthy , age-stratified , and r and omly selected subjects representing the Danish population . The mean ( + /-SD ) plasma total ascorbic acid ( ascorbic acid + DHAA ) concentration was lower in smokers ( 62.8 + /- 24.9 mumol/L ) than in nonsmokers ( 74.9 + /- 23.6 mumol/L ) ( P < 0.001 ) and the DHAA content was 1.8 + /- 4.0 % of the total ascorbic acid in smokers compared with 0.1 + /- 3.1 % in nonsmokers ( P < 0.001 ) . A significant inverse correlation between the DHAA fraction and the total ascorbic acid concentration was found in smokers ( P < 0.002 ) but not in smokers ; the slopes of the linear regressions were significantly different in the two groups ( P < 0.005 ) . The mean plasma concentration of total ascorbic acid was higher in females than in males ( P < 0.005 ) ; this difference persisted in multivariate analysis when smoking was adjusted for . No age dependence could be identified . The data show that smoking results in severe oxidative stress , depletion of the ascorbic acid pool , and insufficient reduction capacity to maintain ascorbic acid in the reduced form in plasma . We suggest that the additional analysis of DHAA allows further differentiation in the assessment of oxidative stress and may provide an objective way of determining vitamin C requirements in smokers . Preliminary findings suggest that a vitamin C dose that results in a plasma concentration of approximately 70 mumol/L or higher is required in smokers BACKGROUND An association between smoking and impaired wound healing has been reported in retrospective studies . The smoking status of a surgical patient may be confounded by social and medical parameters . We have evaluated the effect of smoking in a test wound in volunteers , with special reference to a reliable scientific match between smokers and nonsmokers . METHODS In a prospect i ve open study with blinded assessment , 19 smoking ( 20 cigarettes/day ) and 18 nonsmoking healthy volunteers were matched with respect to baseline characteristics . The deposition of total protein and mature collagen ( expressed as hydroxyproline ) was assessed in an exp and ed polytetrafluoroethylene wound healing model implanted subcutaneously for 10 days . RESULTS The nonsmokers had a 1.8 times higher median amount of hydroxyproline than the smokers ( p < 0.01 ) . The deposition of hydroxyproline was negatively correlated with the consumption of tobacco both before ( r = -0.44 ; p < 0.01 ) and during the study ( r = -0.48 ; p < 0.005 ) . The impairment was specific for the production of collagenous proteins and not other proteins . CONCLUSIONS The synthesis of subcutaneous collagen in smokers is specifically impeded , indicating an impaired wound-healing process . Because mature collagen is the main determinator of strength of an operative wound , the results support the view that patients should be advised to stop smoking before an operation Objective —The role of antioxidants in preventing vascular disease remains controversial . Vascular endothelial growth factor ( VEGF-A ) is important for endothelial and monocyte function . This study investigated the negative effects of smoking on monocyte migratory responsiveness to VEGF-A and the usefulness of vitamin C to prevent smoking-induced monocyte dysfunction . Methods and Results —The chemotactic response of isolated monocytes from a cohort of 17 non-smokers and 10 smokers toward VEGF-A was assessed . VEGF-A significantly stimulated the migration of monocytes in non-smokers ; the monocytes from smokers failed to respond to VEGF-A. Repeated analysis after 2 weeks of vitamin C intake ( 2g/d ) showed a fully restored VEGF-A – induced monocyte migration in smokers . VEGF-A serum levels were not altered by vitamin C. VEGF-A – inducible kinase activity was intact in monocytes from smokers as assessed by in vitro kinase assay . Monocyte dysfunction can be mimicked in vitro by challenging monocytes with a range of reactive oxygen species ( ROS ) . Conclusions —Stimulation of monocyte migration by VEGF-A was severely attenuated in smokers , and the deficit observed was surmounted by vitamin C supplementation . The negative effects of smoking on monocyte function may translate into adverse impacts on VEGF-A – dependent repair processes such as arteriogenesis . These results propose a causative role of oxidative stress in smoking-induced monocyte dysfunction Higher white blood cell counts in smokers compared with nonsmokers have been well documented , but the longitudinal relation between changes in smoking and changes in white blood cells has not been well described . Since 1984 , data have been collected semiannually by the Multicenter AIDS Cohort Study ( MACS ) , a four-center prospect i ve cohort study of acquired immunodeficiency syndrome ( AIDS ) in homosexual men . The study population includes 2,435 participants who were human immunodeficiency virus ( HIV ) seronegative as of September 1994 and who contributed 20,918 person-visits for this analysis . For individuals who modified their smoking behavior , changes in white blood cell counts occurred primarily during the first 6 months following changes in the amount of cigarettes smoked . Among former smokers who resumed smoking , the extent of the increase in white blood cell count depended on the number of cigarettes smoked . Specifically , increases of 241 , 340 , and 740 cells/microliter were observed for smokers who resumed smoking < 1 , 1 to < 2 , and > or = 2 packs/day , respectively . Conversely , smokers who quit smoking had a decrease of white blood cell count : -32 , -629 , and -1,122 cells/microliter for men who previously smoked < 1 , 1 to < 2 , and > or = 2 packs/day , respectively . Long-term ex-smokers , however , still had higher white blood cell counts than did never smokers . There was a high within-individual correlation of white blood cell count in persons who reported a consistent level of smoking ( i.e. , average correlations between two white blood cell counts 6 years apart were 0.51 for never smokers , 0.48 for ex-smokers , 0.56 for men who smoked < 1 pack/day , and 0.43 for men who smoked > or = 1 pack/day ) . These analyses indicate an acute effect of changes in smoking on changes in white blood cell count , a residual effect of having been a smoker , and high long-term tracking for white blood cell count BACKGROUND Smokers are at higher risk of cardiopulmonary and wound-related postoperative complications than non-smokers . Our aim was to investigate the effect of preoperative smoking intervention on the frequency of postoperative complications in patients undergoing hip and knee replacement . METHODS We did a r and omised trial in three hospitals in Denmark . 120 patients were r and omly assigned 6 - 8 weeks before scheduled surgery to either the control ( n=60 ) or smoking intervention ( 60 ) group . Smoking intervention was counselling and nicotine replacement therapy , and either smoking cessation or at least 50 % smoking reduction . An assessor , who was masked to the intervention , registered the occurrence of cardiopulmonary , renal , neurological , or surgical complications and duration of hospital admittance . The main analysis was by intention to treat . FINDINGS Eight controls and four patients from the intervention group were excluded from the final analysis because their operations were either postponed or cancelled . Thus , 52 and 56 patients , respectively , were analysed for outcome . The overall complication rate was 18 % in the smoking intervention group and 52 % in controls ( p=0.0003 ) . The most significant effects of intervention were seen for wound-related complications ( 5 % vs 31 % , p=0.001 ) , cardiovascular complications ( 0 % vs 10 % , p=0.08 ) , and secondary surgery ( 4 % vs 15 % , p=0.07 ) . The median length of stay was 11 days ( range 7 - 55 ) in the intervention group and 13 days ( 8 - 65 ) in the control group . INTERPRETATION An effective smoking intervention programme 6 - 8 weeks before surgery reduces postoperative morbidity , and we recommend , on the basis of our results , this programme be adopted Delayed wound healing may explain postoperative tissue and wound dehiscence in smokers , but the effects of smoking and smoking cessation on the cellular mechanisms remain unclear . Suction blisters were raised in 48 smokers and 30 never smokers . The fluid was retrieved and the epidermal roof was excised . Transepidermal water loss ( TEWL ) was measured after 2 , 4 , and 7 days . Then , the smokers were r and omized to continuous smoking or abstinence with a transdermal nicotine patch or a placebo by concealed allocation . The sequence was repeated after 4 , 8 , and 12 weeks in all smokers and abstainers and in 6 never smokers . Matrix metalloproteinase (MMP)-8 and MMP-1 levels in suction blister fluid were assessed by an enzyme-linked immunosorbent assay . R and om-effects models for repeated measurements were applied and p < or = 0.05 was considered significant . One week after wounding the TEWL was 17.20 ( 14.47 - 19.92 ) g/cm(2 ) hour ( mean , 95 % CI ) in smokers and 13.89 ( 9.46 - 18.33 ) in never smokers ( p<0.01 ) . In abstinent smokers TEWL was 18.95 (15.20 - 22.70)(p<0.01 , when compared with smokers ) . In smokers , MMP-8 was 36.4 ( 24.3 - 48.5 ) ng/mL ( mean , 95 % CI ) and 15.2 ( 1.4 - 30.2 ) ng/mL in never smokers ( p<0.01 ) . Abstinent smokers ' MMP-8 level was 21.2 ng/mL ( 6.6 - 43.0 ) ( p=0.02 , when compared with smokers ) . MMP-1 was unaffected by smoking and abstention . Transdermal nicotine patch did not affect any parameter . We conclude that smoking attenuates epidermal healing and may enhance extracellular matrix degradation . Three months of abstinence from smoking does not restore epidermal healing , whereas 4 weeks of abstinence normalizes suction blister MMP-8 levels . These findings suggest sustained impaired wound healing in smokers and potential reversibility of extracellular matrix degradation OBJECTIVES We sought to determine the effects of nicotine patch therapy , when used to promote smoking cessation , on myocardial ischemia in patients with coronary artery disease . BACKGROUND Nicotine patches substantially increase quit rates among cigarette smokers , but their safety in patients with myocardial ischemia who are attempting to quit smoking is unknown . METHODS This is a prospect i ve study using exercise thallium-201 single-photon emission computed tomography ( SPECT ) to assess serial changes in the total and ischemic myocardial perfusion defect size at baseline while patients were smoking and during treatment with 14- and 21-mg nicotine patches . Entry criteria required that patients 1 ) smoked > or = 1 pack of cigarettes per day ; 2 ) had known coronary artery disease ; and 3 ) had myocardial ischemia ( i.e. , > or = 5 % reversible perfusion defect ) on SPECT . All patients performed symptom-limited treadmill exercise , and the baseline SPECT study served as its own control . We interpreted and computer quantified the SPECT images with no knowledge of the testing sequence . RESULTS Thirty-six of the 40 enrolled patients had exercise SPECT at baseline and during treatment with at least 14-mg nicotine patches . These patients had an initial perfusion defect size of 17.5 + /- 10.6 % while smoking an average of 31 + /- 11 cigarettes per day for 40 + /- 12 years . A significant reduction in the total perfusion defect size ( p < 0.001 ) was observed from baseline ( 17.5 + /- 10.6 % ) to treatment with 14-mg ( 12.6 + /- 10.1 % ) and 21-mg ( 11.8 + /- 9.9 % ) nicotine patches . This reduction occurred despite an increase in treadmill exercise duration ( p < 0.05 ) and higher serum nicotine levels ( p < 0.001 ) . There was a significant correlation between the reduction in defect size and exhaled carbon monoxide levels ( p < 0.001 ) because patients reduced their smoking by approximately 74 % during the trial . CONCLUSIONS Nicotine patches , when used to promote smoking cessation , significantly reduce the extent of exercise-induced myocardial ischemia as assessed by exercise thallium-201 SPECT Cigarette smokers deposit less collagen , expressed as hydroxyproline , in granulation tissue than nonsmokers . We studied the effect of abstinence from smoking and transdermal nicotine patches on deposition of hydroxyproline , proline , type I procollagen , and total proteins . Fifty-four healthy smokers were studied during 10 days of smoking and again from days 10 to 20 following smoking cessation . After the first 10 days of abstinence they were r and omized to double-blind treatment with transdermal nicotine patches of 25 mg/day or placebo for a period of 10 days . During this period and during smoking , an exp and ed polytetrafluoroethylene tube was implanted into the subcutis . Following removal of the implant , total amino acids and peptides were extracted . Hydroxyproline and proline were analyzed by high-pressure liquid chromatography , type I procollagen was analyzed by enzyme-linked immunoassay , and total proteins were determined colorimetrically . In the 39 subjects who complied with the study protocol , abstinence from smoking did not affect the deposition of hydroxyproline , proline , type I procollagen , or total protein in the implants . During abstinence , the type I procollagen level increased by 18 % in the transdermal nicotine patches group and decreased by 10 % in the placebo group ( p<0.05 ) . We conclude that 20 days of abstinence from smoking does not affect collagen deposition in granulation tissue . However , in abstinent smokers , transdermal nicotine patches appears to increase type I collagen synthesis Smoking is a major risk factor for coronary and peripheral vascular disease . This study was design ed to investigate the short-term effects of smoking and nicotine gum on endothelium-dependent ( EDV ) and -independent ( EIDV ) vasodilation in the forearm of young habitual smokers . In 10 subjects , forearm blood flow ( FBF ) during local infusion of metacholine ( 4 microg/min , evaluating EDV ) and sodium nitroprusside ( 10 microg/min , evaluating EIDV ) was assessed before and at 10 min ( early phase ) and 30 - 50 min ( plateau phase ) after the initiation of smoking , using forearm venous occlusion plethysmography . Six subjects underwent similar measurements of FBF before and 30 min after chewing a nicotine gum ( 4 mg ) . As a change in blood pressure was expected , forearm vascular resistance ( FVR ) was used to calculate EDV and EIDV . FVR during metacholine infusion increased from 4.6 + /- 1.4 SD to 5.9 + /- 2.1 mm Hg/ml/min/100 ml tissue during the early and to 5.0 + /- 1.6 mm Hg/ml/min/100 ml tissue at the plateau phase of smoking ( p < 0.01 for both vs. baseline ) and from 4.5 + /- 1.6 to 5.2 + /- 1.6 mm Hg/ml/min/100 ml tissue after chewing the nicotine gum ( p < 0.01 ) . No significant changes in EIDV were seen after smoking or the nicotine gum . When all data were analyzed together , plasma nicotine levels and blood pressure were both independent predictors of endothelial function ( p < 0.001 for both ) . In conclusion , cigarette smoking induced a dose-dependent attenuation in EDV , being maximal shortly after initiation of smoking and persisting up to 30 - 50 min . Nicotine chewing gum induced a similar impairment in EDV Cigarette smoking is associated with glaucoma . Nicotine from cigarette smoking is known to produce hemodynamic changes . We studied the effect of nicotine on the ophtalmic artery flow velocity using transcranial Doppler ultrasound to measure noninvasively the Peak ( systolic ) flow velocity ( Vp ) , mean-envelope flow velocity ( VM ) and end-diastolic flow velocity , as well as using a laser Doppler flowmeter on the finger blood flow of the finger prior to and after administration of 2–4 mg nicotine in a gum base . In a pilot project a group of 18 glaucoma patients and 8 normal subjects were tested with nicotine , and another group of 11 glaucoma patients were tested with placebo . VP , VM , and systolic blood pressure were significantly increased while finger blood flow was significantly decreased when comparing the nicotine-tested glaucoma group with the placebo-tested group ( P=0.02074 , 0.01479 , 0.02185 , and 0.04209 , respectively ) . The nicotine-tested group of normals also showed significant changes in VM , systolic blood pressure , and finger blood flow compared to a placebo group . The responses to the small doses of nicotine used in this study ( approximately one-third that of cigarette smoking ) were not significantly different between the glaucoma and the normal groups Background : Perinatal asphyxia is a major concern in perinatal medicine . Resuscitation and ways to prevent and minimize adverse outcomes after perinatal asphyxia are subject to extensive research . Objectives : In this study we hypothesized that , prior to hypoxia , intravenously administered nicotine might have an effect on how newborn piglets tolerate hypoxia , with regard to the time and degree of damage inflicted , due to its suggested neuroprotective abilities , and further that resuscitation with 21 compared with 100 % oxygen in nicotine-pretreated animals would cause less cerebral damage . Methods : Thirty anesthetized newborn piglets were r and omized to either hypoxia or control groups , and pretreatment with either saline or nicotine . In addition , the nicotine/hypoxia group was r and omized to resuscitation with either 21 or 100 % oxygen for 15 min following hypoxia . Results : We found significantly more necrosis in the striatum and cortex combined ( p = 0.036 ) , and in the striatum alone ( p = 0.026 ) , in the animals pretreated with nicotine and resuscitated with 100 % when compared to 21 % oxygen . There was no significant difference in the cerebellum . We also found significantly increased tolerance to hypoxia as measured by the time interval that the animals endured hypoxia : 103.8 ± 28.2 min in the nicotine-pretreated animals vs. 66.5 ± 19.5 minin the saline-pretreated animals ( p = 0.035 ) . Conclusion : Nicotine enhances newborn piglets ’ ability to endure hypoxia , and resuscitation with 21 % oxygen inflicts less necrosis than 100 % oxygen . The potential neuroprotective effects of nicotine in the newborn brain should be further investigated Study Design . A review of the smoking habits in 426 patients who had been followed prospect ively for 2 years after a lumbar spinal fusion procedure was conducted . Objective . To analyze the effect of pre- and postoperative smoking on clinical and functional outcome after lumbar spinal fusion . Summary of Background Data . Several animal models have shown a negative effect of nicotine on spinal fusion . At this writing , the clinical effect of nicotine on spinal fusion has not been fully clarified . Methods . The study comprised 426 patients who underwent lumbar spinal fusion between 1993 and 1997 . These patients received a mailed question naire regarding their tobacco consumption before and after their surgery . All other data , including preoperative clinical and functional status , were collected prospect ively during a 2-year follow-up period . To assess functional outcome , the Dallas Pain Question naire was used . Results . The question naire was answered by 396 patients ( 93 % ) . Of these patients , 54.5 % ( 20 % more than the background population ) were smokers before the operation . Smoking of more than 10 cigarettes daily before the operation and attempted fusion at two or more levels increased the risk of nonunion : odds ratio , 2.01 ( P < 0.016 ) and odds ratio , 3.03 ( P < 0.001 ) , respectively . Smoking cessation increased fusion rates to near those of nonsmokers . Smoking had no influence on functional outcome , as assessed by the Dallas Pain Question naire , but preoperative smoking predicted a negative answer to the question “ Would you undergo the same treatment again , now that you know the result ? ” ( odds ratio , 1.65;P < 0.054 ) . Conclusions . Smoking was shown to have a negative effect on fusion and overall patient satisfaction , but no measurable influence on the functional outcome as assessed by the Dallas Pain Question naire Wound healing encompasses coagulation , inflammation , angiogenesis , fibroplasia , contraction , epithelialisation and remodeling . A granulation tissue is produced following incision of tissue such as skin , abdominal wall or the gastrointestinal tract , and the strength of the wound is determined primarily by the collagen content early in the healing course . Few models are available to study wound healing in man . The percutaneous insertion of exp and ed poly-tetrafluoroethylene tubes ( ePTFE ) into the subcutaneous tissue has been an established model for 20 years . The procedure is performed using a local anesthesia . The model has a diameter of 2.5 mm , a length of 5 - 10 cm and a pore size of 90 - 120 microns which is substantially more than that of vascular grafts . The polymer accumulates granulation tissue , the architecture of which resembles that of a normal surgical wound . Previous studies on the use of the ePTFE model in wound healing research are summarized in detail . Histological and immunohistochemical analyses of the granulation tissue deposited in the model were undertaken . The content of amino acids following hydrolysis of the granulation tissue was determined applying spectrophotometric or HPLC assays . Collagen amounts accumulated in the model are expressed as hydroxyproline per length of ePTFE or per total protein . Following a study in rats we examined 85 healthy volunteers and 158 surgical patients in the studies . Higher contents of hydroxyproline were found 10 days after implantation as compared to 5 days with considerable inter-person variation . Regarding median values there was a 25 % difference between two measurements performed on two distinct ePTFE tubes from the same person , and a 12 % difference between values obtained from two different pieces of the same ePTFE . Higher accumulation levels of hydroxyproline did not result in higher variability . Deposition of proline in the model correlated closely to total protein content . The ePTFE and a modified PVA model were compared in surgical patients . No reproducible measurements of hydroxyproline deposition were obtained with the PVA model as opposed to the ePTFE model . It is concluded that the modified PVA model is inadequate for determination of collagen deposition in subcutaneous granulation tissue . We found no correlation between collagen deposition levels obtained with placement of the ePTFE model in the subcutaneous tissue of the arm and in an uncomplicated surgical wound of the groin in the same patient , respectively . Significantly higher collagen deposition levels in the model were found in the surgical wound . Conversely , there was a significant correlation between protein deposition levels obtained at the two sites . Patients undergoing minor surgery ( groin hernia repair ) did not differ from healthy non-traumatized volunteers as regards deposition of collagen in subcutaneous tissue of the arm , whereas patients subjected to major general surgery demonstrated a significant decline during the postoperative phase compared to a preoperative evaluation . This decline was enhanced in patients who had infectious complications . Non-smoking volunteers were found to specifically accumulate more collagen ( median value 82 % ) than smokers matched for age and gender . Irrespective of the smoking status women accumulated significantly more collagen in the model than men . These findings were re-tested in a prospect i ve series leading to the same conclusion . Matrix metalloproteinases ( MMP-2 and MMP-9 ) were determined in wound fluid obtained from the subcutaneous cavities of herniotomy wounds 24 and 48 h after operation . A significant and inverse correlation was demonstrated between MMP-9 after 24 h and accumulation levels of collagen in the ePTFE tube 10 days after implantation in the wound . Finally , it was demonstrated that local application of granulocyte-macrophage colony-stimulating factor into the ePTFE model during implantation specifically and dose-dependently reduced the number of fibroblasts and deposition of collagen . The doses chosen for the experiments result ed in both a local and a systemic effect . It is concluded that the minimally invasive ePTFE model , despite a certain level of variability , presently provides one of the best possibilities of evaluation of the wound healing potential in both volunteers and patients under various conditions . We found the model convenient for the assessment of both matrix deposition during wound healing and the influence of several factors including demographic characteristics , trauma , tobacco smoking , drugs and tissue degrading components of the wound Summary . Background : Antioxidants , in particular vitamin C , have been suggested to decrease oxidative DNA damage . Such effects have been shown in mononuclear blood cells in the first few hours after ingestion , whereas studies of longer-term effects in well-nourished humans have been mainly negative . Aim : To investigate the antioxidant effect of vitamin C in terms of oxidative DNA damage measured by the comet assay and DNA repair measured by expression of OGG1 mRNA in blood cells of male smokers given 2 × 250 mg vitamin C daily as plain or slow release tablets combined with plain release vitamin E 2 × 91 mg , or placebo for 4 wk . Results : This study showed a difference in DNA protective effects between a slow release and a plain release vitamin C formulation . Ingestion of slow release vitamin C formulation was associated with fewer endonuclease III and formamidopyrimidine DNA glycosylase sensitive sites measured by the comet assay in mononuclear blood cells obtained 4 h and 8 h after a single tablet and 4 wk after two tablets a day . Ingestion of the vitamin formulation with plain release only indicated a damage-reducing effect 4 h after intake of a single tablet , and the effect was more apparent on endonuclease III than formamidopyrimidine DNA glycosylase sites . Overall the slow release tablets of vitamin C formulation had a more pronounced and a sustained protective effect on base damage compared with the plain release tablets . Plasma vitamin E was unaltered in the first 12 h after ingestion of a single tablet , suggesting that the antioxidant effect was mediated by vitamin C. Differences in plasma vitamin C levels at steady state could not explain the difference between the two vitamin C formulations , whereas wider amplitudes of plasma vitamin C were seen after ingestion of plain release formulation compared to slow release formulation . Assessment of OGG1 mRNA levels by RT-PCR did not indicate increased expression of this DNA repair gene after 4 wk of vitamin supplementation . Conclusion : This study suggests that long-term vitamin C supplementation at high dose , i. e. 500 mg together with vitamin E in moderate dose , 182 mg , decreases the steady-state level of oxidative DNA damage in mononuclear blood cells of smokers Abstract . Objective and design : To determine the influence of vitamin C supplementation ( 500 mg , bd , 14 days ) on the circulating concentrations of soluble ICAM-1 ( a marker of endothelial activation ) , neopterin ( a marker of monocyte activation ) , and neutrophil elastase ( a marker of neutrophil activation ) in smokers and non-smokers in a r and omised , double-blind , placebo-controlled trial in a hospital setting .Subjects : Twenty smokers ( serum cotinine ≥ 20 ng ml−1 ) and 20 age- and gender-matched non-smokers ( serum cotinine ≤ 13.7 ng ml−1 ) . Results : At baseline , there was a significant elevation in the concentration of sICAM-1 in smokers ( median 247 , IQR 199 to 357 ng ml−1 ) compared to non-smokers ( median 207 , IQR 189 to 227 ng ml−1 ; p = 0.014 ) . Vitamin C supplementation did not influence the circulating concentrations of ICAM-1 or neopterin , or leukocyte elastase activity , in smokers , non-smokers , or in the total population . Conclusions : Markers of monocyte and neutrophil activation were not influenced by smoking status in this study population . However , sICAM-1 concentrations were significantly elevated in tobacco smokers , reflecting tobacco-induced vascular activation that is unaffected by Vitamin C supplementation The effects of cigarette smoking fractions on polymorphonuclear leukocyte ( PMN ) chemotaxis were determined using the 51Cr-assay . Water-soluble fractions ( WSF ) of cigarette smoke produced from several tobacco types differed in inhibitory potencies ( i.e. , flue cured greater than or equal to Maryl and greater than or equal to blended greater than Burley greater than or equal to Turkish ) corresponding to the respective unsaturated aldehyde content of the smoke from these tobaccos . Fractionation of cigarette smoke condensate ( CSC ) demonstrated that the more polar fractions were potent inhibitors of chemotaxis whereas those containing nicotine and the polycyclic hydrocarbons were weak inhibitors of chemotaxis . Unlike the inhibitory effects of WSFs , CSC fractions did not inhibit r and om migration and their inhibition of chemotaxis could not be completely prevented by reduced glutathione . These data suggest that while the alpha , beta-unsaturated aldehydes present in the vapor phase of smoke are among the most potent inhibitors of in vitro PMN chemotaxis , other polar , nonvolatile constituents of cigarette smoke also inhibit chemotaxis and by a mechanism which differs from that of the unsaturated aldehydes Objective Clinical studies show that the incidence of postoperative wound complications is higher in smokers than nonsmokers . In this study , we evaluated the effect of abstinence from smoking on incisional wound infection . Methods Seventy-eight healthy subjects ( 48 smokers and 30 never-smokers ) were included in the study and followed for 15 weeks . In the first week of the study , the smokers smoked 20 cigarettes per day . Subsequently , they were r and omized to continuous smoking , abstinence with transdermal nicotine patch ( 25 mg per day ) , or abstinence with placebo patch . At the end of the first week and 4 , 8 , and 12 weeks after r and omization , incisional wounds were made lateral to the sacrum to excise punch biopsy wounds . At the same time identical wounds were made in 6 never-smokers . In 24 never-smokers a wound was made once . All wounds were followed for 2 weeks for development of wound complications . Results A total of 228 wounds were evaluated . In smokers the wound infection rate was 12 % ( 11 of 93 wounds ) compared with 2 % ( 1 of 48 wounds ) in never-smokers ( P < 0.05 ) . Wound infections were significantly fewer in abstinent smokers compared with continuous smokers after 4 , 8 , and 12 weeks after r and omization . No difference between transdermal nicotine patch and placebo was found . Conclusions Smokers have a higher wound infection rate than never-smokers and 4 weeks of abstinence from smoking reduces the incidence of wound infections Background : Although attempts have been made to identify the risk factors leading to complications after combined skin-sparing mastectomy and immediate prosthetic breast reconstruction , hardly any criteria are available to preoperatively distinguish patients in whom such an eventful postoperative course may be expected . Therefore , the authors wanted to establish which factors increase the risk of surgical complications to such a level as to adjust their indications for immediate breast reconstruction after skin-sparing mastectomy . Methods : The authors prospect ively studied the clinical relevance of six patient-related and nine procedure-related characteristics as potential risk factors for a complicated surgical outcome in 400 combined procedures in 309 patients by univariate and multivariate logistic regression analysis . Risk factors that proved significantly correlated with loss of implant by both analyses were accepted as clinical selection criteria that distinguish potential c and i date s with an unacceptably high risk of such loss . Results : Mild complications occurred significantly more often in patients who were older than the mean age of 43 years and in breasts that were more than average sized or operated on by a fellow in oncologic surgery . Implants were lost significantly more often in patients who were obese or smoked and in breasts that were more than average sized . Conclusions : The clinical ly relevant increase of risk of implant loss should lead to reluctance to perform combined skin-sparing mastectomy and immediate prosthetic breast reconstruction in obese patients who smoke ( 32 percent loss ) and in those with more than average sized breasts ( 27 percent loss ) Full-thickness 5 mm punch biopsy wounds were made lateral to the sacrum in 48 smokers and 30 never smokers . After 1 week , the wounds were excised and fixed . The smokers were then r and omized to continuous smoking or abstinence with a transdermal nicotine patch or a placebo patch . The sequence of wounding and excision was repeated after 4 , 8 , and 12 weeks . All excised tissue was stained with hematoxylin-eosin and immunohistochemically for macrophages ( CD68 ) , procollagen 1 N-terminal propeptide ( PINP ) in fibroblasts , and endothelial cells ( CD31 ) . The cellularity was assessed and scored by two independent histopathologists , and for the analysis , proportional odds models and r and om effect models for repeated measurements were applied . Macrophages and PINP-stained fibroblasts were reduced in the smokers ' wounds ( 0.28 [ 0.14 - 0.58 ] [ OR , 95%CI ] ; p=0.01 and 0.37[0.19 - 0.70 ] ; p<0.01 , respectively , when compared with never smokers ' wounds ) . Inflammation scores were marginally affected . Following smoking cessation , inflammatory cell infiltration and macrophages in the wounds increased . PINP-stained fibroblasts were unaffected . Neovascularization was not affected by smoking or abstinence . Wound inflammation and fibroblast proliferation were attenuated in smokers , suggesting delayed healing . Abstinence from smoking restores inflammation , but does not affect proliferation . These findings suggest a pathophysiologic mechanism for postoperative wound infection and dehiscence in smokers and why smoking cessation appears to reduce wound infection but not dehiscence OBJECTIVES The aim of this study was to determine whether nicotine , a constituent of cigarette smoke , contributes to acute endothelial dysfunction after smoking one cigarette . BACKGROUND Animal studies suggest that nicotine might cause an impairment of endothelium-dependent vasodilation via an increase in oxidative stress . METHODS Sixteen healthy smokers were entered into a r and omized , observer-blinded crossover study comparing the effects of nicotine nasal spray ( 1-mg nicotine ) and cigarette smoke ( 1-mg nicotine , 12 mg tar ) on vascular reactivity in the brachial artery . Using high-resolution ultrasound , flow-mediated dilation ( FMD ) and endothelium-independent , nitroglycerin-induced dilation were assessed at baseline and 20 min after the administration of nicotine ( spray or cigarette ) . RESULTS In response to similar increases in nicotine serum levels , FMD values declined from 10.2 + /- 4.4 % to 6.7 + /- 4.0 % after the spray ( mean difference : -3.6 + /- 2.0 % , 95 % confidence interval : -4.6 ; -2.5 , p < 0.0001 ) and from 9.4 + /- 3.8 % to 4.3 + /- 2.8 % after the cigarette ( -5.1 + /- 2.6 % , -6.5 ; -3.7 , p < 0.0001 ) . Nitroglycerin-induced dilation remained similar within both periods . Performing a period effect analysis of variance , a significant influence on FMD was found for the mode of administration ( p = 0.017 ) and the baseline value ( p = 0.021 ) . The effect on FMD was more pronounced after the cigarette than after the spray ( estimated average effect difference : 1.9 % FMD ) . Oxidation parameters did not increase significantly after nicotine spray or tobacco exposure . CONCLUSIONS These results demonstrate that nicotine alone causes acute endothelial dysfunction , although to a lesser extent than smoking a cigarette of the same nicotine yield . However , the precise mechanisms by which nicotine leads to this altered vascular reactivity remain unclear We hypothesized that if nicotine was used in a form that was not adulterated with other hazardous substances found in tobacco , it would increase cutaneous blood flow ( CBF ) result ing in an increase in skin temperature . The effects of nicotine on CBF was investigated in 80 healthy volunteers and 6 patients with peripheral circulation disturbances . Each subject was required to chew nicotine gum ( containing 2 mg nicotine ) for 15 min and the CBF was then measured with laser blood flowmetry . Skin temperature of 35 volunteers was measured with thermography before and after chewing the gum for 15 min . A control study was performed using ordinary gum without nicotine . Increased CBF ( > or = + 1 ml/min/100 g ) was observed in 55 of 86 subjects ( 64 % , 33.7 - 38.6 ml/min/100 g , P < 0.01 ) . An elevation in skin temperature ( > + 0.1 degree C ) was also observed with nicotine gum in 26 of 35 healthy subjects ( 74 % , + 0.62 + /- 0.96 degree C , P < 0.001 ) . The increase in CBF was greater in subjects in which the initial CBF was lower than in others ( P < 0.01 ) . Nicotine gum was found to increase CBF ( 55/86 ) and elevate skin temperature ( 26/35 ) . The smaller the initial CBF value , the greater was the increase in CBF . Nicotine or nicotine derivatives might prove to be useful agents for the treatment of peripheral circulation disturbances The contribution of carbon monoxide ( CO ) to the acute cardiovascular effects of smoking is not clear . Using a double-blind , r and omized , vehicle-controlled study design , we examined the sympathetic and vascular responses to modest increases in carboxyhemoglobin in 10 healthy humans . We measured muscle sympathetic nerve activity ( microneurography ) , forearm blood flow ( plethysmography ) , heart rate , blood pressure , and minute ventilation at baseline and during 60 minutes of CO inhalation ( 1000 ppm during the first 30 minutes and 100 ppm during the last 30 minutes ) . The same measurements were made in a vehicle session ( room air inhalation ) on a separate day . During the first 30 minutes of CO inhalation , carboxyhemoglobin levels increased progressively from 0.2 + /- 0.1 % to 8.3 + /- 0.5 % and were maintained at about this level for a further 30 minutes . Forearm vascular resistance did not change with CO but increased slightly with vehicle ; the effects of CO on muscle sympathetic nerve activity , forearm blood flow , blood pressure , heart rate , and minute ventilation were not significantly different from the effects of vehicle . Modest increases in carboxyhemoglobin levels equivalent to those result ing from cigarette smoking are unlikely to contribute to the acute sympathetic and hemodynamic effects of smoking in healthy humans The deleterious impact of cigarette smoking on cardiovascular health may be in part attributable to a free radical mediated proinflammatory response in circulating monocytes . In the current investigation , the impact of vitamin C supplementation on monocyte gene expression was determined in apoE4 smokers versus non-smokers . A total of 10 smokers and 11 non-smokers consumed 60mg/day of vitamin C for four weeks and a fasting blood sample was taken at baseline and post-intervention for the determination of plasma vitamin C and monocyte gene expression profiles using cDNA array and real time PCR . In apoE4 smokers , supplementation result ed in a 43 % increase in plasma vitamin C concentrations . Furthermore , a number of genes were differentially expressed more than 2-fold in response to treatment , including a downregulation of the proinflammatory mediators tumor necrosis factor ( TNF ) beta , TNF receptor , neurotrophin-3 growth factor receptor , and monocyte chemoattractant protein 1 receptor . The study has identified a number of molecular mechanisms underlying the benefit of vitamin C supplementation in smokers OBJECTIVES In the current study , we used a model of limb ischemia to determine whether nicotine could enhance arteriogenesis , to compare the magnitude of this effect to the angiogenic factor basic fibroblast growth factor ( bFGF ) , and to investigate the mechanisms of the effect . BACKGROUND We have shown previously that nicotine stimulates angiogenesis via stimulation of endothelial nicotinic cholinergic receptors . Stimulation of endothelial nicotinic cholinergic receptors causes endothelial cell proliferation , migration , and formation of capillary networks in vitro and angiogenesis in vivo in conditions of ischemia and inflammation . METHODS New Zeal and White rabbits ( n = 85 ) underwent unilateral femoral artery occlusion and were r and omized to nicotine ( 0.05 to 5.0 microg/kg/day ) , bFGF ( 10 microg/kg/day ) , or vehicle delivered intra-arterially via osmotic minipumps . At day 21 , morphologic changes were assessed by immunohistochemistry and angiography . Blood flow in the ischemic limb was determined by intra-arterial Doppler flow measurements and microsphere distribution . RESULTS Nicotine enhanced capillary density in the ischemic hind-limb to a similar extent as bFGF . Nicotine also increased angiographic score , calf blood pressure ratio , intra-arterial Doppler flow , and microsphere distribution . In vitro , nicotine stimulated monocyte adhesion and transmigration . Nicotine increased by two- to three-fold the expression of monocyte adhesion molecules CD11b and CD11a ; the expression of the endothelial adhesion molecule intercellular adhesion molecule-1 ; and the endothelial release of monocyte chemoattractant protein-1 . CONCLUSIONS In the short term , nicotine promotes angiogenesis and arteriogenesis in the setting of ischemia . The effect of nicotine may be mediated in part by activation of endothelial-monocyte interactions involved in arteriogenesis BACKGROUND Free radicals in cigarette smoke may cause oxidative damage to macromolecules , contributing to cardiovascular diseases and cancer . Decreased plasma antioxidant concentrations may indicate cigarette smoke-related oxidative stress . OBJECTIVE We compared the effects on plasma antioxidant concentrations in cotinine-confirmed active and passive smokers with those in nonsmokers , independent of differences in dietary intakes and other covariates . DESIGN Plasma sample s from 83 smokers , 40 passive smokers , and 36 nonsmokers were analyzed for total ascorbic acid , alpha- and gamma-tocopherols , 5 carotenoids , retinol , and cotinine . Groups were compared by using analysis of variance with adjustment for sex , age , race , body mass index , alcohol intake , triacylglycerol concentration , fruit and vegetable intakes , and dietary antioxidants . RESULTS After adjustment for dietary antioxidant intakes and other covariates , smokers and passive smokers had significantly lower plasma beta-carotene concentrations than did nonsmokers ( 0.15 , 0.17 , and 0.24 micro mol/L , respectively ) and significantly higher gamma-tocopherol concentrations ( 7.8 , 7.8 , and 6.5 micro mol/L , respectively ) . Smokers had significantly lower plasma ascorbic acid and beta-cryptoxanthin concentrations than did nonsmokers and passive smokers ( ascorbic acid : 43.6 , 54.5 , and 54.6 micro mol/L , respectively ; beta-cryptoxanthin : 0.12 , 0.16 , and 0.16 micro mol/L , respectively ) and significantly lower concentrations of lutein and zeaxanthin than did nonsmokers ( 0.33 compared with 0.41 micro mol/L ) . The P values for all the differences described above were < 0.05 . No significant differences in plasma concentrations of alpha-tocopherol , alpha-carotene , total carotenoids , lycopene , or retinol were observed . CONCLUSIONS These results indicate that cigarette smokers and nonsmokers exposed to cigarette smoke have a significantly lower plasma antioxidant status than do unexposed nonsmokers , independent of differences in dietary antioxidant intakes . Further research is required to explain why plasma gamma-tocopherol concentrations were significantly higher in smokers and passive smokers than in nonsmokers The purpose of this r and omized , double-blind , placebo-controlled multicenter trial was to compare topical zinc oxide with placebo mesh on secondary healing pilonidal wounds . Sixty-four ( 53 men ) consecutive patients , aged 17 - 60 years , were central ly r and omized to either treatment with 3 % zinc oxide ( n = 33 ) or placebo ( n = 31 ) by concealed allocation . Patients were followed with strict recording of beneficial and harmful effects including masked assessment of time to complete wound closure . Analysis was carried out on an intention-to-treat basis . Median healing times were 54 days ( interquartile range 42 - 71 days ) for the zinc and 62 days ( 55 - 82 days ) for the placebo group ( p = 0.32 ) . Topical zinc oxide increased ( p < 0.001 ) wound fluid zinc levels to 1,540 ( 1,035 - 2,265 ) microM and decreased ( p < 0.05 ) the occurrence of Staphylococcus aureus in wounds . Fewer zinc oxide ( n = 3 ) than placebo-treated patients ( n = 12 ) were prescribed postoperative antibiotics ( p = 0.005 ) . Serum-zinc levels increased ( p < 0.001 ) postoperatively in both groups but did not differ significantly between the two groups on day 7 . Zinc oxide was not associated with increased pain by the visual analog scale , cellular abnormalities by histopathological examination of wound biopsies , or other harmful effects . Larger clinical trials will be required to show definitive effects of topical zinc oxide on wound healing and infection Numerous studies have shown that cigarette smokers have a lower plasma concentration of ascorbic acid than non-smokers , but only a few have considered the antioxidant status of ex-smokers.1 We report the first controlled study monitoring the early effect of smoking cessation on the concentration of ascorbic acid in plasma . The study was conducted in accordance with the Declaration of Helsinki , and the protocol was approved by the local ethics committee . Two hundred volunteers were recruited through local advertisement and gave signed informed consent . Eligible subjects of both sexes ( aged 35 to 65 years ) had smoked at least 15 cigarettes a day for one year and declared motivation to stop . Exclusion criteria were known presence of disease ; daily intake of drugs , including hormonal contraceptives ; antioxidant supplements within the last month ; BACKGROUND Smoking is associated with surgical wound infections , impaired wound healing , and tissue-destructive disorders . The mechanisms are largely unknown , but changes in the function and activity of inflammatory cells may be involved . METHODS Seventy healthy volunteers ( 54 smokers and 16 never smokers ) were included . The smokers were studied while they smoked and after 20 days of abstinence . After the first 10 days of abstinence , they were r and omized to double-blind treatment with transdermal nicotine patch 25 mg per day or placebo . Venous blood neutrophils and monocytes were sample d and isolated . In 22 r and omly selected smokers and in all never smokers , the oxidative burst and chemotaxis were determined by a chemiluminescence response assay and a modified Boyden chamber technique , respectively . Stimulants were opsonized zymosan , formyl-Met-Leu-Phe , and zymosan-activated serum . RESULTS The neutrophil and monocyte oxidative burst was 50 % and 68 % lower , respectively , in smokers compared to never smokers ( P < .05 ) . Neutrophil chemotaxis was 93 % higher in smokers ( P < .05 ) . Monocyte chemotaxis was lower in smokers compared to never smokers ( P < .05 ) . After 20 days of abstinence , neutrophil oxidative burst increased to the level of never smokers ( P < .05 ) ; monocyte oxidative burst increased by 50 % ( P < .05 ) . Chemotaxis was only marginally affected . The changes induced by abstinence were less pronounced in the transdermal nicotine patch group compared to the placebo group . CONCLUSIONS Smoking attenuates the oxidative burst of inflammatory cells and increases chemotaxis . Three weeks of abstinence normalize the oxidative burst , but affect chemotaxis only marginally Objective : The purpose of this study was to determine the effect of vitamin E and /or vitamin C supplementation on low-density lipoprotein ( LDL ) oxidizability and neutrophil ( PMN ) superoxide anion production in young smokers . Methods : Thirty smokers with a < 5 pack-year history were r and omly assigned to take placebo ; vitamin C ( 1 g/day ) ; vitamin E ( 400 IU/day ) ; or both vitamins in a double-blind fashion . Subjects took the supplements for 8 weeks . At weeks 0 and 8 , blood was collected for isolation of LDL and PMN , and for antioxidant vitamin analysis . LDL was oxidized with a copper ( Cu ) catalyst , and oxidation was measured by formation of conjugated dienes over a 5-hour time course . Lag times and maximum oxidation rates were calculated from the time course data . PMN superoxide anion release was assessed by respiratory burst after stimulation with phorbol ester and opsonized zymosan , and their ability to oxidize autologous LDL following treatment with the above stimuli was measured with the conjugated diene assay . Results : Subjects who received vitamin E alone had a significant increase in the lag phase of Cu-catalyzed LDL oxidation ( week 0 , 118 ± 31 min vs. week 8 , 193 ± 80 min , mean ± SD , p < 0.05 ) , whereas the vitamin C and placebo groups had no changes in LDL oxidation kinetics . The group receiving both vitamins E and C had a significant reduction in oxidation rate ( week 0 , 7.4 ± 2.3 vs. week 8 , 5.1 ± 2.1 , p < 0.05 ) . There were no significant changes for any group in PMN superoxide anion production or PMN LDL oxidation after stimulation with either phorbol ester or opsonized zymosan . Plasma and LDL vitamin E concentrations were significantly increased in both groups that received vitamin E. The subjects who received vitamin C alone had no significant change in plasma vitamin C concentrations ; however , when data were pooled from both groups who received vitamin C , the increases were significant . Conclusion : Vitamin E supplementation of young smokers was effective in reducing Cu-catalyzed LDL oxidizability ; however , vitamin E and /or C supplementation showed few significant effects on the more physiologically relevant PMN function . This casts doubt on the ability of antioxidant supplementation to reduce oxidative stress in smokers in vivo . Therefore , smoking cessation remains the only means by which young smokers can prevent premature coronary heart disease Eight tests investigating the function of circulating polymorphonuclear leukocytes were performed in 68 subjects , half of whom smoked at least 20 cigarettes per day . Comparison of the two groups allowed determination of the in vivo effect of tobacco smoke on the nonspecific defense system of the body . Ingestion ability , oxygen consumption , and bactericidal activity were normal in smokers . Myeloperoxidase and neutrophil alkaline phosphatase activities also were unchanged . The nitroblue tetrazolium reduction and the serum lysozyme levels were slightly increased in smokers . The capillary tube r and om migration , though , was depressed , and intensive smoking further aggravated this change . It is suggested that tobacco smoke acts directly on one ( or several ) unidentified target site of polymorphonuclear leukocytes . This impairment , demonstrated in vivo , probably plays a role in the genesis of the bronchopulmonary diseases so frequent in heavy smokers |
13,253 | 24,853,663 | The Recurrence Score has been shown to be an independent predictor of disease-free survival , overall survival , and distant recurrence-free interval in patients with ER+ , N+ EBC .
Outcomes from decision impact and health economics studies further indicate that the Recurrence Score affects physician treatment recommendations equally in patients with N+ or N0 disease .
It also indicates that a reduction in Recurrence Score-directed chemotherapy is cost-effective .
There is a large body of evidence to support the use of the 21-gene assay Recurrence Score in patients with N+ EBC .
Use of this assay could help guide treatment decisions for patients who are most likely to receive benefit from chemotherapy | The addition of adjuvant chemotherapy to hormonal therapy is recommended for patients with estrogen receptor-positive ( ER+ ) , node-positive ( N+ ) early breast cancer ( EBC ) .
Some of these patients , however , are not likely to benefit from treatment and may , therefore , be overtreated while also incurring unnecessary treatment-related adverse events and health care costs .
The 21-gene Recurrence Score assay has been clinical ly vali date d and recommended for use in patients with ER+ , node-negative ( N0 ) EBC to assess the 10-year risk of distant disease recurrence and predict the likelihood of response to adjuvant chemotherapy .
A growing body of evidence from several large phase III clinical trials reports similar findings in patients with ER+ , N+ EBC . | BACKGROUND The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures . METHODS We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction ( RT-PCR ) assay of 21 prospect ively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative , tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14 . The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospect ively defined algorithm to calculate a recurrence score and to determine a risk group ( low , intermediate , or high ) for each patient . RESULTS Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks . The proportions of patients categorized as having a low , intermediate , or high risk by the RT-PCR assay were 51 , 22 , and 27 percent , respectively . The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk , intermediate-risk , and high-risk groups were 6.8 percent ( 95 percent confidence interval , 4.0 to 9.6 ) , 14.3 percent ( 95 percent confidence interval , 8.3 to 20.3 ) , and 30.5 percent ( 95 percent confidence interval , 23.6 to 37.4 ) . The rate in the low-risk group was significantly lower than that in the high-risk group ( P<0.001 ) . In a multivariate Cox model , the recurrence score provided significant predictive power that was independent of age and tumor size ( P<0.001 ) . The recurrence score was also predictive of overall survival ( P<0.001 ) and could be used as a continuous function to predict distant recurrence in individual patients . CONCLUSIONS The recurrence score has been vali date d as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative , estrogen-receptor-positive breast cancer BACKGROUND PAM50 is a 50-gene test that is design ed to identify intrinsic breast cancer subtypes and generate a Risk of Recurrence ( ROR ) score . It has been developed to be carried out in qualified routine hospital pathology laboratories . PATIENTS AND METHODS One thous and four hundred seventy-eight postmenopausal women with estrogen receptor (ER)+ early breast cancer ( EBC ) treated with tamoxifen or tamoxifen followed by anastrozole from the prospect i ve r and omized ABCSG-8 trial were entered into this study . Patients did not receive adjuvant chemotherapy . RNA was extracted from paraffin blocks and analyzed using the PAM50 test . Both intrinsic subtype ( luminal A/B , HER2-enriched , basal-like ) and ROR score were calculated . The primary analysis was design ed to test whether the continuous ROR score adds prognostic value in predicting distant recurrence ( DR ) over and above st and ard clinical variables . RESULTS In all tested subgroups , ROR score significantly adds prognostic information to the clinical predictor ( P<0.0001 ) . PAM50 assigns an intrinsic subtype to all cases , and the luminal A cohort had a significantly lower ROR at 10 years compared with Luminal B ( P<0.0001 ) . Significant and clinical ly relevant discrimination between low- and high-risk groups occurred also within all tested subgroups . CONCLUSION ( S ) The results of the primary analysis , in combination with recently published results from the ATAC trial , constitute Level 1 evidence for clinical validity of the PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC . A 10-year metastasis risk of < 3.5 % in the ROR low category makes it unlikely that additional chemotherapy would improve this outcome -this finding could help to avoid unwarranted overtreatment . CLINICAL TRIAL NUMBER ABCSG 8 : NCT00291759 Introduction Patients with early-stage breast cancer , treated with endocrine therapy , have approximately 90 % 5-year disease-free survival . However , for patients at higher risk of relapse despite endocrine therapy , additional adjuvant therapy , such as chemotherapy , may be indicated . The challenge is to prospect ively identify such patients . The Mammostrat ® test uses five immunohistochemical markers to stratify patients on tamoxifen therapy into risk groups to inform treatment decisions . We tested the efficacy of this panel in a mixed population of cases treated in a single center with breast-conserving surgery and long-term follow-up . Methods Tissue microarrays from a consecutive series ( 1981 to 1998 ) of 1,812 women managed by wide local excision and postoperative radiotherapy were collected following appropriate ethical review . Of 1,390 cases stained , 197 received no adjuvant hormonal or chemotherapy , 1,044 received tamoxifen only , and 149 received a combination of hormonal therapy and chemotherapy . Median age at diagnosis was 57 , 71 % were postmenopausal , 23.9 % were node-positive and median tumor size was 1.5 cm . Sample s were stained using triplicate 0.6 mm2 tissue microarray cores , and positivity for p53 , HTF9C , CEACAM5 , NDRG1 and SLC7A5 was assessed . Each case was assigned a Mammostrat ® risk score , and distant recurrence-free survival ( DRFS ) , relapse-free survival ( RFS ) and overall survival ( OS ) were analyzed by marker positivity and risk score . Results Increased Mammostrat ® scores were significantly associated with reduced DRFS , RFS and OS in estrogen receptor (ER)-positive breast cancer ( P < 0.00001 ) . In multivariate analyses the risk score was independent of conventional risk factors for DRFS , RFS and OS ( P < 0.05 ) . In node-negative , tamoxifen-treated patients , 10-year recurrence rates were 7.6 ± 1.5 % in the low-risk group versus 20.0 ± 4.4 % in the high-risk group . Further , exploratory analyses revealed associations with outcome in both ER-negative and untreated patients . Conclusions This is the fifth independent study providing evidence that Mammostrat ® can act as an independent prognostic tool for ER-positive , tamoxifen-treated breast cancer . In addition , this study revealed for the first time a possible association with outcome regardless of node status and ER-negative tumors . When viewed in the context of previous results , these data provide further support for this antibody panel as an aid to patient management in early-stage breast cancer The development of tumor biomarkers ready for clinical use is complex . We propose a refined system for biomarker study design , conduct , analysis , and evaluation that incorporates a hierarchal level of evidence scale for tumor marker studies , including those using archived specimens . Although fully prospect i ve r and omized clinical trials to evaluate the medical utility of a prognostic or predictive biomarker are the gold st and ard , such trials are costly , so we discuss more efficient indirect " prospect ive-retrospective " design s using archived specimens . In particular , we propose new guidelines that stipulate that 1 ) adequate amounts of archived tissue must be available from enough patients from a prospect i ve trial ( which for predictive factors should generally be a r and omized design ) for analyses to have adequate statistical power and for the patients included in the evaluation to be clearly representative of the patients in the trial ; 2 ) the test should be analytically and preanalytically vali date d for use with archived tissue ; 3 ) the plan for biomarker evaluation should be completely specified in writing before the performance of biomarker assays on archived tissue and should be focused on evaluation of a single completely defined classifier ; and 4 ) the results from archived specimens should be vali date d using specimens from one or more similar , but separate , studies Purpose : To test the association between risk stratification and outcome in a prospect ively design ed , blinded retrospective study using tissue arrays of available paraffin blocks from the estrogen receptor – expressing , node-negative sample s from the National Surgical Adjuvant Breast and Bowel Project B14 and B20 tamoxifen and chemotherapy trials . Experimental Design : Tissue arrays were stained by immunohistochemistry targeting p53 , NDRG1 , SLC7A5 , CEACAM5 , and HTF9C . Risk stratification was done using predefined scoring rules , algorithm for combining scores , and cutoff points for low-risk , moderate-risk , and high-risk patient strata . Results : In a univariate Cox model , this test was significantly associated with recurrence-free interval [ HR , 1.3 ( 95 % confidence interval , 1.1 - 1.6 ) ; P = 0.006 ] . In a multivariate model it contributed information independent of age , tumor size , and menopausal status ( P = 0.007 ) . The Kaplan-Meier estimates of the proportion of recurrence-free after 10 years were 73 % , 86 % , and 85 % for the high-risk , moderate-risk , and low-risk groups ( P = 0.001 ) . The Kaplan-Meier estimates of the breast-cancer-specific-death rate were 23 % , 10 % , and 9 % ( P < 0.0001 ) . Exploratory analysis in patients ≥60 years old showed Kaplan-Meier estimates of the proportion of recurrence-free of 78 % , 89 % , and 92 % . Both high-risk and low-risk groups showed significant improvement on treatment with cytotoxic chemotherapy . Conclusions : Immunohistochemistry using five monoclonal antibodies assigns breast cancer patients to a risk index that was significantly associated with clinical outcome among the estrogen receptor – expressing , node-negative tamoxifen-treated patients . It seems that the test may be able to identify patients who have greater absolute benefit from adjuvant chemotherapy compared with unstratified patient population s. Exploratory analysis suggests that this test will be most useful in clinical decision making for postmenopausal patients Background We carried out a prospect i ve clinical study to evaluate the impact of the Recurrence Score ( RS ) on treatment decisions in early breast cancer ( EBC ) . Patients and methods A total of 379 eligible women with estrogen receptor positive ( ER+ ) , HER2-negative EBC and 0–3 positive lymph nodes were enrolled . Treatment recommendations , patients ' decisional conflict , physicians ' confidence before and after knowledge of the RS and actual treatment data were recorded . Results Of the 366 assessable patients 244 were node negative ( N0 ) and 122 node positive ( N+ ) . Treatment recommendations changed in 33 % of all patients ( N0 30 % , N+ 39 % ) . In 38 % of all patients ( N0 39 % , N+ 37 % ) with an initial recommendation for chemoendocrine therapy , the post-RS recommendation changed to endocrine therapy , in 25 % ( N0 22 % , N+ 39 % ) with an initial recommendation for endocrine therapy only to combined chemoendocrine therapy , respectively . A patients ' decisional conflict score improved by 6 % ( P = 0.028 ) and physicians ' confidence increased in 45 % ( P < 0.001 ) of all cases . Overall , 33 % ( N0 29 % , N+ 38 % ) of fewer patients actually received chemotherapy as compared with patients recommended chemotherapy pre-test . Using the test was cost-saving versus current clinical practice . Conclusion RS-guided chemotherapy decision-making result ed in a substantial modification of adjuvant chemotherapy usage in node-negative and node-positive ER+ EBC PURPOSE Patients with breast cancer experience progression and respond to treatment in diverse ways , but prognostic and predictive tools for the oncologist are limited . We have used gene expression data to guide the production of hundreds of novel antibody reagents to discover novel diagnostic tools for stratifying carcinoma patients . PATIENTS AND METHODS One hundred forty novel and 23 commercial antisera , selected on their ability to differentially stain tumor sample s , were used to stain paraffin blocks from a retrospective breast cancer cohort . Cox proportional hazards and regression tree analysis identified minimal panels of reagents able to predict risk of recurrence . We tested the prognostic association of these prospect ively defined algorithms in two independent cohorts . RESULTS In both validation cohorts , the Kaplan-Meier estimates of recurrence confirmed that both the Cox model using five reagents ( p53 , NDRG1 , CEACAM5 , SLC7A5 , and HTF9C ) and the regression tree model using six reagents ( p53 , PR , Ki67 , NAT1 , SLC7A5 , and HTF9C ) distinguished estrogen receptor (ER)-positive patients with poor outcomes . The Cox model was superior and distinguished patients with poor outcomes from patients with good or moderate outcomes with a hazard ratio of 2.21 ( P = .0008 ) in validation cohort 1 and 1.88 ( P = .004 ) in cohort 2 . In multivariable analysis , the calculated risk of recurrence was independent of stage , grade , and lymph node status . A model proposed for ER-negative patients failed validation in the independent cohorts . CONCLUSION A panel of five antibodies can significantly improve on traditional prognosticators in predicting outcome for ER-positive breast cancer patients The prognostic accuracy for distant recurrence‐free survival using a 21‐gene reverse‐transcriptase polymerase chain reaction ( RT‐PCR ) assay underwent validation in 668 lymph node‐negative , estrogen receptor‐positive women with early‐stage breast cancer receiving tamoxifen on National Surgical Adjuvant Breast Program ( NSABP ) B‐14 . The predictive accuracy for treatment efficacy also underwent validation in 651 patients r and omized on NSABP B‐20 and 645 patients on NSABP B‐14 TPS104 Background : Multi-gene tumor assays have provided clinical ly useful prognostic information for patients with HR receptor and node-positive breast cancer . The 21-gene RS was shown to be prognostic for patients treated with tamoxifen alone , and exploratory studies suggested that it may be predictive of benefit from chemotherapy . In retrospective analyses from S8814 , patients with low RS appeared to get no benefit from adjuvant CAF chemotherapy , while those with higher RS did . These retrospective data require validation , especially since more modern chemotherapy might be more effective than the regimen used in S8814 . In January 2011 SWOG activated a trial to test the efficacy of using modern chemotherapy regimens in node positive patients with low RS , whose prognosis is still moderately poor but may not benefit from adjuvant chemotherapy based on tumor biology predicted by the RS value . The trial is similar to the Tailor RX study , but focuses on a node-positive population with low and intermediate RS . METHODS Phase III r and omized clinical trial of best endocrine therapy vs. best endocrine therapy and chemotherapy . Patients with 1 to 3 positive lymph nodes , HR-positive and HER2-negative invasive breast cancer with RS ≤ 25 are eligible for r and omization . Approximately , 9,400 patients will be screened to r and omize 4000 , stratified by RS ( 0 - 13 vs. 14 - 25 ) , menopausal status , and axillary surgery ( sentinel node vs.full dissection ) . Patients will be informed of their RS . Trial is powered on finding a significant interaction of treatment assignment and the continuous RS value and subsequently deriving a cutpoint for using the assay to guide treatment decisions . Patients who consent to screening are required to consent to banking of the tumor tissue and blood for further studies . Patient Reported Outcomes will be collected pre , post screening and post-r and omization . The study also has a cost-effectiveness analysis . Status : Open nationwide through participating NCI-funded cooperative groups . NCT01272037 PURPOSE The primary aim of National Surgical Adjuvant Breast and Bowel Project ( NSABP ) B-28 was to determine whether four cycles of adjuvant paclitaxel ( PTX ) after four cycles of adjuvant doxorubicin/cyclophosphamide ( AC ) will prolong disease-free survival ( DFS ) and overall survival ( OS ) compared with four cycles of AC alone in patients with resected operable breast cancer and histologically positive axillary nodes . PATIENTS AND METHODS Between August 1995 and May 1998 , 3,060 patients were r and omly assigned ( AC , 1,529 ; AC followed by PTX [ AC -- > PTX ] , 1,531 ) . Patients > or = 50 years and those younger than 50 years with estrogen receptor ( ER ) or progesterone receptor ( PR ) -positive tumors also received tamoxifen for 5 years , starting with the first dose of AC . Postlumpectomy radiotherapy was m and ated . Postmastectomy or regional radiotherapy was prohibited . Median follow-up is 64.6 months . RESULTS The addition of PTX to AC significantly reduced the hazard for DFS event by 17 % ( relative risk [ RR ] , 0.83 ; 95 % CI , 0.72 to 0.95 ; P = .006 ) . Five-year DFS was 76 % + /- 2 % for patients r and omly assigned to AC -- > PTX compared with 72 % + /- 2 % for those r and omly assigned to AC . Improvement in OS was small and not statistically significant ( RR , 0.93 ; 95 % CI , 0.78 to 1.12 ; P = .46 ) . Five-year OS was 85 % + /- 2 % for both groups . Subset analysis of the effect of paclitaxel according to hormone receptors or tamoxifen administration did not reveal statistically significant interaction ( for DFS , P = .30 and P = .44 , respectively ) . Toxicity with the AC -- > PTX regimen was acceptable for the adjuvant setting . CONCLUSION The addition of PTX to AC result ed in significant improvement in DFS but no significant improvement in OS with acceptable toxicity . No significant interaction between treatment effect and receptor status or tamoxifen administration was observed BACKGROUND In the adjuvant setting , tamoxifen is the established treatment for postmenopausal women with hormone-sensitive breast cancer . However , it is associated with several side-effects including endometrial cancer and thromboembolic disorders . We aim ed to compare the safety and efficacy outcomes of tamoxifen with those of anastrozole alone and the combination of anastrozole plus tamoxifen for 5 years . METHODS Participants were postmenopausal patients with invasive operable breast cancer who had completed primary therapy and were eligible to receive adjuvant hormonal therapy . The primary endpoints were disease-free survival and occurrence of adverse events . Analysis for efficacy was by intention to treat . FINDINGS 9366 patients were recruited , of whom 3125 were r and omly assigned anastrozole , 3116 tamoxifen , and 3125 combination . Median follow-up was 33.3 months . 7839 ( 84 % ) patients were known to be hormone-receptor-positive . Disease-free survival at 3 years was 89.4 % on anastrozole and 87.4 % on tamoxifen ( hazard ratio 0.83 [ 95 % CI 0.71 - 0.96 ] , p=0.013 ) . Results with the combination were not significantly different from those with tamoxifen alone ( 87.2 % , 1.02 [ 0.89 - 1.18 ] , p=0.8 ) . The improvement in disease-free survival with anastrozole was seen in the subgroup of hormone-receptor-positive patients , but not the receptor-negative patients . Incidence of contralateral breast cancer was significantly lower with anastrozole than with tamoxifen ( odds ratio 0.42 [ 0.22 - 0.79 ] , p=0.007 ) . Anastrozole was significantly better tolerated than tamoxifen with respect to endometrial cancer ( p=0.02 ) , vaginal bleeding and discharge ( p<0.0001 for both ) , cerebrovascular events ( p=0.0006 ) , venous thromboembolic events ( p=0.0006 ) , and hot flushes ( p<0.0001 ) . Tamoxifen was significantly better tolerated than anastrozole with respect to musculoskeletal disorders and fractures ( p<0.0001 for both ) . INTERPRETATION Anastrozole is an effective and well tolerated endocrine option for the treatment of postmenopausal patients with hormone-sensitive early breast cancer . Longer follow-up is required before a final benefit : risk assessment can be made Objective To identify the risk of systemic metastases from T1a and T1b N0 breast cancers in patients treated in an academic center , and to seek factors to identify the patients at greatest risk of such failure . Summary Background Data With the demonstration that adjuvant chemotherapy reduces the death rate from breast cancer by roughly one quarter across all risk groups , controversy has reigned regarding possible exclusions from therapy . T1a and T1b N0 tumors ( 1-cm diameter and smaller with negative axillary nodes ) have been considered at low risk for metastasis since the report from Memorial Sloan-Kettering Cancer Center of a 90 % survival rate at 10 years . Subsequent reports have suggested an even more favorable prognosis for this group . However , consensus statements advise selecting some of these women for treatment , and many do receive adjuvant chemotherapy . Methods Sequential patients with breast cancer at the Emory Clinic were prospect ively staged and followed up for outcome . The records of patients with T1a and T1b N0 tumors were review ed for exact tumor diameter , grade , receptor status , adjuvant therapy , and outcome . A corrected data set was stripped of patient identifiers and analyzed by Kaplan-Meier methods . Subgroups were formed based on tumor grade ( 1 vs. 3 ) , adjuvant chemotherapy ( use vs. no use ) , and adjuvant tamoxifen ( use vs. no use ) and were compared via log-rank tests . Results Two hundred eighty-two women were identified . Two developed metastatic disease and one experienced a local failure after breast-conserving treatment . The estimated disease-free survival rate at 10 years was 98.7 % . With only two distant failures and one local failure , there was no significant difference by grade , receptor status , or use of adjuvant chemotherapy or tamoxifen . Conclusions The risk of systemic failure from such tumors barely exceeded 1 % at 10 years . Unless future studies can identify a subgroup at higher risk , the cognitive changes associated with cytotoxic chemotherapy or the loss of estrogen involved do not appear to have sufficient off setting benefit to warrant chemotherapy for this group of women PURPOSE Adjuvant ! is a st and ardized vali date d decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy . Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features . PATIENTS AND METHODS A sample of 465 patients with hormone receptor ( HR ) -positive breast cancer with zero to three positive axillary nodes who did ( n = 99 ) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay . Histologic grade and HR expression were evaluated locally and in a central laboratory . RESULTS Recurrence Score ( RS ) was a highly significant predictor of recurrence , including node-negative and node-positive disease ( P < .001 for both ) and when adjusted for other clinical variables . RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant ! that was adjusted to 5-year outcomes . The 5-year recurrence rate was only 5 % or less for the estimated 46 % of patients who have a low RS ( < 18 ) . CONCLUSION The 21-gene assay was a more accurate predictor of relapse than st and ard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging , such as tumor size and lymph node involvement . The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments |
13,254 | 29,243,265 | RESULTS Among 28 identified articles , the most frequently cited motivators for male blood product donation were as follows : altruism ; positive attitude towards incentives ; health check(s ) ; subjective norms .
Altruism was less pronounced among males compared with females and was combined with ' warm glow ' in novice males ( impure altruism ) .
Perceived health benefits and incentives ( e.g. coffee mugs ) were stronger motivators of males than females . | BACKGROUND AND OBJECTIVES Effective recruitment and retention of male donors are vital for the ongoing provision of blood products .
Compared with females , male donors are less likely to be medically deferred or experience vasovagal reactions and are typically preferred for plasmapheresis donation in voluntary non-remunerated setting s. However , females outnumber males among donors aged under 40 years .
This systematic review aim ed to synthesize evidence and identify key motivators for blood donation among males to inform targeted recruitment/retention campaigns . | BACKGROUND Health tests are often seen as promising donor incentives to improve the supply of blood . However , systematic behavioral evidence on donor recruitment is scarce . STUDY DESIGN AND METHODS To study the effectiveness of a free cholesterol test in attracting new donors and motivating previous donors , two field experiments were conducted . In Study 1 , 2825 nondonors were r and omly assigned to one of three treatments : a solicitation letter , a solicitation letter plus an appeal , or a solicitation letter plus an appeal and the offer of a free cholesterol test . In Study 2 , 8269 previous donors were r and omly assigned to one of three treatments : a st and ard invitation , an invitation plus an appeal , or an invitation plus an appeal and a cholesterol test . Marginal effects from probit estimations were calculated to study the effects of the treatments on donors ' response . RESULTS In Study 1 , only 0.6 percent reacted to the solicitation letter . There were no significant differences in the response rates between the three treatments . In Study 2 , 45.3 percent of the invited previous donors came to donate . The appeal ( marginal effect , -0.5 % ; st and ard error [ SE ] , 1.9 % ) and offering a cholesterol test ( marginal effect , 1.6 % ; SE , 1.8 % ) did not significantly increase the probability of a donation relative to the st and ard invitation . The treatment effects for the cholesterol test did not systematic ally differ between frequent and infrequent donors and female and male donors . There is some evidence that young donors responded relatively most positive to the cholesterol test ( marginal effect , 4.4 % ; SE , 2.2 % ) . CONCLUSIONS Contrary to conclusions from survey studies , free cholesterol testing did not significantly increase donations from nondonors and previous donors during a 3-month campaign . The two studies show that field experiments are an important method to evaluate donation incentives , because measuring donors ' intentions alone can lead to significantly different conclusions BACKGROUND Some blood donation-related adverse events ( AEs ) can negatively impact the blood donor return rate ( BDRR ) and decrease donor retention . STUDY DESIGN AND METHODS One-thous and r and omly selected whole-blood donors were interviewed 3 weeks after a 525-mL index whole-blood donation for seven AEs . The number of return visits and duration of follow-up were recorded for each of the 1000 donors . A negative binomial regression analysis was used to determine the contribution of the four most common AEs to the BDRR , and interactions between these AEs were also evaluated . RESULTS The four most common AEs were bruise alone ( 15.1 % ) , sore arm " alone " ( 7.0 % ) , fatigue " alone " ( 5.1 % ) , and donor reaction " alone " ( 4.2 % ) , where " alone " is defined to also include donors who had a bruise but no other AE . The estimated BDRR for donations without AEs was 1.32 visits per year . The estimated BDRRs for the four most common AEs were : bruise alone , 1.32 visits per year ; sore arm alone , 1.30 visits per year ( 2 % reduction in BDRR ) ; fatigue alone , 1.06 visits per year ( 20 % reduction in BDRR ) ; and donor reaction alone , 0.87 visits per year ( 34 % reduction in BDRR ) . The BDRR for donor reaction , fatigue , and sore arm together was 0.20 visits per year ( 85 % reduction in BDRR ) . CONCLUSION Donor reaction had the most negative impact on the BDRR . There appears to be a synergistic effect between donor reaction , fatigue , and sore arm . Theoretically , amelioration of some AEs has the potential to improve BDRRs BACKGROUND There are no reports in the transfusion medicine literature that describe adverse reactions and donor arm injuries after whole-blood donation based on solicited information . STUDY DESIGN AND METHODS The present study solicited adverse reaction and donor arm injury information from 1000 r and omly selected whole-blood donors approximately 3 weeks after the whole-blood donation . Two 16-gauge phlebotomy needles in use were also compared . RESULTS Thirty-six percent of the donors had one or more adverse effects ( AEs ) . The most common systemic AEs were fatigue ( 7.8 % ) , vasovagal symptoms ( 5.3 % ) , and nausea and vomiting ( 1.1 % ) . The most common arm findings were bruise ( 22.7 % ) , arm soreness ( 10.0 % ) , and hematoma ( 1.7 % ) . Men were half as likely as women to have an AE ( 23 % AE vs. 48 % AE , p < 0.0001 ) . Repeat blood donors had fewer AEs than first-time blood donors ( 36 % AE vs. 47 % AE , p < 0.007 ) , and African-American donors had numbers of AEs similar to those of Caucasian donors ( 31 % AE vs. 38 % AE , p = 0.30 ) . The two phlebotomy needles did not differ in causing blood donor AEs . CONCLUSION AEs after donation and complaints may be more common than previously thought . The postdonation interview is a good tool for defining the blood donor 's experience . It can also be used to evaluate and potentially improve blood donor safety and comfort BACKGROUND Blood supplies in Greece are insufficient to meet the high transfusion needs arising from car accidents and treatment of thalassaemia . This study was design ed to determine Greeks ' opinions about blood donation , in order to identify the reasons for the lack of motivation to donate and allow experts to establish better recruitment campaigns for the enrichment of the donor pool , based on our findings . MATERIAL S AND METHODS The opinions of r and omly selected Greek citizens ( n=800 ) about volunteer blood donation were assessed by means of a st and ardised , anonymous question naire . The results were analysed using the χ(2 ) test and Spearman 's correlation coefficient . RESULTS With regards to attitudes towards intention to donate , only 7.1 % were indifferent , while 88.0 % of the individuals believed that donating blood was an " offer " . Reasons for not donating mainly involved safety ( 36.0 % ) and fear ( 24.0 % ) , whereas need ( 77.9 % ) was the most fundamental positive motivation . Of the people enrolled in the present study , 10.0 % were active donors , 31.3 % occasional donors , 15.0 % rare donors and 36.6 % non-donors . DISCUSSION The considerable percentages of occasional and rare donors in comparison with the low proportion of active donors in the Greek donor pool indicates that " need " is a more important motivation for blood donation than altruism in Greece . These results could be useful for establishing advertising campaigns on blood donation and for a more direct approach to the population , aim ing for a change in mentality in favour of active blood donation |
13,255 | 17,253,449 | Individual studies did find some effects .
However it is impossible to prove or disprove in trials any supposed benefit that derives from God 's response to prayer | BACKGROUND Prayer is an ancient and widely used intervention for alleviating illness and promoting good health .
Whilst the outcomes of trials of prayer can not be interpreted as ' proof/disproof ' of God 's response to those praying , there may be an effect of prayer not dependent on divine intervention .
This may be quantifiable ; which makes this investigation of a widely used health care intervention both possible and important .
OBJECTIVES To review the effectiveness of intercessory prayer as an additional intervention for those with health problems already receiving st and ard medical care . | OBJECTIVE To determine the effect of intercessory prayer , a widely practice d complementary therapy , on cardiovascular disease progression after hospital discharge . PATIENTS AND METHODS In this r and omized controlled trial conducted between 1997 and 1999 , a total of 799 coronary care unit patients were r and omized at hospital discharge to the intercessory prayer group or to the control group . Intercessory prayer , ie , prayer by 1 or more persons on behalf of another , was administered at least once a week for 26 weeks by 5 intercessors per patient . The primary end point after 26 weeks was any of the following : death , cardiac arrest , rehospitalization for cardiovascular disease , coronary revascularization , or an emergency department visit for cardiovascular disease . Patients were divided into a high-risk group based on the presence of any of 5 risk factors ( age = or > 70 years , diabetes mellitus , prior myocardial infa rct ion , cerebrovascular disease , or peripheral vascular disease ) or a low-risk group ( absence of risk factors ) for subsequent primary events . RESULTS At 26 weeks , a primary end point had occurred in 25.6 % of the intercessory prayer group and 29.3 % of the control group ( odds ratio [ OR ] , 0.83 [ 95 % confidence interval ( CI ) , 0.60 - 1.14 ] ; P=.25 ) . Among high-risk patients , 31.0 % in the prayer group vs 33.3 % in the control group ( OR , 0.90 [ 95 % CI , 0.60 - 1.34 ] ; P=.60 ) experienced a primary end point . Among low-risk patients , a primary end point occurred in 17.0 % in the prayer group vs 24.1 % in the control group ( OR , 0.65 [ 95 % CI , 0.20 - 1.36 ] ; P=.12 ) . CONCLUSIONS As delivered in this study , intercessory prayer had no significant effect on medical outcomes after hospitalization in a coronary care unit OBJECTIVE Little is known about the effects of distant healing in chronically ill patients , the population most likely to see a healer in practice . This study investigated whether distant healing as found in normal practice with patients representative of those seeking treatment from healers changes patients ' quality of life substantially . METHOD R and omized , waiting-list controlled study of distant healing ( anonymous , amulet , and allowing for personal contact ) in chronically ill patients . OUTCOME MEASURE Patient-reported quality of life as expressed by the sum of all MOS SF-36 health survey items . RESULTS Sixty patients were treated by various methods of distant healing over 5 months ; 59 patients were put on a waiting list ( control ) . Quality of life improved significantly ( p < 0.0005 ) in the treated group ( 10 points ) , while it remained stable in the control group . Positive expectation was significantly correlated with outcome . CONCLUSION Chronically ill patients who want to be treated by distant healing and know that they are treated improve in quality of life The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas The therapeutic effects of intercessory prayer ( IP ) to the Judeo-Christian God , one of the oldest forms of therapy , has had little attention in the medical literature . To evaluate the effects of IP in a coronary care unit ( CCU ) population , a prospect i ve r and omized double-blind protocol was followed . Over ten months , 393 patients admitted to the CCU were r and omized , after signing informed consent , to an intercessory prayer group ( 192 patients ) or to a control group ( 201 patients ) . While hospitalized , the first group received IP by participating Christians praying outside the hospital ; the control group did not . At entry , chi-square and stepwise logistic analysis revealed no statistical difference between the groups . After entry , all patients had follow-up for the remainder of the admission . The IP group subsequently had a significantly lower severity score based on the hospital course after entry ( P<.01 ) . Multivariant analysis separated the groups on the basis of the outcome variables ( P<.0001 ) . The control patients required ventilatory assistance , antibiotics , and diuretics more frequently than patients in the IP group . These data suggest that intercessory prayer to the Judeo-Christian God has a beneficial therapeutic effect in patients admitted to a CCU OBJECTIVE To conduct a pilot study of the effect of intercessory prayer on patients entering treatment for alcohol abuse or dependence . DESIGN In addition to st and ard treatment , 40 patients admitted to a public substance abuse treatment facility for treatment of alcohol problems who consented to participate were r and omized to receive or not receive intercessory prayer ( double-blind ) by outside volunteers . Assessment s were conducted at baseline , 3 months , and 6 months . RESULTS No differences were found between prayer intervention and nonintervention groups on alcohol consumption . Compared with a normative group of patients treated at the same facility participants in the prayer study experienced a delay in drinking reduction . Those who reported at baseline that a family member or friend was already praying for them were found to be drinking significantly more at 6 months than were those who reported being unaware of anyone praying for them . Greater frequency of prayer by the participants themselves was associated with less drinking , but only at months 2 and 3 . CONCLUSION Intercessory prayer did not demonstrate clinical benefit in the treatment of alcohol abuse and dependence under these study conditions . Prayer may be a complex phenomenon with many interacting variables BACKGROUND The effect of intercessory prayer ( IP ) on outcome in cardiac cases has been evaluated previously , but results are controversial . The goals of the Study of the Therapeutic Effects of Intercessory Prayer ( STEP ) are to evaluate the effects of receipt of additional study IP and awareness of receipt of additional study IP on outcomes in patients undergoing coronary artery bypass graft surgery . STEP is not design ed to determine whether God exists or whether God does or does not respond to IP . METHODS STEP is a multicenter , controlled trial of 1802 patients in 6 US hospitals , r and omized to 1 of 3 groups . Two groups were informed that they may or may not receive 14 consecutive days of additional IP starting the night before coronary artery bypass graft surgery ; Group 1 received IP , Group 2 did not . A third group ( Group 3 ) was informed that they would receive additional IP and did so . Three mainstream religious sites provided daily IP for patients assigned to receive IP . At each hospital , research nurses blinded to patient group assignment review ed medical records to determine whether complications occurred , on the basis of the Society for Thoracic Surgeons definitions . A blinded nurse auditor from the Coordinating Center review ed every study patient 's data against the medical record before release of study forms . RESULTS The STEP Data and Safety Monitoring Board review ed patient safety and outcomes in the first 900 study patients . Patients were enrolled in STEP from January 1998 to November 2000 Abstract Objective : To determine whether remote , retroactive intercessory prayer , said for a group of patients with a bloodstream infection , has an effect on outcomes . Design : Double blind , parallel group , r and omised controlled trial of a retroactive intervention . Setting : University hospital . Subjects : All 3393 adult patients whose bloodstream infection was detected at the hospital in 1990 - 6 . Intervention : In July 2000 patients were r and omised to a control group and an intervention group . A remote , retroactive intercessory prayer was said for the well being and full recovery of the intervention group . Main outcome measures : Mortality in hospital , length of stay in hospital , and duration of fever . Results : Mortality was 28.1 % ( 475/1691 ) in the intervention group and 30.2 % ( 514/1702 ) in the control group ( P for difference=0.4 ) . Length of stay in hospital and duration of fever were significantly shorter in the intervention group than in the control group ( P=0.01 and P=0.04 , respectively ) . Conclusions : Remote , retroactive intercessory prayer said for a group is associated with a shorter stay in hospital and shorter duration of fever in patients with a bloodstream infection and should be considered for use in clinical practice . What is already known on this topic Two r and omised controlled trials of remote intercessory prayer ( praying for persons unknown ) showed a beneficial effect in patients in an intensive coronary care unit A recent systematic review found that 57 % of the r and omised , placebo controlled trials of distant healing showed a positive treatment effect What this study adds Remote intercessory prayer said for a group of patients is associated with a shorter hospital stay and shorter duration of fever in patients with a bloodstream infection , even when the intervention is performed 4–10 years after the Various forms of distant healing ( DH ) , including prayer and " psychic healing , " are widely practice d , but insufficient formal research has been done to indicate whether such efforts actually affect health . We report on a double-blind r and omized trial of DH in 40 patients with advanced AIDS . Subjects were pair-matched for age , CD4 + count , and number of AIDS-defining illnesses and r and omly selected to either 10 weeks of DH treatment or a control group . DH treatment was performed by self-identified healers representing many different healing and spiritual traditions . Healers were located throughout the United States during the study , and subjects and healers never met . Subjects were assessed by psychometric testing and blood draw at enrollment and followed for 6 months . At 6 months , a blind medical chart review found that treatment subjects acquired significantly fewer new AIDS-defining illnesses ( 0.1 versus 0.6 per patient , P = 0.04 ) , had lower illness severity ( severity score 0.8 versus 2.65 , P = 0.03 ) , and required significantly fewer doctor visits ( 9.2 versus 13.0 , P = 0.01 ) , fewer hospitalizations ( 0.15 versus 0.6 , P = 0.04 ) , and fewer days of hospitalization ( 0.5 versus 3.4 , P = 0.04 ) . Treated subjects also showed significantly improved mood compared with controls ( Profile of Mood States score -26 versus 14 , P = 0.02 ) . There were no significant differences in CD4 + counts . These data support the possibility of a DH effect in AIDS and suggest the value of further research BACKGROUND Patients undergoing percutaneous coronary intervention ( PCI ) for unstable coronary syndromes have substantial emotional and spiritual distress that may promote procedural complications . Noetic ( nonpharmacologic ) therapies may reduce anxiety , pain and distress , enhance the efficacy of pharmacologic agents , or affect short- and long-term procedural outcomes . METHODS The Monitoring and Actualization of Noetic Training ( MANTRA ) pilot study examined the feasibility of applying 4 noetic therapies-stress relaxation , imagery , touch therapy , and prayer-to patients in the setting of acute coronary interventions . Eligible patients had acute coronary syndromes and invasive angiography or PCI . Patients were r and omized across 5 treatment groups : the 4 noetic and st and ard therapies . Question naires completed before PCI reflected patients ' religious beliefs and anxiety . Index hospitalization end points included post-PCI ischemia , death , myocardial infa rct ion , heart failure , and urgent revascularization . Mortality was followed up for 6 months after hospitalization . RESULTS Of eligible patients , 88 % gave informed consent . Of 150 patients enrolled , 120 were assigned to noetic therapy ; 118 ( 98 % ) completed their therapeutic assignments . All clinical end points were available for 100 % of patients . Results were not statistically significant for any outcomes comparisons . There was a 25 % to 30 % absolute reduction in adverse periprocedural outcomes in patients treated with any noetic therapy compared with st and ard therapy . The lowest absolute complication rates were observed in patients assigned to off-site prayer . All mortality by 6-month follow-up was in the noetic therapies group . In patients with question naire scores indicating a high level of spiritual belief , a high level of personal spiritual activity , a low level of community-based religious involvement , or a high level of anxiety , noetic therapies appeared to show greater reduction in absolute in-hospital complication rates compared with st and ard therapy . CONCLUSIONS Acceptance of noetic adjuncts to invasive therapy for acute coronary syndromes was excellent , and logistics were feasible . No outcomes differences were significant ; however , index hospitalization data consistently suggested a therapeutic benefit with noetic therapy . Of all noetic therapies , off-site intercessory prayer had the lowest short- and long-term absolute complication rates . Definitive demonstration of treatment effects of this magnitude would be feasible in a patient population about 4 times that of this pilot study . Absolute mortality differences make safety considerations a m and atory feature of future clinical trials in this area BACKGROUND Intercessory prayer is widely believed to influence recovery from illness , but cl aims of benefits are not supported by well-controlled clinical trials . Prior studies have not addressed whether prayer itself or knowledge/certainty that prayer is being provided may influence outcome . We evaluated whether ( 1 ) receiving intercessory prayer or ( 2 ) being certain of receiving intercessory prayer was associated with uncomplicated recovery after coronary artery bypass graft ( CABG ) surgery . METHODS Patients at 6 US hospitals were r and omly assigned to 1 of 3 groups : 604 received intercessory prayer after being informed that they may or may not receive prayer ; 597 did not receive intercessory prayer also after being informed that they may or may not receive prayer ; and 601 received intercessory prayer after being informed they would receive prayer . Intercessory prayer was provided for 14 days , starting the night before CABG . The primary outcome was presence of any complication within 30 days of CABG . Secondary outcomes were any major event and mortality . RESULTS In the 2 groups uncertain about receiving intercessory prayer , complications occurred in 52 % ( 315/604 ) of patients who received intercessory prayer versus 51 % ( 304/597 ) of those who did not ( relative risk 1.02 , 95 % CI 0.92 - 1.15 ) . Complications occurred in 59 % ( 352/601 ) of patients certain of receiving intercessory prayer compared with the 52 % ( 315/604 ) of those uncertain of receiving intercessory prayer ( relative risk 1.14 , 95 % CI 1.02 - 1.28 ) . Major events and 30-day mortality were similar across the 3 groups . CONCLUSIONS Intercessory prayer itself had no effect on complication-free recovery from CABG , but certainty of receiving intercessory prayer was associated with a higher incidence of complications BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials |
13,256 | 21,678,338 | Studies were generally small in size and of varying quality .Scopolamine was more effective than placebo in the prevention of symptoms .
Comparisons between scopolamine and other agents were few and suggested that scopolamine was superior ( versus methscopolamine ) or equivalent ( versus antihistamines ) as a preventative agent .
Although sample sizes were small , scopolamine was no more likely to induce drowsiness , blurring of vision or dizziness compared to other agents .
Dry mouth was more likely with scopolamine than with methscopolamine or cinnarizine .
The use of scopolamine versus placebo in preventing motion sickness has been shown to be effective .
No conclusions can be made on the comparative effectiveness of scopolamine and other agents such as antihistamines and calcium channel antagonists . | BACKGROUND This is an up date of a Cochrane Review first published in The Cochrane Library in Issue 3 , 2004 and previously up date d in 2007 and 2009.Motion sickness , the discomfort experienced when perceived motion disturbs the organs of balance , may include symptoms such as nausea , vomiting , pallor , cold sweats , hypersalivation , hyperventilation and headaches .
The control and prevention of these symptoms has included pharmacological , behavioural and complementary therapies .
Although scopolamine ( hyoscine ) has been used in the treatment and prevention of motion sickness for decades , there have been no systematic review s of its effectiveness .
OBJECTIVES To assess the effectiveness of scopolamine versus no therapy , placebo , other drugs , behavioural and complementary therapy or two or more of the above therapies in combination for motion sickness in persons ( both adults and children ) without known vestibular , visual or central nervous system pathology . | Most clinical trials investigating prevention of seasickness with transdermal scopolamine have been short-term , and little information regarding long-term use is available . We report here a double-blind trial conducted on board a flat-bottomed Republic of Singapore Navy vessel of 2,490 tons , sailing in the South China Sea . The trip lasted 26 d , but self- assessment by the 122 adult male participants ( using a simplified scale quantifying the level of seasickness ) was confined to the 18 d spent at sea . We found that the protection rate with transdermal scopolamine was 46 - 57 % , with maximum benefits to inexperienced participants , during the early preadaptation phase , or in rough seas even after adaptation . Unwanted effects were few and generally minor . We concluded that the benefits of Scopoderm were worth exploiting even for long trips in moderate-to-rough seas In two placebo-controlled , double-blind , r and omized trials scopolamine ( 0.3 mg ) alone or combined with ephedrine ( 25 mg ) was tested for its effectiveness in the prevention of seasickness during 24 h at sea and of motion sickness in rotating chair tests in a laboratory . Scopolamine was effective both alone and in combination with ephedrine , which supports the hypothesis on central cholinergic overactivity in the pathogenesis of motion sickness . Ephedrine did not markedly increase the effectiveness of scopolamine . Side-effects were slight and did not disturb the operating ability of the volunteers The effect of transdermally administered scopolamine ( TTS scopolamine ) ( release rate 5 micrograms/h ) and dimenhydrinate ( 100 mg ) was examined on optovestibular nystagmus in 16 volunteers in a r and omized double-blind trial . A statistically significant decrease in the optokinetic part of nystagmus was observed during all treatments . Most profound reduction was found during treatment with two TTS scopolamine . The vestibular part was reduced by treatment with two TTS scopolamine , only . The results indicate that scopolamine and dimenhydrinate exert their effect in motion sickness by reducing the vestibular and visual influx and by partly inhibiting the integrative functioning of the vestibular nuclei . In their action , the motion sickness drugs seem to assist the cerebellum by diminishing impulses from various orientation reflexes in order to preserve the functional capacity of the central nervous system . Different symptoms in motion sickness seem to arise when the vestibular gain operates beyond the normal range of the cerebellar control mechanisms Space motion sickness has been estimated as affecting between 1/3 and 1/2 of all space flight participants . NASA has at the moment proposed a combination of promethazine and ephedrine ( P/E ) and one of scopolamine and dextroamphetamine ( S/D ) , both given orally , as well as a transdermally applied scopolamine ( TAS ) , as preventive and ameliorative measures . The reported double-blind study , tests the early phase actions and efficacy of the transdermal scopolamine ( Transderm (TM)-V of ALZA Corporation ) and compares these in detail to the oral medications . Motion sickness resistance was tested by st and ardized head movements while accelerating at 0.2 degree/sec2 to a maximum rotation of 240 degrees/sec , with an intermediate plateau of 10 min at 180 degrees/sec . To permit weighting motion sickness protection against other system influences , cardiovascular , psychological ( subjective and objective ) , and visual parameter changes were documented for the three therapeutic modes . The relative impact of the various modalities on operational and experimental components of space missions is discussed . A comparison to intramuscularly administered promethazine ( a backup therapeutic mode suggested for Space Shuttle use ) is also included Summary Three placebo-controlled double-blind studies in healthy volunteers were performed to reveal the psychophysiological effects of scopolamine , ephedrine and their combination . Single intravenous dose of scopolamine 6 µg/kg ( scopolamine hydrobromide 7.4 µg/kg ) impaired various psychomotor functions both subjectively and objective ly . It caused sedation , impairment of coordinative and reactive skills , visual disturbances and impairment of short-term memory . Oral scopolamine hydrobromide in single doses of 0.3 mg and 0.9 mg , or 0.9 mg b.d . for 3 days , had few effects . A slight impairment of short-term memory and a decrease in the flicker fusion threshold were seen . The visual nearpoint and pupil diameter were increased and some subjects reported blurred vision and dizziness during treatment with scopolamine 0.9 mg b.d . Scopolamine showed clear cardiovascular effects in all studies : it decreased heart rate and systolic blood pressure . Ephedrine alone and in combination with scopolamine had no deleterious effects . On the contrary , it antagonized the scopolamine-induced impairment in the flicker fusion test and the decrease in blood pressure and heart rate . In sufficient doses scopolamine impairs various psychomotor and cognitive skills . An oral dose of scopolamine hydrobromide 0.9 mg on average has few effects , although they may be very striking in certain individuals . To avoid unwanted effects and diminition in performance by scopolamine , doses less than 0.9 mg should be used Treatment of acute motion sickness induced by parabolic flight with a preparation of scopolamine placed in the buccal pouch was investigated . Twenty-one subjects flew aboard a KC-135 aircraft operated by the National Aeronautics and Space Administration ( NASA ) which performed parabolic maneuvers result ing in periods of 0-g , 1-g , and 1.8-g . Each subject flew once with a tablet containing scopolamine and once with a placebo in a r and om order , crossover design . Signs and symptoms of motion sickness were systematic ally recorded during each parabola by an investigator who was blind to the content of the tablet . Compared with flights using placebo , flights with buccal scopolamine result ed in significantly lower scores for nausea ( 31%-35 % reduction ) and vomiting ( 50 % reduction in number of parabolas with vomiting ) . Side effects of the drug during flight were negligible . We conclude that buccal scopolamine is more effective than a placebo in treating ongoing motion sickness The efficacy and tolerability of Scopoderm TTS ( SCOTTS ) , a transdermal system containing scopolamine , were compared with those of the oral antiemetic dimenhydrinate ( double-dummy technique ) in a controlled , double-blind , within-patient study including 20 test persons with proven motion sickness . During a 1-h test flight , SCOTTS proved to be as effective as dimenhydrinate . The efficacy and tolerability of both SCOTTS and dimenhydrinate were assessed as to be equally good . Due to its galenic properties , SCOTTS is effective over a 72-h period and therefore is useful in the prevention of motion sickness during long-distance flights , where it is superior to dimenhydrinate INTRODUCTION Despite many existing treatments , airsickness is an issue of concern for soldiers being transported by helicopter . This experiment examined the efficacy of four airsickness treatments and their effects on performance . This study replicated the transport of soldiers in the cabin of an UH-60 Black Hawk helicopter performing many of the flight maneuvers potentially experienced in a night troop transport during turbulent conditions . METHODS A double-blinded , placebo-controlled design was used to compare the effectiveness of four airsickness counter measures to their placebo controls . There were 64 male , non-aviator subjects ( ages 18 - 34 yr ) who were recruited for the study . Of these , 16 subjects were r and omly assigned to each of 4 groups : ( 1 ) promethazine ( 25 mg ) + caffeine ( 200 mg ) ; ( 2 ) meclizine ( 25 mg ) ; ( 3 ) Scopolamine patch ( 1.5 mg ) ; and 4 ) acustimulation wristb and . Each individual participated twice , once with the treatment and once with placebo . RESULTS The findings indicated that only the combination of promethazine + caffeine showed a statistically significant reduction in nausea and motion sickness severity , and an improvement in reaction time when compared with its placebo control . DISCUSSION Data from this study indicated that of the counter measures tested , promethazine + caffeine was the most effective at reducing airsickness while producing the fewest side effects when compared with its placebo . In addition , this study demonstrated that over-the-counter caffeine can serve as an effective stimulant counterpart to promethazine . This may be a more appealing option than employing scheduled sympathomimetic drugs in a combat environment Objective : Space motion sickness is currently treated pharmacologically with the empiric use of the H1 antihistamine promethazine , but use of this intervention is limited by the side effect of significant sedation . This creates a dilemma , as full cognition is particularly important during the same conditions likely to exacerbate the symptoms of space motion sickness . Using overstimulation of the semicircular canals with a rotary chair as a paradigm for space motion sickness , we evaluated four medications , commonly used for the treatment of terrestrial motion sickness and vertigo , for their efficacy in alleviating the simulated symptoms of space motion sickness . Study Design : R and omized , prospect i ve , double-blind study . Setting : Tertiary referral center . Patients : Healthy male and female volunteers , 18 years of age or older , without history of neurologic or psychiatric disorders , and with no known allergies or any previous adverse reactions to the drugs used . Interventions : Lorazepam 1 mg , meclizine 25 mg , promethazine 25 mg , scopolamine 0.4 mg , or placebo . Main Outcome Measure : The ability of each treatment to control the nausea and vomiting associated with our paradigm for space motion sickness was evaluated by measuring time of rotation pre- and posttreatment and time of symptom onset pre- and posttreatment . Results : Only scopolamine effected a mean change in duration of rotation that reached statistical significance when compared with placebo ( p < 0.008 ) , with a greater than 40 % increase in rotation time . Results with promethazine were not statistically significant . Conclusion : Results showed a rank order of efficacy of scopolamine > promethazine > placebo > meclizine > lorazepam . Scopolamine significantly increased rotation time , but none of the treatments result ed in a significant delay to onset of symptoms Transdermal scopolamine has been reported to provide protection against motion sickness , both while sailing at sea ( 7 - 8 h ) and under experimental conditions . In this study , we tested the efficacy of transdermal scopolamine and evaluated its side effects during a 72-h cruise at sea . We tested 38 male volunteers , 20 - 25 years old , who were located on a 3000-ton vessel . The presence of seasickness , defined by Graybiel 's diagnostic criteria , was used to calculate percent protection . When sickness was considered as malaise II or more , the drug provided 74 , 73 , and 39 % protection during the three sailing days , respectively . There were no significant differences in the magnitude of the side effects reported by experimental and placebo groups . We conclude that transdermal scopolamine 's efficacy against seasickness during a 3-day cruise was not associated with significant side effects and , therefore , we find the drug suitable for long-term use by sailing crews We conducted a double‐blind , placebo‐controlled study to evaluate the efficacy and tolerability of transdermal scopolamine in the prevention of motion sickness ( MS ) aboard a frigate during 7 days of continuously moderate or heavy seas . Forty‐nine healthy sailors with a previous history of MS were r and omly assigned to receive a transdermal therapeutic system of scopolamine ( TTS‐S ) or transdermal placebo ( TD‐P ) . Patches were placed behind the ears at least 4 hours before departure and were removed 72 hours later . Subjects were observed on days 1 to 4 and 6 . In the TTS‐S group , both subjective feeling of MS and the incidence of nausea were reduced during the first 2 days . Because of adaptation , differences in signs and symptoms of MS between subjects receiving TTS‐S and TD‐P disappeared after the second day . During the first 3 days , vomiting occurred less often in the TTS‐S group . On day 6 , 3 days after removal of the patch , vomiting occurred in 23 % of the TTS‐S group , probably due to delay in adaptation , but none of the subjects in the TD‐P group vomited . Concentration was not adversely influenced , since the ability to work increased in the TTS‐S group . During prolonged continuous exposure to heavy and moderate seas , 2.5 cm2 TTS‐S discs proved to be efficacious in preventing MS , with xerostomia as a tolerable side effect and no significant ocular side effects The effects of transdermally administered scopolamine ( TTS-scopolamine ) ( release rate 5 micrograms/h , one and two patches ) and dimenhydrinate ( 100 mg ) on caloric , angular acceleration induced and optokinetic nystagmus were examined in 16 volunteers in a r and omized double-blind study . All drugs induced a statistically significant decrease in maximum velocity of caloric nystagmus , as compared with placebo . In the rotatory test , two TTS-scopolamine and dimenhydrinate reduced the vestibular gain significantly . No changes were observed in time constant . In the optokinetic test , all drugs tended to reduce the responses , but a statistically significant reduction was found only after two TTS-scopolamine . The results indicate that the drugs effective against motion sickness reduce the nystagmic response , which at least partly explains the mode of action of the drugs . The target organ of the drugs is presumably the vestibular nucleus , where vestibular and visual impulses are integrated to ensure optimal gain for vestibular orientation reflexes Scopolamine was compared with cinnarizine in a double-blind sea trial involving 179 subjects from the crews of 2 warships . Medication was initiated prophylactically when weather information indicated the approach of nauseogenic conditions . Ship motion was measured during drug treatment periods . In one ship , moderate to severe nauseogenic conditions were encountered ; a parallel group comparison was achieved in this . In the other ship , the motion experienced was of a mild nature ; a crossover comparison was achieved . Scopolamine was shown to be more effective than cinnarizine in protecting against the symptoms of seasickness . In mild motion , cinnarizine was better tolerated than scopolamine in having less marked side effects . As motion severity increased , the comparative tolerability of scopolamine improved Studies were conducted to evaluate the efficacy of scopolamine , absorbed through intact skin , in preventing motion sickness at sea . Efficacy of transdermal scopolamine was compared with oral dimenhydrinate and placebo . Transdermal applications were made 4 to 16 hr before exposure to motion . Dimenhydrinate or placebo was given 1.5 hr before motion and again 2.5 hr after motion began . Comparison with placebo indicated that transdermal scopolamine provided protection against motion sickness at a significance level of p = 0.0001 and oral diphenhydrinate at a level of p = 0.05 . Dry mouth , drowsiness , and blurred vision associated with transdermal scopolamine therapy were minimal The purpose of this study was to examine the effects of scopolamine on the physiological patterns occurring prior to and during motion sickness stimulation . In addition , the use of physiological profiles in the prediction of motion sickness was evaluated . Sixty subjects ingested either 0.6 mg scopolamine , 2.5 mg methscopolamine , or a placebo . Heart rate ( HR ) , respiratory sinus arrhythmia ( an index of vagal tone ) , and electrogastrograms were measured prior to and during the exposure to a rotating optokinetic drum . Compared to the other groups , the scopolamine group reported fewer motion sickness symptoms , and displayed lower HR , higher vagal tone , enhanced normal gastric myoelectric activity , and depressed gastric dysrhythmias before and during motion sickness induction . Distinct physiological profiles prior to drum rotation could reliably differentiate individuals who would develop gastric discomfort from those who would not . Symptom-free subjects were characterized by high levels of vagal tone and low HR across conditions , and by maintaining normal ( 3 cpm ) electrogastrographic activity during drum rotation . It was concluded that scopolamine offered motion sickness protection by initiating a pattern of increased vagal tone and gastric myoelectric stability The effect of transdermally administered scopolamine ( TTS-scopolamine ) ( 2.5 cm2 surface area , one and two patches ) and dimenhydrinate ( 100 mg ) on experimental motion sickness was examined in 16 healthy volunteers in a r and omized double-blind study . Nausea was induced by Coriolis manoeuvre and vertigo by calorization of the ear . In all subjects , scopolamine was found in urine in concentrations indicating adequate absorption of the drug . One TTS-scopolamine , two TTS-scopolamine and dimenhydrinate caused a statistically significant reduction in nausea when compared with placebo . Dimenhydrinate was somewhat more effective against nausea than one TTS-scopolamine . Vertigo was significantly reduced after dimenhydrinate and two TTS-scopolamine . Side effects of both drugs were negligible , though gait disturbances and vertigo could occur occasionally after two TTS-scopolamine . No dose-response relationship was found between the urinary excretion of scopolamine and alleviation of nausea . Dimenhydrinate and TTS-scopolamine are both effective against motion sickness , the latter provided it is applied 6 to 8 hours before exposure to the stimulus causing the motion sickness INTRODUCTION Scopolamine is an effective motion sickness prophylactic , but oral and transdermal formulations are slowly absorbed . To enhance absorption and potentially efficacy , an intranasal formulation of scopolamine ( INSCOP ) was tested . METHOD There were 16 motion sickness susceptible subjects with an average age of 23.5 + /- 3.0 yr and an average score of 11.3 + /- 4.7 on the Modified Motion Sickness Susceptibility Question naire-Short Form who volunteered to participate in the study . Each subject was given 0.4 mg of INSCOP and a placebo in a r and omized , double-blind crossover design and , at 40 min post-dose , experienced Coriolis cross-coupling in a staircase progression until moderate nausea . Efficacy data and cognitive , physiological , and alertness assessment s were collected during baseline control and throughout experimental testing . RESULTS Intranasal scopolamine significantly increased the mean number of head movements tolerated [ INSCOP 275.9 + /- 120.5 , Placebo 230.7 + /- 76.4 ; t ( 15 ) = 2.21 ] . Estimation of medication absorption via plasma concentration indicated the drug was absorbed relatively rapidly to measurable levels by 15 min post-administration . Diastolic blood pressures and heart rate were significantly lower after administration of INSCOP compared to placebo . No significant cognitive or medication side effects were reported . Subjects reported no significant decrease in alertness as indicated by the Karolinska Sleepiness Scale . CONCLUSIONS Results of the current study strongly suggest that intranasal scopolamine is efficacious for the treatment of motion sickness in susceptible individuals with no significant cognitive or sedative effects . Intranasal delivery offers a promising alternative for use in dynamic operational environments without cognitive detriment or increased side effects Abstract Forty-two subjects who had symptoms of nausea or vomiting , when exposed to the motion of rough seas , were given an intramuscular injection of either l -hyoscine hydrobromide ( 0·2 mg . ) or physiological saline solution . Nineteen of the twenty-two subjects given hyoscine reported symptomatic improvement as opposed to nine of the twenty who received the placebo ; this difference is significant at the 5 % level . Side-effects were not severe : there was an equal incidence of drowsiness in both groups but dry mouth was more common after hyoscine . The dose given controlled symptoms within 15 to 30 minutes of administration and a dose of this size might be expected to afford protection for about 4 hours . An injection of this nature could therefore be of value for the rapid control of symptoms in conditions where treatment by mouth is not practicable Following the reports of earlier workers an experiment was carried out to assess the possible value of cupulometric techniques both in elucidating the mechanism of action of anti-motion sickness drugs and in screening new drugs for possible anti-motion sickness effect . The drugs used were (-)-hyoscine and amylobarbitone sodium because although both have central depressant properties in common only (-)-hyoscine has been shown to be consistently effective against motion sickness . There was some evidence to suggest that (-)-hyoscine shortened the duration of post-rotational turning sensation and that both drugs reduced the time constant of decay of post-rotational nystagmus . However , both these effects could well be attributable to generalised depression of the central nervous system . Any more specific pharmacological action was obscured both by habituation effects and idiosyncrasy of individual response : these factors render such tests of doubtful value in the screening of anti-motion sickness drugs In seasickness , the central cholinergic-noradrenergic balance is disturbed . Capsules of identical appearance -- containing scopolamine hydrobromide 0.3 mg , scopolamine hydrobromide 0.3 mg + ephedrine hydrochloride 25 mg , or placebo -- were given prophylactically three times daily to 30 naval cadets during a crossing . In this r and omized , double-blind trial the superiority of scopolamine and scopolamine + ephedrine over placebo was confirmed . Ephedrine did not clearly increase the effectiveness of scopolamine . One subject in the scopolamine group and one in the placebo group interrupted the treatment . The symptoms of seasickness as well as the number of side-effects of the drugs decreased on the third day of the study . Scopolamine alone or in combination with ephedrine proved useful in the prevention of seasickness in young healthy male volunteers The aim of the present study was to investigate the effects of scopolamine ( 1.5 mg , transdermal patch ) and cyclizine ( 50 mg tablet ) , at the doses usually used for the relief of motion sickness , on postural sway , optokinetic nystagmus ( OKN ) and circularvection ( CV ) in humans , using a within-subjects , double-blind , placebo-controlled design . Scopolamine and cyclizine were found to have no significant suppressive effect on these aspects of visual-vestibular interaction . Postural sway and CV were not significantly affected by either drug treatment ; OKN SPV was significantly increased ( p < 0.05 ) , although OKN amplitude and frequency were unaffected . These results suggest that scopolamine and cyclizine , at doses used for the relief of motion sickness , may have minimal suppressive effects on these aspects of visual-vestibular interaction The effectiveness of the Hungarian drug kavinton used to prevent motion sickness was assessed . During the study 8 motion sickness susceptible test subjects were kept in a chamber rotating at a rate of 6 rpm for 5 hours . The effectiveness of the drug taken regularly during the exposure was compared with that of scopolamine and placebo taken as a single dose . The results obtained are suggestive of a positive effect of kavinton as an antimotion drug We assessed the influence of dimenhydrinate , cinnarizine and transdermal scopolamine on the ability to perform simulated naval crew tasks . The effect of single doses of dimenhydrinate , 100 mg , cinnarizine , 50 mg , and one transdermal scopolamine patch on psychomotor performance was evaluated using a double-blind , placebo-controlled , r and omized , crossover design in three separate studies . A total of 60 young naval crew ( 20 for dimenhydrinate , 15 for cinnarizine and 25 for transdermal scopolamine ) underwent a battery of computerized and paper and pencil performance tests , and filled out a question naire on side-effects and well-being self- assessment . Dimenhydrinate significantly impaired decision reaction time and auditory digit span . Most of the subjects who took dimenhydrinate also reported a subjective decrease in well-being and general performance abilities . Cinnarizine and transdermal scopolamine did not affect performance abilities . Cinnarizine was free of significant side-effects . Dry mouth was the only significant side-effect of transdermal scopolamine . These findings could be explained by the well-known sedative properties of dimenhydrinate and not by a specific effect on any particular cognitive or motor function . Our results suggest that dimenhydrinate , 100 mg , adversely affects psychomotor function , whereas single doses of cinnarizine , 50 mg , and transdermal scopolamine appear to be free of side-effects on performance and seem to be a preferable anti-seasickness drug for use by a naval crew To test the prophylactic value of anti-motion sickness drugs , a r and omized double-blind trial was undertaken on 46 young , healthy , male volunteer marines . Comparison was made between a transdermal therapeutic system ( TTS ) containing as the effective agent scopolamine ( TTS-scopolamine ) and proprietary meclozine tablets . An artificial " sea voyage " served to produce motion sickness , each subject sitting by himself on an artificially tilting " isl and " , on two days for 30 minutes . Without treatment , 19 of the 46 subjects developed symptoms of motion sickness requiring treatment . After administration of TTS-scopolamine or meclozine tablets ( double-dummy technique ) the motion sickness score was reduced by 89 % and 59 % , respectively . There was a reduction on the visual analog scale of 98 % and 59 % , respectively . Probability of error ( Fisher 's exact probability test ) for assuming therapeutic advantage of TTS-scopolamine over meclozine tablets was 13.5 % . A pre-set significance level of 5 % was thus not reached . This trial shows that TTS-scopolamine , even in a brief exposure , has at least the same effectiveness as meclozine , in addition to avoiding the gastrointestinal tract and maintaining with certainty a constant blood level over three days Scopolamine has been used successfully for treatment of motion sickness for almost a century and the nasal administration was first studied 50 years ago . However , there never appeared a nasal dosage form . Finally , after finding a stable and suitable formulation for scopolamine , a study to investigate efficacy , safety , and tolerability was conducted , with a r and omised , double-blind , double-dummy , crossover , Latin square design including placebo control and a placebo/placebo control for internal validity at the German Air Force Institute of Aviation Medicine . To assess the efficacy of a new , stable and well-tolerated formulation of scopolamine nasal spray the reproducible induction of whole body vibrations by a rotating chair was chosen and a vali date d seasickness score ( SKS ) . The reduction of SKS showed that scopolamine nasal spray at a concentration of 0.2 % was statistically superior to both placebo and dimenhydrinate ( P=0.003 and 0.004 , respectively ) . There were no signs for a nasal or epipharyngeal irritation of the mucous membrane . Scopolamine nasal spray was found to be an effective and safe treatment in motion sickness , with a fast onset of action within 30 min after administration STUDY OBJECTIVE To evaluate the safety of double-dose transdermal scopolamine patch therapy . DESIGN R and omized , crossover , double-blind study . SETTING Motion sickness clinic in Haifa , Israel . PARTICIPANTS Twenty male sailors aged 18 - 21 years whose seasickness symptoms improved only slightly or not at all with a single transdermal scopolamine patch . INTERVENTION Subjects received either two transdermal scopolamine patches or one scopolamine patch plus a placebo patch for 24 hours ( first session ) . After at least 1 week from the end of the first session , they received the other treatment for 24 hours ( second session ) . MEASUREMENTS AND MAIN RESULTS Plasma scopolamine concentrations , physiologic ( heart rate and blood pressure ) , visual , and cognitive function parameters , and adverse effects were assessed before the first session ( baseline ) and after each 24-hour session . Visual function was tested again 24 hours after patch removal . Subjects also completed an adverse-effects question naire immediately after and 24 hours after patch removal for both treatment sessions . A significant difference was found in mean plasma scopolamine concentrations between the single-dose and double-dose treatments ( 81 vs 127 pg/ml [ therapeutic level 100 pg/ml ] , p<0.01 ) . No significant differences were found in heart rate , blood pressure , cognitive function , or visual function measurements . Mild blurred vision was the only adverse effect for which there was a significant difference between the single-dose and double-dose treatments ; however , this adverse effect was judged to be not clinical ly significant . CONCLUSION Double-dose transdermal scopolamine may improve treatment in patients who fail to respond to a single patch by increasing the plasma scopolamine concentration , without aggravating systemic , visual , or cognitive adverse effects . Thus we recommend that a double dose can be administered safely to these patients |
13,257 | 24,607,083 | Conclusions The clinical course of LBP symptoms followed a pattern that was similar in RCTs and cohort observational studies . | Background Evidence suggests that the course of low back pain ( LBP ) symptoms in r and omised clinical trials ( RCTs ) follows a pattern of large improvement regardless of the type of treatment .
A similar pattern was independently observed in observational studies .
However , there is an assumption that the clinical course of symptoms is particularly influenced in RCTs by mere participation in the trials .
To test this assumption , the aim of our study was to compare the course of LBP in RCTs and observational studies . | Study Design . A r and omized trial . Objective . To evaluate the effectiveness of a semi-intensive multidisciplinary rehabilitation for patients with chronic low back pain in an outpatient setting . Summary and Background Data . Systematic review s have shown that there is strong evidence that intensive multidisciplinary treatment ( > 100 hours ) , which includes functional restoration , improves function among chronic patients with low back pain , and moderate evidence that it reduces pain but contradictory evidence regarding improvement of working ability . However , there is paucity of data whether semi-intensive outpatient multidisciplinary rehabilitation in groups is more effective than individual physiotherapy . Material s and Methods . A total of 120 women employed as healthcare and social care professionals with nonspecific chronic low back pain were recruited from two occupational healthcare centers . The patients were r and omized into two intervention programs . Multidisciplinary rehabilitation ( n = 59 ) was conducted in groups and comprised of physical training , workplace interventions , back school , relaxation training , and cognitive-behavioral stress management methods for 70 hours . The individual physiotherapy ( n = 61 ) included physical exercise and passive treatment methods administered for 10 hours . Main outcome measures were : back pain and sciatic pain intensity , disability , sick leaves , healthcare consumption , symptoms of depression , and beliefs of working ability after 2 years . Results . There were no statistically significant differences between the two treatment groups in main outcome measures just after rehabilitation , at 6- , at 12- , or 24-month follow-up . In both intervention arms , however , the before- and -after comparison showed favorable effects , and the effects were still maintained at 2 years follow-up . Conclusions . The results of this study indicate that semilight outpatient multidisciplinary rehabilitation program for female chronic low back pain patients does not offer incremental benefits when compared with rehabilitation carried out by a physiotherapist having a cognitive-behavioral way of administering the treatment Study Design . A prospect i ve r and omized controlled trial . Objectives . To examine the effectiveness of combined manipulative treatment , stabilizing exercises , and physician consultation compared with physician consultation alone for chronic low back pain . Summary of Background Data . Strong evidence exists that manual therapy provides more effective short-term pain relief than does placebo treatment in the management of chronic low back pain . The evidence for long-term effect is lacking . Methods . Two hundred four chronic low back pain patients , whose Oswestry disability index was at least 16 % , were r and omly assigned to either a manipulative-treatment group or a consultation group . All were clinical ly examined , informed about their back pain , provided with an educational booklet , and were given specific instructions based on the clinical evaluation . The treatment included four sessions of manipulation and stabilizing exercises aim ing to correct the lumbopelvic rhythm . Question naires inquired about pain intensity , self-rated disability , mental depression , health-related quality of life , health care costs , and production costs . Results . At the baseline , the groups were comparable , except for the percentage of employees ( P = 0.01 ) . At the 5- and 12-month follow-ups , the manipulative-treatment group showed more significant reductions in pain intensity ( P < 0.001 ) and in self-rated disability ( P = 0.002 ) than the consultation group . However , we detected no significant difference between the groups in health-related quality of life or in costs . Conclusions . The manipulative treatment with stabilizing exercises was more effective in reducing pain intensity and disability than the physician consultation alone . The present study showed that short , specific treatment programs with proper patient information may alter the course of chronic low back pain OBJECTIVE To evaluate the effectiveness of the addition of back school to exercise and physical treatment modalities in relieving pain and improving the functional status of patients with chronic low back pain . DESIGN A r and omized controlled trial . PATIENTS A total of 146 patients with chronic low back pain were enrolled in the study . METHODS Subjects were divided into 2 groups : the back school group received exercise , physical treatment modalities and a back school programme ; and the control group received exercise and physical treatment modalities . Treatment efficacy was evaluated at the end of treatment and 3 months post-treatment , in terms of pain , measured with the Visual Analogue Scale , and functional status , measured with the Oswestry Low Back Pain Disability Question naire . RESULTS In both groups , Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire were significantly reduced after therapy ( p < 0.01 ) , but the difference between the scores at the end of treatment and 3 months post-treatment was not significant . There was a significant improvement in Visual Analogue Scale and Oswestry Low Back Pain Disability Question naire in the back school group compared with the control group at the end of therapy and 3 months post-treatment ( p < 0.05 ) . CONCLUSION The addition of back school was more effective than exercise and physical treatment modalities alone in the treatment of patients with chronic low back pain Study Design . A r and omized controlled trial with a 6-month follow-up period was conducted . Objective . To compare lumbar extension exercise and whole-body vibration exercise for chronic lower back pain . Summary of Background Data . Chronic lower back pain involves muscular as well as connective and neural systems . Different types of physiotherapy are applied for its treatment . Industrial vibration is regarded as a risk factor . Recently , vibration exercise has been developed as a new type of physiotherapy . It is thought to activate muscles via reflexes . Methods . In this study , 60 patients with chronic lower back pain devoid of “ specific ” spine diseases , who had a mean age of 51.7 years and a pain history of 13.1 years , practice d either isodynamic lumbar extension or vibration exercise for 3 months . Outcome measures were lumbar extension torque , pain sensation ( visual analog scale ) , and pain-related disability ( pain disability index ) . Results . A significant and comparable reduction in pain sensation and pain-related disability was observed in both groups . Lumbar extension torque increased significantly in the vibration exercise group ( 30.1 Nm/kg ) , but significantly more in the lumbar extension group ( + 59.2 Nm/kg ; SEM 10.2;P < 0.05 ) . No correlation was found between gain in lumbar torque and pain relief or pain-related disability ( P > 0.2 ) . Conclusions . The current data indicate that poor lumbar muscle force probably is not the exclusive cause of chronic lower back pain . Different types of exercise therapy tend to yield comparable results . Interestingly , well-controlled vibration may be the cure rather than the cause of lower back pain Background The evidence that exercise intervention is effective for treatment of chronic low back pain comes from trials that are not placebo-controlled . Objective The purpose of this study was to investigate the efficacy of motor control exercise for people with chronic low back pain . Design This was a r and omized , placebo-controlled trial . Setting The study was conducted in an outpatient physical therapy department in Australia . Patients The participants were 154 patients with chronic low back pain of more than 12 weeks ’ duration . Intervention Twelve sessions of motor control exercise ( ie , exercises design ed to improve function of specific muscles of the low back region and the control of posture and movement ) or placebo ( ie , detuned ultrasound therapy and detuned short-wave therapy ) were conducted over 8 weeks . Measurements Primary outcomes were pain intensity , activity ( measured by the Patient-Specific Functional Scale ) , and patient 's global impression of recovery measured at 2 months . Secondary outcomes were pain ; activity ( measured by the Patient-Specific Functional Scale ) ; patient 's global impression of recovery measured at 6 and 12 months ; activity limitation ( measured by the Rol and -Morris Disability Question naire ) at 2 , 6 , and 12 months ; and risk of persistent or recurrent pain at 12 months . Results The exercise intervention improved activity and patient 's global impression of recovery but did not clearly reduce pain at 2 months . The mean effect of exercise on activity ( measured by the Patient-Specific Functional Scale ) was 1.1 points ( 95 % confidence interval [CI]=0.3 to 1.8 ) , the mean effect on global impression of recovery was 1.5 points ( 95 % CI=0.4 to 2.5 ) , and the mean effect on pain was 0.9 points ( 95 % CI=−0.01 to 1.8 ) , all measured on 11-point scales . Secondary outcomes also favored motor control exercise . Limitation Clinicians could not be blinded to the intervention they provided . Conclusions Motor control exercise produced short-term improvements in global impression of recovery and activity , but not pain , for people with chronic low back pain . Most of the effects observed in the short term were maintained at the 6- and 12-month follow-ups Prospect i ve inception cohort . To assess the prognostic value of spinal mechanical load , assessed with the 24-hour schedule ( 24HS ) , in subjects with acute non-specific low back pain ( ALBP ) and to examine the influence of spinal mechanical load on the course of ALBP . In view of the characteristics of the natural course of ALBP , this should be viewed as a persistent condition in many patients rather that a benign self-limiting disease . Therefore , secondary prevention could be beneficial . Spinal mechanical load is a risk factor for ALBP and possibly a ( modifiable ) prognostic factor for persistent ( i.e. recurrent and /or chronic ) LBP . One hundred patients from primary care with ALBP were eligible for inclusion . At 6 months , 88 subjects completed the follow-up . For the follow-up assessment a research assistant , unaware of our interest in the prognostic factors , contacted the subjects by telephone . Question naires were completed focusing on changes in demographic data and on the course and current status of ALBP . Persistent LBP occurred in 60 % subjects . After multivariate regression analysis smoking ( harmful ) and advanced age ( protective ) were associated with persistent LBP . Differences in 24HS scores at baseline and follow-up were univariate-related to persistent LBP . Spinal mechanical load , quantified with the 24HS , is not a prognostic factor for persistent LBP . Modification of spinal mechanical load in terms of 24HS scores could be beneficial for secondary prevention in patients with acute LBP Study Design . A r and omized controlled design superimposed on treatment as usual was used to compare the effects of a cognitive-behavior intervention aim ed at preventing chronicity with two different forms of information . Objective . To develop a coping-oriented preventive intervention applicable in primary care , and to compare its impact with educational information . Summary of Background Data . Preventing long-term disability result ing from spinal pain has proved difficult . The information provided by health care professions and early interventions aim ed at preventing long-term disability may be important , but little scientific evidence exists concerning their use . Methods . A protocol for a six-session cognitive-behavior group intervention was developed on the basis of earlier research . The main focus was to prevent long-term disability by changing patients ’ behaviors and beliefs so they can cope better with their problems . Comparison groups received either a pamphlet shown earlier to have an effect , or a more extensive information package consisting of six installments . All the groups continued to receive treatment as usual in primary care . There were 243 patients with acute or subacute spinal pain who perceived that they were at risk for developing a chronic problem . These patients were r and omized to the cognitive-behavioral intervention or one of the two information groups . Because the aim was to prevent long-term disability , the key outcome variables at the 1-year follow-up assessment were sick absenteeism and health care use . Other variables were pain , function , fear-avoidance beliefs , and cognitions . Results . The comparison groups reported benefits . However , the risk for a long-term sick absence developing was lowered ninefold for the cognitive-behavior intervention group as compared with the risk for the information groups ( relative risk , 9.3 ) . Participants in the cognitive-behavior group also reported a significant decrease in perceived risk . In addition , the cognitive-behavior group demonstrated a significant decrease in physician and physical therapy use as compared with two groups receiving information , in which such use increased . All three groups tended to improve on the variables of pain , fear-avoidance , and cognitions . Conclusions . This study demonstrates that a cognitive-behavior group intervention can lower the risk of a long-term disability developing . These findings underscore the significance of early interventions that specifically aim to prevent chronic problems . This approach might be applied to primary care setting Objective : This article examines the effectiveness of manual therapy with specific adjuvant exercise for treating chronic low back pain and disability . Methods : A single blind , r and omized , controlled trial was employed . Patients were prescribed an exercise program that was tailored to treat their musculoskeletal dysfunctions or given a nonspecific program of general stretching and aerobic conditioning . In addition , patients received manual therapy or sham manual therapy . Participants were seen for 6 weekly sessions and were asked to perform their exercise program twice daily . Results : Seventy-two out of 100 patients completed the study . Multivariate tests conducted for measures of pain and disability revealed a significant group by time interaction ( P = 0.04 and P = 0.05 , respectively ) , indicating differential change in these measures pretreatment to posttreatment as a function of the treatment received . When controlling for pretreatment scores , patients receiving manual therapy with specific adjuvant exercise reported significant reductions in pain . No change in perceived disability was observed , with the exception that patients receiving sham manual therapy with specific adjuvant exercise reported significantly greater disability at posttreatment . Discussion : Manual therapy with specific adjuvant exercise appears to be beneficial in treating chronic low back pain . Despite changes in pain , perceived function did not improve . It is possible that impacting chronic low back pain alone does not address psychosocial or other factors that may contribute to disability . Further studies are needed to examine the long-term effects of these interventions and to address what adjuncts are beneficial in improving function in this population Study Design . Cluster r and omized clinical trial . Objective . To assess the efficacy of a short education program and short physiotherapy program for treating low back pain ( LBP ) in primary care . Summary of Background Data . There is sparse evidence on the effectiveness of education and physiotherapy programs that are short enough to be feasible in primary care . Methods . Sixty-nine primary care physicians were r and omly assigned to 3 groups and recruited 348 patients consulting for LBP ; 265 ( 79.8 % ) were chronic . All patients received usual care , were given a booklet and received a consistent 15 minutes group talk on health education , which focused on healthy nutrition habits in the control group , and on active management for LBP in the “ education ” and “ education + physiotherapy ” groups . Additionally , in the “ education + physiotherapy ” group , patients were given a second booklet and a 15-minute group talk on postural hygiene , and 4 one-hour physiotherapy sessions of exercise and stretching which they were encouraged to keep practicing at home . The main outcome measure was improvement of LBP-related disability at 6 months . Patients ' assessment and data analyses were blinded . Results . During the 6-month follow-up period , improvement in the “ control ” group was negligible . Additional improvement in the “ education ” and “ education + physiotherapy ” groups was found for disability ( 2.0 and 2.2 Rol and Morris Question naire points , respectively ) , LBP ( 1.8 and 2.10 Visual Analogue Scale points ) , referred pain ( 1.3 and 1.6 Visual Analogue Scale points ) , catastrophizing ( 1.6 and 1.8 Coping Strategies Question naire points ) , physical quality of life ( 2.9 and 2.9 SF-12 points ) , and mental quality of life ( 3.7 and 5.1 SF-12 points ) . Conclusion . The addition of a short education program on active management to usual care in primary care leads to small but consistent improvements in disability , pain , and quality of life . The addition of a short physiotherapy program composed of education on postural hygiene and exercise intended to be continued at home , increases those improvements , although the magnitude of that increase is clinical ly irrelevant Background Back pain is common and some sufferers consult GPs , yet many sufferers develop persistent problems . Combining information on risk of persistence and prognostic indicator prevalence provides more information on potential intervention targets than risk estimates alone . Aims To determine the proportion of primary care back pain patients with persistent problems whose outcome is related to measurable prognostic factors . Methods Prospect i ve cohort study of back pain patients ( 30–59 years ) at five general practice s in Staffordshire , UK ( n = 389 ) . Baseline factors ( demographic ; episode duration ; symptom severity ; pain widespreadness ; anxiety ; depression ; catastrophising ; fear-avoidance ; self-rated health ) were assessed for their association with disabling and limiting pain after 12-months . The proportion of those with persistent problems whose outcome was related to each factor was calculated . Results Prevalence of prognostic factors ranged from 23 % to 87 % . Strongest predictors were unemployment ( adjusted relative risk ( RR ) 4.2 ; 95 % CI 2.0 , 8.5 ) and high pain intensity ( 4.1 ; 1.7 , 9.9 ) . The largest proportions of persistent problems were related to high pain intensity ( 68 % ; 95 % CI 27 , 87 % ) and unemployment ( 64 % ; 33 , 82 % ) . Combining these indicated that 85 % of poor back pain outcome is related to these two factors . Poor self-rated health , functional disability , upper body pain and pain bothersomeness were related with outcome for over 40 % of those with persistent problems . Conclusions Several factors increased risk of poor outcome in back pain patients , notably high pain and unemployment . These risks in combination with high prevalence of risk factors in this population distinguish factors that can help identify targets or sub-groups for intervention The placebo and nocebo effect is believed to be mediated by both cognitive and conditioning mechanisms , although little is known about their role in different circumstances . In this study , we first analyzed the effects of opposing verbal suggestions on experimental ischemic arm pain in healthy volunteers and on motor performance in Parkinsonian patients and found that verbally induced expectations of analgesia/hyperalgesia and motor improvement/worsening antagonized completely the effects of a conditioning procedure . We also measured the effects of opposing verbal suggestions on hormonal secretion and found that verbally induced expectations of increase/decrease of growth hormone ( GH ) and cortisol did not have any effect on the secretion of these hormones . However , if a preconditioning was performed with sumatriptan , a 5-HT1B/1D agonist that stimulates GH and inhibits cortisol secretion , a significant increase of GH and decrease of cortisol plasma concentrations were found after placebo administration , although opposite verbal suggestions were given . These findings indicate that verbally induced expectations have no effect on hormonal secretion , whereas they affect pain and motor performance . This suggests that placebo responses are mediated by conditioning when unconscious physiological functions such as hormonal secretion are involved , whereas they are mediated by expectation when conscious physiological processes such as pain and motor performance come into play , even though a conditioning procedure is performed OBJECTIVE To assess the overall effectiveness of spa therapy compared with usual routine drug therapy in chronic low back pain ( LBP ) . METHODS One hundred and twenty-one patients were r and omly allocated to treatment ( n = 59 ) and control ( n = 62 ) groups . In the treatment group , patients underwent routine drug therapy and spa therapy 6 days/week for 3 consecutive weeks in Saint-Nectaire , France . In the control group , patients received routine drug therapy . Effectiveness was assessed based on clinical measures , duration and intensity of pain , Rol and and Morris ' disability question naire , the patient 's overall evaluation of back health , and drug consumption ( analgesic and antiinflammatory ) . Groups were compared using analysis of covariance with repeated measures . RESULTS At 3 weeks , patients in the treatment group had significant improvement in all outcome variables ( p < 0.0001 ) except for the Schober index and analgesic and antiinflammatory drug consumption . At 6 months , improvement was still significant for the same outcome variables ( p < 0.0001 ) , plus a significant reduction in analgesic consumption . CONCLUSION This study suggests both immediate and 6 month effectiveness of spa therapy in chronic LBP . Spa therapy may be beneficial in the management of chronic LBP STUDY DESIGN A double-blind , r and omized controlled trial of a novel educational booklet compared with a traditional booklet for patients seeking treatment in primary care for acute or recurrent low back pain . OBJECTIVE To test the impact of a novel educational booklet on patients ' beliefs about back pain and functional outcome . SUMMARY OF BACKGROUND DATA The information and advice that health professionals give to patients may be important in health care intervention , but there is little scientific evidence of their effectiveness . A novel patient educational booklet , The Back Book , has been developed to provide evidence -based information and advice consistent with current clinical guidelines . METHODS One hundred sixty-two patients were given either the experimental booklet or a traditional booklet . The main outcomes studied were fear-avoidance beliefs about physical activity , beliefs about the inevitable consequences of back trouble , the Rol and Disability Question naire , and visual analogue pain scales . Postal follow-up response at 1 year after initial treatment was 78 % . RESULTS Patients receiving the experimental booklet showed a statistically significant greater early improvement in beliefs which was maintained at 1 year . A greater proportion of patients with an initially high fear-avoidance beliefs score who received the experimental booklet had clinical ly important improvement in fear-avoidance beliefs about physical activity at 2 weeks , followed by a clinical ly important improvement in the Rol and Disability Question naire score at 3 months . There was no effect on pain . CONCLUSION This trial shows that carefully selected and presented information and advice about back pain can have a positive effect on patients ' beliefs and clinical outcomes , and suggests that a study of clinical ly important effects in individual patients may provide further insights into the management of low back pain & NA ; The effects of outpatient group cognitive therapy , relaxation training , and cognitive therapy in combination with relaxation training on chronic low back pain and associated physical and psychosocial disability were evaluated and compared . One‐hundred and two mildly disabled chronic low back pain patients were assigned r and omly to a waiting‐list ( WL ) control condition and the 3 treatments . Patient self‐report and observational measures were obtained pretreatment and post‐treatment for all conditions , and at 6‐ and 12‐month follow‐ups for the treatment conditions . Pain intensity decreased significantly pre‐ to post‐treatment for patients in all 3 treatment conditions , but not the WL condition . Depressive symptoms and disability improved significantly in all conditions ( including the waiting list ) from pretreatment to post‐treatment , with no statistically significant differences among treatments . At both follow‐ups , all 3 treatment groups remained significantly improved from pretreatment , with no statistically significant differences between treatments BACKGROUND CONTEXT Several conservative therapies have been shown to be beneficial in the treatment of chronic low back pain ( CLBP ) , including different forms of exercise and spinal manipulative therapy ( SMT ) . The efficacy of less time-consuming and less costly self-care interventions , for example , home exercise , remains inconclusive in CLBP population s. PURPOSE The purpose of this study was to assess the relative efficacy of supervised exercise , spinal manipulation , and home exercise for the treatment of CLBP . STUDY DESIGN / SETTING An observer-blinded and mixed- method r and omized clinical trial conducted in a university research clinic in Bloomington , MN , USA . PATIENT SAMPLE Individuals , 18 to 65 years of age , who had a primary complaint of mechanical LBP of at least 6-week duration with or without radiating pain to the lower extremity were included in this trial . OUTCOME MEASURES Patient-rated outcomes were pain , disability , general health status , medication use , global improvement , and satisfaction . Trunk muscle endurance and strength were assessed by blinded examiners , and qualitative interviews were performed at the end of the 12-week treatment phase . METHODS This prospect i ve r and omized clinical trial examined the short- ( 12 weeks ) and long-term ( 52 weeks ) relative efficacy of high-dose , supervised low-tech trunk exercise , chiropractic SMT , and a short course of home exercise and self-care advice for the treatment of LBP of at least 6-week duration . The study was approved by local institutional review boards . RESULTS A total of 301 individuals were included in this trial . For all three treatment groups , outcomes improved during the 12 weeks of treatment . Those who received supervised trunk exercise were most satisfied with care and experienced the greatest gains in trunk muscle endurance and strength , but they did not significantly differ from those receiving chiropractic spinal manipulation or home exercise in terms of pain and other patient-rated individual outcomes , in both the short- and long-term . CONCLUSIONS For CLBP , supervised exercise was significantly better than chiropractic spinal manipulation and home exercise in terms of satisfaction with treatment and trunk muscle endurance and strength . Although the short- and long-term differences between groups in patient-rated pain , disability , improvement , general health status , and medication use consistently favored the supervised exercise group , the differences were relatively small and not statistically significant for these individual outcomes Study Design . R and omized controlled trial . Objectives . To investigate the effectiveness and costs of a mini-intervention , provided in addition to the usual care , and the incremental effect of a work site visit for patients with subacute disabling low back pain . Summary of Background Data . There is lack of data on cost-effectiveness of brief interventions for patients with prolonged low back pain . Methods . A total of 164 patients with subacute low back pain were r and omized to a mini-intervention group ( A ) , a work site visit group ( B ) , or a usual care group ( C ) . Groups A ( n = 56 ) and B ( n = 51 ) underwent one assessment by a physician plus a physiotherapist . Group B received a work site visit in addition . Group C served as controls ( n = 57 ) and was treated in municipal primary health care . All patients received a leaflet on back pain . Pain , disability , specific and generic health-related quality of life , satisfaction with care , days on sick leave , and use and costs of health care consumption were measured at 3- , 6- , and 12-month follow-ups . Results . During follow-up , fewer subjects had daily pain in Groups A and B than in Group C ( Group A vs. Group C , P = 0.002 ; Group B vs. Group C , P = 0.030 ) . In Group A , pain was less bothersome ( Group A vs. Group C , P = 0.032 ) and interfered less with daily life ( Group A vs. Group C , P = 0.040 ) than among controls . Average days on sick leave were 19 in Group A , 28 in Group B , and 41 in Group C ( Group A vs. Group C , P = 0.019 ) . Treatment satisfaction was better in the intervention groups than among the controls , and costs were lowest in the mini-intervention group . Conclusions . Mini-intervention reduced daily back pain symptoms and sickness absence , improved adaptation to pain and patient satisfaction among patients with subacute low back pain , without increasing health care costs . A work site visit did not increase effectiveness Abstract Objective To compare the effects of a minimal intervention strategy aim ed at assessment and modification of psychosocial prognostic factors and usual care for treatment of (sub)acute low back pain in general practice . Design Cluster r and omised clinical trial . Setting 60 general practitioners in 41 general practice s. Participants 314 patients with non-specific low back pain of less than 12 weeks ' duration , recruited by their general practitioner . Interventions In the minimal intervention strategy group the general practitioner explored the presence of psychosocial prognostic factors , discussed these factors , set specific goals for reactivation , and provided an educational booklet . The consultation took about 20 minutes . Usual care was not st and ardised . Main outcome measures Functional disability ( Rol and -Morris disability question naire ) , perceived recovery , and sick leave because of low back pain assessed at baseline and after 6 , 13 , 26 , and 52 weeks . Results The dropout rate was 8 % in the minimal intervention strategy group and 9 % in the usual care group . Multilevel analyses showed no significant differences between the groups on any outcome measure during 12 months of follow-up in the whole group or in relevant subgroups ( patients with high scores on psychosocial measures at baseline or a history of frequent or prolonged low back pain ) . Conclusion This study provides no evidence that ( Dutch ) general practitioners should adopt our new treatment strategy aim ed at psychosocial prognostic factors in patients with (sub)acute low back pain . Further research should examine why our new strategy was not more effective than usual care Abstract Objective To measure the effectiveness of routine physiotherapy compared with an assessment session and advice from a physiotherapist for patients with low back pain . Design Pragmatic , multicentre , r and omised controlled trial . Setting Seven British NHS physiotherapy departments . Participants 286 patients with low back pain of more than six weeks ' duration . Intervention Routine physiotherapy or advice on remaining active from a physiotherapist . Both groups received an advice book . Main outcome measures Primary outcome was scores on the Oswestry disability index at 12 months . Secondary outcomes were scores on the Oswestry disability index ( two and six months ) , scores on the Rol and and Morris disability question naire and SF-36 ( 2 , 6 and 12 months ) , and patient perceived benefit from treatment ( 2 , 6 , and 12 months ) . Results 200 of 286 patients ( 70 % ) provided follow up information at 12 months . Patients in the therapy group reported enhanced perceptions of benefit , but there was no evidence of a long term effect of physiotherapy in either disease specific or generic outcome measures ( mean difference in change in Oswestry disability index scores at 12 months −1.0 % , 95 % confidence interval −3.7 % to 1.6 % ) . The most common treatments were low velocity spinal joint mobilisation techniques ( 72 % , 104 of 144 patients ) and lumbar spine mobility and abdominal strengthening exercises ( 94 % , 136 patients ) . Conclusions Routine physiotherapy seemed to be no more effective than one session of assessment and advice from a physiotherapist STUDY DESIGN A r and omized clinical trial . OBJECTIVES To examine the relative efficacy of three active therapies for chronic low back pain . SUMMARY OF BACKGROUND DATA There is much evidence documenting the efficacy of exercise in the conservative management of chronic low back pain , but many questions remain regarding its exact prescription and method of application . The most successful method must be identified to enable refinement of future rehabilitation programs to target the specific needs of the patient with chronic low back pain and the budget of the healthcare provider . METHODS One hundred forty-eight patients with chronic low back pain were r and omized to one of the following treatments , which they attended twice a week for 3 months : 1 ) modern active physiotherapy , 2 ) muscle reconditioning on training devices , or 3 ) low-impact aerobics . Pretherapy and posttherapy , objective measurements of lumbar mobility were performed , and question naires were administered inquiring about self-rated pain and disability , and psychosocial factors . Similar question naires were administered 6 months after therapy . The data were analyzed using the intention-to-treat principle . RESULTS Of the 148 patients , 16 ( 10.8 % ) dropped out of the therapy . One hundred thirty-seven question naires ( 93 % ) were available for analysis at all three time points . After therapy , significant reductions were observed in pain intensity , frequency , and disability ; Fear-Avoidance Beliefs about physical activity ( FABQactivity ) ; and " praying/hoping , " " catastrophizing , " and " pain behavior " coping strategies -- each with no group differences in the extent of the response . These effects were maintained over the subsequent 6 months , with the exception of disability and FABQactivity for the physiotherapy group . There were small but significant posttherapy increases in lumbar mobility , with aerobics and devices showing a greater response than physiotherapy . CONCLUSION The general lack of treatment specificity suggests that the main effects of the therapies were educed not through the reversal of physical weaknesses targeted by the corresponding exercise modality , but rather through some " central " effect , perhaps involving an adjustment of perception in relation to pain and disability . The direct costs associated with administering physiotherapy were three times as great , and devices four times as great , as those for aerobics . Administration of aerobics as an efficacious therapy for chronic low back pain has the potential to relieve some of the huge financial burden associated with the condition Intensive group training using principles of grade d activity has been proven to be effective in occupational care for workers with chronic low back pain . Objective of the study was to compare the effects of an intensive group training protocol aim ed at returning to normal daily activities and guideline physiotherapy for primary care patients with non-specific chronic low back pain . The study was design ed as pragmatic r and omised controlled trial with a setup of 105 primary care physiotherapists in 49 practice s and 114 patients with non-specific low back pain of more than 12 weeks duration participated in the study . In the intensive group training protocol exercise therapy , back school and operant-conditioning behavioural principles are combined . Patients were treated during 10 individual sessions along 20 group sessions . Usual care consisted of physiotherapy according to the Dutch guidelines for Low Back Pain . Main outcome measures were functional disability ( Rol and Morris disability question naire ) , pain intensity , perceived recovery and sick leave because of low back pain assessed at baseline and after 6 , 13 , 26 and 52 weeks . Both an intention-to-treat analysis and a per- protocol analysis were performed . Multilevel analysis did not show significant differences between both treatment groups on any outcome measures during the complete follow-up period , with one exception . After 26 weeks the protocol group showed more reduction in pain intensity than the guideline group , but this difference was absent after 52 weeks . We finally conclude that an intensive group training protocol was not more effective than usual physiotherapy for chronic low back pain Study Design . R and omized , single blind , controlled trial . Objective . To determine the efficacy of 2 components of musculoskeletal physiotherapy on chronic low back disorder . Summary of Background Data . Musculoskeletal physiotherapy encompasses many treatment methods , however , manual therapy and exercises to rehabilitate spinal stabilization are the most frequently used . Despite their popularity , scant evidence supports their use on subjects with chronic low back disorder . Methods . A total of 346 subjects were r and omized to manual therapy , a 10-week spinal stabilization rehabilitation program , or a minimal intervention control group . Data were collected at baseline , and 3 , 6 , 12 , and 24 months after intervention . Outcome measures recorded intensity of low back pain , disability , h and icap , medication , and quality of life . There were 4 main variables combined in a primary component analysis to form a single outcome measure ( i.e. , a measure of dysfunction ) . Results . The results indicated statistically significant improvements in favor of the spinal stabilization group at the 6-month stage in pain ( 65.9 % reduction in symptoms ) and dysfunction ( combined mean reduction of 134 , st and ard error 23.84 ) , and at the 1-year stage in medication ( 34.3 % reduction in medication ) , dysfunction ( combined mean reduction of 134 , st and ard error 18.2 ) , and disability ( mean difference in change 15.71 Oswestry Disability Index , 95 % confidence interval 19.3–10.01 ) . Conclusions . As a component of musculoskeletal physiotherapy , the spinal stabilization program is more effective than manually applied therapy or an education booklet in treating chronic low back disorder over time . Both manual therapy and the spinal stabilization program are significantly effective in pain reduction in comparison to an active control . To our knowledge and up until now , this result has not been shown in patients with chronic low back disorder OBJECTIVE To examine the effect of adding aerobic exercise to conventional physiotherapy treatment for patients with chronic low back pain ( LBP ) in reducing pain and disability . DESIGN R and omized controlled trial . SETTING A physiotherapy outpatient setting in Hong Kong . PARTICIPANTS Patients with chronic LBP ( N=46 ) were recruited and r and omly assigned to either a control ( n=22 ) or an intervention ( n=24 ) group . INTERVENTIONS An 8-week intervention ; both groups received conventional physiotherapy with additional individually tailored aerobic exercise prescribed only to the intervention group . MAIN OUTCOME MEASURES Visual analog pain scale , Aberdeen Low Back Pain Disability Scale , and physical fitness measurements were taken at baseline , 8 weeks , and 12 months from the commencement of the intervention . Multivariate analysis of variance was performed to examine between-group differences . RESULTS Both groups demonstrated a significant reduction in pain ( P<.001 ) and an improvement in disability ( P<.001 ) at 8 weeks and 12 months ; however , no differences were observed between groups . There was no significant difference in LBP relapse at 12 months between the 2 groups ( χ(2)=2.30 , P=.13 ) . CONCLUSIONS The addition of aerobic training to conventional physiotherapy treatment did not enhance either short- or long-term improvement of pain and disability in patients with chronic LBP OBJECTIVE To examine the effects of 2 manual therapy methods compared with one counselling session with a physiotherapist with " advice-only to stay active " for treating low back pain/leg pain and disability . DESIGN A r and omized , controlled trial with a 1-year follow-up . SUBJECTS A total of 134 subjects with low back disorders . METHODS Participants with acute to chronic first or recurrent low back pain , excluding those with " red flag " criteria , were assigned r and omly to one of the 3 intervention groups : an orthopaedic manual therapy group ( n=45 ) , a McKenzie method group ( n=52 ) , and an " advice only to be active " group ( advice-only ) ( n=37 ) . Data on leg and low back pain intensity and disability ( Rol and -Morris Disability question naire ) were collected at baseline , and at 3- , 6- , and 12-month follow-up points . RESULTS At the 3-month follow-up point , significant improvements had occurred in all groups in leg and low back pain and in the disability index , but with no significant differences between the groups . At the 6-month follow-up , leg pain ( -15 mm ; 95 % confidence interval ( CI ) -30 to -1 ) , back pain ( effect : -15 mm ; -27 to -4 ) , and disability index ( -4 points ; -7 to -1 ) improved ( p < 0.05 ) more in the McKenzie method group than in the advice-only group . At the 1-year follow-up , the McKenzie method group had ( p=0.028 ) a better disability index ( -3 points ; -6 to 0 ) than did the advice-only group . In the orthopaedic manual therapy group at the 6-month and 1-year follow-up visits , improvements in the pain and disability index were somewhat better than in the advice-only group ( p=0.067 and 0.068 , respectively ) . No differences emerged between the orthopaedic manual therapy and McKenzie method groups in pain- and disability-score changes at any follow-up . CONCLUSION The orthopaedic manual therapy and McKenzie methods seemed to be only marginally more effective than was one session of assessment and advice-only Introduction : Behaviorally oriented grade d activity interventions have been suggested for sick-listed workers with low back pain on return to work , but have not been extensively evaluated . Methods : One hundred and thirty-four workers were r and omly assigned to either a grade d activity intervention ( n = 67 ) or usual care ( n = 67 ) and followed-up for 12 months . Results : The grade d activity group returned back to work faster with a median of 54 days compared to 67 days in the usual care group . The grade d activity intervention was more effective after approximately 50 days post-r and omization ( HRR = 1.9 , CI = 1.2–3.1 , p = 0.01 ) . Differences between the groups in number of recurrent episodes , total number of days of sick leave due to low back pain , and total number of days of sick leave due to all diagnoses , were in favor of the grade d activity group , although not statistically significant . No effects of the grade d activity intervention were found for functional status or pain . Conclusion : Grade d activity intervention is a valuable strategy to enhance short-term return to work outcomes OBJECTIVE The goal of this study was to compare the effects of trigger point ( TRP ) mesotherapy and acupuncture ( ACP ) mesotherapy in the treatment of patients with chronic low back pain . DESIGN Short term r and omized controlled trial . SETTING 62 subjects with chronic low back pain were recruited at out patients Physical Medicine and Rehabilitation Clinic at the University of Rome " La Sapienza " in the period between July 2006 and May 2008 . INTERVENTION Study subjects were assigned to receive 4 weeks treatments with either trigger point mesotherapy ( TRP mesotherapy , n=29 ) or acupoints mesotherapy ( ACP mesotherapy , n=33 ) . MAIN OUTCOME MEASURES Pain intensity with a pain visual analogic scale ( VAS ) and verbal rating scale ( VRS ) and pain disability with McGill Pain Question naire Short Form ( SFMPQ ) , Rol and Morris Disability Question naire ( RMQ ) and Oswestry Low Back Pain Disability Question aire ( ODQ ) . RESULTS ACP mesotherapy shows a more effective results in VRS and VAS measures in the follow-up ( p(VRS)=<.001 and p(VAS)=<.001 ) . The SF-MPQ measure shows a better results for ACP instead of TRP with statistically significant differences between groups and time ( p=.035 ) . Participants reported a slight discomfort at the time of the inoculation , and 15 % reported slight neck pain in ACP mesotherapy group . CONCLUSIONS Our results suggest that the response to ACP mesotherapy may be greater than the response to TRP mesotherapy in the short term follow-up . This technique could be nevertheless a viable option as an adjunct treatment in an overall treatment planning of CLBP Study Design . Cluster r and omized clinical trial . Objectives . To assess the effectiveness of 2 minimal education programs for improving low back pain (LBP)-related disability in the elderly . Summary of Background Data . No education program has shown effectiveness on low back pain (LBP)-related disability in the elderly . Methods . A total of 129 nursing homes ( 6389 residents ) in northern Spain were invited to participate in the study . The actual participants were 12 nursing homes r and omly assigned to 3 groups and 661 subjects . An independent physician gave a 20-minute talk with slide projections summarizing the content of the Back Book ( active management group ) , the Back Guide ( postural hygiene group ) , and a pamphlet on cardiovascular health ( controls ) . Disability was measured with the Rol and -Morris question naire ( RMQ ) . Blind assessment s were performed before the intervention , and 30 and 180 days later . The effect of the intervention on disability was estimated by generalized mixed linear r and om effects models . Results . Mean age of participants ranged between 79.9 and 81.2 years . Disability improved in all groups , but at the 30-day assessment the postural education group showed an additional improvement of 1.1 ( 95 % confidence interval , 0.2–1.9 ) , RMQ points and at the 180-day assessment the active education group an additional improvement of 2.0 ( 95 % confidence interval , 0.6–3.4 ) . In the subset of subjects with LBP when entering the study , postural education had no advantages over controls , while an additional improvement of 3.0 ( 95 % confidence interval , 1.5– 4.5 ) RMQ points at the 180-day assessment was observed in the active education group . Conclusion . In institutionalized elderly , the h and ing out of the Back Book supported by a 20-minute group talk improves disability 6 months later , and is even more effective in those subjects with LBP Study Design . R and omized controlled trial . Objectives . To compare high- and low-intensity back schools with usual care in occupational health care . Summary of Background Data . The content and intensity of back schools vary widely and the method ologic quality of r and omized controlled trials is generally weak . Until now , no back school has proven to be superior for workers sick-listed because of subacute nonspecific low back pain . Methods . Workers ( n = 299 ) sick-listed for a period of 3 to 6 weeks because of nonspecific low back pain were recruited by the occupational physician and r and omly assigned to a high-intensity back school , a low-intensity back school , or care as usual . Outcome measures were days until return to work , total days of sick-leave , pain , functional status , kinesiophobia , and perceived recovery and were assessed at baseline and at 3 and 6 months of follow-up . Principal analyses were performed according to the intention-to-treat principle . Results . We r and omly allocated 299 workers . Workers in the low-intensity back school returned to work faster compared with usual care and the high-intensity back school , with hazard ratios of 1.4 ( P = 0.06 ) and 1.3 ( P = 0.09 ) , respectively . The comparison between high-intensity back school and usual care result ed in a hazard ratio of 1.0 ( P = 0.83 ) . The median number of sick-leave days was 68 , 75 , and 85 in the low-intensity back school , usual care , and high-intensity back school , respectively . Beneficial effects on functional status and kinesiophobia were found at 3 months in favor of the low-intensity back school . No substantial differences on pain and perceived recovery were found between groups . Conclusions . The low-intensity back school was most effective in reducing work absence , functional disability , and kinesiophobia , and more workers in this group scored a higher perceived recovery during the 6-month follow-up BACKGROUND There is little evidence about the management and course of chronic low back pain in primary care . OBJECTIVES Our aim was to describe the course of chronic low back pain and the performed diagnostic and therapeutic procedures for patients with chronic low back pain in general practice . METHODS Twenty-six GPs involved in the Registration Network Family Practice s participated in this prospect i ve follow-up study . All patients and GPs were asked to complete question naires at baseline and at 4 , 8 and 12 months follow-up . RESULTS The GPs provided information about diagnostic and therapeutic procedures concerning 524 patients with chronic low back pain . Diagnostic tests other than history-taking and physical examination were not frequently used . Medication , mostly NSAIDs , was the most frequently used type of treatment ( 21.6 % ) . The most frequent referrals concerned physiotherapy ( 16.3 % ) and neurology or neurologic surgery ( 6.3 % ) . Information about the course of their chronic low back pain was provided by 368 patients participating in our study . The course of chronic low back pain appeared to be quite stable , as there was only a slight improvement in pain intensity and physical functioning over the 12 months of follow-up . CONCLUSIONS A variety of options for the treatment and referral of chronic low back pain patients is available for and used by GPs . Efforts should be made to establish which diagnostic and therapeutic procedures are the most effective for chronic low back pain Background The Spanish National Health Service is a universal and free health care system . Non-specific low back pain ( LBP ) is a prevalent disorder , generating large health and social costs . The objectives of this study were to describe its management in primary care , to assess patient characteristics that influence physicians ' decisions , and to describe clinical outcome at 2 months . Methods A cross-sectional sample of 648 patients with non-specific low back pain was recruited by 75 physicians ( out of 361 – 20.8 % ) working in 40 primary care centers in 10 of the 17 administrative regions in Spain , covering 693,026 out of the 40,499,792 inhabitants . Patients were assessed on the day they were recruited , and prospect ively followed-up 14 and 60 days later . The principal patient characteristics that were analyzed were : sex , duration of the episode , history of LBP , working status , severity of LBP , leg pain and disability , and results of straight leg raising test . Descriptors of management were : performance of the straight leg raising test , ordering of diagnostic procedures , prescription of drug treatment , referral to physical therapy , rehabilitation or surgery , and granting of sick leave . Regression analysis was used to analyze the relationship between patients ' baseline characteristics and physicians ' management decisions . Only workers were included in the models on sick leave . Results Mean age ( SD ) of included patients was 46.5 ( 15.5 ) years , 367 ( 56.6 % ) were workers , and 338 ( 52.5 % ) were females . Median ( 25th–75th interquartile range ) duration of pain when entering the study was 4 ( 2–10 ) days and only 28 patients ( 4.3 % ) had chronic low back pain . Diagnostic studies included plain radiographs in 43.1 % of patients and CT or MRI scans in 18.8 % . Drug medication was prescribed to 91.7 % of patients , 19.1 % were sent to physical therapy or rehabilitation , and 9.6 % were referred to surgery . The main determinants of the clinical management were duration of the episode and , to a lesser extent , the intensity of the pain ( especially leg pain ) , a positive straight leg raising test , and degree of disability . The main determinant of sick leave was the degree of disability , followed by the characteristics of the labor contract and the intensity of leg pain ( but not low back pain ) . After at least 2 months of treatment , 37 % of patients were still in pain and approximately 10 % of patients had not improved or had worsened . Conclusion Although the use of X-Rays is high , determinants of physicians ' management of LBP in primary care made clinical sense and were consistent with patterns suggested by evidence -based recommendations . However , after 2 months of treatment more than one third of patients continued to have back pain and about 10 % had worsened A r and omised clinical trial in primary care with a 12-months follow-up period . About 135 patients with acute sciatica ( recruited from May 2003 to November 2004 ) were r and omised in two groups : ( 1 ) the intervention group received physical therapy ( PT ) added to the general practitioners ’ care , and ( 2 ) the control group with general practitioners ’ care only . To assess the effectiveness of PT additional to general practitioners ’ care compared to general practitioners ’ care alone , in patients with acute sciatica . There is a lack of knowledge concerning the effectiveness of PT in patients with sciatica . The primary outcome was patients ’ global perceived effect ( GPE ) . Secondary outcomes were severity of leg and back pain , severity of disability , general health and absence from work . The outcomes were measured at 3 , 6 , 12 and 52 weeks after r and omisation . At 3 months follow-up , 70 % of the intervention group and 62 % of the control group reported improvement ( RR 1.1 ; 95 % CI 0.9–1.5 ) . At 12 months follow-up , 79 % of the intervention group and 56 % of the control group reported improvement ( RR 1.4 ; 95 % CI 1.1 ; 1.8 ) . No significant differences regarding leg pain , functional status , fear of movement and health status were found at short-term or long-term follow-up . At 12 months follow-up , evidence was found that PT added to general practitioners ’ care is only more effective regarding GPE , and not more cost-effective in the treatment of patients with acute sciatica than general practitioners ’ care alone . There are indications that PT is especially effective regarding GPE in patients reporting severe disability at presentation Study Design . This study was a prospect i ve , r and omized , controlled study . Objective . To compare the effectiveness of aquatic exercise interventions with l and -based exercises in the treatment of chronic low back pain ( CLBP ) . Summary of Background Data . L and -based exercise and physiotherapy are the main treatment tools used for CLBP . Clinical experience indicates that aquatic exercise may have advantages for patients with musculoskeletal disorders . Methods . A total of 65 patients with CLBP were included in this study . Patients were r and omly assigned to receive aquatic exercise or l and -based exercise treatment protocol . Aquatic exercise program consisted of 20 sessions , 5 × per week for 4 weeks in a swimming pool at 33 ° C . L and -based exercise ( home-based exercise ) program were demonstrated by a physiotherapist on one occasion and then they were given written advice The patients were assessed for spinal mobility , pain , disability , and quality of life . Evaluations were performed before treatment ( week 0 ) and after treatment ( week 4 and week 12 ) . Results . In both groups , statistically significant improvements were detected in all outcome measures ( except modified Schober test ) compared with baseline . However , improvement in modified Oswestry Low Back Pain Disability question naire and physical function and role limitations due to physical functioning subpart of Short-Form 36 Health Survey were better in aquatic exercise group ( P < 0.05 ) . Conclusion . It is concluded that a water-based exercises produced better improvement in disability and quality of life of the patients with CLBP than l and -based exercise Background Exercise benefits patients with chronic nonspecific low back pain ; however , the most effective type of exercise remains unknown . Objective This study compared outcomes after motor control exercises , sling exercises , and general exercises for low back pain . Design This was a r and omized controlled trial with a 1-year follow-up . Setting The study was conducted in a primary care setting in Norway . Patients The participants were patients with chronic nonspecific low back pain ( n=109 ) . Interventions The interventions in this study were low-load motor control exercises , high-load sling exercises , or general exercises , all delivered by experienced physical therapists , once a week for 8 weeks . Measurements The primary outcome measure was pain reported on the Numeric Pain Rating Scale after treatment and at a 1-year follow-up . Secondary outcome measures were self-reported activity limitation ( assessed with the Oswestry Disability Index ) , clinical ly examined function ( assessed with the Fingertip-to-Floor Test ) , and fear-avoidance beliefs after intervention . Results The postintervention assessment showed no significant differences among groups with respect to pain ( overall group difference ) or any of the outcome measures . Mean ( 95 % confidence interval ) group differences for pain reduction after treatment and after 1 year were 0.3 ( −0.7 to 1.3 ) and 0.4 ( −0.7 to 1.4 ) for motor control exercises versus sling exercises , 0.7 ( −0.6 to 2.0 ) and 0.3 ( −0.8 to 1.4 ) for sling exercises versus general exercises , and 1.0 ( −0.1 to 2.0 ) and 0.7 ( −0.3 to 1.7 ) for motor control exercises versus general exercises . Limitations The nature of the interventions made blinding impossible . Conclusions This study gave no evidence that 8 treatments with individually instructed motor control exercises or sling exercises were superior to general exercises for chronic low back pain Study Design . A single blind r and omized controlled trial comparing two models of care for patients with acute simple low back pain . Objectives . To compare two research -based models of care for acute low back pain and investigate the effect of the timing of physical intervention . Summary of Background Data . National guidelines offer conflicting information on the delivery of physical treatment in the management of acute low back pain . The guidelines suggest two different models of care . Direct comparisons between these models are lacking in the literature . The present study aims to compare these approaches to the management of acute low back pain . Methods . Among 804 referred patients , 102 subjects met the specific admission criteria and were r and omly assigned to an “ assess/advise/treat ” group or an “ assess/advise/wait ” group . The intervention consisted of biopsychosocial education , manual therapy , and exercise . Assessment of short-term outcome enables comparison to be made between intervention and advice to stay active . Assessment of long-term outcome enables comparison to be made between early and late intervention . Study outcomes of reported pain ( Visual Analogue Scale ) , functional disability ( the Rol and and Morris Disability Question naire ) , mood ( Modified Zung Self Rated Depression Score , Modified Somatic Perception Question naire , State-Trait Anxiety Inventory ) , general health ( Euroqol ) , and quality of life ( Short Form 36 ) were assessed at baseline , 6 weeks , 3 months , and 6 months . Results . At 6 weeks , the assess/advise/treat group demonstrated greater improvements in disability , mood , general health , and quality of life than patients in the assess/advise/wait group ( P < 0.05 ) . Disability and pain were not significantly different between the groups at long-term follow up ( P > 0.05 ) . However , mood , general health , and quality of life remained significantly better in the assess/advise/treat group ( P < 0.05 ) . Conclusions . At short-term , intervention is more effective than advice on staying active , leading to more rapid improvement in function , mood , quality of life , and general health . The timing of intervention affects the development of psychosocial features . If treatment is provided later , the same psychosocial benefits are not achieved . Therefore , an assess/advise/treat model of care seems to offer better outcomes than an assess/advise/wait model of care CMAJ • MAY 12 , 2009 • 180(10 ) © 2009 Canadian Medical Association or its licensors E47 R and omized trials have traditionally been broadly categorized as either an effectiveness trial or an efficacy trial , although we prefer the terms “ pragmatic ” and “ explanatory . ” Schwartz and Lellouch described these 2 approaches toward clinical trials in 1967 . These authors coined the term “ pragmatic ” to describe trials that help users choose between options for care , and “ explanatory ” to describe trials that test causal research hypotheses ( i.e. , that a given intervention causes a particular benefit ) . We take the view that , in general , pragmatic trials are primarily design ed to determine the effects of an intervention under the usual conditions in which it will be applied , whereas explanatory trials are primarily design ed to determine the effects of an intervention under ideal circumstances . Thus , these terms refer to a trial ’s purpose and , in turn , structure . The degree to which this purpose is met depends on decisions about how the trial is design ed and , ultimately , conducted . Very few trials are purely pragmatic or explanatory . For example , in an otherwise explanatory trial , there may be some aspect of the intervention that is beyond the investigator ’s control . Similarly , the act of conducting an otherwise pragmatic trial may impose some control result ing in the setting being not quite usual . For example , the very act of collecting data required for a trial that would not otherwise be collected in usual practice could be a sufficient trigger to modify participant behaviour in unanticipated ways . Further , several aspects of a trial are relevant , relating to choices of trial participants , health care practitioners , interventions , adherence to protocol and analysis . Thus , we are left with a multidimensional continuum rather than a dichotomy , and a particular trial may display varying levels of pragmatism across these dimensions . In this article , we describe an effort to develop a tool to assess and display the position of any given trial within the pragmatic – explanatory continuum . The primary aim of this tool is to help trialists assess the degree to which design decisions align with the trial ’s stated purpose ( decision-making v. explanation ) . Our tool differs , therefore , from that of Gartlehner and associates in that it is intended to inform trial design rather than provide a method of classifying trials for the purpose of systematic review s. It can , however , also be used by research funders , ethics committees , trial registers and journal editors to make the same assessment , provided trialists declare their intended purpose and adequately report their design decisions . Hence , reporting of pragmatic trials is addressed elsewhere OBJECTIVE To evaluate the analgesic efficacy and safety of tramadol 37.5 mg/acetaminophen 325 mg ( tramadol/APAP ) combination tablets for treatment of chronic low back pain ( LBP ) . METHODS This 91 day , multicenter , outpatient , r and omized , double blind , placebo controlled study enrolled 338 patients with chronic LBP requiring daily medication for > or = 3 months . Patients with at least moderate pain [ pain visual analog scale ( VAS ) with scores > or = 40/100 mm ] after washout were r and omized to tramadol/APAP or placebo . After a 10 day titration , patients received 1 or 2 tablets QID . Primary outcome measure was final pain VAS score . Secondary measures included pain relief , quality of life and physical functioning , efficacy failure , and overall medication assessment s. RESULTS In total , 336 intent-to-treat patients received tramadol/APAP ( n = 167 ) or placebo ( n = 169 ) . Mean baseline pain VAS score was 67.8 . Intent-to-treat analysis showed significantly better mean final pain VAS scores ( 47.4 vs 62.9 ; p < 0.001 ) and mean final pain relief scores ( 1.8 vs 0.7 ; p < 0.001 ) for tramadol/APAP than for placebo . Rol and Disability Question naire scores and physical-related subcategories of the McGill Pain Question naire and the Medical Outcome Study Short Form-36 Health Survey were significantly better for tramadol/APAP patients . More patients rated tramadol/APAP as " very good " or " good " than placebo ( 63.6 vs 25.2 % ; p < 0.001 ) . Kaplan-Meier estimates of cumulative discontinuation rates due to efficacy failures were 22.9 % ( tramadol/APAP ) vs 54.7 % ( placebo ; p < 0.001 ) . The most common treatment related adverse events with tramadol/APAP were nausea ( 12.0 % ) , dizziness ( 10.8 % ) , and constipation ( 10.2 % ) . Average daily dose of tramadol/APAP was 4.2 tablets ( tramadol 158 mg/APAP 1369 mg ) . CONCLUSION Tramadol 37.5 mg/APAP 325 mg combination tablets show efficacy in pain reduction , in measures of physical functioning and quality of life , and in overall medication assessment s , with a tolerability profile comparable with other opioids used for the treatment of chronic LBP OBJECTIVE This study reports pain and disability outcomes up to 4 years for chiropractic and medical patients with low back pain ( LBP ) and assesses the influence of doctor type and pain duration on clinical outcomes . DESIGN Prospect i ve , longitudinal , nonr and omized , practice -based , observational study . SETTING Fifty-one chiropractic and 14 general practice community clinics . SUBJECTS A total of 2870 acute and chronic ambulatory patients with LBP of mechanical origin . METHODS Sixty chiropractic ( DC ) and 111 general practice ( MD ) physicians participated . Primary outcomes were pain , using a 100-point visual analogue scale ( VAS ) , and functional disability , using the Revised Oswestry Disability Question naire . These were measured at baseline and 8 time points . Regression analysis compared acute and chronic DC and MD patients after correcting for baseline differences in the 4 cohorts . RESULTS Most improvement was seen by 3 months and sustained for 1 year ; exacerbation was seen thereafter . Acute patients demonstrated greater relief at all time points . A clinical ly important advantage for chiropractic patients was seen in chronic patients in the short-term ( > 10 VAS points ) , and both acute and chronic chiropractic patients experienced somewhat greater relief up to 1 year ( P<.000 ) . The advantage for DC care was prominent for chronic patients with leg pain below the knee ( P<.001 ) . More than 50 % of chronic patients had over 50 days of pain in the third year . CONCLUSION Study findings were consistent with systematic review s of the efficacy of spinal manipulation for pain and disability in acute and chronic LBP . Patient choice and interdisciplinary referral should be prime considerations by physicians , policymakers , and third-party payers in identifying health services for patients with LBP OBJECTIVE A pilot study to assess the feasibility of a trial to investigate the efficacy of acupuncture compared to placebo needling for the treatment of acute low back pain ( LBP ) . As part of this , the study was design ed to establish the credibility of the placebo control , and to provide data to inform a power analysis to determine numbers for a future trial . STUDY DESIGN A pilot patient and assessor blinded r and omized controlled trial . SETTING Primary care health centre facility , South and East Belfast Trust , Northern Irel and . PATIENTS Patients from the physiotherapy waiting list ( n=48 ) with LBP of less than 12 weeks duration . OUTCOME MEASURES Rol and and Morris Disability Question naire ( RMDQ ) , Visual Analogue Scale ( VAS ) , medication use and an exit question naire were completed at baseline , end of treatment , and at 3 months follow up . RESULTS Ninety-four percent ( 45/48 ) of patients completed assigned treatment , 83 % ( 40/48 ) completed 3 months follow-up . The sham needle used here proved to be credible : 91.7 % in the placebo group believed they had received acupuncture , compared to 95.8 % in the verum acupuncture group . Differences in baseline characteristics were accounted for using ANCOVA . There was no significant difference between groups on the RMDQ over time . For pain , the only statistically significant difference was at the 3 months follow up ( worst VAS , point estimate , 18.7 , 95 % CI 1.5 - 36.0 , p=0.034 ) . The majority of patients were taking some form of analgesic medication for LBP at the start of treatment ( n=44 ; 92 % ) , and at the end of treatment the verum acupuncture group were taking significantly fewer tablets of pain control medication ( mean ( S.D. ) : 1.0+/-0.3 ) than the placebo group ( mean ( S.D. ) : 4.2+/-0.6 , p<0.05 ) . Based upon these data , power analysis ( power=90 % , alpha=0.05 , minimal clinical ly important difference ( MCID ) for RMDQ=2.5 points ) indicated that 120 participants ( 60 per group ) would be needed to complete an adequately powered r and omized controlled trial . CONCLUSIONS This study has demonstrated the feasibility of a r and omized controlled trial of penetrating needle acupuncture compared to a non-penetrating sham for the treatment of acute LBP in primary care ; 120 participants would be required in a fully powered trial . The placebo needle used in this study proved to be a credible form of control Objective To investigate whether placebo effects can experimentally be separated into the response to three components— assessment and observation , a therapeutic ritual ( placebo treatment ) , and a supportive patient-practitioner relationship— and then progressively combined to produce incremental clinical improvement in patients with irritable bowel syndrome . To assess the relative magnitude of these components . Design A six week single blind three arm r and omised controlled trial . Setting Academic medical centre . Participants 262 adults ( 76 % women ) , mean ( SD ) age 39 ( 14 ) , diagnosed by Rome II criteria for and with a score of ≥150 on the symptom severity scale . Interventions For three weeks either waiting list ( observation ) , placebo acupuncture alone ( “ limited ” ) , or placebo acupuncture with a patient-practitioner relationship augmented by warmth , attention , and confidence ( “ augmented ” ) . At three weeks , half of the patients were r and omly assigned to continue in their originally assigned group for an additional three weeks . Main outcome measures Global improvement scale ( range 1 - 7 ) , adequate relief of symptoms , symptom severity score , and quality of life . Results At three weeks , scores on the global improvement scale were 3.8 ( SD 1.0 ) v 4.3 ( SD 1.4 ) v 5.0 ( SD 1.3 ) for waiting list versus “ limited ” versus “ augmented , ” respectively ( P<0.001 for trend ) . The proportion of patients reporting adequate relief showed a similar pattern : 28 % on waiting list , 44 % in limited group , and 62 % in augmented group ( P<0.001 for trend ) . The same trend in response existed in symptom severity score ( 30 ( 63 ) v 42 ( 67 ) v 82 ( 89 ) , P<0.001 ) and quality of life ( 3.6 ( 8.1 ) v 4.1 ( 9.4 ) v 9.3 ( 14.0 ) , P<0.001 ) . All pairwise comparisons between augmented and limited patient-practitioner relationship were significant : global improvement scale ( P<0.001 ) , adequate relief of symptoms ( P<0.001 ) , symptom severity score ( P=0.007 ) , quality of life ( P=0.01 ) . Results were similar at six week follow-up . Conclusion Factors contributing to the placebo effect can be progressively combined in a manner resembling a grade d dose escalation of component parts . Non-specific effects can produce statistically and clinical ly significant outcomes and the patient-practitioner relationship is the most robust component . Trial registration Clinical Trials NCT00065403 Objective To assess the efficacy of acupuncture in the treatment of chronic low back pain . Methods Patients ( n = 60 ) with chronic low back pain were recruited and r and omly allocated to either Acupuncture therapy or Placebo transcutaneous electrical nerve stimulation ( TENS ) groups . Patients were treated weekly for 6 weeks , and blinded assessment s were carried out pre- and post-treatment using the McGill Pain Question naire ( MPQ ) and visual analog scales ( VAS ) for pain , the Short-form 36 quality -of-life question naire , and a simple range of motion measurement . A total of 46 patients completed the trial and were followed up at 6 months . Results Analysis of results using t tests showed that in both groups there were significant pre-post improvements for all scores , except for MPQ scores in the Placebo-TENS group . There was no significant difference between the 2 groups for any of the outcome measures at the end of treatment . Results from the 6-month follow-up would suggest that the response was better in the acupuncture group . Discussion Further research is necessary to fully assess the efficacy of this treatment in combating chronic low back pain using larger sample sizes or alternative control groups Context Low back pain causes frequent disability and lost productive time . Contribution This r and omized trial compared a behavioral-oriented grade d activity program with usual care in 134 Dutch airline company workers who had missed work because of persistent low back pain . Grade d activity consisted of biweekly 1-hour exercise sessions with physiotherapists who emphasized operant-conditioning principles . Over 6 months of follow-up , participants in the grade d activity program missed 58 days of work , while participants receiving usual care missed 87 days . Implication s A behavioral-oriented grade d activity program returned participants with low back pain to work more often than did usual care . The Editors Nonspecific low back pain is an uncomfortable medical condition that causes frequent disability and absence from work . Most episodes of low back pain resolve fairly quickly and cause only short periods of absence from work . However , some workers with low back pain miss work for several days to weeks and are at risk for more permanent disability ( 1 ) . To reduce the individual and socioeconomic burden related to this absenteeism , we need effective intervention strategies in occupational health care setting s that promote safe and rapid return to work . One promising and often-advocated intervention strategy for workers with prolonged nonspecific low back pain is active rehabilitation that is directed toward return to normal activity and work ( 2 ) . Examples are grade d activity interventions that include physical exercise , application of operant-conditioning behavioral principals , and promotion of improved functioning and safe return to work even if pain persists ( 3 - 6 ) . In a r and omized , controlled trial , Lindstrm and colleagues ( 3 , 4 ) found that a grade d activity intervention reduced absence from work more than did traditional care in Swedish workers employed in the automobile industry . We investigate , in a second r and omized , controlled trial , whether absence from work because of low back pain is reduced more with grade d activity intervention than with traditional care in an occupational health care setting in the Netherl and s. Methods Study Design and Sample The study was a single-blind , r and omized , controlled trial in an occupational health services center ( KLM Health , Safety and Environment ) at Schiphol Airport , Amsterdam , the Netherl and s. The center provides occupational health services for all employees of a major Dutch airline ( KLM Royal Dutch Airlines ) . The source sample ( n = 20 000 ) consisted of workers who were employed in the following organizational units of the airline : baggage and aircraft turnaround services , passenger services , engineering and maintenance , cargo , and cabin and cockpit . Workers who were listed as absent from work because of low back pain were invited for a consultation with the occupational physician . Those who were thought to be eligible for inclusion were referred to the research assistant , who judged whether they met the inclusion criteria : full or partial absence from work because of nonspecific low back pain and low back pain symptoms with a minimum duration of 4 weeks in succession . The exclusion criteria were low back pain with radiation below the knee with signs of nerve-root compression ( 7 ) ; cardiovascular contraindications for physical activity , as checked according to the Physical Activities Readiness Question naire ( 8 , 9 ) ; any conflict between worker and employer with legal involvement ; or pregnancy . Workers who met the inclusion criteria were informed of the purpose and procedures of the study and were enrolled after giving informed consent . The Medical Ethical Committee of the VU University Medical Center , Amsterdam , the Netherl and s , approved the study . Treatment Allocation The participants were assigned to grade d activity or usual care on the basis of block r and omization , after prestratification for the organizational unit in the workplace from which they were recruited ( the 5 organizational units listed earlier ) and for the severity of pain symptoms ( scored on a scale of 0 to 10 ; severity scores were < 6 or 6 points ) . This result ed in a total of 10 strata . R and omized , permuted blocks of 4 allocations were generated for each stratum through a computer-generated r and om-sequence table . Opaque , sequentially numbered , sealed envelopes were prepared for each stratum by a research er who was not involved in enrolling the participants or assigning them to their groups . The envelopes contained a sheet of paper that indicated 1 of the 2 interventions . Participants learned their group assignments after a research assistant completed the baseline measurements and delivered the sealed envelopes . Blinding The research assistants who collected the data were blinded to the treatment allocation . All participants were repeatedly asked not to reveal any information about their treatment allocation . The participants and treatment providers were not blinded to treatment allocation . Interventions In the Dutch occupational health care system , occupational physicians guide disabled workers who are absent from work through their disability period . These occupational physicians are employed by occupational health services that are paid for by the companies . The occupational physicians adhere to back pain management strategies that consist of advising workers on ergonomics , prevention , and return-to-work schedules and advising and communicating with other stakeholders ( such as health care providers and representatives of the workplace ) . Disabled workers who participated in the present study were assigned to either grade d activity or usual care within the context of the Dutch occupational health care setting . Grade d Activity The intervention group received the usual guidance from the occupational physician about work-related problems and barriers to return to work as well as the grade d activity intervention supervised by a physiotherapist . Three physiotherapists who worked in a private practice at Schiphol Airport provided the treatment according to the grade d activity protocol . Two of those physiotherapists were also trained as manual therapists , and 1 was also a human movement scientist . Before the study , the physiotherapists had been specifically trained to treat patients with low back pain according to behavioral principles . A research physiotherapist who was experienced in treating patients with chronic pain in rehabilitation centers instructed the physiotherapists in three 2-hour sessions and practice d patienttherapist interactions with them through role-play . Before the study , the physiotherapists treated several patients according to the grade d activity protocol to gain more experience . The physiotherapists made audiotapes of the intervention sessions before and during the study period . The contents of these audiotapes were assessed and discussed with the research physiotherapist in 3 additional meetings . Furthermore , the physiotherapists summarized the treatment after each session , and research ers used these summaries to review the sessions . The same physiotherapist treated participants each time , except for temporary st and -in sessions that were supervised by colleagues because of holidays or other reasons . Specific therapists were not systematic ally selected to treat specific participants ; selection was based on pragmatic reasons , such as the time available in the work schedules of the physiotherapists or the days of treatment preferred by the participants . Table 1 presents the concept and content of the grade d activity intervention . The intervention consisted of 1-hour exercise sessions that participants attended twice per week until they returned completely to regular work or until the maximum therapy duration of 3 months was reached . At the start of the intervention , the physiotherapist inquired about the participant 's medical history and completed a brief physical examination consisting of flexion , extension , and lateroflexion of the lumbar spine and a brief screening for nerve-root pain ( 10 ) . The purpose of the physical examination was to confirm the diagnosis of benign , nonspecific low back pain and to reduce participants ' fears about any presumed underlying disease . The participants were reassured that despite the annoying pain , nothing was seriously wrong with their backs . Subsequently , the physiotherapist and participant decided on a set of general exercises and individually tailored exercises . Both types of exercises had to be performed during each session . The general exercises were aerobic exercises , such as cycling or rowing , and strengthening exercises for large muscle groups , and most were carried out in a gym while using exercise equipment . The strengthening exercises were a floor abdominal sit-up exercise , a dynamic back extension exercise , a leg-press exercise , a latissimus pull-down exercise , and st and ing up from a low chair . Participants in the grade d activity group had to perform not only these general exercises but also individually tailored exercises , which imitated physical tasks at work or difficult and painful activities of daily living . For example , a participant who reported back problems while lifting and moving suitcases from a luggage wagon into an airplane might be given an exercise to practice lifting and moving a suitcase with a certain number of repetitions . During the first 3 sessions , the maximal performance ( for example , the maximum number of repetitions ) was assessed for each exercise separately , and the average score for each exercise over the 3 sessions was used as a baseline value for specifying a gradually progressive exercise scheme . Subsequently , the participant was asked to propose a date for full return to regular work , which would consequently be the end point of the physical exercise program . Before returning to full regular work , participants could return to work with modified hours and duties . Advised by the physiotherapist , the participant Study Design . A r and omized parallel-group comparative trial with a 1-year follow-up period was performed . Objective . To compare the effect of a comprehensive functional restoration program involving intensive physical training , ergonomic training , and behavioral support ( 39 hours per week for 3 weeks ) with the effect of outpatient intensive physical training ( 1.5 hours three times per week for 8 weeks ) . Summary of Background Data . Nonr and omized studies conducted in the United States favor functional restoration for patients with chronic low back pain . Two previously reported r and omized studies from the authors ’ Back Center in Copenhagen concur with this recommendation , although the positive effects in one of the studies had faded out after 2 years . R and omized functional restoration studies in Canada and Finl and have failed to demonstrate any substantive effect . Methods . Initially , 138 patients with chronic low back pain were included in the current study . They then were r and omized to either functional restoration ( n = 64 ) or outpatient intensive physical training ( n = 74 ) . Of the initial 138 patients , 11 never started ( 5 and 6 , respectively ) ; 21 dropped out during treatment ( 8 and 13 ) ; and 7 of the graduates did not take part in the 1-year follow-up evaluation ( 3 and 4 ) . The conclusions were drawn from the 99 patients ( 48 and 51 , respectively ) who graduated and participated in a 1-year follow-up evaluation . The median age of the patients was 42 years ( range , 21–55 years ) The female-to-male ratio was 68 to 31 , and the median sick leave days during the preceding 3 years was 180 ( range , 0–1080 days ) . The average back pain was rated 5.5 on a scale of 0 ( no pain ) to 10 ( maximal pain ) . For these variables , there were no important differences between the groups . However , the functional restoration group tended to be more capable of work at baseline ( 58%vs 42%;P = 0.09 ) . Results . At the 1-year follow-up evaluation , overall assessment favored functional restoration . Otherwise , no significant differences were observed regarding work capability , sick leave for those at work , health care contacts , back pain , leg pain , or self-reported activities of daily living . Conclusions . Only in terms of overall assessment , the functional restoration program was superior to a comparatively short time-consuming outpatient physical training program . Discussion . It may be that lower economic benefits during sick leave in the United States lead to favorable results from functional restoration programs , whereas greater benefits in Canada , Finl and , and Denmark result in different conclusions . Finally , it may be that the difference in results across studies points simply to whether the studies were r and omized BACKGROUND Psychological interventions targeting maladaptive pain behaviors and depressive symptoms are commonly used in the management of chronic pain . OBJECTIVE To compare the effectiveness of psychotherapy , based on client-centered therapy , and exercise for patients with chronic nonspecific low back pain ( LBP ) . SETTING Outpatient physiotherapy and psychotherapy departments within a Brazilian academic institution . DESIGN Thirty-three patients with chronic nonspecific LBP were recruited and r and omized to receive client-centered therapy ( N = 16 ) or exercise ( N = 17 ) for 9 weeks . OUTCOME MEASURES AND DATA ANALYSIS : Pain and disability were measured at baseline , 9 weeks , and 6 months by a 10-cm visual analog scale and by the Brazilian Rol and -Morris Question naire , respectively . Depression was measured at baseline and 9 weeks by the Beck Depression Inventory . Multiple regression analyses with baseline scores as covariates were used to determine the effects of treatment on outcomes . RESULTS For all outcomes at each time point , the exercise group showed greater improvements than psychotherapy . The difference between groups was statistically and clinical ly significant for disability at 9 weeks ( -4.9 points , 95 % CI -9.08 to -0.72 ) . CONCLUSIONS This was the first study to investigate the effects of client-centered therapy and exercise for patients with chronic LBP . Our results showed that client-centered therapy is less effective than exercise in reducing disability at short term STUDY DESIGN A r and omized trial design ed to compare interferential therapy with motorized lumbar traction and massage management for low back pain in a primary care setting . OBJECTIVE To measure and compare the outcome of interferential therapy and management by motorized lumbar traction and massage . SUMMARY OF BACKGROUND DATA Management of low back pain by interferential therapy and motorized lumbar traction and massage is common in Germany . No reports of previous r and omized trials for the outcome from interferential therapy were found . METHODS Consenting patients were r and omly assigned into one of two groups . A pretreatment interview was performed by the patient using a computer-based question naire . It also incorporated the Oswestry Disability Index and a pain visual analog scale . Management consisted of six sessions over a 2- to 3-week period . Oswestry Disability Indexes and pain visual analog scale scores also were obtained immediately after and at 3 months after treatment . RESULTS A total of 152 patients were recruited . The two treatment groups had similar demographic and clinical baseline characteristics . The mean Oswestry Disability Index before treatment was 30 for both groups ( n = 147 ) . After treatment , this had dropped to 25 , and , at 3 months , were 21 ( interferential therapy ) and 22 ( motorized lumbar traction and massage ) . The mean pain visual analog scale score before treatment was 50 ( interferential therapy ) and 51 ( motorized lumbar traction and massage ) . This had dropped , respectively , to 46 and 44 after treatment and to 42 and 39 at 3 months . CONCLUSIONS This study shows a progressive fall in Oswestry Disability Index and pain visual analog scale scores in patients with low back pain treated with either-interferential therapy or motorized lumbar traction and massage . There was no difference in the improvement between the two groups at the end of treatment . Although there is evidence from several trials that traction alone is ineffective in the management of low back pain , this study could not exclude some effect from the concomitant massage BACKGROUND AND PURPOSE Clinicians treating patients with low back pain often use exercise to reduce pain and improve function . The aim of this study was to evaluate the effectiveness of trunk extensor endurance training in reducing pain and decreasing disability in subjects with subacute low back pain ( ie , onset of back pain within 7 days to 7 weeks ) . SUBJECTS AND METHODS Patients were r and omly assigned to either an experimental group or a control group . A visual analog scale and the pain rating index ( PRI ) of the McGill Pain Question naire ( MPQ ) were used to obtain baseline measurements of pain . The Rol and Morris Disability Question naire ( RMDQ ) was used to measure disability , and the Sorensen Test was used to measure trunk extensor endurance . Subjects in the experimental group attended exercise sessions 3 times a week for 6 weeks . Subjects in the control group did not do exercises . Both groups were given back care advice and hot packs for 15 minutes , 3 to 5 times per week . Re assessment s were carried out at 3 and 6 weeks . RESULTS There were differences between the 2 groups at 3 weeks in regard to pain intensity during the evaluation session and pain experienced over the preceding 24 hours , the total MPQ PRI , the sensory component of the MPQ PRI , and the RMDQ . At 6 weeks , no differences were found for pain measurements , disability scores , and holding time on the Sorensen Test . CONCLUSION AND DISCUSSION Trunk extensor endurance training reduced pain and improved function at 3 weeks but result ed in no improvement at 6 weeks when compared with the control group . Endurance exercise is considered to expedite the recovery process for patients with an acute episode of low back pain STUDY DESIGN A prospect i ve , r and omized , controlled trial with a stratification block design in which a Mensendieck exercise program was compared with the experience of a control group . OBJECTIVE To evaluate the effect of a Mensendieck program on the incidence of recurrent episodes of low back pain in patients with a history of the condition who currently are working . SUMMARY OF BACKGROUND DATA One episode of low back pain increases the risk of further episodes of the condition . The Mensendieck approach combines education and exercise . This approach has been used for many years in Sc and inavia and the Netherl and s. However , the effects on low back pain have not been evaluated previously in a r and omized , controlled trial . METHODS A total of 77 men and women , mean age 39.6 years ( range , 21.2 - 49.8 years ) , who had finished treatment for a low back pain episode , were stratified according to incidence of low back pain episodes and symptoms of sciatica over the preceding 3 years . The patients were assigned at r and om to either the Mensendieck program or a control group . The Mensendieck group received 20 group sessions of exercises and ergonomic education in 13 weeks . At 5- and 12-month follow-up examinations , the patients were assessed for recurrence of low back pain , days of sick leave , low back pain , and functional scores . RESULTS After 12 months , there was a significant reduction in recurrent low back pain episodes in the Mensendieck group compared with the control group ( P < 0.05 ) . There was a trend toward fewer days of sick leave because of low back pain in the Mensendieck group , but no significant differences between the groups . There was reduction in pain and improvement in function in both groups , with no significant differences between the groups . CONCLUSIONS A secondary prophylaxis Mensendieck exercise program of 20 group sessions significantly reduced the incidence of low back pain recurrences in a population with history of the condition . However , there were no differences between the groups with regard to days of sick leave , low back pain , and function CONTEXT Patients suffering from chronic low back pain ( cLBP ) are often unsatisfied with conventional medical care and seek alternative therapies . Many mind-body techniques are said to help patients with low back pain by enhancing body awareness , which includes proprioception deficit in cLBP , but have not been rigorously studied in cLBP . Breath therapy is a western mind-body therapy integrating body awareness , breathing , meditation , and movement . Preliminary data suggest benefits from breath therapy for proprioception and low back pain . OBJECTIVE To assess the effect of breath therapy on cLBP . DESIGN R and omized , controlled trial . SETTING Academic medical center . PARTICIPANTS Thirty-six patients with cLBP . INTERVENTIONS Six to eight weeks ( 12 sessions ) of breath therapy versus physical therapy . MAIN OUTCOME MEASURES Pain by visual analog scale ( VAS ) , function by Rol and Scale , overall health by Short Form 36 ( SF-36 ) at baseline , six to eight weeks , and six months . Balance as a potential surrogate for proprioception and body-awareness measured at the beginning and end of treatment . RESULTS Pre- to post-intervention , patients in both groups improved in pain ( VAS : -2.7 with breath therapy , -2.4 with physical therapy ; SF-36 : + 14.9 with breath therapy and + 21.0 with physical therapy ) . Breath therapy recipients improved in function ( Rol and : -4.8 ) and in the physical and emotional role ( SF-36 : + 15.5 and 14.3 ) . Physical therapy recipients improved in vitality ( SF-36 : + 15.0 ) . Average improvements were not different between groups . At six to eight weeks , results showed a trend favoring breath therapy ; at six-months , a trend favoring physical therapy . Balance measures showed no improvements and no correlations with other outcomes . CONCLUSIONS Patients suffering from cLBP improved significantly with breath therapy . Changes in st and ard low back pain measures of pain and disability were comparable to those result ing from high- quality , extended physical therapy . Breath therapy was safe . Qualitative data suggested improved coping skills and new insight into the effect of stress on the body as a result of breath therapy . Balance measures did not seem to be valid measures of clinical change in patients ' cLBP OBJECTIVES To study the relative efficacy of three different treatment for chronic low back pain ( CLBP ) . Two preplanned comparisons were made : ( a ) Spinal manipulative therapy ( SMT ) combined with trunk strengthening exercises ( TSE ) vs. SMT combined with trunk stretching exercises , and ( b ) SMT combined with TSE vs. nonsteroidal anti-inflammatory drug ( NSAID ) therapy combined with TSE . STUDY DESIGN Interdisciplinary , prospect i ve , observer-blinded , r and omized clinical trial with a 1-yr follow-up period . The trial evaluated therapies in combination only and was not design ed to test the individual treatment components . SETTING Primary contact , college out-patient clinic . PATIENTS In total , 174 patients aged 20 - 60 yr were admitted to the study . MAIN OUTCOME MEASURES Patient-rated low back pain , disability , and functional health status at 5 and 11 wk . INTERVENTIONS Five weeks of SMT or NSAID therapy in combination with supervised trunk exercise , followed by and additional 6 wk of supervised exercise alone . RESULTS Individual group comparisons after 5 and 11 wk of intervention on all three main outcome measures did not reveal any clear clinical ly important or statistically significant differences . There seemed to be a sustained reduction in medication use at the 1-yr follow-up . in the SMT/TSE group . Continuance of exercise during the follow-up year , regardless of type , was associated with a better outcome . CONCLUSION Each of the three therapeutic regimens was associated with similar and clinical ly important improvement over time that was considered superior to the expected natural history of long-st and ing CLBP . For the management of CLBP , trunk exercise in combination with SMT or NSAID therapy seemed to be beneficial and worthwhile . The magnitude of nonspecific therapeutic ( placebo ) effects , cost-effectiveness and relative risks of side effects associated with these types of therapy need to be addressed in future studies Study Design . Fifty-two practice s in the East Midl and s , United Kingdom , were included . Objectives . To test the hypothesis that referral for lumbar spine radiography is cost-effective in primary care patients with low back pain of at least 6 weeks ’ duration compared with usual care in which referral is not routine . Summary of Background Data . Lumbar spine radiography is commonly used in the management of low back pain , although the yield of findings that alter clinical management is low . Evidence is needed on the cost-effectiveness of lumbar spine radiographs in patients with low back pain . Methods . A prospect i ve economic analysis alongside a r and omized controlled trial was used . Outcomes included the Rol and disability score , pain , health status scale , EuroQol , satisfaction , direct health care costs ( primary , secondary , and community care ; prescribed and over-the-counter medicines ; special equipment ) , and indirect costs ( informal care , extra expenses , welfare benefits , loss of earnings and productivity ) Results . A total of 210 participants were r and omly assigned to lumbar spine radiography , and 211 , to usual care . At 9 months ’ postr and omization , no difference between the groups was found in any health outcomes other than satisfaction . The intervention group had a higher overall satisfaction score ( 21 vs. 19 , P < 0.01 ) . The intervention group had higher direct costs ( £ 150 vs. £ 109 , P < 0.01 ) . Cost-effectiveness analysis shows that patient satisfaction can be increased using lumbar radiography but at an additional cost ( point estimate £ 20 per point on satisfaction scale ) . The simulated distribution based on trial data shows that only when a 1-point increase in satisfaction is valued at more than £ 50 can it be cl aim ed that radiography is cost-effective in these terms ( incremental net monetary benefit mean = £ 116 , 95 % CI £ 7 , £ 225 ) . Conclusions . Radiography is likely to be cost-effective only when satisfaction is valued relatively highly . Strategies to enhance satisfaction for patients with low back pain without using lumbar radiography should be pursued OBJECTIVE To assess the efficacy of a back school program for patients with a first episode of acute work-related low back pain requiring compensation . DESIGN A r and omized single-blind controlled trial . SETTING A private physiatrics outpatient clinic . PATIENTS The mean duration of low back pain was 15 days . INTERVENTION Eligible patients were r and omized to a st and ard treatment program that included daily physiotherapy ( n = 86 ) or the same program with the addition of back school ( n = 82 ) . The back school program consisted of three 90-minute sessions given by a single trained instructor at 0 , 1 , and 8 weeks . MAIN OUTCOME MEASURES The primary outcomes were the time off work for the presenting episode of back pain and the number and duration of recurrences in the year following the study onset . Secondary outcomes included the level of pain , spinal mobility , active straight-leg raising , and functional disability assessed by the Oswestry and Rol and -Morris scales . RESULTS Those r and omized to the back school group gained significantly more knowledge , based on the multiple choice examination ( p = .0001 ) and performed the exercise program significantly better ( p = .0001 ) than the st and ard care group . There were no differences between the two treatment groups for either of the primary outcomes . The median time to return to work from r and omization was 33 days for both the back school and the st and ard care groups ( p = .48 ) . The number of compensated recurrences of low back pain over 1 year was similar ( back school = 14 , st and ard care = 10 , p = .16 ) , as was the median duration of these episodes ( back school = 25 days , st and ard care = 70 days , p = .21 ) . There were no significant differences favoring the back school group for any of the secondary outcomes at the posttreatment , 6-month , or 12-month assessment s. CONCLUSION A back school intervention in addition to st and ard care result ed in no reduction in the time to return to work or the number or duration of recurrences of low back pain requiring compensation over a period of one year QUESTION Is low level laser therapy an effective adjuvant intervention for chronic low back pain ? DESIGN R and omised trial with concealed allocation , blinded assessors and intention-to-treat analysis . PARTICIPANTS Sixty-one patients who had low back pain for at least 12 weeks . INTERVENTION One group received laser therapy alone , one received laser therapy and exercise , and the third group received placebo laser therapy and exercise . Laser therapy was performed twice a week for 6 weeks . OUTCOME MEASURES Outcomes were pain severity measured using a 10-cm visual analogue scale , lumbar range of motion measured by the Schober Test and maximum active flexion , extension and lateral flexion , and disability measured with the Oswestry Disability Index on admission to the study , after 6 weeks of intervention , and after another 6 weeks of no intervention . RESULTS There was no greater effect of laser therapy compared with exercise for any outcome , at either 6 or 12 weeks . There was also no greater effect of laser therapy plus exercise compared with exercise for any outcome at 6 weeks . However , in the laser therapy plus exercise group pain had reduced by 1.8 cm ( 95 % CI 0.1 to 3.3 , p = 0.03 ) , lumbar range of movement increased by 0.9 cm ( 95 % CI 0.2 to 1.8 , p < 0.01 ) on the Schober Test and by 15 deg ( 95 % CI 5 to 25 , p < 0.01 ) of active flexion , and disability reduced by 9.4 points ( 95 % CI 2.7 to 16.0 , p = 0.03 ) more than in the exercise group at 12 weeks . CONCLUSION In chronic low back pain low level laser therapy combined with exercise is more beneficial than exercise alone in the long term BACKGROUND AND PURPOSE Spinal and muscle flexibility have been studied intensively and used clinical ly as outcome measurements in the rehabilitation of subjects with low back pain . The results of previous studies are contradictory and there is a lack of longitudinal data on the effects of long term therapeutic exercise on flexibility . METHOD A controlled experimental study was conducted to determine the effects of progressive therapeutic exercise on spinal and muscle flexibility . Eighty-six chronic low back pain subjects fulfilled the inclusion criteria and were divided into three study groups : ( 1 ) intensive training group , ( 2 ) home exercise group and ( 3 ) control group . The intervention period lasted three months and measurements were performed at both the beginning of the study and immediately after intervention . Follow-up measurements were carried out six and 12 months after baseline . Spinal flexibility was measured with lumbar flexion , extension , spinal lateral flexion and rotation , and muscle flexibility was measured with measurements of erector spinae , hamstring and iliopsoas muscles . Also self-reported outcomes of the Oswestry Index and Borg Scale -- Back Pain Intensity were used . Associations between change ( pre- to post-treatment ) were determined for the dependent variables . RESULTS The results showed no correlation between flexibility , the Oswestry Index or back pain intensity . After the first three-month period lumbar flexion , extension and spinal rotation decreased among all subjects . Spinal rotation and erector spinae muscle flexibility improved significantly with intensive training . At the nine-month follow-up , erector spine flexibility was still greater than at baseline . Hamstring flexibility increased among the intensive training and home exercise groups from pre- to post-intervention . However , the degree of hamstring flexibility gained during training was subsequently lost following the period without programmed exercise in both training groups . Self-reported outcome variables showed positive changes among the three study groups after the completion of intervention period , but these changes were only able to be maintained during subsequent follow-ups for the intensive training and home exercise groups . CONCLUSIONS The findings suggest that flexibility does not play an important role in coping with chronic low back pain for subjects whose functional limitations are not severe . Also , it appears that the achieved gains in spinal and muscle flexibility may not be able to be maintained without continued exercise DESIGN Forty-two ( 42 ) subjects suffering from chronic low-back pain were matched with the nature of their occupations and then r and omly allocated into : ( 1 ) an electroacupuncture group ( EA ) ; ( 2 ) an electrical heat acupuncture ( EH ) group or ; ( 3 ) a control group . INTERVENTIONS Subjects in the EA group and the EH group received treatment for 20 minutes on a total of 6 acupuncture points . Treatment was delivered twice per week for 4 weeks ( a total of 8 sessions ) . Back exercise was taught to all subjects including the control group as a home program . OUTCOMES MEASURES A numerical rating scale of pain ( NPRS ) , straight leg raise ( SLR ) , and Rol and Morris Disability Question naire ( RMDQ ) were recorded . RESULTS There were significant reduction of NPRS within the EA ( p = 0.000 ) , EH ( p = 0.000 ) , and control ( p = 0.013 ) groups across sessions . Significant between-group differences were shown in session 4 ( p = 0.006 ) , session 8 ( p = 0.001 ) , and 1-month follow-up sessions ( p = 0.001 ) . Posthoc tests showed that the NPRS of the EH group was significantly lower than that of the EA group and the control group by session 4 ( p = 0.004 ) . After session 8 , the NPRS of both the EA group ( p = 0.003 ) and the EH group ( p = 0.001 ) were significantly lower than that of the control group . Such a difference was maintained at least up to the 1-month follow-up . Only the EA group had significant improvement in the measurement of SLR across sessions ( p = 0.000 ) . The between-group difference reached significance level in session 8 ( p = 0.001 ) and at 1-month follow-up ( p = 0.002 ) . Posthoc tests showed that EA group had significantly greater gain than the EH group and the control group . For the RMDQ score , the improvement was statistically significant within each of the three groups over time ( p = 0.000 ) . However , the between-group difference did not reach statistical significance . CONCLUSIONS Our findings suggest that 4 sessions of EH treatment over 2 weeks produced significantly greater reduction in the NPRS than that of the EA or the control . However , EA produced greater improvement in SLR and reduction in RMDQ score than that of the EH and the control Background and Purpose : The purpose of this multicenter r and omized clinical trial was to examine the effectiveness of an extension-oriented treatment approach ( EOTA ) in a subgroup of subjects with low back pain ( LBP ) who were hypothesized to benefit from the treatment compared with similar subjects who received a lumbar spine strengthening exercise program . Methods : Subjects with LBP and symptoms distal to the buttocks that central ized with extension movements were included . Forty-eight subjects were r and omly assigned to groups that received an EOTA ( n=26 ) or a strengthening exercise program ( n=22 ) . Subjects attended 8 physical therapy sessions and completed a home exercise program . Follow-up data were obtained at 1 week , 4 weeks , and 6 months after r and omization . Primary outcome measures were disability ( modified Oswestry Low Back Pain Disability Question naire ) and pain ( Numeric Pain Rating Scale ) . Results : Subjects in the EOTA group experienced greater improvements in disability compared with subjects who received trunk strengthening exercises at 1 week ( mean difference between groups from baseline=8.9 , 95 % confidence interval [CI]=2.0 , 15.9 ) , 4 weeks , ( mean difference=14.4 , 95 % CI=4.8 , 23.9 ) , and 6 months ( mean difference=14.6 , 95 % CI=4.6 , 24.6 ) . The EOTA group demonstrated greater change in pain at the 1-week follow-up only . Discussion and Conclusion : An EOTA was more effective than trunk strengthening exercise in a subgroup of subjects hypothesized to benefit from this treatment approach . Additional research is needed to explore whether an EOTA may benefit other subgroups of patients OBJECTIVE This study compared the dynamic surface electromyographic ( EMG ) activities of back muscles and pain before and after traditional bone setting and physical therapy . METHODS This study was a prospect i ve clinical trial that compared surface EMG dynamic activities after traditional bone setting and physical therapy . Sixty-one patients ( mean age , 41 years ) with nonspecific low back pain were r and omized into two subgroups by treatment . The patients underwent a dynamic EMG evaluation for which they were asked to st and and then bend forward as far as possible , stay fully flexed , and return to st and ing . A flexion-relaxation ratio was calculated by comparing maximal EMG activity while flexing with the average EMG activity in full flexion . Concentric ( maximal EMG activity during extension ) and eccentric ( maximal EMG activity during flexion ) ratios were also used in the analyses . RESULTS Disability , depression , and visual analog scale scores decreased significantly after both treatments . The concentric ratio increased statistically in both groups after the treatments . The study failed to show a significant association between experienced back pain and EMG parameters . CONCLUSIONS Both treatments seem to have a positive influence on back muscle function by improving muscle symmetry ; however , the treatments had no effect on the flexion-relaxation phenomenon after 1 month . Active back exercise at home together with rehabilitation treatments might be effective and improve function for patients with chronic low back pain Manual therapy , exercise and education target distinct aspects of chronic low back pain and probably have distinct effects . This study aim ed to determine the efficacy of a combined physiotherapy treatment that comprised all of these strategies . By concealed r and omisation , 57 chronic low back pain patients were allocated to either the four-week physiotherapy program or management as directed by their general practitioners . The dependent variables of interest were pain and disability . Assessors were blind to treatment group . Outcome data from 49 subjects ( 86 % ) showed a significant treatment effect . The physiotherapy program reduced pain and disability by a mean of 1.5/10 points on a numerical rating scale ( 95 % CI 0.7 to 2.3 ) and 3.9 points on the 18-point Rol and Morris Disability Question naire ( 95 % CI 2 to 5.8 ) , respectively . The number needed to treat in order to gain a clinical ly meaningful change was 3 ( 95 % CI 3 to 8) for pain , and 2 ( 95 % CI 2 to 5 ) for disability . A treatment effect was maintained at one-year follow-up . The findings support the efficacy of combined physiotherapy treatment in producing symptomatic and functional change in moderately disabled chronic low back pain patients & NA ; Using latent class analysis ( LCA ) , a previous study on patients attending primary care identified four courses of low back pain ( LBP ) over the subsequent 6 months . To date , no studies have used longitudinal pain recordings to examine the “ natural ” course of recurrent and chronic LBP in a population ‐based sample of individuals . This study examines the course of LBP in the general population and elaborates on the stability and criterion‐related validity of the clusters derived . A r and om sample of 400 individuals reporting LBP in a population ‐based study was asked to complete a comprehensive question naire at the start and end of the year 's survey , and 52 weekly pain diaries in between . The latter were analyzed using LCA . 305 individuals returned more than 50 % of the diaries . Four clusters were identified ( severe persistent , moderate persistent , mild persistent , and fluctuating ) . The clusters differed significantly with regards to pain and disability . Assessment of cluster stability showed that a considerable proportion of patients in the “ fluctuating ” group changed their classification over time . Three of the four clusters describing the typical course of pain matched the clusters described previously for patients in primary care . Due to the population ‐based design , this study achieves , for the first time , a close insight into the “ natural ” course of chronic and recurrent low back pain , including individuals that did not necessarily visit the general practitioner . The findings will help to underst and better the nature of this pain in the general population OBJECTIVE Flexion distraction is a commonly used form of chiropractic care with chiropractor utilization rates of 58 % . However , no previous r and omized clinical trial has assessed the effectiveness of this form of care . The objective of this investigation was to compare the pain and disability during the year after active care based on treatment group allocation ( Flexion Distraction versus Exercise Program ) . STUDY DESIGN R and omized clinical trial , follow-up . SUBJECTS Two hundred and thirty-five ( 235 ) subjects who were previously r and omized to either chiropractic care ( flexion distraction ) or physical therapy ( exercise program ) within a clinical trial . OUTCOME MEASURES Subjects were followed for 1 year via mailed question naires to assess levels of pain ( Visual Analog Scale ) and dysfunction ( Rol and Morris ) . RESULTS Study subjects had a decrease in pain and disability after intervention regardless of which group they attended ( p < 0.002 ) , however , during the year after care , subjects who received chiropractic care ( flexion distraction therapy ) had significantly lower pain scores than subjects who received physical therapy ( exercise program ) ( p = 0.02 ) . CONCLUSIONS In this first trial on flexion distraction care , flexion distraction was found to be more effective in reducing pain for 1 year when compared to a form of physical therapy Study Design . A stratified r and omized single-blinded clinical trial . Objective . To compare the efficacies of 2 active therapies for chronic low back pain ( CLBP ) . Summary of Background Data . Both a multidisciplinary biopsychosocial rehabilitation program and an intensive individual therapist-assisted back muscle strengthening exercise program used in Denmark have been reported to be effective for the treatment of CLBP . Methods . A total of 286 patients with CLBP were r and omized to either a group-based 12-week program comprising 73 hours of therapist exposure ( approximately 12 h/patient ) : 35 hours of hard physical exercise , 22 hours of light exercise/occupational therapy , and 16 hours of education ( group A ) or a 12-week program comprising 1 hour of personal training twice a week , i.e. , therapist exposure 24 h/patient ( group B ) . At baseline and at 3 , 6 , 12 , and 24 months , patients filled out question naires on pain ( visual analogue scale [VAS]-pain average , which was the primary outcome measure ) , Rol and -Morris disability question naire , global perceived outcome , and 36-Item Short-Form General Health Survey . Data were analyzed using the intention-to-treat principle . Results . Of the 286 patients , 14 patients did not start treatment . Of the remaining patients , 25 ( 9 % ) dropped out of therapy . The 2 groups were comparable regarding baseline characteristic . After treatment , significant improvements were observed with regard to pain , disability , and most of the quality of life dimensions . These effects were sustained over the 24-month follow-up period . There were some statistically significant differences between the 2 groups relating to secondary end points , Rol and -Morris disability question naire , and in the MOS 36-Item Short-Form Health Survey the “ physical functioning ” dimension and the “ physical component summary . ” Conclusion . Both groups showed long-term improvements in pain and disability scores , with only minor statistically significant differences between the 2 groups . The minor outcome difference in favor of the group-based multidisciplinary rehabilitation program is hardly of clinical interest for individual patients Previous studies reported that respiratory feedback ( RFB ) aids in alleviating chronic pain . However , to date , this adjunct treatment has not been rigorously tested against non-contingent ( placebo ) feedback . Forty-two patients with chronic low back pain were r and omized to either RFB or non-contingent RFB . Both groups performed a daily 30-min home training for 15 consecutive days . A respiratory associated relaxation index ( RI ) was measured . Pain levels and a somatosensory profile were assessed before and after intervention . Additionally , pain levels were assessed 3 months after the end of intervention . Secondary outcome parameters included daily functioning , psychopathology , and suggestibility . T-tests showed higher and significant pain reductions for RFB , compared to non-contingent RFB . Between-group comparisons reached no significance . However , changes were more pronounced in the RFB condition , which was also true for the course of the RI and the psychopathological scores . This is the first study using a non-contingent respiratory placebo feedback in a r and omized , controlled design . Within this design previous positive findings of symptom reductions in patients treated with RFB could partially replicated . Nonetheless , tendencies suggest that contingent feedback patients compared to placebo patients profit more from RFB in the long run regarding reduction of chronic pain and psychological distress Objective The primary aim was to determine if laser acupuncture ( LA ) is more effective than sham laser in reducing pain and disability in adults with chronic non-specific low back pain . Methods The design was a double blind , two-group parallel r and omised controlled trial . The active intervention was an 830 nm ( infrared ) , 10 mW , Ga-Al-As laser diode laser for acupuncture and a sham control . The primary outcome measures were changes in pain ( visual analogue scale ) and disability ( Oswestry Disability Index ) at the end of 5–10 treatment sessions . Secondary outcomes were patient global assessment , psychological distress ( Depression Anxiety Stress Scale ) and subjective wellbeing ( Personal Wellbeing Index ) . Follow up was performed at 6 weeks and 6 months after completion of treatment . Results 100 participants were enrolled and treated in a general practice setting . Per protocol analysis of the primary outcome measures using ANOVA suggested that although there was a significant overall improvement in pain and disability after the course of treatments ( p<0.01 ) , there was no significant difference between the intervention and control group in both the primary and most secondary outcome measures . Conclusion This study did not show a specific effect for LA using infrared laser at 0.2 Joules per point for chronic low back pain . The overall intervention appeared effective because of placebo and other factors . As there was some concern about baseline ine quality between the groups further research using tighter inclusion criteria should attempt to replicate the result and examine if a dose response may exist Study Design . The study was a r and omized controlled trial . Treatment was for 8 weeks , with follow-up posttreatment and at 6- , 12- , and 36- months . Objective . The purpose was to evaluate the effect of a grade d exercise intervention emphasizing stabilizing exercises in patients with nonspecific , recurrent low back pain ( LBP ) . Summary of Background Data . Exercise therapy is recommended and widely used as treatment for LBP . Although stabilizing exercises are reportedly effective in the management of certain subgroups of LBP , such intervention protocol s have not yet been evaluated in relation to a more general exercise regimen in patients with recurrent LBP , all at work . Methods . Seventy-one patients recruited consecutively ( 36 men , 35 women ) with recurrent nonspecific LBP seeking care at an outpatient physiotherapy clinic were r and omized into 2 treatment groups ; grade d exercise intervention or daily walks . The primary outcome was perceived disability and pain at 12-month follow-up . Secondary outcomes included physical health , fear-avoidance , and self-efficacy beliefs . Results . Of the participants , 83 % provided data at the 12-month follow-up and 79 % at 36 months . At 12 months , between-group comparison showed a reduction in perceived disability in favor of the exercise group , whereas such an effect for pain emerged only immediately postintervention . Ratings of physical health and self-efficacy beliefs also improved in the exercise group over the long term , though no changes were observed for fear-avoidance beliefs . Conclusion . A grade d exercise intervention , emphasizing stabilizing exercises , for patients with recurrent LBP still at work seems more effective in improving disability and health parameters than daily walks do . However , no such positive results emerged for improvement regarding pain over a longer term , or for fear-avoidance beliefs Abstract We evaluated three different conservative treatment methods for acute low-back pain patients in groups following a manual therapy programme , an intensive training programme , or a general practitioner programme , the latter serving as the control group . Patients aged 19–64 years on sick leave for low-back pain with or without sciatica were included in a prospect i ve r and omised study evaluating outcomes such as impairment , pain , functional disability , socio-economic disability and satisfaction with the treatment or explanations . Evaluation by unbiased observers was performed at 1 , 3 and 12 months . The three treatment groups were comparable at baseline . With regard to satisfaction , the patients in the manual therapy programme and those in the intensive training programme were more satisfied with the treatment than those in the general practitioner programme at all follow-ups . With regard to the explanations of current low-back pain episodes , the patients in the manual therapy programme were more satisfied than those in the general practitioner programme at all follow-ups . The manual therapy programme group were also more satisfied with the explanations than those in the intensive training programme at the 1-month follow-up . However , no differences were revealed between the groups with respect to outcomes on measures of impairment , pain , functional disability or socio-economic disability . All three study groups showed rapid improvement . After 1 month a significant improvement was noted in all outcome values compared with the values on entry to the study . Within the limitations discussed in our study , it is concluded that ( 1 ) patients sick listed with acute low-back pain , with or without sciatica , will be significantly improved after 1 month regardless of conservative treatment programme ; ( 2 ) they will be more satisfied with the treatment if they are referred to a manual treatment programme or a training treatment programme ; ( 3 ) they will be more satisfied with the explanations of the acute low-back problem if they are referred to one of the above groups , especially the manual treatment group ; ( 4 ) they will not show any other differences with respect to subjective and objective variables , either at short-term or at long-term follow-ups Objective : To compare spinal manipulation , back school and individual physiotherapy in the treatment of chronic low back pain . Design : R and omized trial , 12-month follow-up . Setting : Outpatient rehabilitation department . Participants : 210 patients with chronic , non-specific low back pain , 140/210 women , age 59 ± 14 years . Interventions : Back school and individual physiotherapy scheduled 15 1-hour-sessions for 3 weeks . Back school included : group exercise , education/ ergonomics ; individual physiotherapy : exercise , passive mobilization and soft-tissue treatment . Spinal manipulation , given according to Manual Medicine , scheduled 4 to 6 20’-sessions once-a-week . Outcome : Rol and Morris Disability Question naire ( scoring 0 - 24 ) and Pain Rating Scale ( scoring 0 - 6 ) were assessed at baseline , discharge 3 , 6 , and 12 months . Results : 205 patients completed the study . At discharge , disability score decreased by 3.7 ± 4.1 for back school , 4.4 ± 3.7 for individual physiotherapy , 6.7 ± 3.9 for manipulation ; pain score reduction was 0.9 ± 1.1 , 1.1 ± 1.0 , 1.0 ± 1.1 , respectively . At 12 months , disability score reduction was 4.2 ± 4.8 for back school , 4.0 ± 5.1 for individual physiotherapy , 5.9 ± 4.6 for manipulation ; pain score reduction was 0.7 ± 1.2 , 0.4 ± 1.3 , and 1.5 ± 1.1 , respectively . Spinal manipulation was associated with higher functional improvement and long-term pain relief than back school or individual physiotherapy , but received more further treatment at follow-ups ( P<0.001 ) ; pain recurrences and drug intake were also reduced compared to back school ( P < 0.05 ) or individual physiotherapy ( P < 0.001 ) . Conclusions : Spinal manipulation provided better short and long-term functional improvement , and more pain relief in the follow-up than either back school or individual physiotherapy Objective Evaluate the effectiveness of two active interventions , aim ed at secondary prevention of low back pain ( LBP ) , in occupational health . Methods We performed a survey of LBP ( n=2480 ; response rate 71 % ) and r and omized 143 employees ( 66 % males , 45 years ) with LBP over 34 mm on VAS into Rehabilitation ( n=43 ) , Exercise ( n=43 ) or self-care ( n=40 ) groups . Primary outcomes were LBP , physical impairment ( PI ) and health-related quality of life ( HRQoL ) for two years and sickness absence ( SA ) days during four years ( LBP specific , total ) . Results Compared to self-care , exercise reduced LBP at 12 months ( mean difference ( MD ) −12 mm ; 95 % CI −21 to −2 ) and improved HRQoL at 12 and 24 months ( 0.03 ; 0.00 to 0.05 ) , but did not reduce PI . The MDs of SA days in four years were −17 ( −70 to 35 , total ) and −15 ( −47 to 13 , LBP specific ) . Exercise reduced the probability of LBP specific SA during the third and fourth year . Compared to self-care , Rehabilitation reduced LBP at 3 months ( −10 mm ; −19 to −1 ) and 6 months ( −10 mm ; −20 to − 1 ) , but was not effective in HRQoL or PI . The MDs of SA days in four years were −41 ( −93 to 8 ; total ) and 5 ( −30 to 47 ; LBP specific ) . Rehabilitation reduced the probability of total SA during first and second year and amount of total SA days in the fourth year . Conclusions Among employees with relatively mild LBP , both interventions reduced pain , but the effects on SA and PI were minor . Exercise improved HRQoL. The effect sizes were rather small . Trial registration Number Clinical Trials.gov NCT00908102 Study Design . R and omized Clinical Trial . Objective . To identify a subgroup of patients with low back pain who are likely to respond favorably to an intervention including mechanical traction . Summary of Background Data . Previous research has failed to find evidence supporting traction for patients with low back pain . Previous studies have used heterogeneous sample s , although clinical experts tend to recommend traction for a more limited subgroup of patients with low back pain . Methods . Sixty-four subjects ( mean age 41.1 year , 56.3 % female ) with low back and leg pain and signs of nerve root compression were r and omized to receive a 6-week extension-oriented intervention with or without mechanical traction during the first 2 weeks . Between-group comparisons were conducted for changes in pain , disability , and fear-avoidance beliefs . Baseline variables were explored for potential as subgrouping criteria defining a subgroup of subjects likely to benefit from traction . Results . The group receiving traction showed greater improvements in disability ( adjusted mean difference in Oswestry change 7.2 points ) and fear-avoidance beliefs ( adjusted mean difference in FABQPA change 2.6 points ) after 2 weeks . There were no between-group differences after 6 weeks . Two baseline variables were associated with greater improvements with traction treatment ; peripheralization with extension movements and a crossed straight leg raise . Conclusion . A subgroup of patients likely to benefit from mechanical traction may exist . The results of this study suggest this subgroup is characterized by the presence of leg symptoms , signs of nerve root compression , and either peripheralization with extension movements or a crossed straight leg raise . Further research is needed to vali date this finding STUDY DESIGN A r and omized study comparing the results of active rehabilitation and passive control treatment in patients with chronic low back pain with follow-up at 6 months and 1 year . OBJECTIVES To study the efficacy of active rehabilitation on pain , self-experienced disability , and lumbar fatigability . SUMMARY OF BACKGROUND DATA Exercises in an outpatient setting are widely used for the treatment of chronic low back pain . The efficacy of the active rehabilitation approach has been documented in r and omized control studies , but these studies have seldom been focused on lumbar fatigability , which is now recognized as a frequent problem among patients with chronic low back pain . METHODS Fifty-nine middle-aged patients ( 37 men and 22 women ) with nonspecific chronic low back pain were r and omly assigned to 12 weeks ' active rehabilitation or to a passive control treatment ( massage , thermal therapy ) . Pain and disability index , low back pain intensity ( visual analog scale , 100 mm ) , and the objective ly assessed lumbar muscle fatigability ( spectral electromyogram , mean power frequency slope [ MPFSLOPE ] ) in a new 90-second submaximal isoinertial back endurance test were recorded before and after the interventions and at 6-month and 1-year follow-up visits . RESULTS Results of repeated measures multivariate analysis of variance indicated that back pain intensity ( visual analog scale ) and functional disability ( pain and disability index score ) decreased , and lumbar endurance ( MPFSLOPE ) improved significantly more ( P < 0.05 ) in the active rehabilitation group than in the passive control treatment group , when measured at a 1-year follow-up examination . The group difference in visual analog scale and pain and disability index changes became even more significant at the end of 1 year . The change in lumbar endurance was significantly greater in the active rehabilitation group than in the passive control treatment group at the 6-month follow-up , but not at the 1-year follow-up . CONCLUSIONS The active progressive treatment program was more successful in reducing pain and self-experienced disability and also in improving lumbar endurance than was the passive control treatment . However , the group difference in lumbar endurance tended to diminish at the 1-year follow-up Study Design . A multicenter , r and omized , single‐blinded controlled trial with 1‐year follow‐up . Objectives . To evaluate the efficiency of progressively grade d medical exercise therapy , conventional physiotherapy , and self‐exercise by walking in patients with chronic low back pain . Summary and Background Data . Varieties of medical exercise therapy and conventional physiotherapy are considered to reduce symptoms , improve function , and decrease sickness absence , but this opinion is controversial . Methods . Patients with chronic low back pain or radicular pain sick‐listed for more than 8 weeks and less than 52 weeks ( Sickness Certificate II ) were included . The treatment lasted 3 months ( 36 treatments ) . Pain intensity , functional ability , patient satisfaction , return to work , number of days on sick leave , and costs were recorded . Results . Of the 208 patients included in this study , 71 were r and omly assigned to medical exercise therapy , 67 to conventional physiotherapy , and 70 to self‐exercise . Thirty‐three ( 15.8 % ) patients dropped out during the treatment period . No difference was observed between the medical exercise therapy and conventional physiotherapy groups , but both were significantly better than self‐exercise group . Patient satisfaction was highest for medical exercise therapy . Return to work rates were equal for all 3 intervention groups at assessment 15 months after therapy was started , with 123 patients were back to work . In terms of costs for days on sick leave , the medical exercise therapy group saved 906,732 Norwegian Kroner ( NOK ) ( $ 122,531.00 ) , and the conventional physiotherapy group saved NOK 1,882,560 ( $ 254,200.00 ) , compared with the self‐exercise group . Conclusions . The efficiency of medical exercise therapy and conventional physiotherapy is shown . Leaving patients with chronic low back pain untampered poses a risk of worsening the disability , result ing in longer periods of sick leave Study Design . A r and omized clinical trial . Objectives . To compare the effectiveness of medical and chiropractic care for low back pain patients in managed care ; to assess the effectiveness of physical therapy among medical patients ; and to assess the effectiveness of physical modalities among chiropractic patients . Summary of Background Data . Despite the burden that low back pain places on patients , providers , and society , the relative effectiveness of common treatment strategies offered in managed care is unknown . Methods . Low back pain patients presenting to a large managed care facility from October 30 , 1995 , through November 9 , 1998 , were r and omly assigned in a balanced design to medical care with and without physical therapy and to chiropractic care with and without physical modalities . The primary outcome variables are average and most severe low back pain intensity in the past week , assessed with 0 to 10 numerical rating scales , and low back-related disability , assessed with the 24-item Rol and -Morris Disability Question naire . Results . Of 1,469 eligible patients , 681 were enrolled ; 95.7 % were followed through 6 months . The mean changes in low back pain intensity and disability of participants in the medical and chiropractic care-only groups were similar at each follow-up assessment ( adjusted mean differences at 6 months for most severe pain , 0.27 , 95 % confidence interval , -0.32–0.86 ; average pain , 0.22 , -0.25–0.69 ; and disability , 0.75 , -0.29–1.79 ) . Physical therapy yielded somewhat better 6-month disability outcomes than did medical care alone ( 1.26 , 0.20–2.32 ) . Conclusions . After 6 months of follow-up , chiropractic care and medical care for low back pain were comparable in their effectiveness . Physical therapy may be marginally more effective than medical care alone for reducing disability in some patients , but the possible benefit is small OBJECTIVES To examine the relative efficacy of three active therapies for patients with chronic low back pain . METHODS One hundred and forty-eight subjects with chronic low back pain were r and omized to receive , twice weekly for 3 months , ( i ) active physiotherapy , ( ii ) muscle reconditioning on training devices , or ( ii ) low-impact aerobics . Question naires were administered to assess pain intensity , pain frequency and disability before and after therapy and at 6 and 12 months of follow-up . RESULTS One hundred and thirty-two of the 148 patients ( 89 % ) completed the therapy programmes and 127 of the 148 ( 86 % ) returned a question naire at all four time-points . The three treatments were equally efficacious in significantly reducing pain intensity and frequency for up to 1 yr after therapy . However , the groups differed with respect to the temporal changes in self-rated disability over the study period ( P=0.03 ) : all groups showed a similar reduction after therapy , but for the physiotherapy group disability increased again during the first 6 months of follow-up whilst the other two groups showed a further decline . In all groups the values then remained stable up to the 12-month follow-up . The larger group size and minimal infrastructure required for low-impact aerobics rendered it considerably less expensive to administer than the other two programmes . CONCLUSIONS The introduction of low-impact aerobic exercise programmes for patients with chronic low back pain may reduce the enormous costs associated with its treatment The purpose of the present study was to investigate the long-term effect of the Active Back School programme on minimizing recurrences of episodes of low back pain . Forty-three subjects were r and omly allocated to the Active Back School group and 38 to the control group . There were no significant differences between the groups with regard to baseline characteristics . The Active Back School programme comprised 20 lessons each divided into a 20-min theoretical and a 40-min exercise part during a 13-week period . Nine participants ( 11 % ) dropped out during the study period . Recurrence of new low back pain episodes was significantly less ( p = 0.04 ) , and the time from inclusion to the first new low back pain episode was significantly on the side of the Active Back School group ( p < 0.01 ) . The duration of sick leave was found to be significantly shorter ( p < 0.01 ) in the Active Back School group compared to the control group . The Active Back School reduced the recurrence and severity of new low back pain episodes at 36 months ' follow-up The aim of this paper was to study the physical performance , pain , pain behavior and disability in patients with subacute low back pain ( LBP ) . The patients were blue-collar workers and had been sick-listed for 8 weeks due to subacute low back pain . A total of 103 patients were r and omized , 51 of them to the intervention group and the other to a control group . Recordings of physical performance and complaints of LBP were done before and after treatment in the intervention group . The proportion of patients with no complaints of LBP was significantly greater in the intervention group than in the control group at the one-year follow-up . The patients who intra-individually improved their physical performance also intra-individually decreased their complaints of LBP . The intra-individual improvements were suggested to be important for the individual return to work Objectives To evaluate the effects of early access ( EA ) to physical therapy treatment for patients with subacute low back pain compared to access with a 4-week waiting list . Design A prospect i ve , r and omized clinical trial . Setting Primary health care . Patients Sixty consecutive patients with subacute low back pain . Interventions Patients were r and omized either to EA within 2 days for physical examination and individualized physical therapy treatment ( n=32 ) or a control group with a 4-week waiting list ( n=28 ) . Outcome Measures Self-administrated question naires were used for assessment at inclusion , at discharge , and at 6 months . Primary outcome measure was pain intensity assessed by Borg category scale for ratings of perceived pain . Secondary outcomes included the Örebro musculoskeletal pain screening question naire , the Rol and and Morris disability question naire , sick-leave , visits to health care , and physical therapy . Results The results showed no significant differences in pain between the groups at discharge . At 6 months , the reduction of pain was significantly greater in the EA group compared to the control group ( P=0.025 ) . Changes in secondary outcome measures were not significantly different between groups . Conclusions This study indicated that EA to physical therapy result ed in greater improvement in perceived pain at 6 months compared to later access . In this study , EA to physical therapy could be introduced by reorganization without additional re sources Study Design . R and omized controlled trial . Objectives . To Investigate the long-term effectiveness , costs , and effect modifiers of a mini-intervention , provided in addition to the usual care , and the incremental effect of a worksite visit for patients with subacute disabling low back pain ( LBP ) . Summary of Background Data . A mini-intervention was earlier proved to be an effective treatment for subacute LBP . Whether the beneficial effect is sustained is not known . Furthermore , modifiers of a treatment effect are largely unknown . Methods . A total of 164 patients with subacute LBP r and omized into a mini-intervention ( A , n = 56 ) , a mini-intervention plus a worksite visit ( B , n = 51 ) , or the usual care ( C , n = 57 ) . Mini-intervention consisted of a detailed assessment of the patients ’ history , beliefs , and physical findings by a physician and a physiotherapist , followed by recommendations and advice . The usual care patients received the conventional care . Pain , disability , health-related quality of life , satisfaction with care , days on sick leave , and health care consumption and costs were measured during a 24-month follow-up . Thirteen c and i date modifiers were tested for each outcome . Results . There were no differences between the three treatment arms regarding the intensity of pain , the perceived disability , or the health-related quality of life . However , mini-intervention decreased occurrence of daily ( A vs. , C , P = 0.01 ) and bothersome ( A vs. C , P < 0.05 ) pain and increased treatment satisfaction . Costs result ing from LBP were lower in the intervention groups ( A 4670 Euros , B 5990 Euros ) than in C ( C 9510 Euros ) ( A vs. C , P = 0.04 ; and B vs. C , not significant ) . The average number of days on sick leave was 30 in A , 45 in B , and 62 in C ( A vs. C , P = 0.03 ; B vs. C , not significant ) . The perceived risk for not recovering was the strongest modifier of treatment effect . Mental and mental-physical workers in A and B were less often on sick leave than those in C. Conclusions . Mini-intervention is an effective treatment for subacute LBP . Despite lack of a significant effect on intensity of low back pain and perceived disability , mini-intervention , including proper recommendations and advice , according to the “ active approach , ” is able to reduce LBP-related costs . The perceived risk of not recovering was the strongest modifier of treatment effect . In alleviating pain , the intervention was most effective among the patients with a high perceived risk of not recovering BACKGROUND Few studies exist on the prognostic value of demographic , clinical , or psychosocial factors on long-term outcomes for patients with chronic low back pain . OBJECTIVE This study reports on long-term pain and disability outcomes for patients with chronic low back pain , evaluates predictors of long-term outcomes , and assesses the influence of doctor type on clinical outcome . METHODS Sixty chiropractic ( DC ) and 111 general practice ( MD ) physicians participated in data collection for a prospect i ve , longitudinal , practice -based , observational study of ambulatory low back pain of mechanical origin . The primary outcomes , measured at 6 months and 12 months , were pain ( by using the Visual Analog Scale ) , and functional disability ( by using the Revised Oswestry Disability Question naire ) . Satisfaction was a secondary outcome . RESULTS Overall , long-term pain and disability outcomes were generally equivalent for patients seeking care from medical or chiropractic physicians . Medical and chiropractic care were comparable for patients without leg pain and for patients with leg pain above the knee . However , an advantage was noted for chronic chiropractic patients with radiating pain below the knee after adjusting for baseline differences in patient and complaint characteristics between MD and DC cohorts ( adjusted differences = 8.0 to 15.2 ; P < .002 ) . A greater proportion of chiropractic patients were satisfied with all aspects of their care ( P = .0000 ) . The strongest predictors of primary outcomes included an interaction of radiating pain below the knee with provider type and baseline values of the outcomes . Income , smoking , comorbidity , and chronic depression were also identified as predictors of outcomes in this study . CONCLUSION Chiropractic care compared favorably to medical care with respect to long-term pain and disability outcomes . Further study is required to explore the advantage seen for chiropractic care in patients with leg pain below the knee and in the area of patient satisfaction . Identification of patient and treatment characteristics associated with better or worse outcomes may foster changes in physicians ' practice activities that better serve these patients ' needs Study Design . A multicenter assessor-blinded r and omized clinical trial was conducted . Objectives . To investigate the difference in effectiveness of manipulative therapy and interferential therapy for patients with acute low back pain when used as sole treatments and in combination . Summary of Background Data . Both manipulative therapy and interferential therapy are commonly used treatments for low back pain . Evidence for the effectiveness of manipulative therapy is available only for the short-term . There is limited evidence for interferential therapy , and no study has investigated the effectiveness of manipulative therapy combined with interferential therapy . Methods . Consenting subjects ( n = 240 ) recruited following referral by physicians to physiotherapy departments in the ( government-funded ) National Health Service in Northern Irel and were r and omly assigned to receive a copy of the Back Book and either manipulative therapy ( MT ; n = 80 ) , interferential therapy ( IFT ; n = 80 ) , or a combination of manipulative therapy and interferential therapy ( CT ; n = 80 ) . The primary outcome was a change in functional disability on the Rol and Morris Disability Question naire . Follow-up question naires were posted at discharge and at 6 and 12 months . Results . The groups were balanced at baseline for low back pain and demographic characteristics . At discharge all interventions significantly reduced functional disability ( Rol and Morris scale , MT : −4.53 ; 95 % CI , −5.7 to −3.3 vs. IFT : −3.56 ; 95 % CI , −4.8 to −2.4 vs. CT : −4.65 ; 95 % CI , −5.8 to −3.5 ; P = 0.38 ) and pain ( McGill question naire , MT : −5.12 ; 95 % CI , −7.7 to −2.5 vs. IFT : −5.87 ; 95 % CI , −8.5 to −3.3 vs. CT : −6.64 ; 95 % CI , −9.2 to −4.1 ; P = 0.72 ) and increased quality of life ( SF-36 Role-Physical , MT : 28.6 ; 95 % CI , 18.3 to 38.9 vs. IFT : 31.4 ; 95 % CI , 21.2 to 41.5 vs. CT : 30 ; 95 % CI , 19.9 to 40 ; P = 0.93 ) to the same degree and maintained these improvements at 6 and 12 months . No significant differences were found between groups for reported LBP recurrence , work absenteeism , medication consumption , exercise participation , or healthcare use at 12 months ( P > 0.05 ) . Conclusions . For acute low back pain , there was no difference between the effects of a combined manipulative therapy and interferential therapy package and either manipulative therapy or interferential therapy alone Objectives . To assess the efficacy of a prolotherapy injection and exercise protocol in the treatment of chronic nonspecific low back pain . Design . R and omized controlled trial with two-by-two factorial design , triple-blinded for injection status , and single-blinded for exercise status . Setting . General practice . Participants . One hundred ten participants with nonspecific low-back pain of average 14 years duration were r and omized to have repeated prolotherapy ( 20 % glucose/0.2 % lignocaine ) or normal saline injections into tender lumbo-pelvic ligaments and r and omized to perform either flexion/extension exercises or normal activity over 6 months . Main outcome measures Pain intensity ( VAS ) and disability scores ( Rol and -Morris ) at 2.5 , 4 , 6 , 12 , and 24 months . Results . Follow-up was achieved in 96 % at 12 months and 80 % at 2 years . Ligament injections , with exercises and with normal activity , result ed in significant and sustained reductions in pain and disability throughout the trial , but no attributable effect was found for prolotherapy injections over saline injections or for exercises over normal activity . At 12 months , the proportions achieving more than 50 % reduction in pain from baseline by injection group were glucose-lignocaine : 0.46 versus saline : 0.36 . By activity group these proportions were exercise : 0.41 versus normal activity : 0.39 . Corresponding proportions for > 50 % reduction in disability were glucose-lignocaine : 0.42 versus saline 0.36 and exercise : 0.36 versus normal activity : 0.38 . There were no between group differences in any of the above measures . Conclusions . In chronic nonspecific low-back pain , significant and sustained reductions in pain and disability occur with ligament injections , irrespective of the solution injected or the concurrent use of exercises Study Design . A prospect i ve , r and omized controlled trial . Objective . To examine long-term effects and costs of combined manipulative treatment , stabilizing exercises , and physician consultation compared with physician consultation alone for chronic low back pain ( cLBP ) . Summary of Background Data . An obvious gap exists in knowledge concerning long-term efficacy and cost-effectiveness of manipulative treatment methods . Methods . Of 204 patients with cLBP whose Oswestry Disability Index ( ODI ) was at least 16 % , 102 were r and omized into a combined manipulative treatment , exercise , and physician consultation group ( i.e. , a combination group ) , and 102 to a consultation alone group . All patients were clinical ly examined , informed about their back pain , and encouraged to stay active and exercise according to specific instructions based on clinical evaluation . Treatment included 4 sessions of manual therapy and stabilizing exercises aim ed at correcting the lumbopelvic rhythm . Question naires inquired about pain ( visual analog scale [ VAS ] ) , disability ( ODI ) , health-related quality of life ( 15D Quality of Life Instrument ) , satisfaction with care , and costs . Results . Significant improvement occurred in both groups on every self-rated outcome measurement . Within 2 years , the combination group showed only a slightly more significant reduction in VAS ( P = 0.01 , analysis of variance ) but clearly higher patient satisfaction ( P = 0.001 , Pearson & khgr;2 ) as compared to the consultation group . Incremental analysis showed that for combined group compared to consultation group , a one-point change in VAS scale cost $ 512 . Conclusions . Physician consultation alone was more cost-effective for both health care use and work absenteeism , and led to equal improvement in disability and health-related quality of life . It seems obvious that encouraging information and advice are major elements for the treatment of patients with cLBP Study Design . Data were derived from a r and omized controlled trial on the ( cost- ) effectiveness of the implementation of the clinical guidelines on physiotherapy for low back pain in primary care . Objectives . To describe the course of low back pain in patients who are referred to physiotherapy , to identify clinical ly important prognostic factors on different outcomes , and to evaluate the influence of different statistical techniques in developing a prognostic model . Summary of Background Data . Several studies have aim ed to identify prognostic factors for low back pain in primary care . These studies focused on different outcome measures and used various statistical techniques . Methods . Primary outcomes were perceived recovery , improvement in pain , improvement in functioning , and presence of disabling low back pain at 3 and 12 months follow-up . Multivariate logistic regression analyses were performed for each outcome variable . Two cut-off points were used to determine significance with respect to the univariate analysis , and two selection methods were used to build the final multivariate models . The result ing prognostic models were compared . Results . A total of 500 patients were included . Pain and disability reduced considerably in the first 3 months , but further reduction was only modest . Prognostic factors varied for different outcomes , but the duration of the current episode was included in all models generated . Varying the statistical techniques also result ed in a different prognostic model with some change to the amount of variance explained . Conclusions . A substantial proportion of patients still experienced some pain and disability at 12 months follow-up . The most stable predictor of prognosis in low back pain was the duration of the current episode . The choice of statistical method influenced the final model ; however , changes in the explained variance were small BACKGROUND Recommendations for the management of low back pain in primary care emphasise the importance of recognising and addressing psychosocial factors at an early stage . We compared the effectiveness of a brief pain-management programme with physiotherapy incorporating manual therapy for the reduction of disability at 12 months in patients consulting primary care with subacute low back pain . METHODS For this pragmatic , multicentre , r and omised clinical trial , eligible participants consulted primary care with non-specific low back pain of less than 12 weeks ' duration . They were r and omly assigned either a programme of pain management ( n=201 ) or manual therapy ( n=201 ) . The primary outcome was change in the score on the Rol and and Morris disability question naire at 12 months . Analysis was by intention to treat . FINDINGS Of 544 patients assessed for eligibility , 402 were recruited ( mean age 40.6 years ) and 329 ( 82 % ) reached 12-month follow-up . Mean disability scores were 13.8 ( SD 4.8 ) for the pain-management group and 13.3 ( 4.9 ) for the manual-therapy group . The mean decreases in disability scores were 8.8 ( 6.4 ) and 8.8 ( 6.1 ) at 12 months ( difference 0 [ 95 % CI -1.3 to 1.4 ] , p=0.99 ) , and median numbers of physiotherapy visits per patient were three ( IQR one to five ) and four ( two to five ) , respectively ( p=0.001 ) . One adverse reaction ( an exacerbation of pain after the initial assessment ) was recorded . INTERPRETATION Brief pain management techniques delivered by appropriately trained clinicians offer an alternative to physiotherapy incorporating manual therapy and could provide a more efficient first-line approach for management of non-specific subacute low back pain in primary care The present aim was to compare the effects of stabilizing training with those of manual treatment in patients with sub-acute or chronic low-back pain ( LBP ) . Forty-seven patients were r and omized to a stabilizing training group ( ST group ) or a manual treatment group ( MT group ) . The patients underwent a 6-week treatment programme on a weekly basis . Pain , health and functional disability level at the start of treatment , after treatment , and at 3- and 12-month follow-ups were assessed . In the ST group all assessed variables improved significantly ( P<0.05 ) after the treatment period and were maintained long term . After the treatment period there was a significant difference between the groups in assessed function ( P<0.05 ) . More individuals in the ST group had improved than in the MT group . At the 3-month follow-up significantly more improved individuals were evident in the ST group regarding pain , general health and functional disability levels . In the long term , significantly more ( P<0.05 ) patients in the MT group reported recurrent treatment periods . The study did not indicate any clear short-term differences between the groups in the accessed outcome measures . In the long term , however , stabilizing training seemed to be more effective than manual treatment in terms of improvement of individuals and the reduced need for recurrent treatment periods OBJECTIVE Findings of scarcely available studies indicate that there are substantial gaps in intercultural doctor-patient communication . In order to improve intercultural communication in medical practice in The Netherl and s , an educational intervention was developed . The aim of the present study was to examine the effects of this intervention on doctor-patient communication . METHODS Participants ( general practitioners : n=38 ; patients : n=124 ) were assigned at r and om to an intervention or a control group . GPs in the intervention group received 2.5 days training on intercultural communication . Patients in the intervention group were exposed to a videotaped instruction in the waiting room , right before the consultation . Data were collected through videotapes of visits of ethnic minority patients to their GP and home interviews with the patients after their medical visit . Communication behaviour was assessed using the Roter interaction analysis system ( RIAS ) . Interview length was assessed as well . RESULTS The length of the medical encounter increased significantly after having received the intervention . Total number of GP utterances increased significantly too . When comparing relative frequencies on affective and instrumental verbal behaviour of both patients and doctors , no significant changes could be detected . CONCLUSION It is concluded that there seems to be some change in doctor-patient interaction , but RIAS may not be suitable to detect subtle changes in the medical communication process . It is recommended to use other analysis methods to assess cultural differences in medical communication . PRACTICE IMPLICATION S Knowledge about possible antecedents of gaps in intercultural medical communication should be increased in order to be able to design effective interventions for intercultural doctor-patient communication Study Design . A r and omized , assessor-blinded clinical trial was conducted . Objective . To investigate the relative effectiveness of three manual treatments and back school for patients with subacute low back pain . Summary of Background Data . Literature comparing the relative effectiveness of specific therapies for low back pain is limited . Methods . Among the 5925 inquiries , 206 patients met the specific admission criteria , and 200 patients r and omly received one of four treatments for 3 weeks : back school , joint manipulation , myofascial therapy , and combined joint manipulation and myofascial therapy . These patients received assessment s at baseline , after 3 weeks of therapy , and 6 months after the completion of therapy . The primary outcomes were evaluated using visual analog pain scales and Rol and –Morris activity scales . Results . All four groups showed significant improvement in pain and activity scores after 3 weeks of care , but did not show further significant improvement at the 6-month follow-up assessment . No statistically significant between-group differences were found either at the 3-week or 6-month re assessment s. Conclusions . For subacute low back pain , combined joint manipulation and myofascial therapy was as effective as joint manipulation or myofascial therapy alone . Additionally , back school was as effective as three manual treatments Study Design . Pragmatic , r and omized , assessor blinded , clinical trial with economic analysis . Objective . To compare the effectiveness and cost-effectiveness of three kinds of physiotherapy commonly used to reduce disability in chronic low back pain . Summary of Background Data . Physiotherapy reduces disability in chronic back pain , but there are several forms of physiotherapy and it is unclear which is most effective or cost effective . Methods . A total of 212 patients referred to physiotherapy with chronic low back pain were r and omized to receive usual outpatient physiotherapy , spinal stabilization classes , or physiotherapist-led pain management classes . Primary outcome was Rol and Disability Question naire score 18 months from baseline ; secondary measures were pain , health-related quality of life , and time off work . Healthcare costs associated with low back pain and quality -adjusted life years ( QALYs ) were also measured . Results . A total of 71 participants were assigned to usual outpatient physiotherapy , 72 to spinal stabilization , and 69 to physiotherapist-led pain management . A total of 160 ( 75 % ) provided follow-up data at 18 months , showing similar improvements with all interventions : mean ( 95 % confidence intervals ) Rol and Disability Question naire score improved from 11.1 ( 9.6–12.6 ) to 6.9 ( 5.3–8.4 ) with usual outpatient physiotherapy , 12.8 ( 11.4−14.2 ) to 6.8 ( 4.9–8.6 ) with spinal stabilization , and 11.5 ( 9.8–13.1 ) to 6.5 ( 4.5–8.6 ) following pain management classes . Pain , quality of life , and time off work also improved within all groups with no between-group differences . Mean ( SD ) healthcare costs and QALY gain were £ 474 ( 840 ) and 0.99 ( 0.27 ) for individual physiotherapy , £ 379 ( 1040 ) and 0.90 ( 0.37 ) for spinal stabilization , and £ 165 ( 202 ) and 1.00 ( 0.28 ) for pain management . Conclusions . For chronic low back pain , all three physiotherapy regimens improved disability and other relevant health outcomes , regardless of their content . Physiotherapist-led pain management classes offer a cost-effective alternative to usual outpatient physiotherapy and are associated with less healthcare use . A more widespread adoption of physiotherapist-led pain management could result in considerable cost savings for healthcare providers Study Design . A r and omized controlled trial comparing usual care with a program for the coordination of primary health care ( CORE ) for the treatment of subacute low-back pain patients . Objectives . To measure the effectiveness of the CORE program as a mean for implementing clinical practice guidelines for low-back pain in an urban community . Summary of Background Data . Clinical practice guidelines have been developed for primary care physicians and patients on the clinical management of low-back pain . The implementation of the guidelines in a large community is difficult with the multiplicity of medical and nonmedical back care providers and products . The CORE program was design ed to make the guidelines fit in this complex environment . Methods . One hundred ten workers compensated for low-back pain for 4 to 8 weeks in metropolitan Montreal were r and omized in two groups : usual care ( N=56 ) and the CORE program ( N=54 ) . Coordination of primary health care was performed by two primary care physicians and a nurse in liaison with the treating physicians , and included a complete examination , recommendations for the clinical management , and support to carry out the recommendations . All workers were followed for 6 months . Back pain and functional status were assessed at baseline , 3 months , and 6 months . Results . In the 6-month follow-up , the CORE group returned to work 6.6 days ( st and ard error = 8.9 ) quicker than the control group , a difference that was not statistically significant . However , the CORE group showed a sustained improvement in pain and functional status with two-fold differences at the end of the 6 months of follow-up . This represented nine points on the Oswestry scale ( P = 0.02 ) and 12 points on the Quebec Back Pain Disability Scale ( P = 0.01 ) . The CORE group also used three times less specialized imaging tests of the spine at 3 months ( P < 0.01 ) and exercised twice as much at 6 months ( P < 0.05 ) than the controls . Conclusions . The therapeutic results for workers with low-back pain could be improved by implementing the clinical practice guidelines with primary care physicians in a large community , without delaying the return to work . The CORE intervention for back pain patients ishighly relevant to primary care practice . It is simple in its application , flexible to accommo date physicians ’ and patients ’ preferences in health care , and it is effective on patients ’ clinical outcome BACKGROUND Patients with back pain receive quite different care from different types of health care practitioners . We performed a prospect i ve observational study to determine whether the outcomes of and charges for care differ among primary care practitioners , chiropractors , and orthopedic surgeons . METHODS Two hundred eight practitioners in North Carolina were r and omly selected from six strata : urban primary care physicians ( n = 39 ) , rural primary care physicians ( n = 48 ) , urban chiropractors ( n = 32 ) , rural chiropractors ( n = 32 ) , orthopedic surgeons ( n = 29 ) , and primary care providers at a group-model health maintenance organization ( HMO ) ( n = 28 ) . The practitioners enrolled consecutive patients with acute low back pain . The patients were contacted by telephone periodically for up to 24 weeks to assess functional status , work status , use of health care services , and satisfaction with the care received . RESULTS The status at six months was ascertained for 1555 of the 1633 patients enrolled in the study ( 95 percent ) . The times to functional recovery , return to work , and complete recovery from low back pain were similar among patients seen by all six groups of practitioners , but there were marked differences in the use of health care services . The mean total estimated outpatient charges were highest for the patients seen by orthopedic surgeons and chiropractors and were lowest for the patients seen by HMO and primary care providers . Satisfaction was greatest among the patients who went to the chiropractors . CONCLUSIONS Among patients with acute low back pain , the outcomes are similar whether they receive care from primary care practitioners , chiropractors , or orthopedic surgeons . Primary care practitioners provide the least expensive care for acute low back pain |
13,258 | 29,047,028 | Our systematic review and meta- analysis of currently available studies reports that CRT up grade is associated with similar risk for all-cause mortality compared to de novo resynchronization therapy .
Benefits on reverse remodelling and functional capacity improved similarly in both groups suggesting that CRT up grade may be safely and effectively offered in routine practice . | Patients with conventional pacemakers or implanted defibrillators are often considered for cardiac resynchronization therapy ( CRT ) .
Our aim was to summarize the available evidence s regarding the clinical benefits of up grade procedures . | INTRODUCTION cardiac resynchronization therapy ( CRT ) may improve prognosis in patients with chronic right ventricular ( RV ) pacing , and optimal lead position can decrease nonresponders . We evaluated the clinical and echocardiographic response to CRT in patients with previous chronic RV pacing , using pressure-volume loop analyses to determine the optimal left ventricular ( LV ) lead position during implantation . METHODS AND RESULTS In this single-blinded , r and omized , controlled crossover study , 40 patients with chronic RV apical pacing and symptoms of heart failure , decreased LV ejection fraction ( LVEF ) or dyssynchrony were included . During implantation , stroke work ( SW ) , LVEF , cardiac output , and LV dP/dt(max ) were assessed by a conductance catheter . Clinical and echocardiographic response was studied during a 3-month period of RV pacing ( RV period , LV lead inactive ) and a 3-month period of biventricular pacing ( CRT period ) . At the optimal LV lead position , SW ( 37 ± 41 % ) , LVEF ( 16 ± 13 % ) , cardiac output ( 29 ± 16 % ) , and LV dP/dt(max ) increased ( 11 ± 11 % ) significantly during biventricular pacing compared to baseline . Additional benefit could be achieved by pressure-volume loop guided selection of the best left-sided pacing location . RV outflow tract pacing did not improve hemodynamics . During follow-up , symptoms improved during CRT , VO(2,max ) increased 10 % and significant improvements in LVEF , LV volumes , and mitral regurgitation were observed as compared to the RV period . CONCLUSIONS CRT in patients with chronic RV pacing causes significant improvement of both LV function as measured by pressure-volume loops during implantation and clinical and echocardiographic improvement during follow-up . Pressure-volume loops during implantation may facilitate selection of the most optimal pacing site AIMS To investigate whether cardiac resynchronization therapy ( CRT ) by means of biventricular ( BiV ) pacing can improve left ventricular ( LV ) function , remodelling and clinical status in chronically right ventricular ( RV ) paced patients with mild cardiomyopathy . METHODS AND RESULTS Thirty-six chronically ( 10 + /- 7 years ) RV paced patients with left ventricular ejection fraction ( LVEF ) < 40 % or LVEDD > 55 mm , without an established indication for CRT , were subjected to 6 months RV and BiV pacing in a patient-blinded , r and omized crossover design . Treatment-effects of BiV pacing were evaluated for LV function , LV remodelling and clinical status . As compared with RV pacing , BiV pacing significantly improved LV function ( LVEF 46 + /- 12 vs. 39 + /- 12 % and LVFS 24 + /- 7 vs. 21 + /- 7 % ) and reduced LV end-diastolic and end-systolic diameters and volumes ( LVEDD 56 + /- 8 vs. 59 + /- 8 mm , LVESD 43 + /- 8 vs. 47 + /- 9 mm , LVEDV 132 + /- 65 vs.144 + /- 62 mL and LVESV 77 + /- 56 vs. 92 + /- 55 mL , respectively ) . In 19 patients ( 53 % ) response to BiV pacing was clinical ly relevant , defined as LVESV reduction > 15 % . BiV pacing also significantly improved NYHA classification . CONCLUSION BiV pacing following chronic RV pacing may improve LV function and reverse LV remodelling in patients with relatively mild LV dysfunction or remodelling . Hence , up grade to BiV pacing might be considered in chronically RV paced patients with mild cardiomyopathy Background — Benefits of cardiac resynchronization therapy ( CRT ) on morbidity and mortality in selected patients are well known . Although the number of up grade procedures from single- or dual-chamber devices to CRT is increasing , there are only sparse data on the outcomes of up grade procedures compared with de novo CRT . This study aim ed to evaluate clinical response and survival in patients receiving de novo versus up grade CRT defibrillator therapy . Methods and Results — Prospect ively collected outcome data were compared in patients undergoing de novo or up grade CRT defibrillator implantation at 3 implant centers in Germany and Hungary . Clinical response was defined as an improvement by at least one New York Heart Association ( NYHA ) functional class . CRT implantation was performed in 552 consecutive patients of whom 375 underwent a de novo and 177 an up grade procedure . Up grade patients were more often implanted for secondary prevention , suffered more often from atrial fibrillation , chronic kidney disease , diabetes mellitus , and dyslipidemia , and had more often a non-LBBB ( left bundle branch block ) wide QRS complex , and lower left ventricular ejection fraction . Up grade procedures were associated with a lower response rate compared to the de novo group ( 57 % versus 69 % , P univariate=0.008 , P multivariate=0.021 ) . During the follow-up of 37±28 months , survival was worse after up grade compared with de novo CRT defibrillator implantations ( hazard ratio , 1.65 ; 95 % confidence interval , 1.22–2.24 ; P=0.001 ) even after careful adjustment for important baseline variables ( adjusted hazard ratio , 1.68 ; 95 % confidence interval , 1.20–2.34 ; P=0.002 ) and after propensity-score matching ( propensity-adjusted hazard ratio , 1.79 ; 95 % confidence interval , 1.08–2.95 ; P=0.023 ) . Conclusions — Both clinical response and long-term survival were less favorable in patients undergoing CRT up grade compared to de novo implantations BACKGROUND Observational studies suggest that conventional right ventricular apical pacing may have a deleterious effect on left ventricular function . In this study , we examined whether biventricular pacing is superior to right ventricular apical pacing in preventing deterioration of left ventricular systolic function and cardiac remodeling in patients with bradycardia and a normal ejection fraction . METHODS In this prospect i ve , double-blind , multicenter study , we r and omly assigned 177 patients in whom a biventricular pacemaker had been successfully implanted to receive biventricular pacing ( 89 patients ) or right ventricular apical pacing ( 88 patients ) . The primary end points were the left ventricular ejection fraction and left ventricular end-systolic volume at 12 months . RESULTS At 12 months , the mean left ventricular ejection fraction was significantly lower in the right-ventricular-pacing group than in the biventricular-pacing group ( 54.8+/-9.1 % vs. 62.2+/-7.0 % , P<0.001 ) , with an absolute difference of 7.4 percentage points , whereas the left ventricular end-systolic volume was significantly higher in the right-ventricular-pacing group than in the biventricular-pacing group ( 35.7+/-16.3 ml vs. 27.6+/-10.4 ml , P<0.001 ) , with a relative difference between the groups in the change from baseline of 25 % ( P<0.001 ) . The deleterious effect of right ventricular apical pacing occurred in prespecified subgroups , including patients with and patients without preexisting left ventricular diastolic dysfunction . Eight patients in the right-ventricular-pacing group ( 9 % ) and one in the biventricular-pacing group ( 1 % ) had ejection fractions of less than 45 % ( P=0.02 ) . There was one death in the right-ventricular-pacing group , and six patients in the right-ventricular-pacing group and five in the biventricular-pacing group were hospitalized for heart failure ( P=0.74 ) . CONCLUSIONS In patients with normal systolic function , conventional right ventricular apical pacing result ed in adverse left ventricular remodeling and in a reduction in the left ventricular ejection fraction ; these effects were prevented by biventricular pacing . ( Centre for Clinical Trials number , CUHK_CCT00037 . Abstract Aims There is lack of conclusive evidence from r and omized clinical trials on the efficacy and safety of up grade to cardiac resynchronization therapy ( CRT ) in patients with implanted pacemakers ( PM ) or defibrillators ( ICD ) with reduced left ventricular ejection fraction ( LVEF ) and chronic heart failure ( HF ) . The BUDAPEST-CRT Up grade Study was design ed to compare the efficacy and safety of CRT up grade from conventional PM or ICD therapy in patients with intermittent or permanent right ventricular ( RV ) septal/apical pacing , reduced LVEF , and symptomatic HF . Methods and results The BUDAPEST-CRT study is a prospect i ve , r and omized , multicentre , investigator-sponsored clinical trial . A total of 360 subjects will be enrolled with LVEF ≤ 35 % , NYHA functional classes II – IVa , paced QRS ≥ 150 ms , and a RV pacing ≥ 20 % . Patients will be followed for 12 months . R and omization is performed in a 3:2 ratio ( CRT-D vs. ICD ) . The primary composite endpoint is all-cause mortality , a first HF event , or less than 15 % reduction in left ventricular ( LV ) end-systolic volume at 12 months . Secondary endpoints are all-cause mortality , all-cause mortality or HF event , and LV volume reduction at 12 months . Tertiary endpoints include changes in quality of life , NYHA functional class , 6 min walk test , natriuretic peptides , and safety outcomes . Conclusion The results of our prospect i ve , r and omized , multicentre clinical trial will provide important information on the role of cardiac resynchronization therapy with defibrillator ( CRT-D ) up grade in patients with symptomatic HF , reduced LVEF , and wide-paced QRS with intermittent or permanent RV pacing . Clinical trials.gov identifier NCT02270840 BACKGROUND The current guidelines do not clearly state when we should up grade a patient with right ventricular pacing ( RVP ) to cardiac resynchronization therapy ( CRT ) , although the deleterious effect of chronic RVP has been established with recent trials . OBJECTIVES The aims of this study were to compare the long-term survival after CRT in patients up grade d from RVP with that in patients with left bundle branch block ( LBBB ) with QRS duration ≥ 150 ms and to compare the mechanical properties associated with CRT response in these groups . METHODS Overall , 135 patients with implanted CRT from a single center ( 85 ( 63 % ) with native wide LBBB and 50 ( 37 % ) with RVP ) were studied prospect ively . Baseline left ventricular typical contraction pattern was determined using speckle tracking echocardiography in the apical 4-chamber view . The predefined end point was death , heart transplantation , or left ventricular assist device implantation over a period of 4 years . RESULTS Patients with RVP had a significantly favorable long-term outcomes with adjusted hazard ratio of 0.36 ( 95 % confidence interval 0.14 - 0.96 ; P = .04 ) . Both groups had ~70 % of patients with typical contraction pattern . The absence of typical contraction pattern was associated with a higher risk of an end point with adjusted hazard ratio of 5.43 ( 95 % confidence interval 2.31 - 12.72 ; P < .001 ) . In patients with typical contraction pattern , activation of the apical septal segment occurred more frequently in the RVP group and of the base or mid septal segments in the LBBB group . CONCLUSION Patients with HF up grade d from RVP have more favorable long-term outcomes after CRT than do native LBBB patients with QRS duration ≥ 150 ms . Contraction pattern assessment can be used to identify potential responders in the RVP group Background Dual‐chamber ( DDDR ) pacing preserves AV synchrony and may reduce heart failure ( HF ) and atrial fibrillation ( AF ) compared with ventricular ( VVIR ) pacing in sinus node dysfunction ( SND ) . However , DDDR pacing often results in prolonged QRS duration s ( QRSd ) as the result of right ventricular stimulation , and ventricular desynchronization may result . The effect of pacing‐induced ventricular desynchronization in patients with normal baseline QRSd is unknown . Methods and Results Baseline QRSd was obtained from 12‐lead ECGs before pacemaker implantation in MOST , a 2010‐patient , 6‐year , r and omized trial of DDDR versus VVIR pacing in SND . Cumulative percent ventricular paced ( Cum%VP ) was determined from stored pacemaker data . Baseline QRSd < 120 ms was observed in 1339 patients ( 707 DDDR , 632 VVIR ) . Cum%VP was greater in DDDR versus VVIR ( 90 % versus 58 % , P=0.001 ) . Cox models demonstrated that the time‐dependent covariate Cum%VP was a strong predictor of HF hospitalization in DDDR ( hazard ratio [ HR ] , 2.99 [ 95 % CI , 1.15 to 7.75 ] for Cum%VP > 40 % ) and VVIR ( HR 2.56 [ 95 % CI , 1.48 to 4.43 ] for Cum%VP > 80 % ) . The risk of AF increased linearly with Cum%VP from 0 % to 85 % in both groups ( DDDR , HR 1.36 [ 95 % CI , 1.09 , 1.69 ] ; VVIR , HR 1.21 [ 95 % CI 1.02 , 1.43 ] , for each 25 % increase in Cum%VP ) . Model results were unaffected by adjustment for known baseline predictors of HF hospitalization and AF . Conclusions Ventricular desynchronization imposed by ventricular pacing even when AV synchrony is preserved increases the risk of HF hospitalization and AF in SND with normal baseline QRSd . ( Circulation . 2003;107:2932‐2937 . AIMS To compare the clinical response of patients with right ventricular apical pacing ( RVAP ) up grade d to cardiac resynchronization therapy ( CRT ) to that of previously nonpaced heart failure ( HF ) patients who had de novo CRT implantation . BACKGROUND The role of CRT in patients with wide QRS and HF due to RVAP is less well established than in other CRT c and i date s. METHODS Ninety-eight consecutive patients with CRT were studied ( mean age 70 , mean ejection fraction 0.23 ) . Group A : patients having RVAP prior to CRT implantation ( n = 25 ) , group B : patients without prior RVAP ( n = 73 ) . Clinical and echocardiographic parameters were recorded prior to , and 3 months after , CRT implantation . RESULTS Group A patients had a wider QRS at baseline compared to group B ( 203 + /- 32 ms vs 163 + /- 30 ms respectively , P < 0.001 ) , and a shorter 6-minute walking distance ( 222 + /- 118 m vs 362 + /- 119 m , respectively , P < 0.005 ) . Otherwise , clinical and echocardiographic parameters were not different . At follow up , group A patients had an average 0.7 + /- 0.5 decrease in their NYHA functional class , compared to 0.3 + /- 0.7 in group B patients ( P < 0.05 ) . Six-minute walking distance increased by 93 + /- 113 m in group A , versus 36 + /- 120 m in group B ( P = 0.22 ) . There was no difference in echocardiographic response to CRT between the groups . CONCLUSIONS HF patients with prior RVAP demonstrate clinical improvement after upgrading to CRT that is comparable , and in some aspects , even better than that observed in HF patients with native conduction delay who undergo de novo CRT implantation CONTEXT Implantable cardioverter defibrillator ( ICD ) therapy with backup ventricular pacing increases survival in patients with life-threatening ventricular arrhythmias . Most currently implanted ICD devices provide dual-chamber pacing therapy . The most common comorbid cause for mortality in this population is congestive heart failure . OBJECTIVE To determine the efficacy of dual-chamber pacing compared with backup ventricular pacing in patients with st and ard indications for ICD implantation but without indications for antibradycardia pacing . DESIGN The Dual Chamber and VVI Implantable Defibrillator ( DAVID ) Trial , a single-blind , parallel-group , r and omized clinical trial . SETTING AND PARTICIPANTS A total of 506 patients with indications for ICD therapy were enrolled between October 2000 and September 2002 at 37 US centers . All patients had a left ventricular ejection fraction ( LVEF ) of 40 % or less , no indication for antibradycardia pacemaker therapy , and no persistent atrial arrhythmias . INTERVENTIONS All patients had an ICD with dual-chamber , rate-responsive pacing capability implanted . Patients were r and omly assigned to have the ICDs programmed to ventricular backup pacing at 40/min ( VVI-40 ; n = 256 ) or dual-chamber rate-responsive pacing at 70/min ( DDDR-70 ; n = 250 ) . Maximal tolerated medical therapy for left ventricular dysfunction , including angiotensin-converting enzyme inhibitors and beta-blockers , was prescribed to all patients . MAIN OUTCOME MEASURE Composite end point of time to death or first hospitalization for congestive heart failure . RESULTS One-year survival free of the composite end point was 83.9 % for patients treated with VVI-40 compared with 73.3 % for patients treated with DDDR-70 ( relative hazard , 1.61 ; 95 % confidence interval [ CI ] , 1.06 - 2.44 ) . The components of the composite end point , mortality of 6.5 % for VVI-40 vs 10.1 % for DDDR-70 ( relative hazard , 1.61 ; 95 % CI , 0.84 - 3.09 ) and hospitalization for congestive heart failure of 13.3 % for VVI-40 vs 22.6 % for DDDR-70 ( relative hazard , 1.54 ; 95 % CI , 0.97 - 2.46 ) , also trended in favor of VVI-40 programming . CONCLUSION For patients with st and ard indications for ICD therapy , no indication for cardiac pacing , and an LVEF of 40 % or less , dual-chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental by increasing the combined end point of death or hospitalization for heart failure Background — Prospect i ve studies defining the risk associated with pacemaker or implantable cardioverter-defibrillator replacement surgeries do not exist . These procedures are generally considered low risk despite results from recent retrospective series reporting higher rates . Methods and Results — We prospect ively assessed predefined procedure-related complication rates associated with elective pacemaker or implantable cardioverter-defibrillator generator replacements over 6 months of follow-up . Two groups were studied : those without ( cohort 1 ) and those with ( cohort 2 ) a planned transvenous lead addition for replacement or up grade to a device capable of additional therapies . Complications were adjudicated by an independent events committee . Seventy-two US academic and private practice centers participated . Major complications occurred in 4.0 % ( 95 % confidence interval , 2.9 to 5.4 ) of 1031 cohort 1 patients and 15.3 % ( 95 % confidence interval , 12.7 to 18.1 ) of 713 cohort 2 patients . In both cohorts , major complications were higher with implantable cardioverter-defibrillator compared with pacemaker generator replacements . Complications were highest in patients who had an up grade to or a revised cardiac resynchronization therapy device ( 18.7 % ; 95 % confidence interval , 15.1 to 22.6 ) . No periprocedural deaths occurred in either cohort , although 8 later procedure-related deaths occurred in cohort 2 . The 6-month infection rates were 1.4 % ( 95 % confidence interval , 0.7 to 2.3 ) and 1.1 % ( 95 % confidence interval , 0.5 to 2.2 ) for cohorts 1 and 2 , respectively . Conclusions — Pacemaker and implantable cardioverter-defibrillator generator replacements are associated with a notable complication risk , particularly those with lead additions . These data support careful decision making before device replacement , when managing device advisories , and when considering up grade s to more complex systems . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00395447 BACKGROUND Chronic right ventricular pacing has been reported to promote cardiac dyssynchrony . The PAVE trial prospect ively compared chronic biventricular pacing to right ventricular pacing in patients undergoing ablation of the AV node for management of atrial fibrillation with rapid ventricular rates . METHODS AND RESULTS One hundred and eighty-four patients requiring AV node ablation were r and omized to receive a biventricular pacing system ( n = 103 ) or a right ventricular pacing system ( n = 81 ) . The study endpoints were change in the 6-minute hallway walk test , quality of life , and left ventricular ejection fraction . Patient characteristics were similar ( 64 % male ; age : 69 + /- 10 years , ejection fraction : 0.46 + /- 0.16 ; 83 % , NYHA Class II or III ) . At 6 months postablation , patients treated with cardiac resynchronization had a significant improvement in 6-minute walk distance , ( 31 % ) above baseline ( 82.9 + /- 94.7 m ) , compared to patients receiving right ventricular pacing , ( 24 % ) above baseline ( 61.2 + /- 90.0 m ) ( P = 0.04 ) . There were no significant differences in the quality -of-life parameters . At 6 months postablation , the ejection fraction in the biventricular group ( 0.46 + /- 0.13 ) was significantly greater in comparison to patients receiving right ventricular pacing ( 0.41 + /- 0.13 , P = 0.03 ) . Patients with an ejection fraction < or=45 % or with NYHA Class II/III symptoms receiving a biventricular pacemaker appear to have a greater improvement in 6-minute walk distance compared to patients with normal systolic function or Class I symptoms . CONCLUSION For patients undergoing AV node ablation for atrial fibrillation , biventricular pacing provides a significant improvement in the 6-minute hallway walk test and ejection fraction compared to right ventricular pacing . These beneficial effects of cardiac resynchronization appear to be greater in patients with impaired systolic function or with symptomatic heart failure AIMS Effects of cardiac resynchronization therapy ( CRT ) in patients with right ventricular pacing and congestive heart failure ( CHF ) have only been reported in limited series . CRT in patients with atrial fibrillation remains controversial . Patients with AV junctional ablation offer a unique opportunity to study the effects of CRT in patients with right ventricular pacing combined with atrial fibrillation . The aims of the present study were to evaluate the effects of upgrading to biventricular pacing patients with CHF , permanent atrial fibrillation , and prior ablation of the atrioventricular ( AV ) junction followed by conventional right ventricular pacing . METHODS AND RESULTS We studied 16 consecutive patients with permanent atrial fibrillation treated by AV junctional ablation . After a mean follow-up of 20+/-19 months ( 6 weeks to 5 years ) they were successfully up grade d to biventricular pacing for severe CHF . Parameters were prospect ively evaluated at baseline and at 6 months . The 14 surviving patients at 6 months demonstrated significant improvement ( P<0.02 ) in New York Heart Association class but the exercise test parameters remained unchanged . Cardiothoracic ratio decreased by 5 % ( P=0.04 ) , end-systolic diameter by 8 % ( P=0.001 ) , end-diastolic diameter by 4 % ( P=0.08 ) , systolic pulmonary artery pressure by 17 % ( P<0.0001 ) and mitral regurgitation area by 40 % ( P<0.05 ) . Ejection fraction increased by 17 % ( P=0.11 ) and fractional shortening by 24 % ( P=0.01 ) . CONCLUSION CRT improves left ventricular performance and functional status in patients with permanent atrial fibrillation and prior remote right ventricular pacing BACKGROUND Right ventricular pacing restores an adequate heart rate in patients with atrioventricular block , but high percentages of right ventricular apical pacing may promote left ventricular systolic dysfunction . We evaluated whether biventricular pacing might reduce mortality , morbidity , and adverse left ventricular remodeling in such patients . METHODS We enrolled patients who had indications for pacing with atrioventricular block ; New York Heart Association ( NYHA ) class I , II , or III heart failure ; and a left ventricular ejection fraction of 50 % or less . Patients received a cardiac-resynchronization pacemaker or implantable cardioverter-defibrillator ( ICD ) ( the latter if the patient had an indication for defibrillation therapy ) and were r and omly assigned to st and ard right ventricular pacing or biventricular pacing . The primary outcome was the time to death from any cause , an urgent care visit for heart failure that required intravenous therapy , or a 15 % or more increase in the left ventricular end-systolic volume index . RESULTS Of 918 patients enrolled , 691 underwent r and omization and were followed for an average of 37 months . The primary outcome occurred in 190 of 342 patients ( 55.6 % ) in the right-ventricular-pacing group , as compared with 160 of 349 ( 45.8 % ) in the biventricular-pacing group . Patients r and omly assigned to biventricular pacing had a significantly lower incidence of the primary outcome over time than did those assigned to right ventricular pacing ( hazard ratio , 0.74 ; 95 % credible interval , 0.60 to 0.90 ) ; results were similar in the pacemaker and ICD groups . Left ventricular lead-related complications occurred in 6.4 % of patients . CONCLUSIONS Biventricular pacing was superior to conventional right ventricular pacing in patients with atrioventricular block and left ventricular systolic dysfunction with NYHA class I , II , or III heart failure . ( Funded by Medtronic ; BLOCK HF Clinical Trials.gov number , NCT00267098 . ) Background : Because of specific method ological difficulties in conducting r and omized trials , surgical research remains dependent predominantly on observational or non‐r and omized studies . Few vali date d instruments are available to determine the method ological quality of such studies either from the reader 's perspective or for the purpose of meta‐ analysis . The aim of the present study was to develop and vali date such an instrument BACKGROUND There are few studies on cardiac resynchronization therapy ( CRT ) in heart failure ( HF ) patients with preexisting right ventricular ( RV ) pacing . The purpose of this study was to determine the efficacy of CRT upgrading in RV-paced patients and the predictivity of electromechanical dyssynchrony parameters ( EDP ) evaluated by st and ard echocardiography ( ECHO ) and tissue Doppler imaging ( TDI ) . METHODS Thirty-eight consecutive patients with HF [ New York Heart Association ( NYHA ) class III or IV , LVEF < 35 % ] , prior continuous RV pacing , and absence of atrial fibrillation were enrolled in the presence of a paced QRS > or = 150 ms and evaluated by ECHO and TDI . A responder was defined as a patient with a favorable change in NYHA class and neither HF hospitalization nor death , plus an absolute increase of LVEF > or = 10 units . RESULTS At six-months follow-up , the whole study population had significant improvement in symptoms , systolic function , and QRS duration ( P < 0.001 ) ; 32 ( 84 % ) patients had a favorable clinical outcome , 25 ( 66 % ) were considered responders according to the previous definition . Postimplant QRS was similarly reduced in both responders and nonresponders , whereas EDP had a significant improvement only in responders ( P < 0.05 ) . Using EDP , 23 ( 79 % ) patients were responders compared with 2 ( 22 % ) patients without mechanical dyssynchrony ( P = 0.002 ) . CONCLUSIONS In HF patients with previous RV pacing , CRT is effective to improve clinical , functional outcome , and LV performance and to reduce electromechanical dyssynchrony in a large proportion of patients . Dyssynchrony evaluated by st and ard and TDI ECHO can be useful for CRT selection of paced patients INTRODUCTION Left bundle brunch block ( LBBB ) and right ventricular stimulation ( RVS ) may be associated with asynchrony and heart failure . Differences between these two entities and their response to cardiac resynchronization therapy ( CRT ) are not well defined . METHODS Patients receiving CRT from 1999 to 2006 were analyzed for cardiac events and prognosis separated between primary implants for LBBB ( n = 221 ) and up grade s from RVS ( n = 107 ) . A subgroup of 105 patients ( LBBB = 69 ; RVS = 36 ) was studied in more detail ( New York Heart Association [ NYHA ] , quality of life , brain natriuretic peptide , peak VO2 , left ventricular ejection fraction [ LVEF ] , wedge pressure , Cardiac Index , QRS , left-right preejection period using pulsed wave doppler , septum-lateral wall motion delay using tissue doppler imaging ) at baseline and after 1 year . RESULTS Age ( 68.4 + /- 11 years vs 68.7 + /- 15 years , n. s. ) , NYHA class ( 3.1 vs 3.1 , n. s. ) , LVEF ( 26.4 vs 28.1 , n. s. ) , and clinical parameters were comparable between LBBB and RVS . The latter group consisted of more patients with chronic atrial fibrillation ( 14 % vs 37 % , P = 0.03 ) . After 1 year , NYHA class ( -0.8 + /- 0.8 vs -0.6 + /- 0.8 , n. s. ) , LVEF ( + 13.7 + /- 14 % vs + 8.7 + /- 10 % , n. s. ) , and clinical parameters improved similarly . After a median follow-up of 2.33 + /- 1.8 years in the LBBB versus 2.43 + /- 1.9 years in the RVS group , there was no difference in long-term prognosis or cardiac events in the total cohort ( 5-year event rate , 53 % vs 55 % , P = n. s. ) . CONCLUSION Up grade patients showed similar baseline parameters and response to CRT as to primary implants . No difference in events or long-term prognosis could be observed BACKGROUND Few studies have assessed the long-term effects of cardiac resynchronization therapy ( CRT ) in patients with advanced heart failure ( HF ) and previously right ventricular apical pacing ( RVAP ) . AIMS To assess the clinical and hemodynamic impact of upgrading to biventricular pacing in patients with severe HF and permanent RVAP in comparison with patients who had CRT implantation as initial therapy . METHODS AND RESULTS Thirty-nine patients with RVAP , advanced HF ( New York Heart Association [ NYHA ] III-IV ) , and severe depression of left ventricular ejection fraction ( LVEF ) were up grade d to biventricular pacing ( group A ) . Mean duration of RVAP before upgrading was 41.8 + /- 13.3 months . Clinical and echocardiographic results were compared to those obtained in a group of 43 patients with left bundle branch block and similar clinical characteristics undergoing " primary " CRT ( group B ) . Mean follow-up was 35 + /- 10 months in patients of group A and 38 + /- 12 months in group B. NYHA class significantly improved in groups A and B. LVEF increased from 0.23 + /- 0.07 to 0.36 + /- 0.09 ( P < 0.001 ) and from 0.26 + /- 0.02 to 0.34 + /- 0.10 ( P < 0.001 ) , respectively . Hospitalizations were reduced by 81 % and 77 % ( P < 0.001 ) . Similar improvements in echocardiographic signs of ventricular desynchronization were also observed . CONCLUSION Patients up grade d to CRT exhibit long-term clinical and hemodynamic benefits that are similar to those observed in patients treated with CRT as initial strategy BACKGROUND Biventricular ( BiV ) stimulation lowers morbidity and mortality in patients with drug-refractory congestive heart failure ( CHF ) , depressed left ventricular ( LV ) function , and ventricular dyssynchrony in absence of indication for permanent cardiac pacing . This pilot , single-blind , r and omized , cross-over study examined the safety and efficacy of upgrading conventional pacing systems to BiV stimulation in patients with advanced CHF . METHODS We included 56 patients in New York Heart Association ( NYHA ) functional classes III or IV despite optimal drug treatment and ventricular dyssynchrony ( interventriclar delay > 40 ms or LV preejection delay > 140 ms ) in need of pacemaker replacement . We compared the patients ' functional status , arrhythmias , and st and ard echocardiographic measurements during 3 months of conventional , single right ventricular ( RV ) versus 3 months of BiV stimulation . RESULTS There were 44 patients in the cross-over phase . QRS duration was shortened by 23 % and LV preejection delay by 16 % with BiV stimulation . NYHA functional class , 6-minute hall walk and quality of life score were significantly improved with BiV stimulation compared with single RV pacing by 18 % , 29 % , and 19 % , respectively . No significant difference was observed in the ventricular arrhythmia burden or LV reverse remodeling between the 2 periods . CONCLUSIONS This pilot study showed that upgrading from RV pacing to BiV pacing significantly improves symptoms and exercise tolerance in chronically paced patients with advanced CHF and mechanical dyssynchrony AIMS To investigate whether patients with previously implanted conventional pacemakers and severe heart failure benefit from an up grade to a biventricular system . METHODS AND RESULTS Study inclusion criteria were New York Heart Association ( NYHA ) classes III and IV , dominant paced rhythm , and no left bundle branch block in the pre-pacing ECG . Ten patients with pacemakers ( four VVIR due to slow atrial fibrillation and six DDDR , of which four were due to high-degree atrioventricular block and two to sinus node disease ) were up grade d to a biventricular pacing ( BVP ) system . The median duration of pacing before the up grade was 5.7 years . Assessment s of 6-min walk test , symptom score , brain natriuretic peptide ( pro-BNP ) , and echocardiography were made pre-operatively . After a run-in period of 1 month in BVP following the up grade , the patients were r and omized to a 2-month period in either BVP or right ventricular pacing ( RVP ) , followed by 2 months in the other mode , in a double-blind crossover fashion . After each period , the pre-operative measurements were repeated . After study completion , patients were asked to select their preferred period . The median 6-min walking distance was significantly longer in BVP ( 400 m ) vs. RVP ( 315 m ) , P = 0.02 . The symptom score was also significantly better in BVP ( P = 0.005 ) . Median pro-BNP was significantly lower in BVP than in RVP , 3,030 vs. 5,064 ng/L ( P = 0.005 ) . Six patients dem and ed an early crossover in RVP but none in BVP ( P = 0.015 ) , and all patients except one expressed a preference for BVP . However , echo parameters did not show any significant differences between BVP and RVP . CONCLUSION Pacemaker patients with heart failure and dominant paced heart rhythm benefit substantially from an up grade to BVP , in terms of physical performance and symptoms . The up grade result ed in significantly improved cardiac function as reflected by reduced levels of pro-BNP AIMS Cardiac resynchronization therapy ( CRT ) is an effective treatment for a subset of patients with chronic heart failure . Data on the benefit of CRT in heart failure patients with previous right ventricular pacemakers or st and ard defibrillators are sparse . METHODS AND RESULTS The European ( HFA , Heart Failure Association/EHRA , European Heart Rhythm Association ) CRT Survey enrolled patients from 141 centres in 13 countries in Europe collecting baseline demographic , echocardiographic , clinical , and implant data , with follow-up at ∼1 year . The present analysis reports implantation data and 1 year outcomes regarding New York Heart Association ( NYHA ) class , global patient assessment , hospitalizations , complications , and mortality in patients undergoing de novo CRT implantations compared with those receiving an up grade of a previously implanted device ( pacemaker or implantable cardioverter-defibrillators ) . This analysis includes 2367 CRT implant procedures of which 692 ( 28 % ) were up grade s to CRT . Distribution of NYHA functional class and left ventricular function were similar between the groups . Procedural duration was also similar , although fluoroscopy time was shorter in the ' up grade s ' . There was no difference in the frequency of peri-procedural complications . There were similar improvements in NYHA functional class and similar reduction in QRS duration , but more patients reported unchanged global assessment status in the up grade d group . Total and cause-specific mortality at 1 year was low and the same in both groups . CONCLUSIONS More than one quarter of all CRT procedures are up grade s from existing systems , although this group has not been subject to r and omized clinical trials . Our data suggest that there are no significant differences in clinical outcomes or complication rates between up grade s and de novo procedures . Clinical study no NCT 01185392 AIMS Cardiac resynchronization therapy ( CRT ) is indicated in patients with heart failure and bundle branch block . It is less clear whether this includes patients with pre-existing right ventricular pacemaker/defibrillator systems , particularly with respect to implantation success and clinical benefit . METHODS AND RESULTS In consecutive patients scheduled for CRT , we prospect ively compared implantation success , procedural parameters , and clinical response in ' de novo ' vs. up grade procedures of previously implanted right ventricular systems . CRT implantation was attempted in 79 consecutive patients ( 64 + /- 11 years , 63 male , 38 ischaemic , 41 non-ischaemic cardiomyopathy ) . De novo implantation was performed in 61 patients , up grade procedures in 18 patients . Implant success ( 92 vs. 94 % , P = 1.00 ) , procedure duration ( 153 + /- 43 vs. 164 + /- 65 min , P = 0.51 ) , fluoroscopy time ( 25 + /- 18 vs. 32 + /- 22 min , P = 0.18 ) or dose ( 40 + /- 31 vs. 52 + /- 49 Gy/cm(2 ) , P = 0.35 ) , and response rate ( 66 vs. 59 % , P = 0.5 ) were comparable for both groups . CONCLUSION Procedural aspects , implantation success , and clinical response to CRT were comparable for patients undergoing de-novo vs. up grade procedures . Accordingly , patient selection for upgrading should be the same as for new CRT implantation |
13,259 | 27,772,555 | There was some evidence that psychosocial factors , particularly depression , were associated with medication adherence following ACS . | OBJECTIVE Medication non-adherence following acute coronary syndrome ( ACS ) is associated with poor clinical outcomes .
A systematic review and meta- analysis were undertaken to identify psychosocial factors associated with medication adherence in patients with ACS . | Background — The benefits of medication adherence to control cardiovascular disease ( CVD ) are well defined , yet multiple studies have identified poor adherence . The influence of life chaos on medication adherence is unknown . Because this is a novel application of an instrument , our preliminary objective was to underst and patient factors associated with chaos . The main objective was to evaluate the extent to which an instrument design ed to measure life chaos is associated with CVD-medication nonadherence . Methods and Results — Using baseline data from an ongoing r and omized trial to improve postmyocardial infa rct ion ( MI ) management , multivariable logistic regression identified the association between life chaos and CVD-medication nonadherence . Patients had hypertension and a myocardial infa rct ion in the past 3 years ( n=406 ) . Nearly 43 % reported CVD-medication nonadherence in the past month . In simple linear regression , the following were associated with higher life chaos : medication nonadherence ( & bgr;=1.86 ; 95 % confidence interval [ CI ] , 0.96–2.76 ) , female sex ( & bgr;=1.22 ; 95 % CI [ 0.22–2.24 ] ) , minority race ( & bgr;=1.72 ; 95 % CI [ 0.78–2.66 ] ) , having less than high school education ( & bgr;=2.05 ; 95 % CI [ 0.71–3.39 ] ) , low health literacy ( & bgr;=2.06 ; 95 % CI [ 0.86–3.26 ] ) , and inadequate financial status ( & bgr;=1.93 ; 95 % CI [ 0.87–3.00 ] ) . Being married ( & bgr;=−2.09 , 95 % CI [ −3.03 to −1.15 ] ) was associated with lower life chaos . As chaos quartile increased , patients exhibited more nonadherence . In logistic regression , adjusting for sex , race , marital status , employment , education , health literacy , and financial status , a 1-unit life chaos increase was associated with a 7 % increase ( odds ratio , 1.07 ; 95 % CI [ 1.02–1.12 ] ) in odds of reporting medication nonadherence . Conclusions — Our results suggest that life chaos may be an important determinant of medication adherence . Life chaos screenings could identify those at risk for nonadherence . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : Background Adherence to evidence based medicines in patients who have experienced a myocardial infa rct ion remains low . Individual ’s beliefs towards their medicines are a strong predictor of adherence and may influence other factors that impact on adherence . Objective To investigate if community pharmacists discussing patients ’ beliefs about their medicines improved medication adherence at 12 months post myocardial infa rct ion . Setting This study included 200 patients discharged from a public teaching hospital in Queensl and , Australia , following a myocardial infa rct ion . Patients were r and omised into intervention ( n = 100 ) and control groups ( n = 100 ) and followed for 12 months . Method All patients were interviewed between 5 to 6 weeks , at 6 and 12 months post discharge by the research er using the repertory grid technique . This technique was used to elicit the patient ’s individualised beliefs about their medicines for their myocardial infa rct ion . In the intervention group , patients ’ beliefs about their medicines were communicated by the research er to their community pharmacist . The pharmacist used this information to tailor their discussion with the patient about their medication beliefs at design ated time points ( 3 and 6 months post discharge ) . The control group was provided with usual care . Main outcome measure The difference in non-adherence measured using a medication possession ratio between the intervention and control groups at 12 months post myocardial infa rct ion . Results There were 137 patients remaining in the study ( intervention group n = 72 , control group n = 65 ) at 12 months . In the intervention group 29 % ( n = 20 ) of patients were non-adherent compared to 25 % ( n = 16 ) of patients in control group . Conclusion Discussing patients ’ beliefs about their medicines for their myocardial infa rct ion did not improve medication adherence . Further research on patients beliefs should focus on targeting non-adherent patients whose reasons for their non-adherence is driven by their medication beliefs Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items BACKGROUND Adherence to evidence -based cardiovascular ( CV ) medications after an acute myocardial infa rct ion ( MI ) is low after the first 6 months . The use of fixed-dose combinations ( FDC ) has been shown to improve treatment adherence and risk factor control . However , no previous r and omized trial has analyzed the impact of a polypill strategy on adherence in post-MI patients . OBJECTIVES The cross-sectional FOCUS ( Fixed-Dose Combination Drug for Secondary Cardiovascular Prevention ) study ( Phase 1 ) aim ed to eluci date factors that interfere with appropriate adherence to CV medications for secondary prevention after an acute MI . Additionally , 695 patients from Phase 1 were r and omized into a controlled trial ( Phase 2 ) to test the effect of a polypill ( containing aspirin 100 mg , simvastatin 40 mg , and ramipril 2.5 , 5 , or 10 mg ) compared with the 3 drugs given separately on adherence , blood pressure , and low-density lipoprotein cholesterol , as well as safety and tolerability over a period of 9 months of follow-up . METHODS In Phase 1 , a 5-country cohort of 2,118 patients was analyzed . Patients were r and omized to either the polypill or 3 drugs separately for Phase 2 . Primary endpoint was adherence to the treatment measured at the final visit by the self-reported Morisky-Green question naire ( MAQ ) and pill count ( patients had to meet both criteria for adherence at the in-person visit to be considered adherent ) . RESULTS In Phase 1 , overall CV medication adherence , defined as an MAQ score of 20 , was 45.5 % . In a multivariable regression model , the risk of being nonadherent ( MAQ < 20 ) was associated with younger age , depression , being on a complex medication regimen , poorer health insurance coverage , and a lower level of social support , with consistent findings across countries . In Phase 2 , the polypill group showed improved adherence compared with the group receiving separate medications after 9 months of follow-up : 50.8 % versus 41 % ( p = 0.019 ; intention-to-treat population ) and 65.7 % versus 55.7 % ( p = 0.012 ; per protocol population ) when using the primary endpoint , attending the final visit with MAQ = 20 and high pill count ( 80 % to 110 % ) combined , to assess adherence . Adherence also was higher in the FDC group when measured by MAQ alone ( 68 % vs. 59 % , p = 0.049 ) . No treatment difference was found at follow-up in mean systolic blood pressure ( 129.6 mm Hg vs. 128.6 mm Hg ) , mean low-density lipoprotein cholesterol levels ( 89.9 mg/dl vs. 91.7 mg/dl ) , serious adverse events ( 23 vs. 21 ) , or death ( 1 , 0.3 % in each group ) . CONCLUSIONS For secondary prevention following acute MI , younger age , depression , and a complex drug treatment plan are associated with lower medication adherence . Meanwhile , adherence is increased in patients with higher insurance coverage levels and social support . Compared with the 3 drugs given separately , the use of a polypill strategy met the primary endpoint for adherence for secondary prevention following an acute MI . ( Fixed Dose Combination Drug [ Polypill ] for Secondary Cardiovascular Prevention [ FOCUS ] ; NCT01321255 ) BACKGROUND Although smoking cessation is essential for prevention of secondary cardiovascular disease ( CVD ) , many smokers do not stop smoking after hospitalization . Mild depressive symptoms are common during hospitalization for CVD . We hypothesized that depressive symptoms measured during hospitalization for acute CVD would predict return to smoking after discharge from the hospital . METHODS This was a planned secondary analysis of data from a placebo-controlled , double-blind , r and omized trial of bupropion hydrochloride therapy in 245 smokers hospitalized for acute CVD . All subjects received smoking counseling in the hospital and for 12 weeks after discharge . Depressive symptoms were measured during hospitalization with the Beck Depression Inventory ( BDI ) , and smoking cessation was biochemically vali date d at 2-week , 12-week , and 1-year follow-up . The effect of depressive symptoms on smoking cessation was assessed using multiple logistic regression and survival analyses . RESULTS Twenty-two percent of smokers had moderate to severe depressive symptoms ( BDI > or= 16 ) during hospitalization . These smokers were more likely to resume smoking by 4 weeks after discharge ( P= .007 ; incidence rate ratio , 2.40 ; 95 % confidence interval , 1.48 - 3.78 ) than were smokers with lower BDI scores . Smokers with low BDI scores were more likely to remain abstinent than were those with high BDI scores at 3-month follow-up ( 37 % vs 15 % ; adjusted odds ratio , 3.02 ; 95 % confidence interval , 1.28 - 7.09 ) and 1-year follow-up ( 27 % vs 10 % ; adjusted odds ratio , 3.77 ; 95 % confidence interval , 1.31 - 10.82 ) . We estimate that 27 % of the effect of the BDI score on smoking cessation was mediated by nicotine withdrawal symptoms . CONCLUSIONS Moderate to severe depressive symptoms during hospitalization for acute CVD are independently associated with rapid relapse to smoking after discharge and lower rates of smoking cessation at long-term follow-up . The relationship was mediated in part by the stronger nicotine withdrawal symptoms experienced by smokers with higher depressive symptoms OBJECTIVE To further develop and trial a brief in-hospital illness perception intervention for myocardial infa rct ion ( MI ) patients . METHODS One hundred and three patients admitted with acute MI were r and omized to receive either st and ard care or st and ard care plus an illness perception intervention , which consisted of three half-hour patient sessions and one half-hour patient- and -spouse session delivered in hospital . Patients were followed up to 6 months . The main outcome was the difference between groups in rate of return to work . RESULTS The intervention group had a faster rate of return to work than the control group , and more patients in the intervention group had returned to full time work by 3 months than in the control group . At discharge , patients in the intervention group demonstrated changes in causal attributions regarding their MI and higher perceived underst and ing of their condition , which remained at the 6-month follow-up . They also reported a better underst and ing of the information given in hospital , higher intentions to attend cardiac rehabilitation classes , lower anxiety about returning to work , greater increases in exercise , and made fewer phone calls to their general practitioner about their heart condition at follow-up . CONCLUSION This study replicates the findings of an earlier trial that a brief in-hospital illness perception intervention can change perceptions and improve rates of return to work in MI patients . It increases the generalizability of the intervention to the current broader definition of MI and to patients who have had previous infa rcts OBJECTIVE Poor social support is associated with recurrent cardiac events following acute coronary syndrome ( ACS ) . Interventions have largely targeted emotional support , but practical support may be particularly important in encouraging recovery behaviors . We assessed whether practical and emotional support differentially predicted medication adherence and rehabilitation attendance following ACS . METHODS This prospect i ve observational clinical cohort study involved 262 survivors of verified ACS , recruited from four coronary care units in the London area . Practical and emotional support were measured in hospital , and depression , 7 - 10 days after discharge . Medication adherence and rehabilitation attendance were assessed by telephone interview 12 months after hospitalization . RESULTS Nearly one third of patients ( 29.8 % ) had no practical supports , 16 % had one , and 54.2 % had two or more sources of practical support . Patients with greater practical support were more likely to adhere to medication ( P=.034 ) independently of age , gender , marital status , clinical risk profile , and depression . There was also an association with rehabilitation attendance ( P=.034 ) , but this was no longer significant after depression had been taken into account . Emotional support was unrelated to medication adherence and rehabilitation attendance . CONCLUSIONS Cardiac patients with greater practical support may receive more prompts about medications , help with filling prescriptions and assistance with cardiac rehabilitation attendance . These behaviors can influence long-term recovery Abstract BACKGROUND : The persistence of depressive symptoms after hospitalization is a strong risk factor for mortality after acute coronary syndromes ( ACS ) . Poor adherence to secondary prevention behaviors may be a mediator of the relationship between depression and increased mortality . OBJECTIVE : To determine whether rates of adherence to risk reducing behaviors were affected by depressive status during hospitalization and 3 months later . DESIGN : Prospect i ve observational cohort study . SETTING : Three university hospitals . PARTICIPANTS : Five hundred and sixty patients were enrolled within 7 days after ACS . Of these , 492 ( 88 % ) patients completed 3-month follow-up . MEASUREMENTS : We used the Beck Depression Inventory ( BDI ) to assess depressive symptoms in the hospital and 3 months after discharge . We assessed adherence to 5 risk-reducing behaviors by patient self-report at 3 months . We used χ2 analysis to compare differences in adherence among 3 groups : persistently nondepressed ( BDI<10 at hospitalization and 3 months ) ; remittent depressed ( BDI ≥10 at hospitalization ; < 10 at 3 months ) ; and persistently depressed patients ( BDI ≥10 at hospitalization and 3 months ) . RESULTS : Compared with persistently nondepressed , persistently depressed patients reported lower rates of adherence to quitting smoking ( adjusted odds ratio [ OR ] 0.23 , 95 % confidence interval [ 95 % CI ] 0.05 to 0.97 ) , taking medications ( adjusted OR 0.50 , 95 % CI 0.27 to 0.95 ) , exercising ( adjusted OR 0.57 , 95 % CI 0.34 to 0.95 ) , and attending cardiac rehabilitation ( adjusted OR 0.5 , 95 % CI 0.27 to 0.91 ) . There were no significant differences between remittent depressed and persistently nondepressed patients . CONCLUSIONS : Persistently depressed patients were less likely to adhere to behaviors that reduce the risk of recurrent ACS . Differences in adherence to these behaviors may explain in part why depression predicts mortality after ACS Objective : Posttraumatic stress disorder ( PTSD ) symptoms have been reported in patients with coronary vascular disease , after the trauma of a myocardial infa rct ion ( MI ) . The effect of these symptoms on post-MI disease control has not been eluci date d. We conducted a study that sought to determine whether PTSD symptoms post-MI are associated with increased likelihood of cardiovascular readmission and with nonadherence to treatment recommendations . Methods : Patients were recruited during a visit in a cardiology clinic 6 months post-MI and were followed for 1 year . Adherence to aspirin was measured by platelet thromboxane production ( an indication of aspirin 's effect ) . Medical outcome was measured as rate of admission due to cardiovascular causes during the follow-up period . Self-report measures of PTSD ( Impact of Event Scale ) , Depression , and Global Distress ( SCL-90-R ) were administered at enrollment . Results : Seventy-three patients were studied . Above-threshold PTSD symptom scores at enrollment , but not depression or global distress scores , were significant predictors of nonadherence to aspirin and of an increased likelihood of cardiovascular readmission over the course of the following year . Conclusions : PTSD symptoms predicted poor disease control in this cohort of MI survivors . The data suggest that screening MI survivors for symptoms of PTSD may be beneficial if this high-risk population is to be targeted for interventions Objective This study was design ed to examine whether a brief hospital intervention design ed to alter patients ’ perceptions about their myocardial infa rct ion ( MI ) would result in a better recovery and reduced disability . Design In a prospect i ve r and omized study , 65 consecutive patients with their first MI aged were assigned to receive an intervention design ed to alter their perceptions about their MI or usual care from rehabilitation nurses . Patients were assessed in hospital before and after the intervention and at 3 months after discharge from hospital . Results The intervention caused significant positive changes in patients ’ views of their MI . Patients in the intervention group also reported they were better prepared for leaving hospital ( p < .05 ) and subsequently returned to work at a significantly faster rate than the control group ( p < .05 ) . At the 3-month follow-up , patients in the intervention group reported a significantly lower rate of angina symptoms than control subjects ( 14.3 vs. 39.3 , p < .03 ) . There was no significant differences in rehabilitation attendance between the two groups . Conclusions An in-hospital intervention design ed to change patients ’ illness perceptions can result in improved functional outcome after MI Background —Antiplatelet therapy and antithrombin therapy have been demonstrated to reduce the risk of cardiac events in patients presenting with acute coronary syndrome , yet all effective therapies also increase the risk of bleeding . Methods and Results —In the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events ( CURE ) trial , 12 562 patients were r and omized to clopidogrel or placebo in addition to aspirin , and the primary outcome was cardiovascular ( CV ) death , myocardial infa rct ion ( MI ) , or stroke . The benefits were consistent among those undergoing percutaneous coronary intervention ( PCI ) [ 9.6 % for clopidogrel , 13.2 % for placebo ; relative risk ( RR ) , 0.72 ; 95 % CI , 0.57 to 0.90 ] , coronary artery bypass grafting ( CABG ) surgery ( 14.5 % for clopidogrel 16.2 % for placebo ; RR , 0.89 ; 95 % CI , 0.71 to 1.11 ) , and medical therapy only ( 8.1 % for clopidogrel , 10.0 % for placebo ; RR , 0.80 ; 95 % CI , 0.69 to 0.92 ; test for interaction among strata , 0.53 ) . For CABG during the initial hospitalization ( 530 for placebo , 485 for clopidogrel ) , the frequency of CV death , MI or stroke before CABG was 4.7 % for placebo and 2.9 % for clopidogrel ( RR , 0.56 ; 95 % CI , 0.29 to 1.08 ) . For the entire study , there was a 1 % excess of major bleeding but no significant excess of life-threatening bleeding . Among patients undergoing CABG , the rates of life-threatening bleeding were 5.6 % for clopidogrel and 4.2 % for placebo ( RR , 1.30 ; 95 % CI , 0.91 to 1.95 ; both nonsignificant ) . Conclusions —The benefits versus risks of early and long-term clopidogrel therapy ( freedom from CV death , MI , stroke , or life-threatening bleeding ) are similar in those undergoing revascularization ( CABG or PCI ) and in the study population as a whole . Overall , the benefits of starting clopidogrel on admission appear to outweigh the risks , even among those who proceed to CABG during the initial hospitalization Low rates of adherence to hypertensive therapy limit patients ' securing the full benefits of treatment . While some factors related to adherence have been identified , research on the effectiveness of interventions to increase adherence levels is sparse . The present study was design ed to assess the impact of a series of different interventions on a group of some 400 patients , all under the care of private physicians in a small community . A factorial design was employed to deliver four , sequential educational interventions , about four months apart , to r and omly selected sub-groups . Interviews before and after each intervention provided information concerning self-reported adherence , health status , health beliefs , and personal characteristics . Pertinent medical records and pharmacy data were also obtained . The first intervention — printed material —did not significantly affect adherence . The second and fourth interventions —nurse telephone calls and social support — each increased medication taking and the third intervention — self-monitoring — led to better weight control . There was no cumulative impact of the interventions and different aspects of regimens were not signiticantly related to one another OBJECTIVE Coronary heart disease ( CHD ) is a leading cause of illness and death in Western society . The present study was design ed to evaluate the utility of illness perceptions and medication beliefs in predicting secondary preventive behaviour among patients with CHD . An extended version of Leventhal 's self-regulatory model ( SRM ) was used as a theoretical framework for this study [ Leventhal H , Nerenz DR , Steele DJ . Illness perceptions and coping with health threat . In : Baum A , Taylor SE , Singer JE , editors . H and book of psychology and health , Volume IV : social psychological aspects of health . Hillsdale ( NJ ) : Erlbaum , 1984 . pp . 219 - 52 ; Horne R , Weinman J. Self-regulation and self-management in asthma : exploring the role of illness perceptions and treatment beliefs in explaining non-adherence to preventer medication . Psychol Health 2002;17(1):17 - 32 ] . METHOD Medical and demographic data were gathered from the medical charts of 1611 patients with established CHD from 35 r and omly selected general practice s. Self-report data about patients ' lifestyles ( diet , exercise , smoking , alcohol consumption and medication adherence ) and information on illness and medication beliefs were provided from postal question naire ( 1084 patients responded ; 69 % response rate ) . The relationship between patients ' beliefs and their secondary preventive behaviour was examined using regression analyses . RESULTS Illness perceptions appeared to be only weak predictors of smoking , exercise , diet , alcohol consumption and medication adherence , accounting for about 2 % of the variance in these behaviours . Medication beliefs were moderately related to medication adherence , accounting for about 7 % of the variance in scores . A strong belief in the necessity of one 's medication and a lower level of concern about one 's medication were associated with higher levels of adherence . CONCLUSIONS An illness perception approach did not prove helpful in predicting secondary preventive behaviour among this group of patients . However , beliefs about medications appear to be reasonable predictive of medication adherence Background —The Clopidogrel in Unstable angina to prevent Recurrent Events ( CURE ) trial demonstrated that clopidogrel , given early and continued long term , was superior to placebo in patients with non-ST – elevation acute coronary syndromes receiving aspirin . The purpose of the present analysis was to estimate the treatment effect Zof clopidogrel in patients who were stratified according to their risk of future cardiovascular events . Methods and Results — Patients ( n=12 562 ) who presented within 24 hours after the onset of symptoms were r and omized to receive clopidogrel ( 300 mg followed by 75 mg daily ) or placebo in addition to aspirin for 3 to 12 months . Treatment effect was analyzed in various risk groups according to the Thrombolysis in Myocardial Infa rct ion ( TIMI ) risk score . The TIMI risk model was vali date d in the CURE population ( C statistic , 0.634 ) . The primary composite outcome of cardiovascular death , myocardial infa rct ion , or stroke increased proportionally with increasing risk according to the TIMI risk score . The impact of clopidogrel versus placebo on the rate of the primary outcome was as follows : low-risk group ( TIMI score 0 to 2 ) , 4.1 % versus 5.7 % ( relative risk [ RR ] , 0.71 ; 95 % confidence interval [ CI ] , 0.52 to 0.97;P < 0.04 ) , intermediate-risk group ( TIMI score 3 to 4 ) , 9.8 % versus 11.4 % ( RR , 0.85 ; 95 % CI , 0.74 to 0.98;P < 0.03 ) , and high-risk group ( TIMI score 5 to 7 ) , 15.9 % versus 20.7 % ( RR , 0.73 ; 95 % CI , 0.60 to 0.90;P < 0.004 ) . There was no evidence of statistical heterogeneity among the groups . Conclusions —The benefit of clopidogrel demonstrated in the CURE trial is consistent in low- , intermediate- , and high-risk patients with acute coronary syndromes ( as stratified by TIMI risk score ) , thus supporting its use in all patients with documented non – ST elevation acute coronary syndromes PURPOSE To determine the rates of patient adherence to key evidence -based therapies at 6 months after hospital discharge for an acute coronary syndrome . METHODS In this nonr and omized , prospect i ve , multinational , multicenter study , adherence to aspirin , beta-blockers , statins , or angiotensin-converting enzyme ( ACE ) inhibitors 6 months after discharge for myocardial infa rct ion or unstable angina was assessed in 21,408 patients aged 18 years or older . Patients were enrolled at 104 tertiary and community hospitals representing a broad range of care facilities and practice setting s ( e.g. , teaching vs. nonteaching ) . RESULTS Of 13,830 patients , discontinuation of therapy was observed at 6-month follow-up in 8 % of those taking aspirin on discharge , 12 % of those taking beta-blockers , 20 % of those taking ACE inhibitors , and 13 % of those taking statins . In a multivariate analysis , adherence to beta-blocker therapy was higher in patients with a myocardial infa rct ion ( odds ratio [ OR ] = 1.25 ; 95 % confidence interval [ CI ] : 1.06 to 1.47 ) , hypertension ( OR = 1.33 ; 95 % CI : 1.15 to 1.54 ) , ST-segment elevation myocardial infa rct ion ( OR = 1.33 ; 95 % CI : 1.11 to 1.61 ) , or non-ST-segment elevation myocardial infa rct ion ( OR = 1.25 ; 95 % CI : 1.08 to 1.45 ) . Aspirin adherence was higher among patients cared for by cardiologists ( OR = 1.45 ; 95 % CI : 1.19 to 1.75 ; P < 0.001 ) than among those cared for by nonspecialists . Male sex and prior heart failure were associated with improved adherence to ACE inhibitor therapy . Hypertension was associated with poorer adherence to statin therapy ( OR = 0.85 ; 95 % CI : 0.74 to 0.99 ; P = 0.04 ) . CONCLUSION Among patients prescribed key evidence -based medications at discharge , 8 % to 20 % were no longer taking their medication after 6 months . The reasons for noncompliance are complex , and may be eluci date d by future studies of medical and social determinants BACKGROUND The CURE study demonstrated the benefit of clopidogrel in patients with non-ST elevation ( NSTE ) acute coronary syndromes ( ACSs ) , including those undergoing percutaneous coronary intervention ( PCI ) . It did not report the relation between clopidogrel and timing of PCI or , more specifically , the role of clopidogrel in patients managed with an early interventional strategy , the current preferred treatment option for patients with NSTE ACSs . In the present study , we examined the relation between clopidogrel therapy , timing of PCI , and cardiovascular ( CV ) events in patients participating in the CURE study . METHODS A total of 12562 patients with NSTE ACSs was r and omized in double-blind fashion to clopidogrel or placebo ( 300 mg loading dose , then 75 mg/d ) in addition to aspirin for up to 1 year . We analyzed the data of the 2658 CURE patients undergoing PCI and related the incidence of outcome events ( CV death/myocardial infa rct ion [ MI ] ) to timing of PCI after r and omization : early ( < 48 hours , median 1.0 day , n = 370 ) , intermediate ( > or = 48 hours to initial hospital discharge , median 6.8 days , n = 1360 ) , and late ( after initial hospital discharge , median 47.6 days , n = 928 ) . RESULTS Clopidogrel showed consistent treatment benefit over the 12-month ( mean 9 months ) follow-up period irrespective of timing of PCI ( relative risk [ RR ] 0.53 for the early group , RR 0.72 for the intermediate group , RR 0.70 for the late group ) . After adjustment for propensity to undergo PCI , the greatest treatment benefit of clopidogrel was observed in patients undergoing PCI < 48 hours after r and omization ( RR 0.45 , 95 % CI 0.21 - 0.96 , P = .038 ) , although with overlap between groups . The lowest absolute event rate ( 6.7 % CV death/MI ) was observed in patients treated with clopidogrel and undergoing PCI within 48 hours . There was no increased risk of major bleeding in the early PCI group . CONCLUSIONS The benefit of therapy with clopidogrel in addition to aspirin in patients presenting with NSTE ACSs was significant irrespective of the timing of PCI . The combination of clopidogrel and an early ( < 48 hours ) interventional strategy was associated with low absolute event rates for CV death/nonfatal MI Although angina pectoris is the most common symptom of coronary artery disease , some patients do not experience angina during ischemic episodes . The effects of asymptomatic ( silent ) heart disease on patient self-management have rarely been studied . Studies of other patient population s with asymptomatic illnesses indicate that patients with silent myocardial ischemia might adhere less well to a prophylactic medication regimen than would those with symptomatic ischemia . Depression , a state associated with poor adherence to medical regimens is more common among patients with symptomatic ischemia . For prevention of thromboembolic events , 37 patients with documented ischemic heart disease who denied having anginal symptoms and 28 patients who reported almost daily symptoms were given a 3-week supply of low-dose aspirin packaged in an unobtrusive electronic adherence monitor . All other medications were provided in st and ard pill bottles . The symptomatic patients removed their prescribed aspirin on 62.4 % of the days ; the patients with silent ischemia took their medication on 77.3 % of the days . Possible explanations for these results , their clinical implication s , and directions for future research are discussed We sought to identify patients at risk for premature discontinuation of thienopyridines and to develop a risk score for thienopyridine adherence after coronary stent implantation . Patients were prospect ively included from December 2007 to March 2008 . At 1-month follow-up , all patients were given the Morisky question naire and asked if they had stopped taking thienopyridines . Multivariate analysis identified predictors of thienopyridine discontinuation ; points were assigned to each variable according to the odds ratios and the c-statistic of the score was calculated . Mean age of the 400 patients included was 61.0 ± 10.4 years ; 66 patients ( 16.5 % ) stopped thienopyridines after 1 month . Reasons for discontinuation were cost ( 62 % ) , lack of information ( 17 % ) , and recommendation by another doctor to stop treatment ( 15 % ) . Factors associated with discontinuation included unmarried status ( odds ratio 2.48 , p = 0.046 ) , lack of private health insurance ( odds ratio 4.68 , p = 0.041 ) , acute coronary syndrome ( odds ratio 2.31 , p = 0.004 ) , nondiabetics ( odds ratio 2.20 , p = 0.041 ) , and patients who earned < 2 times ( odds ratio 8.23 , p < 0.001 ) and 2 to 3 times ( odds ratio 4.46 , p = 0.021 ) the minimum wage . Total risk score was 0 to 14 points and was strongly associated with thienopyridine discontinuation . For total scores of 0 to 4 , 5 to 8 , 9 to 12 , and ≥13 , 0 % , 7 % , 20 % , and 37 % of patients , respectively , stopped thienopyridines ( c-statistic 0.76 , p < 0.0001 ) . Risk score was also significantly associated with complete adherence as assessed by the Morisky question naire ( c-statistic 0.74 , p < 0.001 ) . In conclusion , we have identified patients at risk for premature discontinuation of thienopyridines using variables obtained before stent implantation and developed a risk score that accurately predicts premature thienopyridine discontinuation Background Whether having a stable and predictable lifestyle is associated with health care use and health status among HIV patients is unknown . Objective To develop and test the reliability and validity of a measure of life chaos for adults with HIV and examine its association with health care use and health status . Design Prospect i ve cohort study . Participants Two hundred twenty HIV-infected persons recruited from those who tested positive in a mobile testing van and from HIV clinics serving low-income population s. Measurements Participants completed a survey every 6 months , assessing their health care use , SF-12 mental and physical health status and life chaos . Results Cronbach ’s alpha for the six-item measure of chaos was .67 . Those without a spouse or partner and those with one or more unmet social service needs , such as housing or transportation , had higher chaos scores . Compared to those with less chaos , those with more chaos were less likely to have two or more outpatient visits ( adjusted odds ratio [ OR ] 0.48 , 95 % confidence interval [ CI ] : 0.24–0.98 ) , more likely to have two or more missed visits ( adjusted OR 2.30 , 95%CI : 1.20–4.41 ) in the 6 months before study enrollment and had lower mental health status at enrollment and at follow-up . Life chaos was not associated with emergency department visits or physical health status . Conclusions We created a new measure of life chaos , which was associated with outpatient visits and mental health status . Chaos may be an important barrier to regular medical care . Future studies need to test this measure in more diverse population s and those with other diseases OBJECTIVE This study examined whether social network size and partner stress predicted medication adherence , cardiac rehabilitation attendance , and quality of life 12 months following hospitalization for an acute coronary syndrome ( ACS ) . DESIGN ACS patients ( N = 193 , M age = 60.6 years , SD = 11.4 years , 23 % female ) were recruited shortly following admission to 4 local hospitals . A prospect i ve design was employed with follow-up data collected 12 months following hospital admission . MAIN OUTCOME MEASURES Data were gathered on social network size and partner stress . The main outcomes assessed at 12 months were medication adherence , cardiac rehabilitation attendance , and quality of life ( Short Form 36 ) . RESULTS Partner stress predicted medication nonadherence , odds ratio : 2.89 , ( 95 % CI = 1.21 , 6.95 ) . ACS patients with large social networks were more likely to attend rehabilitation , odds ratio : 3.42 , ( 95 % CI = 1.42 , 8.25 ) . Analyses were adjusted for age , gender , clinical risk scores , readmission/recurrence , and negative affectivity . Both partner stress and smaller social network size were associated with poorer quality of life . CONCLUSION Social network size and partner stress may partly exert their influence on coronary heart disease morbidity and mortality through recovery behaviors and maintenance of quality of life BACKGROUND The presence of depression after an acute coronary syndrome ( ACS ) is associated with worse prognosis and lower adherence to risk-reducing behaviors . We reported earlier that an enhanced depression care intervention reduces depression symptoms and major adverse cardiac events . This study evaluates the impact of the depression intervention on health behavior and blood pressure control . METHODS Between 2005 and 2008 , 157 patients who remained persistently depressed 3 months after ACS were r and omized to a 6-month depression intervention ( initial patient preference for problem-solving therapy and /or pharmacotherapy , followed by stepped care ; 80 patients ) or to usual care ( 77 patients ) . At r and omization , and then 2 , 4 , and 6 months later , patients were asked if they ( 1 ) missed taking their aspirin ; ( 2 ) followed a heart healthy diet ; ( 3 ) exercised regularly ; and ( 4 ) used tobacco products . Blood pressure was measured before r and omization and 6 months later . RESULTS At the end of the intervention , there was no significant improvement in the percentage of intervention compared to control group patients who adhered to aspirin ( + 3 % versus -1 % , P = .23 ) , followed a healthy diet ( + 10 % versus + 8 % , P = .39 ) , exercised regularly ( + 5 % versus + 4 % , P = .65 ) , abstained from tobacco ( -3 % versus -1 % , P = .77 ) , or had controlled blood pressure ( + 6 % versus + 16 % , P = .26 ) . CONCLUSION Despite improving depression , enhanced depression care after an ACS did not improve health behavior or blood pressure control compared to usual care . Research is needed to test whether adding an adherence intervention to enhanced depression care can improve adherence and cardiovascular prognosis in depressed patients post-ACS Type D personality , the combination of negative affectivity ( NA ) and social inhibition ( SI ) , is an emerging risk factor in cardiovascular disease . This study aim ed to examine one possible behavioural mechanism to explain the link between Type D and ill-health . It was hypothesised that Type D personality would predict medication adherence in myocardial infa rct ion ( MI ) patients . In a prospect i ve study , 192 MI patients ( 54 females and 138 males ) completed measures of Type D personality and provided demographic and medical information 1 week post-MI , and then 131 patients went on to complete a self-report measure of medication adherence 3 months post-MI . It was found that Type D personality predicts adherence to medication , after controlling for demographic and clinical risk factors . Critically , the constituent components of Type D , NA and SI , interact to predict medication adherence , after controlling for the effects of each component separately . Poor adherence to medication may represent one mechanism to explain why Type D cardiac patients experience poor clinical outcome , in comparison to non-Type D patients . Interventions , which target the self-management of medication , may be useful in these high-risk patients BACKGROUND The superiority of clopidogrel and aspirin versus aspirin alone for up to 1 year in patients who undergo percutaneous coronary intervention ( PCI ) after presenting with acute coronary syndromes without ST-segment elevation was demonstrated in the PCI-CURE study . We evaluated the long-term cost-effectiveness of clopidogrel use for up to 1 year using patient-level outcomes and re source use from PCI-CURE , and estimates of life expectancy gains based on external sources . METHODS PCI-CURE involved 2658 patients who underwent PCI between 1998 and 2000 after being r and omized in the CURE trial to clopidogrel ( n = 1313 ) or placebo ( n = 1345 ) . Roughly two thirds ( clopidogrel n = 821 , placebo n = 909 ) underwent PCI during the initial hospitalization ( early PCI ) . Costs were applied to hospitalizations according to diagnosis-related group . Clopidogrel was assigned the average wholesale price of 3.22 dollars per day . Life expectancy gains result ing from the prevention of major clinical events were estimated using external sources . RESULTS Average total costs were higher with clopidogrel ( difference [ based on costing method ] 253 dollars-423 dollars ) . For patients who underwent PCI during the initial hospitalization , the difference ranged from 155 dollars lower to 90 dollars higher with clopidogrel . The estimated life expectancy gain with clopidogrel was 0.0885 years , whereas it was 0.0962 years for the early PCI subgroup . Incremental cost per year of life gained with clopidogrel ranges from 2856 dollars to 4775 dollars overall and from dominant ( life expectancy benefit with cost savings ) to 935 dollars for the early PCI subgroup . CONCLUSIONS Clopidogrel given for up to 1 year in patients undergoing PCI after presentation with acute coronary syndromes is a highly cost-effective treatment strategy BACKGROUND Nonadherence to medications is common , but the determinants and consequences are poorly defined . The objectives of this study were to identify patient and myocardial infa rct ion ( MI ) treatment factors associated with medication therapy discontinuation and to assess the impact of medication discontinuation 1 month after MI on 12-month mortality . METHODS This was a multicenter prospect i ve cohort of patients with MI enrolled in the Prospect i ve Registry Evaluating Myocardial Infa rct ion : Event and Recovery study . The outcomes were use of aspirin , beta-blockers , and statins at 1 month after MI hospitalization among patients discharged with all 3 medications as well as 12-month mortality . RESULTS Of 1521 patients discharged with all 3 medications , 184 discontinued use of all 3 medications , 56 discontinued use of 2 medications , 272 discontinued use of 1 medication , and 1009 continued taking all 3 medications at 1 month . In multivariable analyses , patients not graduating from high school ( odds ratio [ OR ] , 1.76 ; 95 % confidence interval [ CI ] , 1.20 - 2.60 ) were more likely to discontinue use of all medications . The effect of increasing age on medication therapy discontinuation was greater for females ( OR , 1.77 ; 95 % CI , 1.34 - 2.34 ) than males ( OR , 1.23 ; 95 % CI , 1.02 - 1.47 ) . Patients who discontinued use of all medications at 1 month had lower 1-year survival ( 88.5 % vs 97.7 % ; log-rank P<.001 ) compared with patients who continued to take 1 or more medication(s ) . In multivariable survival analysis , medication therapy discontinuation was independently associated with higher mortality ( hazards ratio , 3.81 ; 95 % CI , 1.88 - 7.72 ) . Results were consistent when evaluating discontinuation of use of aspirin , beta-blockers , and statins separately . CONCLUSIONS Medication therapy discontinuation after MI is common and occurs early after discharge . Patients who discontinue taking evidence -based medications are at increased mortality risk . These findings suggest the need to improve the transition of care from the hospital to outpatient setting to ensure that patients continue to take medications that have mortality benefit Objective To assess the relationship among Type D personality , self-efficacy , and medication adherence in patients with coronary heart disease . Methods The study design was prospect i ve and observational . Type D personality , self-efficacy for illness management behaviors , and medication adherence were measured 3 weeks after hospitalization for acute coronary syndrome in 165 patients ( mean [ st and ard deviation ] age = 61.62 [ 10.61 ] years , 16 % women ) . Self-reported medication adherence was measured 6 months later in 118 of these patients . Multiple linear regression and mediation analyses were used to address the study research questions . Results Using the original categorical classification , 30 % of patients with acute coronary syndrome were classified as having Type D personality . Categorically defined patients with Type D personality had significantly poorer medication adherence at 6 months ( r = −0.29 , p < .01 ) . Negative affectivity ( NA ; r = −0.25 , p = .01 ) and social inhibition ( r = −0.19 , p = .04 ) , the components of Type D personality , were associated with medication adherence 6 months after discharge in bivariate analyses . There was no evidence for the interaction of NA and social inhibition , that is , Type D personality , in the prediction of medication adherence 6 months after discharge in multivariate analysis . The observed association between NA and medication adherence 6 months after discharge could be partly explained by indirect effects through self-efficacy in mediation analysis ( coefficient = −0.012 ; 95 % bias-corrected and accelerated confidence interval = −0.036 to −0.001 ) . Conclusions The present data suggest the primacy of NA over the Type D personality construct in predicting medication adherence . Lower levels of self-efficacy may be a mediator between higher levels of NA and poor adherence to medication in patients with coronary heart disease . Abbreviations ACS = acute coronary syndrome ; SD = st and ard |
13,260 | 22,146,234 | The review found that VMP and MPT can both be considered more clinical ly effective than MP for the first-line treatment of MM in people for whom high-dose therapy and SCT would not be appropriate .
CTDa was more effective than MP in terms of complete response but data on survival outcomes did not meet the inclusion criteria .
Cost-effectiveness analysis indicated that MPT has a greater probability of being cost-effective than either VMP or CTDa .
CONCLUSIONS Service provision is unlikely to change greatly . | BACKGROUND Multiple myeloma ( MM ) is the second most common haematological cancer in the UK .
MM is not curable but can be treated with a combination of supportive measures and chemotherapy that aim to extend the duration and quality of survival .
The majority of patients are not able to withst and intensive treatment , such as high-dose chemotherapy with autologous stem cell transplantation ( SCT ) , and so they are offered single-agent or combination chemotherapy .
Combination therapies typically include chemotherapy with an alkylating agent and a corticosteroid .
More recently , combination therapies have incorporated drugs such as thalidomide ( Thalidomide Celgene ® , Celgene ) and bortezomib ( Velcade ® , Janssen-Cilag ) .
OBJECTIVE To assess the clinical effectiveness and cost-effectiveness of bortezomib or thalidomide in combination chemotherapy regimens with an alkylating agent and a corticosteroid for the first-line treatment of MM . | This study evaluated the cost effectiveness of bortezomib in relapsed , refractory myeloma , relative to best supportive care ( BSC ) and thalidomide . Data were derived from the phase 2 pivotal study of bortezomib , a Delphi panel of six myeloma thought leaders , and published literature . Objective assumptions regarding treatment choices and consequences ( response and complications ) , and actual cost data were used . Bortezomib was found to be cost effective relative to BSC and thalidomide . Sensitivity analyses demonstrated the robustness of the results . These data suggest that bortezomib provides a cost-effective treatment option and the best value ( in terms of cost/life-yr gained ) among the currently available therapeutic options for relapsed , refractory myeloma BACKGROUND In multiple myeloma , combination chemotherapy with melphalan plus prednisone is still regarded as the st and ard of care in elderly patients . We assessed whether the addition of thalidomide to this combination , or reduced-intensity stem cell transplantation , would improve survival . METHODS Between May 22 , 2000 , and Aug 8 , 2005 , 447 previously untreated patients with multiple myeloma , who were aged between 65 and 75 years , were r and omly assigned to receive either melphalan and prednisone ( MP ; n=196 ) , melphalan and prednisone plus thalidomide ( MPT ; n=125 ) , or reduced-intensity stem cell transplantation using melphalan 100 mg/m2 ( MEL100 ; n=126 ) . The primary endpoint was overall survival . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00367185 . FINDINGS After a median follow-up of 51.5 months ( IQR 34.4 - 63.2 ) , median overall survival times were 33.2 months ( 13.8 - 54.8 ) for MP , 51.6 months ( 26.6-not reached ) for MPT , and 38.3 months ( 13.0 - 61.6 ) for MEL100 . The MPT regimen was associated with a significantly better overall survival than was the MP regimen ( hazard ratio 0.59 , 95 % CI 0.46 - 0.81 , p=0.0006 ) or MEL100 regimen ( 0.69 , 0.49 - 0.96 , p=0.027 ) . No difference was seen for MEL100 versus MP ( 0.86 , 0.65 - 1.15 , p=0.32 ) . INTERPRETATION The results of our trial provide strong evidence to indicate that the use of thalidomide in combination with melphalan and prednisone should , at present , be the reference treatment for previously untreated elderly patients with multiple myeloma BACKGROUND Since 1960 , oral melphalan and prednisone ( MP ) has been regarded as the st and ard of care in elderly multiple myeloma patients . This multicentre r and omised trial compared oral MP plus thalidomide ( MPT ) with MP alone in patients aged 60 - 85 years . METHODS Patients with newly diagnosed multiple myeloma were r and omly assigned to receive oral MP for six 4-week cycles plus thalidomide ( n=129 ; 100 mg per day continuously until any sign of relapse or progressive disease ) or MP alone ( n=126 ) . Analysis was intention-to-treat . This study is registered at , number NCT00232934 . RESULTS Patients treated with thalidomide had higher response rates and longer event-free survival ( primary endpoints ) than patients who were not . Combined complete or partial response rates were 76.0 % for MPT and 47.6 % for MP alone ( absolute difference 28.3 % , 95 % CI 16.5 - 39.1 ) , and the near-complete or complete response rates were 27.9 % and 7.2 % , respectively . 2-year event-free survival rates were 54 % for MPT and 27 % for MP ( hazard ratio [ HR ] for MPT 0.51 , 95 % CI 0.35 - 0.75 , p=0.0006 ) . 3-year survival rates were 80 % for MPT and 64 % for MP ( HR for MPT 0.68 , 95 % CI 0.38 - 1.22 , p=0.19 ) . Rates of grade 3 or 4 adverse events were 48 % in MPT patients and 25 % in MP patients ( p=0.0002 ) . Introduction of enoxaparin prophylaxis reduced rate of thromboembolism from 20 % to 3 % ( p=0.005 ) . CONCLUSION Oral MPT is an effective first-line treatment for elderly patients with multiple myeloma . Anticoagulant prophylaxis reduces frequency of thrombosis . Longer follow-up is needed to assess effect on overall survival Health‐related quality of life ( HRQL ) was prospect ively measured during the phase III APEX trial of bortezomib versus dexamethasone in relapsed multiple myeloma patients . The European Organisation for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire – Core ( QLQ‐C30 ) and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group – Neurotoxicity ( NTX ) side‐effects question naires were administered at baseline and every 6 weeks up to 42 weeks . Patients receiving bortezomib ( 1·3 mg/m2 , days 1 , 4 , 8 and 11 for eight 3‐week cycles , then days 1 , 8 , 15 and 22 for three 5‐week cycles ; n = 296 ) demonstrated significantly better mean Global Health Status over the study versus patients receiving dexamethasone ( 40 mg/d , days 1–4 , 9–12 , and 17–20 for four 5‐week cycles , then days 1–4 only for five 4‐week cycles ; n = 302 ) , plus significantly better physical health , role , cognitive , and emotional functioning scores , lower dyspnoea and sleep symptom scores , and better NTX question naire score , using multiple imputation to account for missing data . Results were similar using available‐ data analyses . Sensitivity analyses suggested that improved HRQL with bortezomib is at least partially explained by improved survival . These results show that bortezomib was associated with significantly better multidimensional HRQL compared with dexamethasone , consistent with the better clinical outcomes seen with bortezomib OBJECTIVES To investigate the subjective well-being of patients with newly diagnosed multiple myeloma who were treated in a t and em transplantation programme . METHODS Fifty-one patients participated in the prospect i ve , longitudinal question naire study . The EORTC QLQ-C30 and the EuroQol-5D were administered 2 wk after completion of vincristine , adriamycin and dexamethason/vincristine , adriamycin and methyl prednison ( VAD/VAMP ) chemotherapy , both at hospital discharge after treatment with high-dose melphalan ( HDM ) and 1 month after this hospital discharge , at hospital admission , at the day of hospital discharge for peripheral stem cell transplantation ( PSCT ) and at 6 and 12 months following discharge after PSCT . RESULTS Overall , patients ' functioning improved during treatment and follow-up , with significant decreases shortly following PSCT . Shortly after HDM and PSCT , patients reported a considerable increase in levels of soreness in the mouth ( + 26/+36 points on a scale ranging form 0 to 100 ; P < 0.01 ) , change of taste ( + 23/+21 points ; P < 0.05/NS ) , nausea/vomiting ( + 26/+27 points ; P < 0.01/ < 0.05 ) , appetite loss ( + 40/+43 points ; P < 0.001 ) and diarrhoea ( + 25/+36 points ; P < 0.01 ) . However , none of these symptoms persisted during follow-up . CONCLUSION The intensive treatment programme was subjectively being well tolerated by the majority of patients . The duration of declined quality of life after administration of HDM seemed to be short . The duration of subjective recovery after PSCT remained uncertain , but in any case was present at the 6 month follow-up . Together with the rather good results in survival , the evaluation of quality of life invites further exploration of double transplantations in multiple myeloma OBJECTIVE To study the clinical course of patients with multiple myeloma ( MM ) that relapses after initial therapy . PATIENTS AND METHODS Patients with MM , seen at the Mayo Clinic in Rochester , Minn , between January 1 , 1985 , and December 31 , 1998 , were identified from a prospect ively maintained data base . Our study population consisted of 578 patients with newly diagnosed MM who were followed up and monitored throughout their clinical course at our institution . RESULTS The median age of the 578 patients with MM was 65 years ( range , 26 - 92 years ) ; 228 patients ( 39 % ) were women . The median follow-up of 71 surviving patients was 55 months ( range , 0 - 202 months ) . The overall survival ( OS ) for the 578 patients at 1 , 2 , and 5 years was 72 % , 55 % , and 22 % , respectively ; the median OS from initial therapy was 28.4 months . The median OS of 355 patients who experienced relapse after initial treatment was 17.1 months from initiation of the second therapy , and 84 % died within 5 years . The duration of response decreased consistently with each successive regimen . Patients with a high plasma cell labeling index ( > or = 1.0 % ) , low platelet count ( < 150 x 10(9)/L ) , high creatinine level ( > or = 2.0 mg/dL ) , and low albumin level ( < 3.0 g/dL ) had a poorer prognosis . CONCLUSIONS Our study revealed decreasing response duration with increasing number of salvage regimens , probably reflecting acquired drug resistance and an increasing proliferative rate of the myeloma cells . Patients who experienced relapse after initial treatment and received salvage therapy had a median survival of nearly 1.5 years . This must be remembered when making treatment decisions for these patients and must be factored in when assessing the efficacy of new therapies In a population -based study , the Nordic Myeloma Study Group found a survival advantage for high-dose melphalan with autologous blood stem-cell support compared to conventional chemotherapy in myeloma patients under 60 yr of age ( risk ratio : 1.62 ; confidence interval [ CI ] 1.22–2.15 ; p=0.001 ) . A study of health-related quality of life ( HRQoL ) was integrated in the trial , using the EORTC QLQ-C30 question naire . Of the 274 patients receiving intensive therapy 221 ( 81 % ) were compared to 113 ( 94 % ) of 120 patients receiving conventional melphalan-prednisone treatment . Prior to treatment , there were no statistically significant differences in any HRQoL score between the two groups . One month after the start of induction chemotherapy , the patients on intensive treatment had more sleep disturbance than the control patients . At 6 mo , corresponding to a mean of 52 d after high-dose melphalan , the patients on intensive treatment had moderately lower scores for global QoL and role and social functioning and there was also a significantly higher score for appetite loss . At 12 and 24 mo , the HRQoL was similar to that of the control patients . At 36 mo , there was a trend toward less fatigue , pain , nausea , and appetite loss in the intensive-treatment group . Thus , the 18 mo of prolonged survival seem to be associated with a good health-related quality of life . Despite the moderate HRQoL reduction associated with the early intensive chemotherapy phase , this treatment modality must be regarded as an important step forward in the care of multiple myeloma A prospect i ve r and omised phase III study in patients < or = 65 years old with previously untreated multiple myeloma ( MM ) , intensive chemotherapy followed by myeloablative chemotherapy and autologous stem-cell rescue was compared with intensive chemotherapy alone . This economic evaluation was based on detailed data from patient charts and hospital information systems . In the intention-to-treat analysis , mean total treatment and follow-up costs of the myeloablative treatment arm were 81,643 euros compared to 68,802 euros for the chemotherapy arm ( P=0.09 ) . Costs per quality -adjusted life year were 51,357 euros versus 37,328 euros . In the clinical study , no significant differences were found in overall survival after a median follow-up of 33 months from r and omisation . Intensive chemotherapy is regarded as st and ard therapy for younger patients with previously untreated MM . Cost-effectiveness of myeloma therapy after 3 years of follow up seems not to be favoured by myeloablative treatment with autologous stem-cell rescue High-dose melphalan and autologous hematopoietic stem cell transplantation ( HSCT ) is a st and ard treatment for myeloma , but very little is known about the psychosocial or quality -of-life difficulties that these patients encounter during treatment . Data regarding older patients is particularly scarce . Using a prospect i ve design , this investigation evaluated 94 patients at stem cell collection and again after high-dose therapy and transplantation . Outcomes included quality -of-life ( FACT-BMT ) and psychosocial adjustment ( ie , Brief Symptom Inventory , Impact of Events Scale , and Satisfaction with Life Scale ) . Findings were compared with age- and sex-adjusted population norms and with transplantation patient norms . At stem cell collection , physical deficits were common , with most patients scoring 1 st and ard deviation below population norms for physical well-being ( 70.2 % ) and functional well-being ( 57.5 % ) , and many reporting at least moderate fatigue ( 94.7 % ) and pain ( 39.4 % ) . Clinical ly meaningful levels of anxiety ( 39.4 % ) , depression ( 40.4 % ) , and cancer-related distress ( 37.0 % ) were evident in a notable proportion of patients . After transplantation , there was a worsening of transplant-related concerns ( P < .05 ) , depression ( P < .05 ) , and life-satisfaction ( P < .001 ) ; however , pain improved ( P < .01 ) , and social functioning was well preserved . Overall , the declines in functioning after transplantation were less pronounced than anticipated . Older patients were not more compromised than younger ones ; in multivariate analyses , they reported better overall quality of life ( P < .01 ) and less depression ( P < .05 ) before transplantation . Our findings emphasize the importance of early screening and intervention BACKGROUND Patients with myeloma who relapse after high-dose chemotherapy have few therapeutic options . Since increased bone marrow vascularity imparts a poor prognosis in myeloma , we evaluated the efficacy of thalidomide , which has antiangiogenic properties , in patients with refractory disease . METHODS Eighty-four previously treated patients with refractory myeloma ( 76 with a relapse after high-dose chemotherapy ) received oral thalidomide as a single agent for a median of 80 days ( range , 2 to 465 ) . The starting dose was 200 mg daily , and the dose was increased by 200 mg every two weeks until it reached 800 mg per day . Response was assessed on the basis of a reduction of the myeloma protein in serum or Bence Jones protein in urine that lasted for at least six weeks . RESULTS The serum or urine levels of paraprotein were reduced by at least 90 percent in eight patients ( two had a complete remission ) , at least 75 percent in six patients , at least 50 percent in seven patients , and at least 25 percent in six patients , for a total rate of response of 32 percent . Reductions in the paraprotein levels were apparent within two months in 78 percent of the patients with a response and were associated with decreased numbers of plasma cells in bone marrow and increased hemoglobin levels . The microvascular density of bone marrow did not change significantly in patients with a response . At least one third of the patients had mild or moderate constipation , weakness or fatigue , or somnolence . More severe adverse effects were infrequent ( occurring in less than 10 percent of patients ) , and hematologic effects were rare . As of the most recent follow-up , 36 patients had died ( 30 with no response and 6 with a response ) . After 12 months of follow-up , Kaplan-Meier estimates of the mean ( + /-SE ) rates of event-free survival and overall survival for all patients were 22+/-5 percent and 58+/-5 percent , respectively . CONCLUSIONS Thalidomide is active against advanced myeloma . It can induce marked and durable responses in some patients with multiple myeloma , including those who relapse after high-dose chemotherapy OBJECTIVES To estimate models , via ordinary least squares regression , for predicting Euro Qol 5D ( EQ-5D ) , Short Form 6D ( SF-6D ) , and 15D utilities from scale scores of the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 ) . METHODS Forty-eight gastric cancer patients , split up into equal subgroups by age , sex , and chemotherapy scheme , were interviewed , and the survey included the QLQ-C30 , SF-36 , EQ-5D , and 15D instruments , along with sociodemographic and clinical data . Model predictive ability and explanatory power were assessed by root mean square error ( RMSE ) and adjusted R(2 ) values , respectively . Pearson 's r between predicted and reported utility indices was compared . Three r and om sub sample s , half in size the initial sample , were created and used for " external " validation of the modeling equations . RESULTS Explanatory power was high , with adjusted R(2 ) reaching 0.909 , 0.833 , and 0.611 for 15D , SF-6D , and EQ-5D , respectively . After normalization of RMSE to the range of possible values , the prediction errors were 12.0 , 5.4 , and 5.6 % for EQ-5D , SF-6D , and 15D , respectively . The estimation equations produced a range of utility scores similar to those achievable by the st and ard scoring algorithms . Predicted and reported indices from the validation sample s were comparable thus confirming the previous results . CONCLUSIONS Evidence on the ability of QLQ-C30 scale scores to validly predict 15D and SF-6D utilities , and to a lesser extent , EQ-5D , has been provided . The modeling equations must be tried in future studies with larger and more diverse sample s to confirm their appropriateness for estimating quality -adjusted life-year in cancer-patient trials including only the QLQ-C30 The initial analysis of the oral combination melphalan , prednisone , and thalidomide ( MPT ) in newly diagnosed patients with myeloma showed significantly higher response rate and longer progression-free survival ( PFS ) than did the st and ard melphalan and prednisone ( MP ) combination and suggested a survival advantage . In this up date d analysis , efficacy and safety end points were up date d. Patients were r and omly assigned to receive oral MPT or MP alone . Up date d analysis was by intention to treat and included PFS , overall survival ( OS ) , and survival after progression . After a median follow-up of 38.1 months , the median PFS was 21.8 months for MPT and 14.5 months for MP ( P = .004 ) . The median OS was 45.0 months for MPT and 47.6 months for MP ( P = .79 ) . In different patient subgroups , MPT improved PFS irrespective of age , serum concentrations of beta(2)-microglobulin , or high International Staging System . Thalidomide or bortezomib administration as salvage regimens significantly improved survival after progression in the MP group ( P = .002 ) but not in the MPT group ( P = .34 ) . These data confirm activity of MPT for PFS but failed to show any survival advantage . New agents in the management of relapsed disease could explain this finding . The study is registered at www . clinical trials.gov as # NCT00232934 PURPOSE Until recently , melphalan and prednisone were the st and ards of care in elderly patients with multiple myeloma . The addition of thalidomide to this combination demonstrated a survival benefit for patients age 65 to 75 years . This r and omized , placebo-controlled , phase III trial investigated the efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed myeloma . PATIENTS AND METHODS Between April 2002 and December 2006 , 232 previously untreated patients with myeloma , age 75 years or older , were enrolled and 229 were r and omly assigned to treatment . All patients received melphalan ( 0.2 mg/kg/d ) plus prednisone ( 2 mg/kg/d ) for 12 courses ( day 1 to 4 ) every 6 weeks . Patients were r and omly assigned to receive 100 mg/d of oral thalidomide ( n = 113 ) or placebo ( n = 116 ) , continuously for 72 weeks . The primary end point was overall survival . RESULTS After a median follow-up of 47.5 months , overall survival was significantly longer in patients who received melphalan and prednisone plus thalidomide compared with those who received melphalan and prednisone plus placebo ( median , 44.0 v 29.1 months ; P = .028 ) . Progression-free survival was significantly prolonged in the melphalan and prednisone plus thalidomide group ( median , 24.1 v 18.5 months ; P = .001 ) . Two adverse events were significantly increased in the melphalan and prednisone plus thalidomide group : grade 2 to 4 peripheral neuropathy ( 20 % v 5 % in the melphalan and prednisone plus placebo group ; P < .001 ) and grade 3 to 4 neutropenia ( 23 % v 9 % ; P = .003 ) . CONCLUSION This trial confirms the superiority of the combination melphalan and prednisone plus thalidomide over melphalan and prednisone alone for prolonging survival in very elderly patients with newly diagnosed myeloma . Toxicity was acceptable |
13,261 | 19,821,380 | Ziprasidone may be a slightly less efficacious antipsychotic drug than amisulpride , olanzapine and risperidone .
Its main advantage is the low propensity to induce weight gain and associated adverse effects . | BACKGROUND In many countries of the industrialised world second generation ( ' atypical ' ) antipsychotics have become the first line drug treatment for people with schizophrenia .
The question as to whether , and if so how much , the effects of the various new generation antipsychotics differ is a matter of debate .
In this review we examined how the efficacy and tolerability of ziprasidone differs from that of other second generation antipsychotics .
OBJECTIVES To evaluate the effects of ziprasidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses . | BACKGROUND C-reactive protein ( CRP ) , intercellular adhesion molecule-1 ( ICAM-1 ) , vascular cell adhesion molecule-1 ( VCAM-1 ) , and E-selectin are systemic inflammatory markers ( IM ) that positively correlate with cardiovascular ( CV ) risk . Despite the known CV effects of atypical antipsychotics , there is limited prospect i ve data on IM changes during treatment . METHODS The IM outcomes were compared between antipsychotic treatment groups in the CATIE ( Clinical Antipsychotic Trials of Intervention Effectiveness ) schizophrenia trial phase 1 with subjects with laboratory assessment s at baseline and 3 months ( n = 789 ) . RESULTS There were significant treatment differences in CRP , E-selectin , and ICAM-1 at 3 months , with a differential impact of baseline values on the CRP and ICAM-1 results . In overall comparisons , quetiapine and olanzapine had the highest median levels for CRP , and olanzapine for E-selectin and ICAM-1 . Olanzapine was significantly different after baseline adjustment than perphenazine ( p = .001 ) for E-selectin , and in those with low baseline CRP ( < 1 mg/L ) , olanzapine was significantly different than perphenazine ( p < .001 ) , risperidone ( p < .001 ) , and ziprasidone ( p = .002 ) for CRP . Perphenazine had the lowest 3-month ICAM-1 levels in subjects with baseline ICAM-1 above the median , but the differences were not statistically significant versus olanzapine ( p = .010 ) , quetiapine ( p = .010 ) , and risperidone ( p = .006 ) after controlling for multiple comparisons . The 18-month repeated measures CRP analysis confirmed the significantly higher values for olanzapine in those with low baseline CRP . CONCLUSIONS This analysis provides further evidence for differential antipsychotic metabolic liabilities as measured by changes in systemic inflammation . C-reactive protein might emerge as a useful target for CV risk outcomes in schizophrenia patients Few pharmacological intervention studies have examined the impact of medication on social cognition , particularly emotion perception . The goal of this r and omized , double-blind study is to compare the effects of several second generation antipsychotics and a first generation antipsychotic , perphenazine , on emotion perception in individuals with schizophrenia . Patients were assigned to receive treatment with olanzapine , queitapine fumarate , risperidone , ziprasidone or perphenazine for up to 18 months . Eight hundred and seventy three patients completed an emotion perception test immediately prior to r and omization and after 2 months of treatment . We also examined baseline predictors of emotion perception change . Most treatments were associated with a small , non-statistically significant improvement in emotion perception at two months , although they did not differ from one another . Greater improvement in emotion perception at 2 months was significantly predicted by lower baseline emotion perception and higher baseline neurocognitive functioning , and marginally predicted by less time on an antipsychotic BACKGROUND One of the major challenges in the design of double-blind flexible-dosing clinical trials comparing active drugs is the selection of dosing regimens that are equivalent across drugs . This study uses data from the CATIE schizophrenia trial to evaluate the hypothesis that drugs that were dosed somewhat higher in the trial than in typical practice would show greater efficacy and more side effects , especially at high capsule levels , than drugs that were dosed at lower relative strengths . METHODS CATIE was a large ( N=1460 ) r and omized trial comparing 5 antipsychotics in patients with chronic schizophrenia . The blind was maintained in CATIE by prescribing identical-looking capsules of each medication . Dosing was flexible , such that PIs could prescribe from one to four capsules per day , and could modify the dose based on a patient 's symptoms and side effects . Capsule strengths for olanzapine ( 7.5 mg ) and quetiapine ( 200 mg ) were relatively higher than for risperidone ( 1.5 mg ) , perphenazine ( 8 mg ) or ziprasidone ( 40 mg ) . Proportional hazards models of time to all cause discontinuation and mixed regression models for continuous measures of symptoms , quality of life and side effects were used to test for interactions between r and omly assigned drug and number of capsules prescribed per visit . We hypothesized that if a dosing bias was present , the flex-dosing design would result in a significant interaction such that drugs with higher relative dosing per capsule would be more effective and have more side effects than drugs with lower relative dosing and that this effect would be greatest at the largest prescribed dosing regimen ( 4 capsules ) . RESULTS There were no significant interactions between drug assignment and number of capsules in the proportional hazards analyses of time to all cause discontinuation ( p=.77 , excluding ziprasidone and .74 in the ziprasidone cohort ) or in the mixed model analysis of PANSS symptoms ( p=.49 ) , quality of life ( p=.45 ) ; or measures of tardive dyskinesia ( AIMS , p=.47 ) . However a significant interaction was observed on the Barnes akathisia scale ( p=.0005 ) , on the Simpson Angus EPS scale ( p=.10 ) and on the analysis of weight ( p=0.014 ) . Paired comparisons did not show the hypothesized pattern of relationships for akathisia or EPS , but such a pattern was suggested for olanzapine in the analysis of weight although it emerged at 2 , 3 and 4 capsules indicating a general drug effect rather than a relative dosing difference . CONCLUSION Dosing biases do not seem to have affected the results of the CATIE trial We compared the efficacy and safety of ziprasidone and aripiprazole in the treatment of acutely ill patients with schizophrenia . Patients were r and omized to receive double-blind treatment with ziprasidone ( 80–160 mg/day ) , or aripiprazole ( 10–30 mg/day ) for up to 4 weeks . Primary efficacy measures were the Clinical Global Impression of Severity scale ( CGI-S ) and Brief Psychiatric Rating Scale ( BPRSd ) total ( derived from the Positive and Negative Syndrome Scale ) . Noninferiority for ziprasidone ( N=125 ) relative to aripiprazole ( N=128 ) was established for CGI-S score ( P=0.007 ) , but was not confirmed for BPRSd total score ( P=0.248 ) . Effect sizes for within-group improvement , however , were robust for both ziprasidone and aripiprazole ( effect size range 1.0–1.1 for CGI-S ; and range 1.1–1.2 for BPRSd total ) . A mixed model repeated measures analysis of BPRSd total score favored ziprasidone at day 4 compared with aripiprazole ( P=0.04 ) , with no significant differences between treatment groups at other visits ( P=0.001 for interaction between treatment and visit ) . No statistically significant difference was found in CGI-S score between groups across all visits . Our findings suggest that ziprasidone and aripiprazole exhibit similar efficacy and tolerability profiles in the treatment of acute schizophrenia . Differences between the two drugs in the onset of therapeutic effect warrant further investigation This 18-week , r and omized , flexible-dose , double-blind , double-dummy trial evaluated ziprasidone as an alternative to clozapine in treatment-refractory schizophrenia patients . Patients had a DSM-IV diagnosis of schizophrenia , a history of resistance and /or intolerance to at least three acute cycles with different antipsychotics given at therapeutic doses , PANSS score > or=80 , and CGI-S score > or=4 . Patients were r and omized to ziprasidone ( 80 - 160 mg/day , n=73 ) or clozapine ( 250 - 600 mg/day , n=74 ) . On the primary ITT-LOCF analysis , baseline-to-endpoint decreases in PANSS total scores were similar in the ziprasidone ( -25.0+/-22.0 , 95 % CI -30.2 to -19.8 ) and clozapine ( -24.5+/-22.5 , 95 % CI -29.7 to -19.2 ) groups . A progressive and significant reduction from baseline in PANSS total score was observed from day 11 in both study arms . There were also significant improvements on PANSS subscales , CGI-S , CG-I , CDSS , and GAF , without between-drug differences . The two treatment groups had similar rates of early discontinuations due to AEs . AEs were mostly of similar mild-moderate severity in the two groups . There were also no detrimental effects on prolactin , renal and liver function , hematology , and cardiovascular parameters . However , ziprasidone but not clozapine showed a significant reduction of SAS and AIMS scores . Moreover , when compared with clozapine , ziprasidone also had a more favorable metabolic profile , with significant endpoint differences in weight , fasting glucose , total cholesterol , LDL cholesterol , and triglycerides . In conclusion , this trial indicates that both ziprasidone and clozapine , having comparable efficacy coupled with satisfactory general safety and tolerability , may be regarded as valuable options for the short-term treatment of difficult-to-treat schizophrenia patients with a history of multiple resistance and /or intolerance to antipsychotics . The more favorable metabolic profile of ziprasidone may represent an added value that could guide clinicians , at least in the presence of patients at high risk for metabolic disorders PURPOSE Previous analysis of data from CATIE showed that patients r and omly assigned to switch to a new medication were more likely to discontinue study drug than those who stayed on the medication they had been taking prior to r and omization . This study addresses additional outcomes measures evaluating symptoms , neurocognition , quality of life , neurological side effects , weight , and health costs . First , considering patients r and omized to olanzapine or risperidone , outcomes among patients who had been on the drug to which they were r and omized prior to CATIE ( N=129 " stayers " ) were compared to outcomes of those who switched to either of these two drugs ( N=269 " switchers " ) . A second set of analyses considered patients on baseline monotherapy with olanzapine ( N=297 ) ; risperidone ( N=252 ) or quetiapine ( n=87 ) and compared those r and omly assigned to stay on each of these medications with those assigned to switch to any of the other five phase 1 medications in CATIE . In mixed models of each outcome the independent variable of primary interest represented stay vs. switch , with multivariate adjustment for potential confounding factors . RESULTS With one exception , there were no significant differences between stayers and switchers on any outcome measure in either set of analyses . The exception was that , in the second set of analyses , patients who stayed on olanzapine showed greater weight gain than those who switched from olanzapine to other drugs . CONCLUSION Switching to a new medication yielded no advantage over staying on the previous medication . Staying on olanzapine was associated with greater weight gain OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate BACKGROUND Violence is an uncommon but significant problem associated with schizophrenia . AIMS To compare antipsychotic medications in reducing violence among patients with schizophrenia over 6 months , identify prospect i ve predictors of violence and examine the impact of medication adherence on reduced violence . METHOD Participants ( n=1445 ) were r and omly assigned to double-blinded treatment with one of five antipsychotic medications . Analyses are presented for the intention-to-treat sample and for patients completing 6 months on assigned medication . RESULTS Violence declined from 16 % to 9 % in the retained sample and from 19 % to 14 % in the intention-to-treat sample . No difference by medication group was found , except that perphenazine showed greater violence reduction than quetiapine in the retained sample . Medication adherence reduced violence , but not in patients with a history of childhood antisocial conduct . Prospect i ve predictors of violence included childhood conduct problems , substance use , victimisation , economic deprivation and living situation . Negative psychotic symptoms predicted lower violence . CONCLUSIONS Newer antipsychotics did not reduce violence more than perphenazine . Effective antipsychotics are needed , but may not reduce violence unrelated to acute psychopathology INTRODUCTION Treatment resistance in schizophrenia often leads to add-on of atypical antipsychotics to clozapine . METHODS In a r and omized trial , we recently obtained evidence for comparable efficacy and differential side effects of clozapine in combination with ziprasidone ( CZ , N=12 ) versus risperidone ( CR , N=12 ) . Here , we present the open-label , long-term evaluations of these patients after 26 and 52 weeks . RESULTS Sustained improvements of psychopathology as assessed by PANSS ( positive and negative syndrome scale ) , SANS ( scale for the assessment of negative symptoms ) , and HAMD ( Hamilton depression scale ) were documented in both sub sample s being treated according to protocol , while dropouts reduced the study sample after 26 ( CZ : reduced by -4 ; CR : -2 ) and 52 weeks ( CZ : -0 ; CR : -5 ) . We observed a slight increase of akathisia in the CZ group whereas general clozapine-associated side effects improved . DISCUSSION The combinations of clozapine with ziprasidone or risperidone exhibit long-term efficacy , but the level of evidence is limited . Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary CONTEXT Second-generation ( atypical ) antipsychotics ( SGAs ) are more expensive than first-generation ( typical ) antipsychotics ( FGAs ) but are perceived to be more effective , with fewer adverse effects , and preferable to patients . Most evidence comes from short-term efficacy trials of symptoms . OBJECTIVE To test the hypothesis that in people with schizophrenia requiring a change in treatment , SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs . DESIGN A noncommercially funded , pragmatic , multisite , r and omized controlled trial of antipsychotic drug classes , with blind assessment s at 12 , 26 , and 56 weeks using intention-to-treat analysis . SETTING Fourteen community psychiatric services in the English National Health Service . PARTICIPANTS Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects . INTERVENTIONS R and omized prescription of either FGAs or SGAs ( other than clozapine ) , with the choice of individual drug made by the managing psychiatrist . MAIN OUTCOME MEASURES Quality of Life Scale scores , symptoms , adverse effects , participant satisfaction , and costs of care . RESULTS The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded . Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores . Participants reported no clear preference for either drug group ; costs were similar . CONCLUSIONS In people with schizophrenia whose medication is changed for clinical reasons , there is no disadvantage across 1 year in terms of quality of life , symptoms , or associated costs of care in using FGAs rather than nonclozapine SGAs . Neither inadequate power nor patterns of drug discontinuation accounted for the result OBJECTIVE This double-blind study compared a second generation ( atypical ) antipsychotic drugs compared to a representative older agent for patients with schizophrenia who use or avoid illicit substances . METHODS Schizophrenic subjects were recruited at 57 U.S. sites and r and omly assigned to olanzapine , perphenazine , quetiapine , risperidone or ziprasidone for up to 18 months . The primary aim of this analysis was to delineate differences between the overall effectiveness of these five treatments among patients who used or did not use illicit substances . RESULTS There were no significant differences between treatment groups in time to all-cause treatment discontinuation among patients who use illicit drugs ( median 3.3 to 6.8 months ) . Among non-users time to treatment discontinuation was significantly longer for patients treated with olanzapine ( median 13.0 months ) than perphenazine ( 5.9 months ) , risperidone ( 5.6 months ) , or quetiapine ( 5.0 months ) ; time to discontinuation for ziprasidone ( 4.3 months ) was even shorter , although the latter difference was not significant . The difference between risperidone and quetiapine , although small , was significant . All remaining differences were non-significant . Similar results were found for discontinuation due to inefficacy . There were no differences between illicit users and non-users in symptom reduction and global improvement , after adjustment for differential duration of treatment . Differences in discontinuation results were attenuated by non-compliance , but the trends persisted after controlling for treatment compliance . CONCLUSIONS Among patients with chronic schizophrenia who avoid use of illicit drugs , olanzapine was more effective than other antipsychotics as reflected by longer time to all-cause discontinuation , but illicit substance abuse attenuated this advantage , reinforcing the need for concurrent substance abuse treatment Background No clear recommendations exist regarding which antipsychotic drug should be prescribed first for a patient suffering from psychosis . The primary aims of this naturalistic study were to assess the head-to-head effectiveness of first-line second-generation antipsychotics with regards to time until drug discontinuation , duration of index admission , time until readmission , change of psychopathology scores and tolerability outcomes . Methods Patients ≥ 18 years of age admitted to the emergency ward for symptoms of psychosis were consecutively r and omized to risperidone ( n = 53 ) , olanzapine ( n = 52 ) , quetiapine ( n = 50 ) , or ziprasidone ( n = 58 ) , and followed for up to 2 years . Results A total of 213 patients were included , of which 68 % were males . The sample represented a diverse population suffering from psychosis . At admittance the mean Positive and Negative Syndrome Scale ( PANSS ) total score was 74 points and 44 % were antipsychotic drug naïve . The primary intention-to-treat analyses revealed no substantial differences between the drugs regarding the times until discontinuation of initial drug , until discharge from index admission , or until readmission . Quetiapine was superior to risperidone and olanzapine in reducing the PANSS total score and the positive subscore . Quetiapine was superior to the other drugs in decreasing the PANSS general psychopathology subscore ; in decreasing the Clinical Global Impression - Severity of Illness scale score ( CGI-S ) ; and in increasing the Global Assessment of Functioning - Split version , Functions scale score ( GAF-F ) . Ziprasidone was superior to risperidone in decreasing the PANSS positive symptoms subscore and the CGI-S score , and in increasing the GAF-F score . The drugs performed equally with regards to most tolerability outcomes except a higher increase of hip-circumference per day for olanzapine compared to risperidone , and more galactorrhoea for risperidone compared to the other groups . Conclusions Quetiapine appears to be a good starting drug c and i date in this sample of patients admitted to hospital for symptoms of psychosis . Trial Registration Clinical Trials.gov ID ; URL : http://www . clinical trials.gov/ : The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas OBJECTIVE The authors ' goal was to compare the efficacy and tolerability of 6 months ' treatment with flexible-dose ziprasidone and olanzapine in patients with schizophrenia or schizoaffective disorder . METHOD Brief Psychiatric Rating Scale ( BPRS ) scores and Clinical Global Impression ( CGI ) severity scores were obtained for 126 responders to a 6-week acute study of olanzapine and ziprasidone during a blinded 6-month continuation study and optional extension study . RESULTS Comparable improvements in BPRS and CGI severity scores were seen with both drugs . Olanzapine produced significant increases from acute- study baseline values in weight and body mass index and within-group increases in total cholesterol , low-density lipoprotein cholesterol , and fasting insulin . Between-group differences were not significant for lipids and insulin . Mean QTc values at endpoint were 407.1 msec ( baseline mean=406.0 msec ) and 394.4 msec ( baseline mean=399.7 msec ) for ziprasidone and olanzapine , respectively . No patient had a QTc interval > or = 500 msec . CONCLUSIONS Ziprasidone and olanzapine had comparable long-term efficacy ; olanzapine was associated with significant weight gain and metabolic alterations BACKGROUND This study evaluated the effectiveness of first- and second-generation antipsychotics in reducing family burden associated with schizophrenia . METHODS The family caregivers of 623 SCID-diagnosed patients enrolled in the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) r and omly assigned to a first-generation antipsychotic ( perphenazine ) or one of four second-generation drugs ( olanzapine , quetiapine , risperidone or ziprasidone ) were interviewed about re sources provided and stresses experienced at baseline and followed for 18 months . Patient symptoms , side effects and service use were assessed as well . Hierarchical regression analyses evaluated the effect of treatment assignment on four burden factors : problem behavior , re source dem and s and disruption , impairment in activities of daily living and patient helpfulness . Intention-to-treat analyses with all available observations classified based on initial treatment assignment , including observations after medications changed were followed by secondary analyses excluding observations after the first medication change , i.e. only considering initial medication . RESULTS Despite significant reductions on the problem behavior and re source dem and s/disruption factors , there were no significant differences between perphenazine and any of the second-generation medications . When only initial treatment period observations were included , patients were perceived as more helpful when medicated with perphenazine as compared to risperidone . In comparisons between second-generation drugs , patients on quetiapine were perceived as more helpful than those on risperidone ( p=0.004 ) . CONCLUSION In this 18-month r and omized trial , there was no evidence of superiority of second-generation antipsychotics in relieving family burden Tardive dyskinesia ( TD ) is a movement disorder characterized by involuntary oro‐facial , limb , and truncal movements . As a genetic basis for inter‐individual variation is assumed , there have been a sizeable number of c and i date gene studies . All subjects met diagnostic criteria for schizophrenia and were r and omized to receive antipsychotic medications as participants in the Clinical Antipsychotic Trials of Intervention Effectiveness project ( CATIE ) . TD was assessed via the Abnormal Involuntary Movement Scale at regular intervals . Probable TD was defined as meeting Schooler – Kane criteria at any scheduled CATIE visit ( 207/710 subjects , 29.2 % ) . A total of 128 c and i date genes were studied in 710 subjects—2,580 SNPs in 118 c and i date genes selected from the literature ( e.g. , dopamine , serotonin , glutamate , and GABA pathways ) and composite genotypes for 10 drug‐metabolizing enzymes . No single marker or haplotype association reached statistical significance after adjustment for multiple comparisons . Thus , we found no support for either novel or prior associations from the literature . © 2009 Wiley‐Liss , BACKGROUND Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia ; however , their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated . We aim ed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol , in first-episode schizophrenia . METHODS We did an open r and omised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites , in 14 countries . Eligible patients were aged 18 - 40 years , and met diagnostic criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder . 498 patients were r and omly assigned by a web-based online system to haloperidol ( 1 - 4 mg per day ; n=103 ) , amisulpride ( 200 - 800 mg per day ; n=104 ) , olanzapine ( 5 - 20 mg per day ; n=105 ) , quetiapine ( 200 - 750 mg per day ; n=104 ) , or ziprasidone ( 40 - 160 mg per day ; n=82 ) ; follow-up was at 1 year . The primary outcome measure was all-cause treatment discontinuation . Patients and their treating physicians were not blinded to the assigned treatment . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N68736636 . FINDINGS The number of patients who discontinued treatment for any cause within 12 months was 63 ( Kaplan-Meier estimate 72 % ) for haloperidol , 32 ( 40 % ) for amisulpride , 30 ( 33 % ) for olanzapine , 51 ( 53 % ) for quetiapine , and 31 ( 45 % ) for ziprasidone . Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride ( hazard ratio [ HR ] 0.37 , [ 95 % CI 0.24 - 0.57 ] ) , olanzapine ( HR 0.28 [ 0.18 - 0.43 ] ) , quetiapine ( HR 0.52 [ 0.35 - 0.76 ] ) , and ziprasidone ( HR 0.51 [ 0.32 - 0.81 ] ) . However , symptom reductions were virtually the same in all the groups , at around 60 % . INTERPRETATION This pragmatic trial suggests that clinical ly meaningful antipsychotic treatment of first-episode of schizophrenia is achievable , for at least 1 year . However , we can not conclude that second-generation drugs are more efficacious than is haloperidol , since discontinuation rates are not necessarily consistent with symptomatic improvement INTRODUCTION Head-to-head comparisons of antipsychotics have predominantly included patients with chronic conditions . The aim of the present study was to compare the efficacy and tolerability of ziprasidone and olanzapine in patients with recent-onset schizophrenia . METHODS The study was an 8-week , double-blind , parallel-group , r and omized , controlled multicenter trial ( NCT00145444 ) . Seventy-six patients with schizophreniform disorder , schizophrenia or schizoaffective disorder ( diagnosis < 5 y ) , and a maximum lifetime antipsychotic treatment < 16 weeks participated in the study . Efficacy of ziprasidone ( 80 - 160 mg/d ) and olanzapine 10 - 20 mg was measured using the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impression ( CGI ) Scale , the Calgary Depression Scale for Schizophrenia ( CDSS ) , and the Heinrich Quality of Life Scale ( HQLS ) ; tolerability assessment s included laboratory assessment s , body weight , and electroencephalogram . RESULTS Olanzapine ( n = 34 ) and ziprasidone ( n = 39 ) showed equal efficacy as measured by the PANSS , CDSS , CGI , and HQLS . However , mean weight gain was significantly higher in the olanzapine group ( 6.8 vs 0.1 kg , P < .001 ) . Ziprasidone was associated with decreasing levels of triglycerides , cholesterol , and transaminases , while these parameters increased in the olanzapine group ( all P values < .05 ) . There were no significant differences in fasting glucose and prolactin levels or in cardiac or sexual side effects . Patients on ziprasidone used biperiden for extrapyramidal side effects more frequently ( P < .05 ) . DISCUSSION The results of this study indicate that ziprasidone and olanzapine have comparable therapeutic efficacy but differ in their side effect profile . However , there is a risk of a type II error with this sample size . Clinical ly significant weight gain and laboratory abnormalities appear early after initiating treatment and are more prominent with olanzapine , while more patients on ziprasidone received anticholinergic drugs to treat extrapyramidal symptoms Background There is an ongoing debate over whether atypical antipsychotics are more effective than typical antipsychotics in the treatment of schizophrenia . This naturalistic study compares atypical and typical antipsychotics on time to all-cause medication discontinuation , a recognized index of medication effectiveness in the treatment of schizophrenia . Methods We used data from a large , 3-year , observational , non-r and omized , multisite study of schizophrenia , conducted in the U.S. between 7/1997 and 9/2003 . Patients who were initiated on oral atypical antipsychotics ( clozapine , olanzapine , risperidone , quetiapine , or ziprasidone ) or oral typical antipsychotics ( low , medium , or high potency ) were compared on time to all-cause medication discontinuation for 1 year following initiation . Treatment group comparisons were based on treatment episodes using 3 statistical approaches ( Kaplan-Meier survival analysis , Cox Proportional Hazards regression model , and propensity score-adjusted bootstrap resampling methods ) . To further assess the robustness of the findings , sensitivity analyses were performed , including the use of ( a ) only 1 medication episode for each patient , the one with which the patient was treated first , and ( b ) all medication episodes , including those simultaneously initiated on more than 1 antipsychotic . Results Mean time to all-cause medication discontinuation was longer on atypical ( N = 1132 , 256.3 days ) compared to typical antipsychotics ( N = 534 , 197.2 days ; p < .01 ) , and longer on atypicals compared to typicals of high potency ( N = 320 , 187.5 days ; p < .01 ) , medium potency ( N = 140 , 213.5 days ; p < .01 ) , and low potency ( N = 74 , 208.7 days ; p < .01 ) . Among the atypicals , only clozapine , olanzapine , and risperidone had significantly longer time to all-cause medication discontinuation compared to typicals , regardless of potency level , and compared to haloperidol with prophylactic anticholinergic treatment . When compared to perphenazine , a medium-potency typical antipsychotic , only clozapine and olanzapine had a consistently and significantly longer time to all-cause medication discontinuation . Results were confirmed by sensitivity analyses . Conclusion In the usual care of schizophrenia patients , time to medication discontinuation for any cause appears significantly longer for atypical than typical antipsychotics regardless of the typical antipsychotic potency level . Findings were primarily driven by clozapine and olanzapine , and to a lesser extent by risperidone . Furthermore , only clozapine and olanzapine therapy showed consistently and significantly longer treatment duration compared to perphenazine , a medium-potency typical antipsychotic We compared the efficacy of ziprasidone and amisulpride in the treatment of negative symptoms and overall psychopathology in subjects who had chronic schizophrenia with predominantly negative symptoms . This multicentre , 12-week , double-blind study r and omly assigned subjects with predominantly negative-symptom schizophrenia [ i.e. Positive and Negative Syndrome Scale ( PANSS ) Negative Subscale score ≥6 points greater than Positive Subscale score ] to ziprasidone ( 40–80 mg b.i.d . ; n=60 ) or amisulpride ( 50–100 mg b.i.d . ; n=63 ) . The primary efficacy variable was the change from baseline in PANSS Negative Subscale score . Secondary efficacy variables included change in scores for PANSS Total , Global Assessment of Functioning , Brief Psychiatric Rating Scale derived from PANSS Total and Core , Clinical Global Impression (CGI)–Severity and CGI – Improvement . For the change in PANSS Negative Subscale score , a ratio to assess the equivalence of the treatment groups was calculated from the least squares mean changes from baseline , with equivalence cl aim ed if the lower limit of the 95 % confidence interval of the ratio exceeded 0.60 . Mean daily dose , adjusted for differential numbers of subjects and differential days between visits , was 118.0 mg for ziprasidone and 144.7 mg for amisulpride . Mean PANSS Negative Subscale scores improved over the 12-week treatment period for intent-to-treat subjects , evaluable subjects ( subjects with ≥4 weeks of double-blind treatment and no protocol deviations ) and completers in both treatment groups . Ziprasidone demonstrated efficacy comparable to amulsipride in improving negative symptoms and global psychopathology . The groups demonstrated comparable improvements in secondary efficacy variables . Both agents were generally well tolerated , with comparably low incidences of movement disorders . In subjects with negative symptom – prominent schizophrenia , ziprasidone in mean daily doses of 118 mg was equivalent to amisulpride in mean daily doses of 148 mg in ameliorating negative symptoms and comparable in improving overall psychopathology and global illness severity CONTEXT Neurocognitive impairment in schizophrenia is severe and is an important predictor of functional outcome . The relative effect of the second-generation ( atypical ) antipsychotic drugs and older agents on neurocognition has not been comprehensively determined . OBJECTIVE To compare the neurocognitive effects of several second-generation antipsychotics and a first-generation antipsychotic , perphenazine . DESIGN R and omized , double-blind study of patients with schizophrenia assigned to receive treatment with olanzapine , perphenazine , quetiapine fumarate , or risperidone for up to 18 months as reported previously by Lieberman et al. Ziprasidone hydrochloride was included after its approval by the Food and Drug Administration . SETTING Fifty-seven sites participated , including academic sites and treatment mental health facilities representative of the community . PATIENTS From a cohort of 1460 patients in the treatment study , 817 completed neurocognitive testing immediately prior to r and omization and then after 2 months of treatment . MAIN OUTCOME MEASURES The primary outcome was change in a neurocognitive composite score after 2 months of treatment . Secondary outcomes included neurocognitive composite score change at 6 months and 18 months after continued treatment and changes in neurocognitive domains . RESULTS At 2 months , treatment result ed in small neurocognitive improvements of z = 0.13 for olanzapine ( P<.002 ) , 0.25 for perphenazine ( P<.001 ) , 0.18 for quetiapine ( P<.001 ) , 0.26 for risperidone ( P<.001 ) , and 0.12 for ziprasidone ( P<.06 ) , with no significant differences between groups . Results at 6 months were similar . After 18 months of treatment , neurocognitive improvement was greater in the perphenazine group than in the olanzapine and risperidone groups . Neurocognitive improvement predicted longer time to treatment discontinuation , independently from symptom improvement , in patients treated with quetiapine or ziprasidone . CONCLUSIONS After 2 months of antipsychotic treatment , all groups had a small but significant improvement in neurocognition . There were no differences between any pair of agents , including the typical drug perphenazine . These results differ from the majority of previous studies , and the possible reasons are discussed To measure the long-term changes in weight and plasma lipids after switching antipsychotic treatment to ziprasidone , three 52-week , open-label extension studies of ziprasidone in out patients ( N=185 ) with schizophrenia or schizoaffective disorder successfully completing one of three , 6-week switch studies were carried out . Pre-switch treatment consisted of risperidone ( n=43 ) , olanzapine ( n=71 ) , or conventional antipsychotic agents ( n=71 ) . The maximum length of exposure to ziprasidone was 58 weeks . Nonfasting total cholesterol and triglyceride levels were obtained at baseline and at weeks 6 , 19 , 32 , 45 , and 58 . Weight was measured at baseline and during each follow-up visit ; height was recorded at baseline for the purpose of body mass index ( BMI ) calculation . Efficacy measures included the Positive and Negative Syndrome Scale and Clinical Global Impression — Severity scale which were obtained at baseline and major follow-up points . Clinical ly significant sustained improvements in weight , BMI , total cholesterol , and triglyceride levels were observed among patients switched to ziprasidone from risperidone or olanzapine . Switching from conventional antipsychotics was not associated with significant changes in weight and lipid parameters . Mean reductions in weight from baseline to study endpoint were 9.8 kg ( p<0.001 ) and 6.9 kg ( p<0.005 ) for patients previously treated with olanzapine and risperidone , respectively . These findings demonstrate that switching from risperidone or olanzapine to ziprasidone is associated with sustained , clinical ly significant improvements in weight and plasma lipids OBJECTIVE Uncertainty regarding the degree to which persons with schizophrenia may lack decision-making capacity , and what the predictors of capacity may be led us to examine the relationship between psychopathology , neurocognitive functioning , and decision-making capacity in a large sample of persons with schizophrenia at entry into a clinical trial . METHOD In the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) schizophrenia trial , a clinical trial sponsored by the National Institute of Mental Health design ed to compare the effectiveness of antipsychotic drugs , subjects were administered the MacArthur Competence Assessment Tool- Clinical Research ( MacCAT-CR ) and had to demonstrate adequate decision-making capacity before r and omization . The MacCAT-CR , the Positive and Negative Syndrome Scale ( PANSS ) , and an extensive neurocognitive battery were completed for 1447 study participants . RESULTS The neurocognitive composite score and all 5 neurocognitive subscores ( verbal memory , vigilance , processing speed , reasoning , and working memory ) were positive correlates of the MacCAT-CR underst and ing , appreciation , and reasoning scales at baseline . Higher levels of negative symptoms , but not positive symptoms , were inversely correlated with these three MacCAT-CR scales . Linear regression models of all three MacCAT-CR scales identified working memory as a predictor ; negative symptoms made a small contribution to the underst and ing and appreciation scores . CONCLUSIONS Negative symptoms and aspects of neurocognitive functioning were correlated with decision-making capacity in this large sample of moderately ill subjects with schizophrenia . In multiple regression models predicting performance on the MacCAT-CR scales , working memory was the only consistent predictor of the components of decision-making capacity . Individuals with schizophrenia who have prominent cognitive dysfunction , especially memory impairment , may warrant particular attention when participating in research BACKGROUND Recent data have suggested few differences in the cognitive effects of antipsychotic medications . However , assessment of such effects can be complex , due to a number of factors . Clozapine has previously shown greater clinical and lesser cognitive benefits than other atypicals . This study compared the cognitive benefits of clozapine and ziprasidone in schizophrenia patients ( n=130 ) with a history of either failure to respond to or intolerance of previous adequate antipsychotic treatments . METHODS Patients were r and omized ( double-blind ) to either clozapine or ziprasidone in a single country ( Italy ) , multi-site trial . The cognitive assessment s examined episodic memory ( RAVLT ) , executive functioning ( Stroop test ) , and processing speed ( Trail-making test ( TMT ) Parts A and B ) . RESULTS Analyses found statistically significant within-group improvements for ziprasidone in learning and delayed recall on the RAVLT and on TMT Parts A and B. Clozapine-treated patients improved on the RAVLT , but not on the TMT . A composite cognitive score improved from baseline in both groups , but the improvements were significantly larger in the ziprasidone group ( p=.029 ) . IMPLICATION S These results indicated that cognitive functioning improved following treatment with ziprasidone in patients with a history of either treatment resistance or intolerance , and that the effects are comparable or greater than those observed with clozapine . One interpretation of these findings is that clozapine treatment interferes with the performance benefits associated with practice The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptics is a major challenge . Clozapine , an atypical antipsychotic drug , has long been of scientific interest , but its clinical development has been delayed because of an associated risk of agranulocytosis . This report describes a multicenter clinical trial to assess clozapine 's efficacy in the treatment of patients who are refractory to neuroleptics . DSM-III schizophrenics who had failed to respond to at least three different neuroleptics underwent a prospect i ve , single-blind trial of haloperidol ( mean dosage , 61 + /- 14 mg/d ) for six weeks . Patients whose condition remained unimproved were then r and omly assigned , in a double-blind manner , to clozapine ( up to 900 mg/d ) or chlorpromazine ( up to 1800 mg/d ) for six weeks . Two hundred sixty-eight patients were entered in the double-blind comparison . When a priori criteria were used , 30 % of the clozapine-treated patients were categorized as responders compared with 4 % of chlorpromazine-treated patients . Clozapine produced significantly greater improvement on the Brief Psychiatric Rating Scale , Clinical Global Impression Scale , and Nurses ' Observation Scale for Inpatient Evaluation ; this improvement included " negative " as well as positive symptom areas . Although no cases of agranulocytosis occurred during this relatively brief study , in our view , the apparently increased comparative risk requires that the use of clozapine be limited to selected treatment-resistant patients Background Newer antipsychotic medications have been reported to enhance cognitive functioning in schizophrenia . Head to head studies with double-blind methods are still relatively few in number . Objectives To compare the relative cognitive enhancing effects of ziprasidone and olanzapine in the treatment of acutely ill in patients with schizophrenia or schizoaffective disorder . Procedures In this 6-week , multicenter , double-blind , parallel- design ed trial , patients were r and omized to ziprasidone or olanzapine . No patient who had ever received a complete treatment trial with either of these medications previously was entered into the study . Cognitive testing measuring attention , motor speed , memory , executive functioning , and verbal skills were performed on all patients at baseline and endpoint . Results Treatment with either ziprasidone or olanzapine was associated with statistically significant improvements from baseline in attention , memory , working memory , motor speed , and executive functions . Treatment with olanzapine was also associated with a statistically significant improvement in verbal fluency . No statistically significant differences between these medications were found in the magnitude of improvement from baseline on any of the cognitive measures ( other than verbal fluency in an exploratory analysis ) . Observed changes were not associated with changes in clinical symptoms measured using the PANSS or changes in movement disorders . Conclusions During 6 weeks of treatment , ziprasidone and olanzapine demonstrated substantial and comparable cognitive-enhancing effects relative to previous treatment . These effects were noted in all aspects of cognitive functioning previously proven to predict functional outcome in schizophrenia . No overall differences were detected between the medications in terms of the extent of cognitive enhancement BACKGROUND More head-to-head comparisons of antipsychotics are needed to discern the relative efficacy and safety profiles of these compounds . Thus , we compared ziprasidone and risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder . METHOD Patients with DSM-III-R acute exacerbation of schizophrenia or schizoaffective disorder were r and omly assigned to double-blind ziprasidone 40 to 80 mg b.i.d . ( N = 149 ) or risperidone 3 to 5 mg b.i.d ( N = 147 ) for 8 weeks . Primary efficacy measures included Positive and Negative Syndrome Scale ( PANSS ) total score and Clinical Global Impressions-Severity of Illness scale ( CGI-S ) score ; secondary measures included scores on the PANSS negative sub-scale , CGI-Improvement scale ( CGI-I ) , and PANSS-derived Brief Psychiatric Rating Scale ( BPRSd ) total and core items . Safety assessment s included movement disorder evaluations , laboratory tests , electrocardiography , vital signs , and body weight . Efficacy analyses employed a prospect ively defined Evaluable Patients cohort . Treatment equivalence was conferred if the lower limit of the 95 % confidence interval of the ziprasidone/risperidone ratio of least-squares mean change from baseline was > 0.60 . Data were gathered from August 1995 to January 1997 . RESULTS Equivalence was demonstrated in PANSS total scores , CGI-S scores , PANSS negative subscale scores , BPRSd total and core item scores , and PANSS total and CGI-I responder rates . Both agents were well tolerated . Risperidone exhibited a significantly higher Movement Disorder Burden ( MDB ) score ( p < .05 ) and higher incidences of prolactin elevation and clinical ly relevant weight gain . However , compared with current recommendations , study dosing may have been high for some risperidone-treated patients ( mean dose = 7.4 mg/day ) and low for some ziprasidone-treated patients ( mean dose = 114.2 mg/day ) . CONCLUSION Both agents equally improved psychotic symptoms , and both were generally well tolerated , with ziprasidone demonstrating a lower MDB score and less effect on prolactin and weight than risperidone OBJECTIVE To examine the clinical characteristics of individuals with schizophrenia that develop tardive dyskinesia ( TD ) associated with antipsychotic treatment . METHODS Baseline data on 1460 patients with schizophrenia were collected as part of the Clinical Antipsychotic Trials of Intervention Effectiveness schizophrenia study . Subjects who met Schooler-Kane criteria for probable TD were compared to those without TD . Multiple regression analyses were used to examine the relationship between TD and clinical variables . RESULTS 212 subjects met the Schooler-Kane criteria for probable TD and 1098 had no history or current evidence of TD . Subjects with TD were older , had a longer duration of receiving antipsychotic medication , and were more likely to have been receiving a conventional antipsychotic and an anticholinergic agent . After controlling for important baseline covariates , diabetes mellitus ( DM ) and hypertension did not predict TD , whereas substance abuse significantly predicted TD . Differences in cognitive functioning were not significantly different after controlling for baseline covariates . The TD subjects also had higher ratings of psychopathology , EPSE , and akathisia . CONCLUSION Our results confirm the established relationships between the presence of TD and age , duration of treatment with antipsychotics , treatment with a conventional antipsychotic , treatment with anticholinergics , the presence of EPS and akathisia , and substance abuse . Subjects with TD had higher ratings of psychopathology as measured by the PANSS . We found no support for DM or hypertension increasing the risk of TD , or for TD being associated with cognitive impairment OBJECTIVE We compared the response to antipsychotic treatment between patients with and without tardive dyskinesia ( TD ) and examined the course of TD . METHOD This analysis compared 200 patients with DSM-IV-defined schizophrenia and TD and 997 patients without TD , all of whom were r and omly assigned to receive one of 4 second-generation antipsychotics . The primary clinical outcome measure was time to all-cause treatment discontinuation , and the primary measure for evaluating the course of TD was change from baseline in Abnormal Involuntary Movement Scale ( AIMS ) score . Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to compare treatment discontinuation between groups . Changes in Positive and Negative Syndrome Scale ( PANSS ) and neurocognitive scores were compared using mixed models and analysis of variance . Treatment differences between drugs in AIMS scores and all-cause discontinuation were examined for those with TD at baseline . Percentages of patients meeting criteria for TD postbaseline or showing changes in AIMS scores were evaluated with χ(2 ) tests . Data were collected from January 2001 to December 2004 . RESULTS Time to treatment discontinuation for any cause was not significantly different between the TD and non-TD groups ( χ(2)(1 ) = 0.11 , P = .743 ) . Changes in PANSS scores were not significantly different ( F(1,974 ) = 0.82 , P = .366 ) , but patients with TD showed less improvement in neurocognitive scores ( F(1,359 ) = 6.53 , P = .011 ) . Among patients with TD , there were no significant differences between drugs in the decline in AIMS scores ( F(3,151 ) = 0.32 , P = .811 ) ; 55 % met criteria for TD at 2 consecutive visits postbaseline , 76 % met criteria for TD at some or all postbaseline visits , 24 % did not meet criteria for TD at any subsequent visit , 32 % showed a ≥ 50 % decrease in AIMS score , and 7 % showed a ≥ 50 % increase in AIMS score . CONCLUSIONS Schizophrenia patients with and without TD were similar in time to discontinuation of treatment for any cause and improvement in psychopathology , but differed in neurocognitive response . There were no significant differences between treatments in the course of TD , with most patients showing either persistence of or fluctuation in observable symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00014001 The efficacy , safety and tolerability of ziprasidone versus the comparators olanzapine , risperidone or quetiapine were investigated in adult patients with chronic schizophrenia , schizoaffective and schizophreniform disorders , with lack of efficacy or intolerance to their previous antipsychotic treatment based on clinical judgement of the investigator . A total of 293 patients were r and omized to 12 weeks treatment with either ziprasidone 80–160 mg/day ( n=147 ) or with one of the comparator drugs ( n=146 ) . In the latter group the investigator could choose between olanzapine 10–20 mg/day ( n=24 ) , risperidone 4–8 mg/day ( n=22 ) or quetiapine 300–750 mg/day ( n=97 ) . The study comprised four visits including a baseline examination prior to r and omization and further examinations at the end of weeks 1 , 4 and 12 . Ziprasidone was non-inferior ( defined as a difference of = 7 units or less on the PANSS scale to the disadvantage of ziprasidone . ) to the composite group ( olanzapine , risperidone or quetiapine ) on the total PANSS score as well as on all subscores ( P<0.0001 ) ; there were no significant between-group differences in the CGI-S and I and UKU scores . Ziprasidone-treated patients lost an average of 2.1 kg in the 12 weeks of the study , the mean weight for risperidone and quetiapine remained unchanged , and patients receiving olanzapine gained 3.1 kg on average BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P<0.001 ) or risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism Objective : The objective of this study is to compare olanzapine with ziprasidone therapy in patients with schizophrenia or schizoaffective disorder and experiencing depressive symptoms . Methods : This r and omized , double-blind , 24-week , fixed-dose study compared olanzapine ( n = 202 ) and ziprasidone ( n = 192 ) for patients with schizophrenia or schizoaffective disorder and experiencing prominent depressive symptoms . Outcome measures included change in Calgary Depression Scale for Schizophrenia ( CDSS ) score from baseline to 8 weeks ( primary outcome ) and changes in CDSS , Montgomery-Åsberg Depression Rating Scales , Positive and Negative Syndrome Scale , and Global Assessment of Functioning ( GAF ) scores for 24 weeks . Statistical analyses included mixed-effects model repeated measures ( primary analysis ) and change from baseline to last observation carried forward ( LOCF ) . Results : At baseline , patients had moderate depressive symptoms ( mean Montgomery-Åsberg Depression Rating Scales total score , 27.3 ) . For 8 weeks , patients treated with olanzapine or ziprasidone had significant improvements on CDSS . Treatment group differences were not statistically significant ( P = 0.493 , mixed-effects model repeated measures ; P = 0.497 , LOCF ) . For 24 weeks , olanzapine-treated patients showed significantly greater improvements in depressive symptoms ( results varied by depression measure and statistical approach ) and GAF ( P < 0.017 , LOCF ) . A significantly higher proportion of olanzapine-treated patients completed the study ( 44.6 % vs 29.7 % ; P = 0.003 ) and remained longer on medication ( median , 163 vs 73 days , P < 0.001 ) , compared with ziprasidone-treated patients . Olanzapine-treated patients experienced significantly ( P < 0.05 ) greater increases in triglycerides , HgbA1c , and weight . Conclusions : For 24 weeks , olanzapine-treated patients had greater and more sustained participation in treatment , during which time significantly greater improvements were observed in depressive symptoms and GAF scores , along with increases in weight and certain metabolic parameters as compared with ziprasidone-treated patients OBJECTIVE The Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) study examined the comparative effectiveness of antipsychotic treatments for individuals with chronic schizophrenia . Patients who had discontinued antipsychotic treatment in phases 1 and 2 were eligible for phase 3 , in which they selected one of nine antipsychotic regimens with the help of their study doctor . We describe the characteristics of the patients who selected each treatment option and their outcomes . METHOD Two hundred and seventy patients entered phase 3 . The open-label treatment options were monotherapy with oral aripiprazole , clozapine , olanzapine , perphenazine , quetiapine , risperidone , ziprasidone , long-acting injectable fluphenazine decanoate , or a combination of any two of these treatments . RESULTS Few patients selected fluphenazine decanoate ( n=9 ) or perphenazine ( n=4 ) . Similar numbers selected each of the other options ( range 33 - 41 ) . Of the seven common choices , those who selected clozapine and combination antipsychotic treatment were the most symptomatic , and those who selected aripiprazole and ziprasidone had the highest body mass index . Symptoms improved for all groups , although the improvements were modest for the groups starting with relatively mild levels of symptoms . Side effect profiles of the medications varied considerably but medication discontinuations due to intolerability were rare ( 7 % overall ) . CONCLUSIONS Patients and their doctors made treatment selection s based on clinical factors , including severity of symptoms , response to prior treatments , and physical health status . Fluphenazine decanoate was rarely used among those with evidence of treatment non-adherence and clozapine was underutilized for those with poor previous response . Combination antipsychotic treatment warrants further study OBJECTIVE To examine treatment-specific changes in health-related quality of life ( QOL ) among patients with schizophrenia and to assess the association between clinical and QOL improvement . METHOD This post hoc analysis used the findings of a 28-week , r and omized , multicenter trial of patients with schizophrenia ( DSM-IV ) treated with olanzapine ( 10 - 20 mg/day ) or ziprasidone ( 80 - 160 mg/day ) . Data were collected from August 2001 to December 2002 . Efficacy was measured using the Positive and Negative Syndrome Scale ( PANSS ) . Quality of life was assessed with the generic health self-administered Medical Outcomes Study Short-Form 36-Item Health Survey ( SF-36 ) and the disease-specific expert-administered Heinrichs-Carpenter Quality of Life Scale ( QLS ) . Mixed-effects-repeated- measures and last-observation-carried-forward approaches were used to assess the effects of treatment on QOL and the association of clinical outcomes to QOL outcomes . RESULTS Olanzapine- and ziprasidone-treated patients demonstrated similar improvement from baseline to endpoint on the SF-36 and QLS . All correlations between changes in PANSS scores and the SF-36 were significant ( p < .001 ) , ranging from -0.159 to -0.400 . All correlations between changes in PANSS scores and the QLS were significant ( p < .0001 ) , ranging from -0.286 to -0.603 . The correlations between the 2 QOL measures were generally significant but small to moderate in magnitude . CONCLUSIONS The results of this study indicate that , in patients with schizophrenia , olanzapine and ziprasidone treatment are associated with significant QOL and clinical improvements . Further , the significant correlation between change scores on the PANSS and QOL measures suggests that treatment-related clinical improvements are associated with improved health-related and disease-specific QOL . CLINICAL TRIALS REGISTRATION Clinical Study Results .org identifier 2347 OBJECTIVE Cognitive impairment , manifested as mild to moderate deviations from psychometric norms , is present in many but not all schizophrenia patients . The purpose of the present study was to compare the effect of haloperidol with that of second-generation antipsychotic drugs on the cognitive performance of patients with schizophreniform disorder or first-episode schizophrenia . METHODS Subjects were 498 patients with schizophreniform disorder or first-episode schizophrenia who were r and omly assigned to open-label haloperidol ( 1 to 4 mg/day [ N=103 ] ) , amisulpride ( 200 to 800 mg/day [ N=104 ] ) , olanzapine ( 5 to 20 mg/day [ N=105 ] ) , quetiapine ( 200 to 750 mg/day [ N=104 ] ) , or ziprasidone ( 40 to 160 mg/day [ N=82 ] ) . The Rey Auditory Verbal Learning Test , Trail Making Test Part A and Part B , WAIS Digit Symbol Test , and Purdue Pegboard Test were administered at baseline and the 6-month follow-up evaluation . RESULTS Compared with scores at baseline , composite cognitive test scores improved for all five treatment groups at the 6-month follow-up evaluation . However , there were no overall differences among the treatment groups . In addition , there was a weak correlation between the degree of cognitive improvement and changes in Positive and Negative Syndrome Scale scores . CONCLUSION Treatment with antipsychotic medication is associated with moderate improvement in the cognitive test performance of patients who have schizophreniform disorder or who are in their first episode of schizophrenia . The magnitude of improvement does not differ between treatment with haloperidol and treatment with second-generation antipsychotics . Moreover , cognitive improvement is weakly related to symptom change BACKGROUND According to the American Psychiatric Association Clinical Practice Guidelines for schizophrenia , second-generation antipsychotics may be specifically indicated for the treatment of depression in schizophrenia . We examined the impact of these medications on symptoms of depression using the data from the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) , conducted between January 2001 and December 2004 . METHOD Patients with DSM-IV-defined schizophrenia ( N = 1,460 ) were assigned to treatment with a first-generation antipsychotic ( perphenazine ) or one of 4 second-generation drugs ( olanzapine , quetiapine , risperidone , or ziprasidone ) and followed for up to 18 months ( phase 1 ) . Patients with tardive dyskinesia were excluded from the r and omization that included perphenazine . Depression was assessed with the Calgary Depression Scale for Schizophrenia ( CDSS ) . Mixed models were used to evaluate group differences during treatment with the initially assigned drug . An interaction analysis evaluated differences in drug response by whether patients had a baseline score on the CDSS of ≥ 6 , indicative of a current major depressive episode ( MDE ) . RESULTS There were no significant differences between treatment groups on phase 1 analysis , although there was a significant improvement in depression across all treatments . A significant interaction was found between treatment and experiencing an MDE at baseline ( P = .05 ) , and further paired comparisons suggested that quetiapine was superior to risperidone among patients who were in an MDE at baseline ( P = .0056 ) . CONCLUSIONS We found no differences between any second-generation antipsychotic and the first-generation antipsychotic perphenazine and no support for the clinical practice recommendation , but we did detect a signal indicating a small potential difference favoring quetiapine over risperidone only in patients with an MDE at baseline ABSTRACT Objective : To examine the effectiveness of aripiprazole in schizophrenia in a naturalistic setting in 14 European countries . Methods : This multicentre , open-label study of aripiprazole evaluated out patients with schizophrenia for whom a medication switch was clinical ly reasonable or antipsychotic initiation was required . Patients ( n = 833 ) were r and omized in a 4:1 ratio to aripiprazole ( recommended starting dose 15 mg/day , permitted adjustment 10–30 mg/day ) ( n = 680 ) or another antipsychotic ( safety control [ SC ] group ) ( n = 153 ) for 8 weeks . The control group received an antipsychotic different to their recent pre- study medication . The primary effectiveness measure was the Clinical Global Impression – Improvement ( CGI – I ) score of aripiprazole-treated patients at Week 8 ( last observation carried forward [ LOCF ] ) . Patients ’ and caregivers ’ medication preference was assessed using the Preference of Medication ( POM ) question naire . The Investigator Assessment Question naire ( IAQ ) was used to record investigators ’ assessment s of their patients ’ responses to the study antipsychotic . Adverse events ( AEs ) were recorded . Results : At endpoint ( Week 8 , LOCF ) , the mean CGI – I score of 3.16 ( 95 % confidence interval , [ CI ] : 3.04 , 3.28 ) demonstrated the effectiveness of aripiprazole . At endpoint , 43 % of aripiprazole-treated patients showed a response ( CGI – I score = 1/2 ) . Aripiprazole was rated as slightly or much better than previous antipsychotic at endpoint by 68 % of patients and 65 % of caregivers . The mean CGI – I score ( Week 8 , LOCF ) for the SC group was 3.37 ( 95 % CI : 3.14 , 3.60 ) . No major differences in the occurrence of AEs were noted between aripiprazole- and SC-treated patients . Limitations : As this is an open-label design , there may have been a bias . Secondly , the study was not powered to show differences between treatment groups and no statistical comparisons were planned . Thirdly , 8 weeks is too short to evaluate long-term effectiveness . Conclusions : Aripiprazole was effective , well tolerated and well accepted by patients and caregivers in this naturalistic study Altered expression of central muscarinic and nicotinic acetylcholine receptors in hippocampal and cortical regions may contribute to the cognitive impairment exhibited in patients with schizophrenia . Increasing cholinergic activity through the use of a cholinesterase inhibitor ( ChEI ) therefore represents a possible strategy for cognitive augmentation in schizophrenia . We examined the efficacy and safety of the ChEI donepezil as cotreatment for mild to moderate cognitive impairment in schizophrenia or schizoaffective disorder in a prospect i ve , 12-week , placebo-controlled , double-blind , parallel-group study . In total , 250 patients ( 18–55 years ) with schizophrenia or schizoaffective disorder who were clinical ly stabilized on risperidone , olanzapine , quetiapine , ziprasidone , or aripiprazole , alone or in combination , were enrolled at 38 outpatient psychiatric clinics in the United States . Patients were r and omized to donepezil 5 mg q.d . for 6 weeks then 10 mg q.d . for 6 weeks , or placebo administered as oral tablets . The primary outcome measure was the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) neurocognitive battery composite score . In the intent-to-treat sample ( donepezil , n=121 ; placebo , n=124 ) , both treatments showed improvement in the composite score from baseline to week 12 . At week 12 , cognitive improvement with donepezil was similar to that with placebo ( last-observation-carried-forward effect size , 0.277 vs 0.411 ; p=0.1182 ) and statistically significantly inferior for the observed-cases analysis ( 0.257 vs 0.450 ; p=0.044 ) . There was statistically significant improvement in the Positive and Negative Syndrome Assessment Scale negative symptoms score for placebo compared with donepezil , while total and positive symptom scores were similar between both treatments . Statistically significant improvements in positive symptoms score and Clinical Global Impression-Improvement for donepezil compared with placebo were noted at Week 6 . Treatment-emergent adverse events ( AEs ) were observed for 54.5 % of donepezil- and 61.3 % of placebo-treated patients ; most AEs were rated as mild to moderate in severity . Donepezil was safe and well-tolerated but was not effective compared with placebo as a cotreatment for the improvement of cognitive impairment in this patient population . A significant and surprisingly large placebo/ practice effect was observed among placebo-treated patients , and is a serious consideration in future clinical trial study design s for potential cognitive enhancing compounds in schizophrenia Objective : This r and omized , double-blind , multicentre extension study compared the efficacy , tolerability , and safety of ziprasidone and risperidone for schizophrenia or schizoaffective disorder . Methods : Patients who had responded to treatment for an acute exacerbation of illness in an 8–week study received ziprasidone , 80 to 160 mg/day ( n = 62 ) , or risperidone , 6 to 10 mg/day ( n = 77 ) , for up to 44 additional weeks . Primary efficacy variables included changes in Positive and Negative Syndrome Scale ( PANSS ) total score and Clinical Global Impression Severity ( CGI-S ) score . Tolerability and safety assessment s included movement disorders , adverse events , study discontinuation rates , and weight and metabolic parameters . Results : Both the ziprasidone and risperidone groups showed statistical improvement from baseline in PANSS and CGI-S scores at study end point with no significant differences between treatment groups . More risperidone-treated patients completed the study ( 41.6 % ) than ziprasidone-treated patients ( 33.9 % ) , but the difference was not statistically significant . Ziprasidone-treated patients who completed the study showed greater improvement in depressive symptoms assessed by Montgomery and Asberg Depression Rating Scale than risperidone-treated patients ( P < 0.05 ) . Ziprasidone was associated with a more favourable effect on extrapyramidal symptom ( EPS ) measures and prolactin as well as less weight gain than risperidone . Median dosages were ziprasidone 120 mg/day and risperidone 8 mg/day . Conclusions : Ziprasidone and risperidone demonstrated similar efficacy during long-term treatment of patients with schizophrenia or schizoaffective disorder . While more subjects on risperidone completed the extension study , ziprasidone was associated with fewer adverse effects on weight , EPS measures , and prolactin than risperidone Rationale Antipsychotic-induced parkinsonism ( AIP ) is a severe adverse affect of neuroleptic treatment . Interindividual heterogeneity in AIP development and severity is associated with risk factors such as antipsychotic drug type , old age , and female gender . There is evidence for genetic predisposition to develop AIP but the variants that confer susceptibility or protection are mostly unknown . Objective To identify genes related to AIP susceptibility , we performed a pharmacogenomic genome-wide association study ( GWAS ) for AIP severity . Methods Three hundred ninety-seven American schizophrenia patients who participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)-GWAS project were included in our analysis . Patients had been r and omized to treatment with antipsychotic monotherapy for periods ranging from 2 weeks to 18 months during phase 1 of the CATIE trial . They were regularly assessed for AIP severity using the modified Simpson – Angus Scale ( SAS ) . For statistical analysis , patients were dichotomized as cases ( average SAS mean global score > 0.3 during CATIE phase 1 , N = 199 ) or controls ( average SAS mean global score 0 , N = 198 ) . Results Using logistic regression and controlling for population stratification , age , gender , SAS score at baseline , and concomitant use of anticholinergic drugs , we identified several single-nucleotide polymorphisms associated with AIP severity . Although none reached the GWAS significance level of P < 4.2 × 10−7 , some promising c and i date genes for further research on genetic predisposition to AIP were identified including EPF1 , NOVA1 , and FIGN . Conclusions Our finding may contribute to underst and ing of the pathophysiology of AIP as well as to a priori identification of patients vulnerable for development of AIP Introduction : In the context of a large , r and om assignment , controlled study evaluating the relative effectiveness and safety of antipsychotic medication ( CATIE ) , we examined the relationship between treatment outcome and 2 family variables : their presence and their ability to support treatment adherence . Methods : Post hoc , we assessed the 50 study patients ( 40 of whom had families ) and their families by dividing them into 2 groups . The first had a family/significant other , available and mostly supportive , to work collaboratively on adherence with the treatment team ( n = 27 ) . The second group either did not have the family/significant other or , if they did , lacked support for long-term maintenance ( n = 23 ) . Next , we examined outcome on 2 measures : study completion ( vs discontinuation ) and global outcome . Results : Of 27 patients with available/supportive families , 23 remained in treatment for the full study course . In contrast , 13 of 23 patients , who were discontinued or dropped out , either did not have families or , if they had them , were unable to support adherence ( P < 0.01 ) . As to global outcome , 24 of the 27 patients who had supportive families improved , compared with only 9 of the 23 of the other group ( P < 0.001 ) . Discussion : In summary , in the context of a large medication efficacy-effectiveness trial , we present data suggesting that having a " family " available and supportive ( regardless of the interpersonal issues between patient and family ) improves outcome mediated by improving long-term adherence Chlorpromazine and haloperidol are benchmark antipsychotic drugs which are frequently used as st and ards in antipsychotic drug trials.1,2 For example , in the review on second-generation antipsychotic drugs by Davis et al.3 , haloperidol was by far the most frequently used comparator followed by chlorpromazine . To better define the relative efficacy and safety of both compounds is therefore important for the methodology of r and omized controlled trials ( RCTs ) and for clinical practice where both agents are still frequently used OBJECTIVE Limited r and omized , controlled trial data exist on possible differences between atypical antipsychotics in efficacy , overall tolerability , and important indices of health status . The authors compared the efficacy and tolerability of ziprasidone and olanzapine in the treatment of acutely ill in patients with schizophrenia or schizoaffective disorder . METHOD In this 6-week , multicenter , double-blind , parallel- design , flexible-dose trial , patients were r and omly assigned to receive ziprasidone ( N=136 ) or olanzapine ( N=133 ) . Primary efficacy measures were improvement in Brief Psychiatric Rating Scale and Clinical Global Impression ( CGI ) severity scale scores ; secondary measures were scores on the CGI improvement scale , Positive and Negative Syndrome Scale , and Calgary Depression Scale for Schizophrenia . Tolerability assessment s included fasting lipid profiles , fasting glucose and insulin measurements , electrocardiography , and monitoring of vital signs and body weight . RESULTS The overall mean daily doses were 129.9 mg ( SD=27.3 ) for ziprasidone and 11.3 mg ( SD=2.8 ) for olanzapine . Both antipsychotics were efficacious in improving symptoms and global illness severity . The two treatment groups did not differ significantly in primary or secondary efficacy measures at endpoint or in by-visit analysis . Both agents were well tolerated . Body weight , total cholesterol , triglycerides , and low-density lipoprotein cholesterol significantly increased with olanzapine but not with ziprasidone ; all between-group comparisons of these variables were significant and favored ziprasidone . Olanzapine , but not ziprasidone , was associated with significant increases in fasting insulin level . No patient in either group exhibited a corrected QT interval > /=500 msec . CONCLUSIONS During 6 weeks ' treatment , ziprasidone and olanzapine demonstrated comparable antipsychotic efficacy . Differences favoring ziprasidone were observed in metabolic parameters BACKGROUND Recent literature documents a stronger association between nonfasting triglycerides ( TG ) and cardiovascular risk compared to fasting TG . Given concerns over antipsychotic effects on serum TG , this analysis explored changes in nonfasting TG in phase 1 of the CATIE Schizophrenia Trial . METHODS Change in nonfasting TG , adjusted for baseline value , was compared between antipsychotic treatment groups using subjects with nonfasting laboratory assessment s at baseline and 3 months . RESULTS Among the 246 subjects there were significant treatment differences in 3-month change from baseline ( p=0.009 ) . The greatest increases in median and adjusted mean nonfasting TG levels were seen among those r and omized to quetiapine ( mean+54.7 mg/dl , median+26 mg/dl ) and olanzapine ( mean+23.4 mg/dl , median+26.5 mg/dl ) , while ziprasidone was neutral ( mean+0.0 mg/dl , median+8 mg/dl ) , and decreases were seen with risperidone ( mean -18.4 mg/dl , median -6.5 mg/dl ) and perphenazine ( mean -1.3 mg/dl , median -22 mg/dl ) . Pairwise comparisons indicated a significant between-group difference for perphenazine vs. olanzapine ( p=0.002 ) and a trend for perphenazine vs. quetiapine ( p=0.006 ) . CONCLUSIONS This analysis provides further evidence for differential antipsychotic metabolic liabilities , and confirms signals for the effects of olanzapine and quetiapine on serum TG seen in earlier CATIE analyses . Future consensus recommendations will clarify the role of nonfasting TG monitoring in routine clinical practice In September 2005 the New Engl and Journal of Medicine ( NEJM ) published the first results from phase I of the CATIE ( Clinical Antipsychotic Trials of Intervention Effectiveness ) study ( Lieberman et al. , 2005 ) . CATIE is a l and mark study in schizophrenia research . Its importance lies in its independence , sample size , duration and attempt to be more representative of clinical practice than many r and omized controlled trials ( RCTs ) . In this editorial we review the study design , key findings and implication s of the phase I data as presented in the NEJM paper . CATIE is funded by the National Institute of Mental Health ( NIMH ) , its design and analysis is independent of the pharmaceutical industry . Phase 1 compared four atypical ( second-generation ) antipsychotics ( olanzapine , quetiapine , risperidone , ziprasidone ) with perphenazine , a conventional ( first-generation ) antipsychotic , in terms of overall effectiveness . Perphenazine was selected as the conventional comparator due to its low incidence of extrapyramidal symptoms ( EPS ) . Nearly 1500 patients with schizophrenia were r and omized in phase 1 and followed under double-blind conditions for up to 18 months or until treatment was discontinued for any reason . This makes CATIE the largest and longest independent trial in schizophrenia . Its independence is important as industry-sponsored trials are more likely to report results that favour the sponsor ’s compound than are independent studies ( Ahmer et al. , 2005 ) . Possible explanations include publication bias and bias in trial design . Phase 2 and 3 of CATIE , results yet to be published , relate to the outcome of patients leaving the preceding phase and include a clozapine treatment arm . Future CATIE publications will address issues including cost effectiveness , cognitive functioning and the reversibility of adverse effects that developed in earlier phases . In most drug trials in schizophrenia the primary outcome measure is change in score from baseline to endpoint on an observer-rated symptom scale , usually the Positive and Negative Syndrome Scale ( PANSS ) . CATIE was innovative in that the primary outcome measure was the time to discontinuation of treatment for any reason . This is a global measure of effectiveness that encompasses the patients ’ and clinicians ’ views on efficacy , tolerability and the likelihood of a more suitable medication being available . Secondary outcome measures included the specific reasons for discontinuation , scores on the PANSS and the incidence of adverse effects . A criticism of many RCTs is that , by nature of their inclusion and exclusion criteria , they recruit a subgroup of patients that are not representative of those seen in clinical practice . CATIE had broad inclusion and minimal exclusion criteria ( the main exclusion criteria were patients who were in their first episode or treatment resistant ) . It was conducted in a variety of treatment setting s including university clinics , state mental health agencies and private units . Consequently the sample is more representative of clinical practice than many RCTs . For example in those entering CATIE the prevalence of drug dependence/abuse and alcohol dependence/abuse within the past 5 years was 29 % and 25 % respectively while 20 % had hypertension and 11 % had type I or 2 diabetes at baseline . We will concentrate on four key findings . First , discontinuation rates on all treatments were high , ranging from 64 % to 82 % . Second , the time to discontinuation for any reason was longest for the olanzapine group . Third , the incidence of EPS , as assessed by observer rating scale scores , did not differ significantly between perphenazine and the atypicals . Finally olanzapine was associated with greater weight gain and more metabolic abnormalities than comparator groups . The finding of high discontinuation rates with all treatments is disappointing . Within the total sample 74 % of patients discontinued the study medication before 18 months ( median duration of treatment = 6 months ) . In all treatment groups the highest proportion of discontinuations was due to patient choice , followed by lack of efficacy or intolerability . Exactly how the research ers differentiated ‘ patient choice ’ from lack of efficacy and intolerability is unclear . For all drugs , except olanzapine , lack of efficacy accounted for more discontinuations than intolerability . Discontinuation rates are likely to be lower in clinical practice than in CATIE ; blindness and r and om allocation to drug treatment Objective : The aim of this paper was to review whether the $ 50 m spent by the US National Institute of Mental Health in doing the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) trials found any useful evidence to change the clinical management of schizophrenia by psychiatrists . Conclusions : The CATIE trials were conducted in the US on 1460 enrolled patients in an effort to track how the drugs used to treat schizophrenia actually work in clinical practice ( rather than in 6-week clinical trials ) . In a complex 3-phase design , patients were r and omized to various types of ( mostly ) atypical antipsychotic drugs . Some 69–74 % of patients switched antipsychotics for one reason or another during the 18 months of treatment . Some of the results were expensive confirmations of known prior results ; of the commonly prescribed drugs , clozapine was the most effective , and olanzapine and ziprasidone caused the most and fewest metabolic side effects , respectively . The most stunning finding was that psychiatrists tend to ignore life-threatening , treatable medical conditions in patients presenting for treatment with schizophrenia . Of patients entering the study , 45 % had untreated diabetes , 89 % had untreated hyperlipidemias and 62 % had untreated hypertension . This study failed to reveal anything of significant importance in the psychopharmacological treatment of schizophrenia , but did expose a woeful st and ard in the medical management of schizophrenia offered by psychiatrists . Psychiatrists should learn to properly treat diabetes , hyperlipidemia and hypertension when detected OBJECTIVE This study examined the relative effects of the second-generation antipsychotic drugs and an older representative agent on psychosocial functioning in patients with chronic schizophrenia . METHOD Consenting patients were enrolled in the NIMH Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) project . In phase 1 , patients were r and omly assigned to receive olanzapine , perphenazine , quetiapine , risperidone , or ziprasidone for up to 18 months . Clozapine was included for patients who chose this pathway after discontinuing phase 1 due to inefficacy ; all other patients received another second-generation antipsychotic . Psychosocial functioning was assessed using the Quality of Life Scale . RESULTS Psychosocial functioning modestly improved for the one-third of phase 1 patients who reached the primary Quality of Life Scale analysis endpoint of 12 months ( average effect size 0.19 SD units ) . Although for several of the drugs individually there were significant changes from baseline , overall there were no significant differences between the different agents . Results were similar at 6 and 18 months . There were no significant differences among the treatment groups in the amount of change in the Quality of Life Scale total score or subscale scores at 6 , 12 , or 18 months . Patients treated with clozapine in the efficacy pathway made comparable gains . Early treatment discontinuations , especially among patients most impaired at baseline , limited the ability to achieve more substantial functional gains . CONCLUSIONS All antipsychotic treatment groups in all phases made modest improvements in psychosocial functioning . There were no differences among them after 6 , 12 , or 18 months . More substantial improvements would likely require more intensive adjunctive psychosocial rehabilitation interventions BACKGROUND Ziprasidone has been used to treat schizophrenia since 2000 . It is unknown whether its modest QTc-prolonging effect increases cardiovascular event risk . PURPOSE To describe the study design of the Ziprasidone Observational Study of Cardiac Outcomes ( ZODIAC ) . METHOD The study was conducted between February 2002 and February 2006 . One-year follow-up for the primary endpoint of nonsuicide death ended in April 2007 . ZODIAC is an open-label , r and omized , postmarketing study enrolling patients with schizophrenia in naturalistic practice in 18 countries . The primary outcome measure was the rate of nonsuicide mortality in the year after initial recommendation for therapy . Subjects were r and omly assigned to either ziprasidone or olanzapine , after which follow-up was conducted by investigators aware of the assigned exposure . A physician-administered question naire collected baseline information on patients ' demographics , medical and psychiatric history , and concomitant medication use . Data were self-reported by patients or reported by enrolling physicians . RESULTS ZODIAC enrolled 18,240 patients with schizophrenia . Most ( 73.0 % ) were from the United States or Brazil . Patients ' baseline mean age was 41.6 years , 55.1 % were male , and 60.0 % were white . At baseline , approximately 18 % had hypertension , 14.8 % had hyperlipidemia , 46.5 % currently smoked , 28.9 % had a body mass index > or= 30 kg/m(2 ) , and 7.7 % had diabetes . Mean time from schizophrenia diagnosis to study enrollment was 10.4 years and mean Clinical Global Impressions scale score was 5.2 ( range : 1 - 8 ) . Nearly one third of patients had ever attempted suicide . Seventy-one percent were using antipsychotics at baseline . Almost 80 % were using concomitant medications , with 29.5 % using antidepressants , 25.4 % using anxiolytics , and 19.0 % using mood stabilizers . Less than 3 % were using antihypertensives or statins . CONCLUSIONS ZODIAC is a uniquely design ed study with an initial r and omization to ziprasidone or olanzapine and follow-up largely consistent with usual practice ( i.e. , many characteristics of a nonexperimental study ) . Baseline data suggest this study population has a substantial prevalence of cardiovascular risk factors . Concomitant medications were used frequently , although hyperlipidemia and hypertension may be undertreated . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00174447 Employment has been increasingly recognized as an important goal for individuals with schizophrenia . Previous research has shown mixed results on the relationship of specific antipsychotic medications to employment outcomes , with some studies finding greater benefits for second-generation antipsychotic medications ( SGAs ) over first-generation antipsychotic medication ( FGAs ) . A r and omized controlled trial ( CATIE ) examined medication assignment and both employment outcomes and participation in psychosocial rehabilitation ( PSR ) among 1,121 individuals with a diagnosis of schizophrenia r and omized to SGAs ( olanzapine , quetiapine , risperidone , ziprasidone ) or one FGA ( perphenazine ) . Service use and employment were assessed at quarterly interviews . There were no differences between medication groups on employment outcomes or participation in PSR . Consistent with other CATIE results , there were no differences in employment or participation in PSR among these five medications , including the FGA perphenazine BACKGROUND Predefined response and remission criteria may hold more clinical relevance than mean scores on rating scales . We compared the effectiveness of low doses of haloperidol and regular doses of second generation antipsychotics ( SGAs ) on > or=50 % response and remission . METHODS In an open r and omized clinical trial in 14 countries , 498 unselected first-episode patients with schizophrenia were assigned to haloperidol ( 1 - 4 mg/d ; n=103 ) , amisulpride ( 200 - 800 mg/d ; n=104 ) , olanzapine ( 5 - 20mg/d ; n=105 ) , quetiapine ( 200 - 750 mg/d ; n=104 ) , or ziprasidone ( 40 - 160 mg/d ; n=82 ) . Primary outcomes were > or=50 % response and remission within 12 months , as measured with the Positive and Negative Syndrome Scale . Analysis was by intention-to-treat . RESULTS Within 12 months , the proportions of patients with > or=50 % response were 37 % for haloperidol , 67 % for amisulpride , 67 % for olanzapine , 46 % for quetiapine , and 56 % for ziprasidone . Comparisons with haloperidol showed a higher likelihood for > or=50 % response with amisulpride ( hazard ratio [ HR ] 2.27 , [ 95 % CI 1.51 - 3.42 ] ) , olanzapine ( HR 2.07 [ 1.38 - 3.10 ] ) , and ziprasidone ( HR 1.62 [ 1.02 - 2.56 ] ) . Within 12 months , the proportions of patients in remission were 17 % for haloperidol , 40 % for amisulpride , 41 % for olanzapine , 24 % for quetiapine , and 28 % for ziprasidone . Comparisons with haloperidol showed a better chance for remission on amisulpride ( HR 2.49 , [ 95 % CI 1.43 - 4.35 ] ) , olanzapine ( HR 2.58 [ 1.48 - 4.48 ] ) , quetiapine ( HR 1.96 [ 1.06 - 3.64 ] ) , and ziprasidone ( HR 2.03 [ 1.07 - 3.87 ] ) . CONCLUSIONS Substantial proportions of first-episode patients with schizophrenia showed clinical ly meaningful response and remission rates within 12 months . The proportions of response and remission were higher for most SGAs as compared to haloperidol A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials The authors provide an overview of the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) sponsored by the National Institute of Mental Health . CATIE was design ed to compare a proxy first-generation antipsychotic , perphenazine , to several newer drugs . In phase 1 of the trial , consenting patients were r and omly assigned to receive olanzapine , perphenazine , quetiapine , risperidone , or ziprasidone for up to 18 months on a double-blind basis . Patients with tardive dyskinesia were excluded from being r and omly assigned to perphenazine and were assigned to one of the four second-generation antipsychotics in phase 1A . Clozapine was included in phase 2 of the study . Overall , olanzapine had the longest time to discontinuation in phase 1 , but it was associated with significant weight and metabolic concerns . Perphenazine was not significantly different in overall effectiveness , compared with quetiapine , risperidone , and ziprasidone . Also , perphenazine was found to be the most cost-effective drug . Clozapine was confirmed as the most effective drug for individuals with a poor symptom response to previous antipsychotic drug trials , although clozapine was also associated with troublesome adverse effects . There were no differences in neurocognitive or psychosocial functioning in response to medications . Subsequent r and omizations suggest that a poor response to an initial medication may mean that a different medication will be more effective or better tolerated . Although the CATIE results are controversial , they are broadly consistent with most previous antipsychotic drug trials and meta-analyses ; however , the results may not generalize well to patients at high risk of tardive dyskinesia . Patient characteristics and clinical circumstances affected drug effectiveness ; these patient factors are important in making treatment choices OBJECTIVE Most r and omized drug trials in schizophrenia exclude patients with comorbidities such as suicidality or substance use , which may limit the generalizability of the results . We aim ed to evaluate the generalizability of the results of these trials in participants of a r and omized clinical trial with broad inclusion criteria . METHOD In 50 sites in 14 countries , 498 patients with first-episode psychosis ( DSM-IV schizophrenia , schizoaffective disorder , or schizophreniform disorder ) were recruited between December 2002 and January 2006 in an open , r and omized clinical drug trial with 12 months of follow-up . Baseline characteristics and follow-up data were compared between patients with versus patients without baseline suicidality and /or substance use . RESULTS Of the 489 participants with data on baseline suicidality and substance use , 153 ( 31 % ) patients were suicidal and /or using substances . Groups differed on only a few of the many baseline characteristics tested : comorbid patients were younger ( 25.1 vs 26.5 years of age ; P < .01 ) , less often female ( 25 % vs 47 % ; P < .001 ) or married ( 4 % vs 17 % ; P < .001 ) , had fewer years of education ( 11.8 vs 12.8 ; P < .001 ) , and experienced lower levels of overall psychosocial functioning ( Global Assessment of Functioning ; 38.4 vs 40.8 ; P < or= .05 ) and higher levels of depression ( Calgary Depression Scale for Schizophrenia ; 6.1 vs 4.6 ; P < .001 ) . At follow-up , comorbid patients showed shorter time to (re)hospitalization and reported higher levels of depression than patients without comorbidity ( hazard ratio = 2.02 , P = .004 ; chi(2)(7 ) = 17.25 , P = .016 , respectively ) , without differences on other outcome measures . CONCLUSIONS Although it appears that the generalizability of antipsychotic treatment trials in first-episode patients is not seriously affected by the exclusion of patients with suicidal symptoms and /or substance use , research ers should be cautious about the exclusion of such patients . TRIAL REGISTRATION controlled-trials.com Identifier : IS RCT N68736636 OBJECTIVE The efficacy and safety of olanzapine were compared with those of ziprasidone . METHOD This was a multicenter r and omized , double-blind , parallel-group , 28-week study of patients with schizophrenia . Patients were r and omly assigned to treatment with 10 - 20 mg/day of olanzapine or 80 - 160 mg/day of ziprasidone . The primary efficacy measure was the Positive and Negative Syndrome Scale total score . Secondary efficacy and safety measures included Positive and Negative Syndrome Scale subscales as well as mood , quality of life , and extrapyramidal symptom scales . Safety was evaluated by recording treatment-emergent adverse events and measuring vital signs and weight . RESULTS The study was completed by significantly more olanzapine-treated patients ( 165 of 277 , 59.6 % ) than ziprasidone-treated patients ( 115 of 271 , 42.4 % ) . At 28 weeks , the olanzapine-treated patients showed significantly more improvement than the ziprasidone-treated patients on the Positive and Negative Syndrome Scale overall scale and all subscales and on the Clinical Global Impression ratings of severity of illness and improvement . The responder rate was higher for olanzapine than for ziprasidone . Extrapyramidal symptoms were not significantly different between groups in change-to-endpoint analyses , but results favored olanzapine on baseline-to-maximum changes . Weight change was significantly greater with olanzapine ( mean=3.06 kg , SD=6.87 ) than with ziprasidone ( mean=-1.12 kg , SD=4.70 ) . Fasting lipid profiles were significantly superior in the ziprasidone group ; there was no significant difference in fasting glucose level . CONCLUSIONS Olanzapine treatment result ed in significantly greater psychopathology improvement and higher response and completion rates than ziprasidone treatment , while ziprasidone was superior for weight change and lipid profile BACKGROUND Cognitive deficits are a core feature in schizophrenia . Cognitive deficits appear to be present at the onset of schizophrenia and persist after remission of psychotic symptoms . As cognitive deficits are associated with poor functional outcome , they form an important focus of treatment . There are relatively few head-to-head comparisons of the effects of second generation antipsychotics on cognition in recent onset schizophrenia . This is the first study to compare the effects of a short term treatment of olanzapine versus ziprasidone on cognitive functioning in recent onset schizophrenia . An earlier study conducted in chronic patients revealed an enhancement of cognition after treatment for both agents , but the extent of improvement was not significantly different between ziprasidone and olanzapine . METHOD Patients with recent onset schizophrenia with limited previous exposure to medical treatment underwent a double blind r and omized controlled treatment trial . Fifty-six patients completed the neuropsychological testing procedure prior to r and omization and after eight weeks of treatment and were included in the analysis . We tested cognitive functioning in general and verbal memory in particular . We calculated a single unweighted composite score based on nine cognitive tests to determine general cognitive functioning . RESULTS Cognition appeared enhanced after treatment , but was not significantly different between treatment groups , neither for the verbal memory measures , nor for the neurocognitive composite score . Furthermore , cognitive enhancement did not correlate to clinical improvement . CONCLUSION Cognitive deficits are not a reason for preferentially prescribing one of the two second generation antipsychotics tested over the other The goal of the study was to characterize population pharmacokinetics ( PPK ) for perphenazine in patients with schizophrenia from the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) . Patients ( n = 156 ) received 8 to 32 mg of perphenazine daily for 14 to 600 days for a total of 421 plasma concentrations measurements . Nonlinear mixed-effects modeling was used to determine PPK characteristics of perphenazine . One- and 2-compartment models with various r and om effect implementations and mixture distributions were evaluated . Objective function values and goodness-of-fit plots were used as model selection criteria . Age , weight , sex , race , smoking , and concomitant medications were evaluated as covariates . A 1-compartment linear model with proportional error best described the data . The population mean clearance and volume of distribution for perphenazine were 483 L/h and 18 200 L , respectively . Race and smoking status had significant impacts on perphenazine clearance estimates . In addition , the estimated population mean clearance was 48 % higher in nonsmoking African Americans than in nonsmoking other races ( 512 L/h vs 346 L/h ) . Active smokers eliminated perphenazine 159 L/h faster than nonsmokers in each race . Clearances for smoking African Americans versus smokers in other races were 671 L/h versus 505 L/h , respectively Abstract Patients suffering from schizophrenic psychoses sometimes insufficiently respond to antipsychotic monotherapy and then combination approaches are preferred . We aim ed in validating the add-on of ziprasidone and risperidone to clozapine , and we performed a r and omised head-to-head trial . Patients with partial response to clozapine were r and omly attributed to augmentation with ziprasidone ( n = 12 ) or risperidone ( n = 12 ) . Efficacy assessment s included the Positive and Negative Syndrome Scale ( PANSS ) , the Scale for the Assessment of Negative Symptoms ( SANS ) , the Hamilton Depression Scale ( HAMD ) , the Clinical Global Impression ( CGI ) and the Global Assessment of Functioning ( GAF ) . Furthermore , several safety and tolerability measures were obtained . After six weeks , both groups showed significant reductions of positive and negative symptoms . In addition , affective state , psychosocial functioning and clozapine side effects improved without significant differences between the groups . Both approaches were well tolerated . However , the ziprasidone group experienced a small elongation of the QTc interval and a reduction of extrapyramidal symptoms . Patients under clozapine – risperidone therapy developed a rise of serum prolactin levels . The clozapine augmentation with ziprasidone or risperidone result ed in significant psychopathological improvements . The side effects differed between the treatment groups . Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary |
13,262 | 28,157,275 | CTG during labour is associated with reduced rates of neonatal seizures , but no clear differences in cerebral palsy , infant mortality or other st and ard measures of neonatal wellbeing .
However , continuous CTG was associated with an increase in caesarean sections and instrumental vaginal births .
Research should also address the possible contribution of the supine position to adverse outcomes for babies , and assess whether the use of mobility and positions can further reduce the low incidence of neonatal seizures and improve psychological outcomes for women | BACKGROUND Cardiotocography ( CTG ) records changes in the fetal heart rate and their temporal relationship to uterine contractions .
The aim is to identify babies who may be short of oxygen ( hypoxic ) to guide additional assessment s of fetal wellbeing , or determine if the baby needs to be delivered by caesarean section or instrumental vaginal birth .
This is an up date of a review previously published in 2013 , 2006 and 2001 .
OBJECTIVES To evaluate the effectiveness and safety of continuous cardiotocography when used as a method to monitor fetal wellbeing during labour .
The question remains as to whether future r and omised trials should measure efficacy ( the intrinsic value of continuous CTG in trying to prevent adverse neonatal outcomes under optimal clinical conditions ) or effectiveness ( the effect of this technique in routine clinical practice ) .Along with the need for further investigations into long-term effects of operative births for women and babies , much remains to be learned about the causation and possible links between antenatal or intrapartum events , neonatal seizures and long-term neurodevelopmental outcomes , whilst considering changes in clinical practice over the intervening years ( one-to-one-support during labour , caesarean section rates ) . | A prospect i ve study of 50 consecutive children who convulsed in the first 28 days of life is in progress . The surviving children are now aged from four to six years . The incidence of simple hypocalcaemic tetany in these children was low ( 14 per cent ) and its benign outcome has been confirmed . In considering neonatal seizures from other causes , the outcome at age four years is as follows : 26 per cent are dead ; 33 per cent show adverse sequelae ; 5 per cent are of question able status ; and 36 per cent appear to be normal . A wide range of h and icap is present among the sample . Seizures have recurred in 20 per cent of all children surviving the neonatal period OBJECTIVE Our purpose was to compare the predictive value of intrapartum fetal pulse oximetry with that of fetal blood analysis for an abnormal neonatal outcome in case of an abnormal fetal heart rate . STUDY DESIGN A prospect i ve multicenter observational study was conducted from June 1994 to November 1995 . Fetal oxygen saturation was continuously recorded with a Nellcor N-400 fetal pulse oximeter in case of an abnormal fetal heart rate during labor . Simultaneous readings of fetal oxygen saturation and fetal blood analysis obtained before birth ( i.e. , either at full dilatation or before cesarean section when indicated ) were compared with the neonatal status . The criteria for an abnormal neonatal outcome were ( 1 ) an umbilical arterial blood pH < or = 7.15 and ( 2 ) a combined variable including 5-minute Apgar score < or = 7 , umbilical arterial pH < or = 7.15 , secondary respiratory distress , transfer in a neonatal care unit , or neonatal death . RESULTS At a 7.20 threshold for fetal scalp pH and 30 % for fetal oxygen saturation ( i.e. , the 10th percentile in the study population ) , the predictive value of fetal pulse oximetry was similar to that of fetal blood analysis for an arterial umbilical pH < or = 7.15 and for an abnormal neonatal outcome ( positive predictive value 56 % vs 55 % , negative predictive value 81 % vs 82 % , sensitivity 29 % vs 35 % , and specificity 93 % vs 91 % , respectively ) . The receiver-operator characteristic curve showed similar performance of either technique for cutoff values < or = 7.20 for fetal blood pH and < or = 30 % for fetal oxygen saturation , whereas fetal pulse oximetry became superior at higher thresholds . CONCLUSION The predictive value of intrapartum fetal pulse oximetry can be favorably compared with that of fetal blood analysis . R and omized controlled management trials can now be performed to assess potential clinical benefits of this new tool A controlled prospect i ve study of the differential effects of intrapartum fetal monitoring on mothers and infants has been conducted at Denver General Hospital , Denver , Colorado . A total of 690 high-risk obstetric patients in labor were r and omly assigned to one of three monitoring groups -- auscultation , electronic fetal monitoring alone , or electronic monitoring with the option to scalp sample . There were no differences in immediate infant outcomes in any measured category ( Apgar scores , cord blood gases , neonatal death , neonatal morbidity , nursery course ) among the three groups . There were no differences in rates of infant or maternal infections . The cesarean section rate was markedly increased in the electronically monitored groups , especially in the electronically monitored alone ( 18 % ) as compared with the auscultated ( 6 % ) ( P less than 0.005 ) . In this controlled trial electronic monitoring did not improve neonatal outcomes and the mothers were at increased risk of cesarean section In a large r and omized , controlled study of fetal heart rate monitoring with either continuous electronic fetal heart monitoring or auscultation at specified intervals , only one pattern of deviation in the fetal heart rate correlated significantly with neonatal neurologic examinations at 0 to 48 hours and 72 hours to 1 week : late decelerations in stage 1 and in stage 2 . Other variables from labor and delivery , specifically , duration of labor after hospital admission , failure of labor to progress , number of fetal scalp pH values , and presence of meconium were important predictors of neonatal outcome in the regression analyses . The fetal heart rate deviations did contribute significantly to the percent variance accounted for in the regression analyses with neonatal outcomes of Apgar scores at 1 and 5 minutes and serial neonatal neurologic examinations A controlled prospect i ve study of the effects of fetal monitoring on mothers and infants was conducted at Denver General Hospital , Denver , Colorado . A total of 690 high-risk patients in labor were r and omly assigned to one of three groups ; auscultation alone , electronic fetal monitoring and electronic fetal monitoring with the option to obtain a scalp pH sample . Maternal and neonatal infectious morbidity after vaginal or cesarean delivery was unchanged with internal fetal monitoring . Despite frequent antibiotic prophylaxis ( 95 % cesarean section v. 11 % vaginal ) , cesarean section was the most significant factor associated with increased maternal puerperal infectious morbidity ( 13.75 % cesarean section v. 3.9 % vaginal ) . Although hours of labor , hours of rupture of membranes , hours of internal catheter , number of exams and presence of meconium were not associated with increased maternal infection , prolonged hours of internal catheter usage greater than 8 hours and prolonged rupture of membranes greater than 12 hours were associated with increased antibiotic usage in the neonate OBJECTIVE To compare different methods of intrapartum foetal heart rate monitoring in high risk pregnancies in detecting foetal heart rate abnormalities , need for operative delivery for foetal distress , and neonatal mortality and short term neonatal morbidity . DESIGN A prospect i ve r and omised controlled trial . SETTING Women in labour at a referral maternity hospital . PATIENTS Women who were 37 weeks or more pregnant with singleton cephalic presentation and normal foetal heart rate prior to entry into the study . INTERVENTION Women were r and omly allocated using sealed opaque envelopes to either continuous electronic foetal heart rate monitoring or intermittent monitoring using h and held doppler foetal heart rate detector . OUTCOME MEASURES These include abnormal foetal heart rate patterns , need for operative delivery for foetal distress , neonatal mortality , Apgar scores , admission to NNU , neonatal seizures , and hypoxic encephalopathy . RESULTS R and omisation achieved good comparability between the two groups . Abnormal FHR patterns were more frequent in the electronic group ( 54 pc versus 32 pc ) . Caesarean section rate was not significantly different in the two groups ( 28 pc versus 24 pc ) although slightly higher compared to overall for the unit ( 18pc ) . Foetal outcome was also comparable between the two groups . CONCLUSIONS Asphyxia can be detected with a h and held doppler just as reliably as by the use of electronic monitors and their use should be further evaluated and promoted in obstetric units caring for high risk pregnancies in developing countries with scarce re sources Abstract Objective : To compare effectiveness of different methods of monitoring intrapartum fetal heart rate . Design : Prospect i ve r and omised controlled trial . Setting : Referral maternity hospital , Harare , Zimbabwe . Subjects : 1255 women who were 37 weeks or more pregnant with singleton cephalic presentation and normal fetal heart rate before entry into study . Interventions : Intermittent monitoring of fetal heart rate by electronic monitoring , Doppler ultrasound , use of Pinard stethoscope by a research midwife , or routine use of Pinard stethoscope by attending midwife . Main outcome measures - Abnormal fetal heart rate patterns , need for operative delivery for fetal distress , neonatal mortality , Apgar scores , admission to neonatal unit , neonatal seizures , and hypoxic ischaemic encephalopathy . Results : Abnormalities in fetal heart rate were detected in 54 % ( 172/318 ) of the electronic monitoring group , 32 % ( 100/312 ) of the ultrasonography group , 15 % ( 47/310 ) of the Pinard stethoscope group , and 9 % ( 28/315 ) of the routine monitoring group . Caesarean sections were performed for 28 % ( 89 ) , 24 % ( 76 ) , 10 % ( 32 ) , and 15 % ( 46 ) of the four groups respectively . Neonatal outcome was best in the ultrasonography group : hypoxic ischaemic encephalopathy occurred in two , one , seven , and 10 cases in the four groups respectively ; neonatal seizures occurred only in the last two groups ( six and nine cases respectively ) ; and deaths occurred in eight , two , five , and nine cases respectively . Conclusions : Abnormalities in fetal heart rate were more reliably detected by Doppler ultrasonography than with Pinard stethoscope , and its use result ed in good perinatal outcome . The use ofrelatively cheap ultrasound monitors should be further evaluated and promoted in obstetric units caring for high risk pregnancies in developing countries with scarce re sources OBJECTIVE Recent developments permit the use of pulse oximetry to evaluate fetal oxygenation in labor . We tested the hypothesis that the addition of fetal pulse oximetry in the evaluation of abnormal fetal heart rate patterns in labor improves the accuracy of fetal assessment and allows safe reduction of cesarean deliveries performed because of nonreassuring fetal status . STUDY DESIGN A r and omized , controlled trial was conducted concurrently in 9 centers . The patients had term pregnancies and were in active labor when abnormal fetal heart rate patterns developed . The patients were r and omized to electronic fetal heart rate monitoring alone ( control group ) or to the combination of electronic fetal monitoring and continuous fetal pulse oximetry ( study group ) . The primary outcome was a reduction in cesarean deliveries for nonreassuring fetal status as a measure of improved accuracy of assessment of fetal oxygenation . RESULTS A total of 1010 patients were r and omized , 502 to the control group and 508 to the study group . There was a reduction of > 50 % in the number of cesarean deliveries performed because of nonreassuring fetal status in the study group ( study , 4 . 5 % ; vs. control , 10.2 % ; P = .007 ) . However , there was no net difference in overall cesarean delivery rates ( study , n = 147 [ 29 % ] ; vs. control , 130 [ 26 % ] ; P = .49 ) because of an increase in cesarean deliveries performed because of dystocia in the study group . In a blinded partogram analysis 89 % of the study patients and 91 % of the control patients who had a cesarean delivery because of dystocia met defined criteria for actual dystocia . There was no difference between the 2 groups in adverse maternal or neonatal outcomes . In terms of the operative intervention for nonreassuring fetal status , there was an improvement in both the sensitivity and the specificity for the study group compared with the control group for the end points of metabolic acidosis and need for resuscitation . CONCLUSION The study confirmed its primary hypothesis of a safe reduction in cesarean deliveries performed because of nonreassuring fetal status . However , the addition of fetal pulse oximetry did not result in an overall reduction in cesarean deliveries . The increase in cesarean deliveries because of dystocia in the study group did appear to result from a well-documented arrest of labor . Fetal pulse oximetry improved the obstetrician 's ability to more appropriately intervene by cesarean or operative vaginal delivery for fetuses who were actually depressed and acidotic . The unexpected increase in operative delivery for dystocia in the study group is of concern and remains to be explained Objective : The present study was design ed to assess the utility of Doppler velocimetry in the setting of non-reassuring cardiotocography tracings . Methods : Two hundred fifty six women with term singleton pregnancies were enrolled in a controlled trial . Patients received either routine cardiotocograpic ( CTG ) monitoring , or CTG with the addition of Doppler velocimetry in cases of non-reassuring CTG tracings . The results were analyzed according to protocol . Results : In the CTG+Doppler group , there was a trend toward lower risk of neonatal metabolic acidosis than in the CTG group , although the incidence was rare . The CTG+Doppler group had significantly lower rates of cesarean section for fetal distress , and improved neonatal outcomes . Conclusions : We conclude that intrapartum fetal Doppler velocimetry , when combined with CTG , increases the clinicians ’ ability to accurately identify fetal hypoxia , and decreases the rate of Cesarean section In a r and omized controlled trial involving 12,964 women , a policy of continuous electronic intrapartum fetal heart monitoring was compared with an alternative policy of intermittent auscultation , both policies including an option to measure fetal scalp blood pH. Women allocated to electronic fetal heart monitoring had shorter labors and received less analgesia . The caesarean delivery rates were 2.4 % for electronic fetal heart monitoring and 2.2 % for intermittent auscultation but this small difference arose from the identification of nearly twice as many fetuses with low scalp pH ( less than 7.20 ) in the electronic fetal heart monitoring group . The forceps delivery rate was 8.2 % in the electronic fetal heart monitoring group compared with 6.3 % in the intermittent auscultation group , and this excess was explained by more instrumental deliveries prompted by fetal heart rate abnormalities . There were 14 stillbirths and neonatal deaths in each group , with a similar distribution of causes . There were no apparent differences in the rates of low Apgar scores , need for resuscitation , or transfer to the special care nursery . Cases of neonatal seizures and persistent abnormal neurological signs followed by survival were twice as frequent in the intermittent auscultation group , and this differential effect was related to duration of labor . Follow-up at 1 year of babies who survived neonatal seizures revealed three clearly abnormal infants in each group . The implication s of these findings for both theory and practice are discussed Objective To compare the efficacy in detecting signs of fetal hypoxia in labour of intermittent ( I‐group ) versus continuous ( C‐group ) electronic fetal monitoring in women with low or moderate risk factors for fetal distress Predictions about perinatal outcome in very low birth weight infants were studied in a r and omized clinical trial of electronic fetal monitoring and periodic auscultation to assess the effect of diagnostic monitoring information on clinicians ' ability to predict perinatal outcomes . The only predictions consistently correct before monitoring information was available were those regarding infant survival ( 88 % correct , kappa [ K ] = 0.40 , P < .001 for the electronic fetal monitoring group ; 80 % correct , K = 0.35 , P < .01 for the periodic auscultation group ) . After monitoring , predictions of 5-minute Apgar scores and arterial cord pH were significantly more accurate , and clinicians ' confidence in their predictions increased significantly in both the electronic fetal monitoring and the auscultation groups . Predictions of 5-minute Apgar scores were significantly more accurate in the electronic fetal monitoring group ( 92 % correct , K = 0.80 ) than in the periodic auscultation group ( 61 % correct , K = 0.28 ) ( Z difference = 3.04 ; P < .01 ) . We conclude that clinicians gain information during intrapartum monitoring that generally leads to improved predictions and increased confidence in predictions . In this study , they made more accurate predictions about 5-minute Apgar scores with electronic fetal monitoring , suggesting that electronic fetal monitoring may provide better information about neonatal well-being than does periodic auscultation . Improved information , as measured by clinical predictions , is probably highly valued by patients and clinicians and may be an important determinant of acceptance of this diagnostic technology In a prospect i ve clinical r and omized investigation 487 women had the condition of the fetus during labour supervised by means of stethoscope ( AUS ) , while 482 women went through labour under surveillance of electronic fetal monitoring , cardiotocography ( EFM ) . 349 women refused to participate in the investigation ( NAI ) and had delivery conducted according to the normal procedures of the department ( 70 % AUS , 30 % EFM ) . Significantly more pathological fetal heart rate patterns ( FHR ) were found in the EFM group compared to the AUS group in both the first and the second stage of labour . As a result significantly more vacuum extraction s were performed in the EFM group than in the AUS group , while no statistical difference was found between the groups in the incidence of acute cesarean sections carried out for asphyxia . One case of intrapartum death occurred in the AUS group . No differences were found in Apgar scores after 1 and 5 min or in neonatal morbidity at examination on the 2nd and 5th days after delivery . A tendency towards more biochemically compromised children was found in the AUS group . The specificity for both methods was found to be acceptably high ( 80 % ) , while the predictive value for both methods was low ( 50 % ) . More research is therefore urgently needed to evaluate supplementary investigations and parameters for the evaluation of the intrapartum fetal condition OBJECTIVE This guideline provides new recommendations pertaining to the application and documentation of fetal surveillance in the antepartum and intrapartum period that will decrease the incidence of birth asphyxia while maintaining the lowest possible rate of obstetrical intervention . Pregnancies with and without risk factors for adverse perinatal outcomes are considered . This guideline presents an alternative classification system for antenatal fetal non-stress testing and intrapartum electronic fetal surveillance to what has been used previously . This guideline is intended for use by all health professionals who provide antepartum and intrapartum care in Canada . OPTIONS Consideration has been given to all methods of fetal surveillance currently available in Canada . OUTCOMES Short- and long-term outcomes that may indicate the presence of birth asphyxia were considered . The associated rates of operative and other labour interventions were also considered . EVIDENCE A comprehensive review of r and omized controlled trials published between January 1996 and March 2007 was undertaken , and MEDLINE and the Cochrane Data base were used to search the literature for all new studies on fetal surveillance both antepartum and intrapartum . The level of evidence has been determined using the criteria and classifications of the Canadian Task Force on Preventive Health Care . SPONSOR This consensus guideline was jointly developed by the Society of Obstetricians and Gynaecologists of Canada and the British Columbia Perinatal Health Program ( formerly the British Columbia Reproductive Care Program or BCRCP ) and was partly supported by an unrestricted educational grant from the British Columbia Perinatal Health Program Intrapartum electronic fetal heart rate monitoring of the high-risk obstetric patient is thought to improve the perinatal outcome . A prospect i ve r and omized study of 483 high-risk obstetric patients in labor was carried out comparing the effectiveness of electronic fetal monitoring with auscultation of fetal heart tones . The infant outcome was measured by neonatal death , Apgar scores , cord blood gases , and neonatal nursery morbidity . There were no differences in the infant outcomes in any measured category between the electronically monitored group and the auscultated group . The cesarean section rate was markedly increased in the monitored group ( 16.5 vs. 6.8 per cent in the auscultated patients ) . The presumptive benefits of electronic fetal monitoring for improving fetal outcome were not found in this study Intrapartum electronic fetal heart rate ( FHR ) monitoring and fetal blood gas sampling were compared with periodic auscultation of FHR in a multicentered r and omized trial of preterm singleton pregnancies with fetal weights of 700–1750 g. Two hundred forty-six pregnancies were studied ( electronic FHR monitoring N = 122 , auscultation N = 124 ) . Perinatal or infant death was associated with 14 % of pregnancies with electronic FHR monitoring and 15 % with auscultation . No significant differences were noted in the prevalence of low five-minute Apgar scores , intrapartum acidosis , intracranial hemorrhage , or frequency of cesarean section ( P > .10 ) . Compared with electronic FHR monitoring , intrapartum auscultation as done in this study is unlikely to be associated with detectable differences in perinatal outcomes within the high-risk setting of preterm labor Objective : To determine whether continuous intrapartum electronic fetal heart rate monitoring ( EFM ) is associated with decreased perinatal mortality and morbidity compared with intermittent auscultation . Methods : The study was conducted simultaneously at two university hospitals in Athens , Greece ( Alex and ra and Marika Iliadi Hospitals ) from October 1 , 1990 to June 30 , 1991 . All patients with singleton living fetuses and gestational ages of 26 weeks or greater were eligible for inclusion . The participants were assigned to continuous EFM or intermittent auscultation based on the flip of a coin . Both groups were followed during labor according to the most recent ACOG guidelines . However , fetal scalp blood pH and crossover from one group to the other were not used . Results : A total of 1428 patients were included , 746 in the EFM group and 682 in the auscultation group . There were no differences between the groups in terms of maternal age , gravidity , parity , gestational age , and number of antepartum high-risk factors . More patients monitored electronically received oxytocin for either augmentation ( 52.4 versus 38.1 % ; P = .0001 ) or induction ( 15.6 versus 7 % ; P = .0001 ) . The length of labor was longer in the EFM group ( first stage 6.1 ± 4.3 versus 5.5 ± 3.7 hours ; P = .006 ; second stage 29.4 ± 18.6 versus 26.9 ± 16.9 minutes ; P = .01 ) . There was a higher incidence of nonreassuring fetal heart rate patterns in the EFM group ( 23.4 versus 10.7 % ; P = .0001 ) and a higher rate of surgical intervention ( 11.2 versus 4.8 % ; P = .0001 ) . This difference pertained to both vacuum extraction ( 5.8 versus 2.4 % ; P = .002 ) and cesarean delivery for suspected fetal distress ( 5.3 versus 2.3 % ; P = .005 ) . There were no differences in 1- and 5-minute Apgar scores , fetal acidosis at birth , need for neonatal resuscitation , neonatal intensive care unit admission , use of assisted ventilation , neonatal hospital stay , or any other neonatal complications . Two neonatal deaths occurred in the EFM group and nine perinatal deaths in the auscultation group ( two intrapartum and seven neonatal deaths ) . The perinatal mortality rates were 2.6 per 1000 and 13 per 1000 total births , respectively ( P = .04 ) . The two deaths in the EFM group and three of the neonatal deaths in the auscultation group may not have been prevented by intrapartum monitoring ; however , four neonatal deaths from the auscultation group occurred in depressed ( 5-minute Apgar scores less than 7 ) , acidotic ( cord artery pH at or below 7.13 ) infants . The perinatal death rate related to fetal hypoxia was significantly less in the EFM group ( zero of 746 versus six of 682 ; P = .03 ) . Conclusion : In this controlled trial , intrapartum EFM , as the primary and only method of intrapartum fetal surveillance , was associated with decreased perinatal mortality due to fetal hypoxia but also with higher rates of surgical intervention for suspected fetal distress OBJECTIVE Our purpose was to compare continuous intrapartum electronic fetal heart rate monitoring with intermittent auscultation for detecting fetal acidemia at birth . STUDY DESIGN Data from a previously published r and omized trial of electronic fetal heart rate monitoring versus intermittent auscultation were analyzed to identify any differences between the two methods in detecting fetal acidemia at birth . Fetal acidemia at birth was defined as the presence of cord blood arterial pH < 7.15 . RESULTS A total of 1419 patients with umbilical cord blood acid-base measurements were identified , 739 in the electronic FHR monitoring group and 680 in the auscultation group . Electronic FHR monitoring had significantly better sensitivity ( 97 % vs 34 % , p < 0.001 ) , lower specificity ( 84 % vs 91 % , p < 0.001 ) , higher positive predictive value ( 37 % vs 22 % , p < 0.05 ) , and higher negative predictive value ( 99.5 % vs 95 % , p < 0.001 ) in detecting fetal acidemia at birth . In addition , electronic FHR monitoring was significantly better in detecting all types of acidemia : metabolic ( 95.5 % vs 26.5 % , p < 0.001 ) , mixed ( 95 % vs 37.5 % , p < 0.001 ) , and respiratory ( 100 % vs 41.5 % , p < 0.001 ) . CONCLUSION These data suggest that electronic FHR monitoring is superior to intermittent auscultation in detecting fetal acidemia at birth Most of the previous r and omized controlled trials have shown no advantage of electronic fetal monitoring ( EFM ) over intermittent auscultation ( IA ) in either lowor high-risk pregnancies [ 1—3 ] , but studies specifically regarding postcesarean pregnancies are sparse . The American College of Obstetricians and Gynecologists recommends both EFM and IA as equally effective in monitoring labor in women with postcesarean pregnancies , whereas British protocol recommends continuous electronic fetal monitoring [ 4 ] . In India , IA is the st and In a r and omised trial involving 13,079 liveborn children intrapartum care by electronic fetal heart rate monitoring , with scalp blood sampling when indicated , was associated with a 55 % reduction in neonatal seizures . Re assessment , when aged 4 , of the 9 children in the intensively monitored group and 21 in the control group who survived after neonatal seizures showed that 3 such children in each group had cerebral palsy . A fourth child in the intensively monitored group with cerebral palsy had had transient abnormal neurological signs during the neonatal period . 8 other children in the intensively monitored group and 7 in the control group who had not had abnormal neurological signs in the neonatal period also had cerebral palsy . 16 ( 78 % ) of the total of 22 cases of cerebral palsy had not shown clinical signs suggestive of intrapartum asphyxia . Thus , compared with intermittent intrapartum monitoring , intensive monitoring has little , if any , protective effect against cerebral palsy : We report the views of 200 women interviewed as part of a large r and omized controlled trial in a Dublin hospital to compare a policy of continuous intrapartum fetal heart rate monitoring ( EFM ) with an alternative policy of intermittent auscultation using a Pinard stethoscope ( IA ) . More women allocated to EFM reported that they felt restricted in their movements than did those allocated to IA . On the other h and , we found no evidence that the method of monitoring either influenced the support that they said they experienced or provided significant reassurance or made them feel more or less in control . There is a suggestion that women monitored with EFM were more likely to be left alone for short periods . This study suggests that the method of monitoring was less important to women in this hospital than the support and reassurance they received from staff and companions . Personal and continuous care from a midwife for all women in labor is a key feature of the hospital 's policy and our study suggests that , in general , this policy was successfully translated into both IA and EFM practice , although the association between the use of EFM and an increase in women being left alone for short periods indicates a need for caution During a r and omized clinical trial concerning alternative methods of intrapartum fetal surveillance ( electronic fetal monitoring ( EFM ) and auscultation ( AUS ) ) an investigatory interview was carried out . Out of 655 expecting mothers the antepartum preference of EFM was 39.5 % , of AUS 32.3 % and 28.1 % were undecided ( UD ) . EFM was especially preferred by obstetrical high-risk patients . Reasons for preference of AUS were a natural childbirth , a non-technological milieu , and the lack of supposed discomfort from sensors and belts . The pregnant women found as major advantages of EFM continuous observation and the possibility of quick intervention . Postpartum 385 patients were again interviewed . The majority upheld the original preference if that method was used . If the non-preferred method had been applied many would stick to the primary preference although a tendency to prefer the experienced method was seen . The patients who antepartum preferred AUS , but had EFM , became more positive toward the method , and a significantly increased number were positively influenced by the EFM signal/trace and found the method promoting their partner 's involvement in labor . Enforced immobility , however , was a major disadvantage as well as the technical milieu . If EFM is to be accepted by a majority of women giving birth it is necessary to increase the pregnant women 's knowledge of the method and to take milieu factors into consideration in order to reduce the intrinsic depersonalization of EFM In a multicenter , r and omized clinical trial , we assessed the early neurologic development of 93 children born prematurely whose heart rates were monitored electronically during delivery and compared it with that of 96 children born prematurely whose heart rates were periodically monitored by auscultation . All the children were singletons with cephalic presentation , and all weighed less than or equal to 1750 g at birth . The mental and psychomotor indexes of the Bayley Scales of Infant Development ( st and ardized mean score + /- SD , 100 + /- 16 ) and a formal neurologic examination were administered at three follow-up visits ( at 4 , 8 , and 18 months of age , corrected for gestational age ) . At 18 months , the mean mental-development scores in the groups receiving electronic fetal monitoring and periodic auscultation were 100.5 + /- 2.4 and 104.9 + /- 1.8 , respectively ( P greater than 0.1 ) . The mean psychomotor-development scores in the two groups at 18 months were 94.0 + /- 2.4 and 98.3 + /- 1.8 , respectively ( P greater than 0.1 ) . The incidence of cerebral palsy was higher in the electronically monitored group--20 percent as compared with 8 percent in the group that was monitored by auscultation ( P less than 0.03 ) . In the electronic-fetal-monitoring group ( but not in the periodic-auscultation group ) , the risk of cerebral palsy increased with the duration of abnormal fetal-heart-rate patterns , as assessed by retrospective review ( chi 2 trend = 12.71 , P less than 0.001 ) . The median time to delivery after the diagnosis of abnormal fetal-heart-rate patterns was 104 minutes with electronic fetal monitoring , as compared with 60 minutes with periodic auscultation . We conclude that as compared with a structured program of periodic auscultation , electronic fetal monitoring does not result in improved neurologic development in children born prematurely Intrapartum continuous fetal heart rate monitoring has been routinely performed at the Jessop Hospital for Women for some years . However , no controlled trials had ever been performed to show its advantages over intermittent auscultation in low-risk patients . A prospect i ve r and omized study of 504 patients compared continuous fetal heart rate monitoring with intermittent auscultation . There was no significant difference between the two groups in neonatal deaths , Apgar scores , maternal and neonatal morbidity , and cord blood gases . The cesarean section rate was significantly increased ( p less than 0.05 ) in the monitored patients but this did not seem attributable to fetal monitoring . No beneficial or deleterious effects of continuous fetal heart rate monitoring in labor were shown To determine if perceptions of preterm labor and birth differed between women who were monitored by electronic fetal monitoring ( EFM ) or by periodic auscultation , 135 subjects were r and omly assigned to one of two treatment groups on admission to a tertiary perinatal care setting . The first group received external monitoring by continuous Doppler and tocodynamometer when membranes were intact , and with an internal fetal scalp electrode and pressure catheter once membranes were ruptured . The second group received periodic monitoring with a DeLee fetoscope or amplified Doppler . All women were cared for on a one-to-one basis by expert study nurses . Subjects completed a question naire about their labor experience during their postpartum hospital stay . There was no statistically significant difference between the two groups on the study measures [ T2(7,81 ) = 13.65 ; F = 1.82 ; P greater than 0.05 ] . Forty-four percent of the variance in women 's global evaluation of labor was explained by their perceptions of nursing support . These findings suggest that mothers ' perceptions of their preterm labor are less influenced by the technologic interventions used than by the supportive care received from nurses A controlled prospect i ve study was conducted to evaluate possible effects of the use of three intrapartum fetal monitoring techniques on the offspring of high-risk mothers in labor after at least 34 weeks ' gestation . Six hundred and ninety women were r and omly assigned to one of the three monitoring groups : auscultation alone , electronic monitoring alone , and electronic monitoring with option to obtain fetal scalp pH. There were no significant differences among the three groups of offspring with respect to neonatal mortality or morbidity , Apgar scores , cord blood gas values , or Brazelton examinations at ages 2 to 3 days . Assessment of the infants at 9 months revealed no significant differences in their growth and development as assessed by physical examination . Bayley Scales of Infant Development , and Milani-Comparetti tests . The frequency of delivery by cesarean section was significantly higher in the electronically monitored group than in the auscultated group . This study failed to show beneficial effects of electronic fetal monitoring over auscultated monitoring for high-risk but relatively mature fetuses |
13,263 | 30,261,057 | No consistent pattern was found between either type of environment targeted , number of type of environment targeted , or the child 's targeted socio-cognitive determinants and intervention effectiveness .
DISCUSSION School-based interventions with direct parental involvement have the potential to improve children 's weight status , physical activity and sedentary behavior . | BACKGROUND The aims of this systematic review were to study the effectiveness of primary school-based physical activity , sedentary behavior and nutrition interventions with direct parental involvement on children 's BMI or BMI z-score , physical activity , sedentary behavior and nutrition behavior and categorize intervention components into targeted socio-cognitive determinants and environmental types using the Environmental Research framework for weight Gain prevention . | This study reports the effect of the Fruits and Vegetables Make the Marks intervention , a school-based fruit and vegetable intervention consisting of a home economics classroom component and parental involvement and encouraged participation in the Norwegian School Fruit Programme , all delivered during the school year of 2001 - 02 . Nine r and omly chosen schools received the intervention and 10 schools served as control schools . Participating pupils completed question naires at baseline ( September 2001 ) , at Follow-up 1 ( May-June 2002 ) and at Follow-up 2 ( May 2003 ) . A total of 369 pupils ( 69 % ; mean age , 11.3 years at baseline ) participated in all three surveys . No effect of the intervention was found for intake of fruit and vegetables eaten at school or all day , neither at Follow-up 1 nor at Follow-up 2 . On analysing the effects on potential mediators , significant differences between intervention and control groups were found for Awareness of the five-a-day recommendations only . The intervention programme was rated as very good by the teachers , and the pupils reported that they enjoyed it . However , the intervention failed to change fruit and vegetable intake , probably because it did not succeed in changing the pupils ' preferences for or the accessibility of fruit and vegetables -- the two strongest correlates of children 's fruit and vegetable intake BACKGROUND AND OBJECTIVES With prevalence of childhood obesity increasing rapidly , developing of effective and sustainable intervention strategies is becoming more and more important for the prevention of childhood obesity in China . A trial was developed to evaluate the effect of comprehensive school-based intervention on childhood obesity . METHODS AND STUDY DESIGN A multi-center cluster r and omized controlled trial was conducted among urban children ( n=9,867 ) aged 6 - 13 years in 38 primary schools from six large cities . Comprehensive intervention , nutrition education and physical activity interventions were carried out among children . Nutrition education was also targeted towards teachers , parents and health workers in intervention schools . The program was implemented for 2 semesters from May 2009 to May 2010 . RESULTS The combined prevalence of overweight and obesity increased by 1.5 percent ( 22.7 % vs 24.2 % , p<0.001 ) in control group while 0.2 percent in comprehensive intervention group ( 23.6 % vs 23.8 % , p=0.954 ) after intervention ( p=0.067 ) . The effect was significantly stronger among girls than boys ( -1.4 % vs -0.9 % , p=0.028 ) . A significant intervention effect was found on BMI for -0.3 kg/m2 ( 95 % confidence interval ( CI ) : -0.4 , -0.2 ; p<0.001 ) , BMI z scores for -0.14 ( 95 % CI : -0.18 , -0.11 ; p<0.001)，body fat for -0.8 percent ( 95 % CI : -0.9 , -0.6 ; p<0.001 ) , waist circumference for -0.5 cm ( 95 % CI : -0.6 , -0.3 ; p<0.001 ) , blood serum glucose for -0.20 mmol/L ( 95 % CI : -0.24 , -0.16 ; p<0.001 ) and cholesterol for -0.32 mmol/L ( 95 % CI : -0.34 , -0.30 ; p<0.001 ) . CONCLUSIONS We observed moderately significant effects on combined prevalence of overweight and obesity , BMI , BMI z scores , waist circumference , percentage body fat , glucose and lipid for a comprehensive school-based intervention of childhood obesity in China Background Childhood obesity has been increasing rapidly worldwide . There is limited evidence for effective lifestyle interventions to prevent childhood obesity worldwide , especially in developing countries like China . The objective of this study was to assess the effectiveness of a school-based multi-component lifestyle childhood obesity prevention program ( the CLICK-Obesity study ) in Mainl and China . Methods A cluster r and omized controlled trial was developed among grade 4 students from 8 urban primary schools ( 638 students in intervention , 544 as control ) in Nanjing City , China . Students were r and omly allocated to the control or intervention group at school-level . A one-year multi-component intervention program ( classroom curriculum , school environment support , family involvement and fun programs/events ) together with routine health education was provided to the intervention group , while the control group received routine health education only . The main outcome variables assessed were changes in body mass index , obesity occurrence , obesity-related lifestyle behaviors and knowledge . Results Overall , 1108 ( 93.7 % ) of the 1182 enrolled students completed the intervention study . The intervention group had a larger marginal reduction than did the control group in overall mean BMI value ( -0.32±1.36 vs. -0.29±1.40 , p = 0.09 ) , although this was not significant . Compared with the control group , the intervention group was more likely to decrease their BMI ( OR = 1.44 , 95%CI = 1.10 , 1.87 ) by 0.5 kg/m2 or above , increase the frequency of jogging/running ( OR = 1.55 , 95%CI = 1.18 , 2.02 ) , decrease the frequency of TV/computer use ( OR = 1.41 , 95%CI = 1.09 , 1.84 ) and of red meat consumption ( OR = 1.50 , 95%CI = 1.15 , 1.95 ) , change commuting mode to/from school from sedentary to active mode ( OR = 2.24 , 95%CI = 1.47 , 3.40 ) , and be aware of the harm of selected obesity risk factors . Conclusions The school-based lifestyle intervention program was practical and effective in improving health behaviors and obesity-related knowledge for children in China . This study provides important policy implication s on school-based intervention programs for modifications of obesity-related lifestyles . Trial Registration Chinese Clinical Trial Registry Background Multi-level , longer-term obesity prevention interventions that focus on inequalities are scarce . Fun ‘ n healthy in Morel and ! aim ed to improve child adiposity , school policies and environments , parent engagement , health behaviours and child wellbeing . Methods All children from primary schools in an inner urban , culturally diverse and economically disadvantaged area in Victoria , Australia were eligible for participation . The intervention , fun ‘ n healthy in Morel and ! , used a Health Promoting Schools Framework and provided schools with evidence , school research data and part time support from a Community Development Worker to develop health promoting strategies . Comparison schools continued as normal . Participants were not blinded to intervention status . The primary outcome was change in adiposity . Repeated cross-sectional design with nested longitudinal sub sample . Results Students from twenty-four primary schools ( clusters ) were r and omised ( aged 5–12 years at baseline ) . 1426 students from 12 intervention schools and 1539 students from 10 comparison schools consented to follow up measurements . Despite increased prevalence of healthy weight across all schools , after 3.5 years of intervention there was no statistically significant difference between trial arms in BMI z score post-intervention ( Mean ( sd ) : Intervention 0.68(1.16 ) ; Comparison : 0.72(1.12 ) ; Adjusted mean difference ( AMD ) : -0.05 , CI : -0.19 to 0.08 , p = 0.44 ) . Children from intervention schools consumed more daily fruit serves ( AMD : 0.19 , CI:0.00 to 0.37 , p = 0.10 ) , were more likely to have water ( AOR : 1.71 , CI:1.05 to 2.78 , p = 0.03 ) and vegetables ( AOR : 1.23 , CI : 0.99 to 1.55 , p = 0.07 ) , and less likely to have fruit juice/cordial ( AOR : 0.58 , CI:0.36 to 0.93 , p = 0.02 ) in school lunch compared to children in comparison schools . More intervention schools ( 8/11 ) had healthy eating and physical activity policies compared with comparison schools ( 2/9 ) . Principals and schools highly valued the approach as a catalyst for broader positive school changes . The cost of the intervention per child was $ 65 per year . Conclusion The fun n healthy in Morel and ! intervention did not result in statistically significant differences in BMI z score across trial arms but did result in greater policy implementation , increased parent engagement and re sources , improved child self-rated health , increased fruit , vegetable and water consumption , and reduction in sweet drinks . A longer-term follow up evaluation may be needed to demonstrate whether these changes are sustainable and impact on childhood overweight and obesity . Clinical trial registration ACTRN12607000385448 ( Date su bmi tted 31/05/2007 ; Date registered 23/07/2007 ; Date last up date d 15/12/2009 ) Background Childhood obesity has been a serious public health problem . An effective school-based physical activity ( PA ) intervention is still lacking in China . This study aim ed to assess the effectiveness of a school-based physical activity intervention during 12 weeks on obesity and related health outcomes in school children . Methods It was a non-r and omized controlled trial . Altogether 921 children aged 7 to 15 years were recruited at baseline survey . Children in the intervention group ( n = 388 ) participated in a multi-component physical activity intervention during 12 weeks that included improvement of physical education , extracurricular physical activities for overweight/obese students , physical activities at home , and health education lectures for students and parents . Children ( n = 533 ) in the control group participated in usual practice . Results Participants had mean age of 10.4 years , mean body mass index ( BMI ) of 19.59 kg/m2 , and 36.8 % of them were overweight or obese at baseline survey . The change in BMI in intervention group ( −0.02 ± 0.06 kg/m2 ) was significantly different from that in control group ( 0.41 ± 0.08 kg/m2 ) . The adjusted mean difference was −0.43 kg/m2 ( 95 % CI : −0.63 to −0.23 kg/m2 , P < 0.001 ) . The effects on triceps , subscapular , abdominal skinfold thickness and fasting glucose were also significant in intervention group compared with control group ( all P < 0.05 ) . The change in duration of moderate to vigorous physical activity ( MVPA ) in intervention group ( 8.9 ± 4.3 min/day ) was significantly different from that in control group ( −13.8 ± 3.3 min/day ) . The adjusted mean difference was 22.7 min/day ( 95 % CI : 12.2 to 33.2 min/day , P < 0.001 ) . Conclusions The school-based , multi-component physical activity intervention was effective to decreasing levels of BMI , skinfold thickness , fasting glucose and increasing duration of MVPA . These findings provided evidence for the development of effective and feasible school-based obesity interventions .Trial registration Clinical trials.gov Identifier : NCT02074332 ( 2014 - 02 - 26 The purpose of the study was to investigate the effects of a school-based prevention program on physical activity , fitness , and obesity . We performed a prospect i ve study in eight Bavarian primary schools ( n = 724 children , 8.4 ± 0.7 years ) r and omized one to one to either an intervention school ( IS , n = 427 ) or a control school ( CS , n = 297 ) . Children in IS attended 10 health-related lessons at school over a period of 1 year . Parents and teachers attended two and three educational health-related lessons , respectively , and also received 10 newsletters on health issues . Daily physical activity ( ≥ 60 min/day ) , physical fitness ( six-item test battery ) , and anthropometric data were obtained at baseline and after 1 year . Physical activity and physical fitness increased in IS , but it failed to reach significant intervention effects . Nevertheless , a reduction in waist circumference was observed for all children [ mean change 1.7 cm ; 95 % confidence interval ( CI ) 1.2 - 2.3 ; P < 0.001 ) . This effect was more pronounced in overweight children ( > 90th percentile , n = 99 , mean change 3.2 cm ; 95 % CI 1.5 - 4.8 ; P < 0.001 ) . This easily administered preventative program involving children , parents , and teachers revealed that a generalized approach increasing physical activity will even be favorable in a subgroup of obese children BACKGROUND The objective of this study , focused on parents and children to reduce sedentary behavior , consumption of soft drinks and high-fat and salt containing snacks , and increase the consumption of fruits and vegetables , was to assess the effect of a six month intervention and an 18 month follow-up intervention on the body mass index , food consumption and physical activity of 2nd and 3rd grade elementary school children . METHODS This was a r and omized cluster controlled trial . School children were selected from 2nd and 3rd ( n = 532 ) grade . MEASUREMENTS BMI z-score for age and sex was calculated and classified according to the WHO ( 2006 ) . Abdominal obesity was defined as WC > 90th of NHANES III . RESULTS At six months of the study differences were observed in BMI , -0.82 ( p = 0.0001 ) . At 24 months , results such as an increase of z-score BMI and waist circumference , a decrease in abdominal obesity , eighth per cent remission and an incidence of 18 % of overweight and obesity were observed . Additionally , an increase ( p = 0.007 ) in vegetable intake and physical activity ( p = 0.0001 ) was also reported , along with a decrease in sedentary activities and the consumption of snacks high in fat and salt . CONCLUSIONS The results of this study indicate that with a comprehensive intervention there is a positive response to lifestyle changes and a reduction of abdominal obesity BACKGROUND Identification of the behavioural , normative and control beliefs influencing children 's behaviour is an important prerequisite in design ing effective interventions . The current study aims to evaluate the effectiveness of an intervention program , based on the Theory of Planned Behaviour ( TPB ) , on obesity indices and blood pressure ( BP ) in Ioannina , Greece . METHODS Participants were 646 fifth grade pupils ( 360 girls and 286 boys ) . The intervention group ( IG ) consisted of 321 children in 13 r and omly selected schools while the rest ( n = 325 children ) served as the control group ( CG ) . Based on the outcome of the TPB question naire , the intervention focused on overcoming the barriers in accessing physical activity areas , increasing the availability of fruits and vegetables and increasing parental support . General linear mixed model and mediating variable analysis were used to evaluate the differences between the two groups and to test whether changes in certain dietary , physical activity and anthropometrical indices mediated the effect of the intervention on BP . RESULTS IG had higher consumption of fruits and lower consumption of fats/oils and sweets/beverages compared with the CG . Intervention 's effect on BMI could be explained by the changes in fruit and fats/oils intake whereas the reduction of systolic and diastolic BP could be explained by the reduction of BMI . CONCLUSIONS The findings indicate favourable changes in BP and obesity indices after the implementation of a 1-year school-based intervention program based on the TPB . These results highlight the importance of developing a social and physical environment that promotes balanced eating behaviours and extra-curricular access to physical activity venues Objective : To evaluate the feasibility and efficacy of the ‘ Healthy Dads , Healthy Kids ’ ( HDHK ) program , which was design ed to help overweight fathers lose weight and be a role model of positive health behaviors for their children . Design : R and omized controlled trial . Participants : A total of 53 overweight/obese men ( mean ( s.d . ) age=40.6 ( 7.1 ) years ; body mass index ( BMI ) = 33.2 ( 3.9 ) ) and their primary school-aged children ( n=71 , 54 % boys ; mean ( s.d . ) age=8.2 ( 2.0 ) years ) were r and omly assigned ( family unit ) to either ( i ) the HDHK program ( n=27 fathers , n=39 children ) or ( ii ) a wait-list control group ( n=26 fathers , n=32 children).Intervention : Fathers in the 3-month program attended eight face-to-face education sessions . Children attended three of these sessions . Outcomes : The primary outcome was fathers ’ weight . Fathers and their children were assessed at baseline , and at 3- and 6-month follow-up , for weight , waist circumference , BMI , blood pressure , resting heart rate ( RHR ) , objective ly measured physical activity and self-reported dietary intake . Results : Intention-to-treat analysis revealed significant between-group differences at 6 months for weight loss ( P<0.001 ) , with HDHK fathers losing more weight ( −7.6 kg ; 95 % confidence interval ( CI ) −9.2 , −6.0 ; d=0.54 ) than control group fathers ( 0.0 kg ; 95 % CI −1.4 , 1.6 ) . Significant treatment effects ( P<0.05 ) were also found for waist circumference ( d=0.62 ) , BMI ( d=0.53 ) , systolic blood pressure ( d=0.92 ) , RHR ( d=0.66 ) and physical activity ( d=0.91 ) , but not for dietary intake . In children , significant treatment effects ( P<0.05 ) were found for physical activity ( d=0.74 ) , RHR ( d=0.51 ) and dietary intake ( d=0.84 ) . Conclusion : The HDHK program result ed in significant weight loss and improved health-related outcomes in fathers and improved eating and physical activity among children . Targeting fathers is a novel and efficacious approach to improving health behavior in their children INTRODUCTION Family- and school-based interventions for childhood obesity have been widely applied ; however , the prevalence of childhood obesity remains high . The purpose of this RCT is to evaluate the effectiveness of a family-individual-school-based comprehensive intervention model . DESIGN Cluster RCT . SETTING / PARTICIPANTS Fourteen primary schools were selected from 26 primary schools in a district of Shanghai , China , and then r and omly divided into intervention and control groups with seven schools in each . The trial started with first- grade students . A total of 1,287 students in the intervention group and 1,159 in the control group were studied overall . INTERVENTION The baseline study was conducted in January 2011 , and family-individual-school-based interventions started in March 2011 and ended in December 2013 for intervention group students . Three follow-up studies were conducted in January 2012 , January 2013 , and January 2014 . Data analysis was conducted in March 2014 . MAIN OUTCOME MEASURES Students ' weight and height were measured . The prevalence of obesity/overweight and BMI z-scores were calculated and analyzed using a generalized estimating equation approach . RESULTS The overall prevalence of overweight/obesity declined from 28.92 % in 2011 to 24.77 % in 2014 , with a difference of 4.15 % in the intervention group compared with a 0.03 % decline ( from 30.71 % to 30.68 % ) in the control group . The intervention group had significantly lower odds of developing obesity or overweight and had decreased average BMI z-scores compared with the control group , especially for obese or overweight students . CONCLUSIONS The family-individual-school-based comprehensive intervention model is effective for controlling childhood obesity and overweight R and omized controlled trials ( RCTs ) are essential for evaluating the efficacy of clinical interventions , where the causal chain between the agent and the outcome is relatively short and simple and where results may be safely extrapolated to other setting s. However , causal chains in public health interventions are complex , making RCT results subject to effect modification in different population s. Both the internal and external validity of RCT findings can be greatly enhanced by observational studies using adequacy or plausibility design s. For evaluating large-scale interventions , studies with plausibility design s are often the only feasible option and may provide valid evidence of impact . There is an urgent need to develop evaluation st and ards and protocol s for use in circumstances where RCTs are not appropriate Background : Be Active Eat Well ( BAEW ) was a multifaceted community capacity-building program promoting healthy eating and physical activity for children ( aged 4–12 years ) in the Australian town of Colac . Objective : To evaluate the effects of BAEW on reducing children 's unhealthy weight gain . Methods : BAEW had a quasi-experimental , longitudinal design with anthropometric and demographic data collected on Colac children in four preschools and six primary schools at baseline ( 2003 , n=1001 , response rate : 58 % ) and follow-up ( 2006 , n=839 , follow-up rate : 84 % ) . The comparison sample was a stratified r and om selection of preschools ( n=4 ) and primary schools ( n=12 ) from the rest of the Barwon South Western region of Victoria , with baseline assessment in 2003–2004 ( n=1183 , response rate : 44 % ) and follow-up in 2006 ( n=979 , follow-up rate : 83 % ) . Results : Colac children had significantly lower increases in body weight ( mean : −0.92 kg , 95 % CI : −1.74 to −0.11 ) , waist ( −3.14 cm , −5.07 to −1.22 ) , waist/height ( −0.02 , −0.03 to −0.004 ) , and body mass index z-score ( −0.11 , −0.21 to −0.01 ) than comparison children , adjusted for baseline variable , age , height , gender , duration between measurements and clustering by school . In Colac , the anthropometric changes were not related to four indicators of socioeconomic status ( SES ) , whereas in the comparison group 19/20 such analyses showed significantly greater gains in anthropometry in children from lower SES families . Changes in underweight and attempted weight loss were no different between the groups . Conclusions : Building community capacity to promote healthy eating and physical activity appears to be a safe and effective way to reduce unhealthy weight gain in children without increasing health inequalities Purpose . This study aim ed to examine the effect of a multicomponent intervention program on consumption of sugar-sweetened beverages ( SSBs ) , and lifestyle factors associated with SSB intake , in Hispanic children from low-income families . Design . A five-wave longitudinal study using a quasi-experimental design was conducted . Setting . Five elementary schools in West Texas served as the setting . Subjects . Participants included 555 predominantly Hispanic children ( ages 5–9 years ) from low-income families and their parents ( n = 525 ) . Intervention . A multicomponent intervention program was implemented . Measures . Children 's anthropometric measures were obtained . Their weight status was determined based on body mass index for age and gender . Parents responded to a demographic question naire , a shelf inventory , an acculturation scale , and a family survey . Analysis . Growth curve analyses were used to test differences between intervention and comparison participants ' SSB intake and to examine potential covariates . Results . Comparison group children 's daily SSB intake significantly increased over time ( B = 1.06 ± .40 ounces per month , p < .01 ) , but this linear increase of SSB was slowed down by the intervention ( B = −.29 ± .12 , p < .05 ) . More daily TV time , more fast food intake , and more types of SSBs available at home were associated with higher SSB intake . Conclusion . Risk factors of childhood obesity were associated with each other . The intervention program produced a modest reduction in SSB consumed by economically disadvantaged and predominantly Hispanic children BACKGROUND Childhood obesity has become a health problem in urban areas in China . Intervention to reduce childhood obesity should be of high priority . School-based intervention programmes are needed to deal with the growing prevalence of childhood obesity in China . METHODS Five primary schools were selected r and omly for this study in the Beijing urban area in China ; two were allocated to the intervention group and three to the control group . A total of 2425 children ( 1029 children in intervention schools and 1396 children in control schools ) took part in the study for 3 years . In the intervention group , children and their parents were involved in a programme of nutrition education and physical activity . Control school students followed their usual health and physical education curriculum with no extra intervention . RESULTS After the 3-year intervention , the prevalence of overweight and obesity were significantly lower in the intervention schools than in the control schools ( overweight : 9.8 % vs. 14.4 % , P < 0.01 ; obesity : 7.9 % vs. 13.3 % , P < 0.01 ) . The prevalence of overweight and obesity decreased by 26.3 % and 32.5 % in intervention schools respectively after intervention . The prevalence of overweight and obesity increased in control schools . There was also significant difference in body mass index between intervention and control schools ( 18.2 + /- 2.6 vs. 20.3 + /- 3.4 , P < 0.01 ) after intervention . More non-obese children became obese in the control schools ( 7.0 % ) than in the intervention schools ( 2.4 % ) at end line ( P < 0.01 ) . Among the children who were obese at baseline , 49.2 % remained obese at end line in intervention schools while 61.9 % remained obese in control schools ( P < 0.01 ) . CONCLUSIONS Our study showed that an intervention programme could be feasible in schools in Beijing , China . The prevalence of overweight and obesity was reduced in schoolchildren in Beijing through an intervention focused on nutrition education and physical activity . Overweight and obesity children as well as normal weight children and their parents should be involved in such an intervention programme The purpose of this study was to evaluate the effectiveness of a new school-based food co-op program , Brighter Bites ( BB ) , to increase fruit and vegetable intake , and home nutrition environment among low-income 1st grade rs and their parents . This was a non-r and omized controlled comparative effectiveness trial ( 2013 - 2015 ) . Six schools received BB ( n=407 parent-child dyads ) ; six comparison schools implemented a coordinated school health program ( n=310 parent-child dyads ) in Houston , Texas , 2013 - 2015 . Brighter Bites ( BB ) is a 16-week school-based food co-op comprising weekly distribution of fresh produce ( 50 servings ) ; nutrition education in schools and for parents ; and weekly recipe tastings . Measurements included parent-reported home nutrition environment surveys , and food frequency question naires for parent and child . Intervention effects were examined using multivariate analyses . At baseline , the sample was 71 % Hispanic , 24 % African American ; 43 % of 1st grade rs were overweight/obese . Children receiving BB had significant increases in intake of fruit servings ( P=0.046 ) , vegetable servings ( P=0.049 ) , and decreased intake of added sugars ( P=0.014 ) . Among parents , there were significant increases in fruit consumed ( P=0.032 ) ; vegetable intake increased baseline to midpoint but not post-intervention . Among BB families , there were significant improvements in the home environment including underst and ing and usage of nutrition facts labels to make food purchases ( P<0.05 ) , frequency of cooking ( P=0.007 ) , rules and practice s regarding eating family meals ( P=0.022 ) , serving fruits ( P=0.005 ) and vegetables ( P=0.028 ) at meals , and limiting portion sizes ( P=0.016 ) . In conclusion , a school-based food co-op model shows promising results in improving dietary habits and home nutrition environment among low-income families BACKGROUND No national policy for health education in schools exists to date in Greece . The first attempt to apply a school-based health education intervention program was launched in 1992 on all 4,171 pupils registered in the first grade in two counties of Crete . The 1,510 pupils registered in a third county served as controls . METHODS The school-based intervention and the seminars organized for parents were primarily aim ed at improving children 's diet , fitness , and physical activity . Pupils in the first grade in a representative sample of 40 schools were examined prior to the intervention program on a variety of health knowledge , dietary , physical activity , fitness , anthropometric , and biochemical indices . The same measurements were taken after 3 years of the program on 288 intervention group and 183 control group pupils . RESULTS Positive serum lipid level changes occurred to a greater extent in the intervention group than the control group . BMI increased less in the intervention group than for controls . The increase in health knowledge and physical activity and fitness levels occurred to a higher extent in the intervention group compared to controls . CONCLUSIONS The short-term changes observed in the present study are markedly encouraging and indicate great potential for progressive improvement . Continuation and expansion of such a program may prove to be beneficial in initiating long-term changes OBJECTIVE To evaluate the 4-year outcome of a school-based health promotion on weight status as part of the Kiel Obesity Prevention Study ( KOPS ) . RESEARCH METHODS AND PROCEDURES Within a cluster- sample d quasi-r and omized controlled trial , 1764 children at 6 and 10 years of age were assessed between 1996 and 2005 in 32 primary schools in Kiel , North Germany . Six nutrition units followed by 20-minute running games were performed within the first year at school . Prevalence , incidence , and remission of overweight were main outcome measures . RESULTS The 4-year change in BMI was + 11.6 % , with increases in prevalence of overweight and obesity from 5.2 % to 11.1 % and 3.9 % to 5.1 % , respectively . Cumulative 4-year incidence of overweight and obesity was 9.2 % and 3.1 % , respectively . Intervention had no effect on mean BMI . The effect on prevalence was significant in children from families with high socioeconomic status [ odds ratio ( OR ) , 0.35 ; 95 % confidence interval ( CI ) , 0.14 to 0.91 ] and marginally significant in children of normal-weight mothers ( OR , 0.57 ; 95 % CI , 0.33 to 1.00 ) . Cumulative 4-year incidence of overweight was lower only in intervention children from families with high socioeconomic status ( OR , 0.26 ; 95 % CI , 0.07 to 0.87 ) . Remission of overweight was most pronounced in children of normal-weight mothers ( OR , 5.43 ; 95 % CI , 1.28 to 23.01 ) . Prevalence of underweight was unchanged . The intervention had minor but favorable effects on lifestyle . DISCUSSION A school-based health promotion has sustainable effects on remission and incidence of overweight ; it was most pronounced in children of normal-weight mothers and children from families with high socioeconomic status . There was no effect on obesity . The data argue in favor of additional measures of prevention OBJECTIVE To explore the effects of an innovative school-based intervention for increasing physical activity . METHODS 226 children ( 5 - 7 years old ) r and omly selected from 12 Australian primary schools were recruited to a cluster r and omised trial with schools r and omly allocated to intervention or control conditions . The 13-week intervention comprised : ( 1 ) altering the school playground by introducing loose material s and ( 2 ) a teacher-parent intervention exploring perceptions of risk associated with children 's free play . The primary outcomes were total accelerometer counts and moderate-vigorous physical activity during break times . Testing took place in Sydney , 2009 - 2010 . RESULTS 221 participants were tested at baseline . Mixed-effect multilevel regression revealed a small but significant increase from the intervention on total counts ( 9400 counts , 95 % CI 3.5 - 15.2 , p=0.002 ) and minutes of MVPA ( 1.8 min , 95 % CI 0.5 - 3.1 , p=0.006 ) ; and a decrease in sedentary activity ( 2.1 min , 95 % CI 0.5 - 3.8 , p=0.01 ) during break times . We retested children in one intervention school after 2 years ; they maintained the gains . CONCLUSIONS Capturing children 's intrinsic motivations to play while simultaneously helping adults reconsider views of free play as risky provided increases in physical activity during break times . Using accelerometry as the sole measure of physical activity may underestimate the effect . TRIAL REGISTRATION ACTRN12611000089932 Background Community-based interventions are needed to reduce the burden of childhood obesity . Purpose To evaluate the impact of a multi-level promotora-based ( Community Health Advisor ) intervention to promote healthy eating and physical activity and prevent excess weight gain among Latino children . Methods Thirteen elementary schools were r and omized to one of four intervention conditions : individual/family level ( Family-only ) , school/community level ( Community-only ) , combined ( Family + Community ) , or a measurement-only condition . Participants were 808 Latino parents and their children enrolled in kindergarten through 2nd grade . Measures included parent and child body mass index ( BMI ) and a self-administered parent survey that assessed several parent and child behaviors . Results There were no significant intervention effects on children ’s BMI z-score . The family intervention changed several obesity-related child behaviors ( e.g. , fruit/vegetable consumption ) and these were mediated by changes in parenting variables ( e.g. , parent monitoring ) . Conclusion A promotora-based behavioral intervention was efficacious at changing parental factors and child obesity-related health behaviors |
13,264 | 30,894,638 | Our results demonstrate that PNB + IVS ( rank 1 ) and SPA ( rank 2 ) were the most effective methods for pain control .
In conclusion , the most effective way to alleviate PBx-related pain appears to be PNB + IVS and SPA . | We aim ed to compare the effectiveness of various local anesthetic methods for controlling prostate biopsy ( PBx ) related pain using network meta- analysis . | PURPOSE We evaluated the efficiency of various amounts of local anesthesia and various numbers of injection sites to determine the most effective pain control with the least number of injections and the amount of injected medium in patients who underwent transrectal ultrasound guided prostate biopsy . MATERIAL S AND METHODS Transrectal ultrasound guided 8 core biopsy of the prostate was performed in 175 consecutive men . Patients were r and omized into 7 groups with 25 per group . Group 1 received 5 cc saline and groups 2 to 7 received 2.5 , 5 or 10 cc 1 % lidocaine injected as local anesthesia at basal or basal plus apical locations . The patients were then evaluated for pain and other complications to determine whether there was a difference regarding groups . RESULTS Mean pain scores were significantly lower than in saline group for all anesthesia injected groups except group 2 with a 2.5 cc bilateral basal injection . The most effective pain control was achieved by 10 cc anesthetic injections . Basal plus apical injections were not superior than only basal injections for pain control . There was no significant difference in the hematuria , hematospermia , rectal bleeding or infection rate among the groups . Increasing the number of injections and amount of lidocaine had no effect on complication rates . CONCLUSION Our placebo controlled , prospect i ve , r and omized study indicated that 10 cc local anesthetic injections supply significantly better pain control than lower doses for periprostatic nerve blockade during prostate biopsy . Although bilateral basal plus apical 10 cc lidocaine injections result ed in the lowest mean pain score , there was no statistically significant difference from 10 cc bilateral basal injections Introduction : To test the hypothesis that periprostatic block could completely relief prostatic biopsy-associated pain . Material s and Methods : Patients scheduled for transrectal ultrasound guided prostate biopsy were r and omized ( 1:1:1 ratio ) to no analgesia ( group A ) , endorectal enema of 1 % lidocaine gel ( group B ) or transrectal periprostatic block ( group C ) . All patients underwent 10 core TRUS-guided biopsy . After the procedure , a ten visual analogue pain score ( VAS ) from 0 = no discomfort to 10 = severe pain was administered to the biopsied patients and a global estimation of pain associated with the procedure was obtained . The study design included interim analysis of pain score after the first 60 patients were enrolled . Kruskal-Wallis test for unpaired data was used for statistical analysis . Data are presented as mean , median ( range ) . Results : Sixty patients were enrolled between May 2003 and December 2003 and all patients were evaluable . Mean and median age was 68.5 and 69 ( range 53–82 ) years , respectively . Mean and median PSA was 86.8 and 9 ng/ml ( range 0.58–4.111 ) , respectively . No major side effects were observed . Patients in group A scored at VAS a median 4 , mean 5.5 ± 2.3 ( range 3–10 ) . Patients in group B scored a median 4 , mean 5.5 ± 2.7 ( range 3–10 ) ( p = 0.237 ) . Patients receiving periprostatic injections of carbocaine ( group C ) scored a median 0 , mean 0.5 ± 0.8 ( range 0–2 ) . The level of pain reported by this group of patients was significantly different from those reported by patients who performed prostatic biopsy without anesthesia or with intrarectal anesthetic jelly ( p = 0.00001 ) . In the periprostatic block group 65 % of patients referred no pain after the procedure ( VAS = 0 ) while all patients in the other groups experience some degree of pain . Conclusion : The use of bilateral periprostatic block is a very effective and useful technique , well tolerated by the patient , which almost completely abolishes the pain and discomfort associated with the prostatic biopsy procedure Background : We aim to compare the degree of pain control and complications in three types of anesthesia using periprostatic nerve block ( PPNB ) plus intrarectal local anesthesia ( IRLA ) , low-dose spinal anesthesia , and intravenous ( IV ) sedation in patients undergoing transrectal ultrasound (TRUS)-guided prostate biopsy . Material s and Methods : In this clinical trial study , 106 patients were participated from December 2015 to December 2016 at Alzahra Hospital , Isfahan , Iran . Patients were r and omly allocated into three groups to receive PPNB plus IRLA ( n = 36 ) , low-dose spinal anesthesia ( n = 35 ) and IV sedation ( n = 35 ) before TRUS-guided prostate biopsy . Pain scores were recorded using a 10 point visual analog scale right after the biopsy was done . Early and late complications were assessed using a question naire after the procedure and in follow-up of patients . Results : Overall , the pain score in the low-dose spinal anesthesia group was significantly lower than PPNB plus IRLA and IV sedation groups ( P < 0.001 ) . The differences in pain scores between PPNB plus IRLA group and IV sedation group were not significant ( P = 0.30 ) . Urinary retraction and fever were significantly more frequent in low-dose spinal anesthesia and IV sedation , retrospectively ( P = 0.04 , P = 0.03 ) . No significant difference in late complications was found among the groups . Conclusion : This study demonstrates that low-dose spinal anesthesia is superior to PPNB plus IRLA and IV sedation in terms of pain controlling and was associated with higher tolerance of the examination and patient comfort PURPOSE Transrectal ultrasonography guided prostate biopsy is the principle procedure in the histological diagnosis of prostate cancer . Recently a trend toward increasing the number of cores has been popularized . This practice further increases the need for a proper anesthetic application . However , there is no consensus on a st and ard local anesthetic strategy , while groups at most institutions currently prefer periprostatic anesthesia . We prospect ively evaluated the contribution of intraprostatic anesthesia for transrectal prostate biopsies even when the sampling number was doubled to 12 cores . MATERIAL S AND METHODS A total of 200 patients who underwent prostate biopsy with transrectal ultrasound guidance were included . The 2 groups received the usual periprostatic anesthesia . Consequently patients were prospect ively r and omized into 2 groups . Group 1 received additional intraprostatic lidocaine injection , while group 2 received the same amount of injection of 0.9 % NaCl . The efficiency of applied local anesthesia was assessed by a visual analog pain scale . RESULTS The study groups were comparable regarding patient age , prostate size and cancer rate . Pain scores revealed that the combination of intraprostatic and periprostatic local anesthesia provided significantly better pain control than periprostatic infiltration alone . No difference was observed regarding the morbidity rate in the 2 groups . CONCLUSIONS The current study suggested that adding intraprostatic local anesthesia provides a significantly efficient strategy during transrectal ultrasound prostate biopsy , even in cases of 12-core sampling . Subsequent trials are needed to establish a st and ard analgesia policy for prostate biopsy We assessed the analgesic efficacy of levobupivacaine when administered as an adjuvant to diclofenac sodium in prostate biopsy pain management and effects of prostate biopsy on sexual function . Ninety patients underwent transrectal ultrasound (TRUS)‐guided biopsy of the prostate and were r and omly assigned to three groups : group D received diclofenac sodium suppository ; Group L received periprostatic injection of levobupivacaine ; group DL received diclofenac suppository and levobupivacaine in addition . Patients were asked to use a visual analogue scale score ( VAS ) question naire about pain after 10 core prostate biopsy . Sixty‐two patients reported to be prostate cancer‐free underwent further evaluation with the International Index of Erectile Function‐5 ( IIEF‐5 ) question naire at 1 and 3 months after biopsy . Mean pain scores during prostate biopsy were significantly lower in group DL and were superior to the group L and group D ( P < 0.001 ) . Mean IIEF‐5 score prior to biopsies was significantly higher when compared with the mean IIEF‐5 score 1 month after biopsy ( P < 0.0001 ) . Mean IIEF‐5 scores 1 month after biopsy were significantly lower when compared with the mean IIEF‐5 scores 3 months after biopsy ( P = 0.002 ) . TRUS‐guided prostate biopsies have a statistically significant impact on short‐term erectile function , but this difference is not clinical ly significant ; however , medium‐term erectile function is not affected both statistically and clinical ly OBJECTIVES To introduce two forms of anesthesia and compare them with st and ard local anesthesia techniques . METHODS A total of 114 consecutive patients underwent prostate needle biopsy . The patients were sequentially r and omized to receive different kinds of anesthesia : 2 % rectal lidocaine gel , 40 % dimethyl sulfoxide ( DMSO ) with lidocaine , perianal injection of 1 % lidocaine , or periprostatic nerve block . Pain perception was separately assessed for probe insertion and biopsies using a visual pain analog score . One-way analysis of variance was used to compare the data scale among the four groups . A linear regression model was used to define the independent variables that predicted the level of pain . RESULTS The groups were similar in terms of age , prostate-specific antigen levels , digital rectal examination findings , prostate volume , pain tolerance , biopsy time , and number of cores taken . The lowest pain scores for probe insertion were for the perianal injection and DMSO/lidocaine groups ( 0.89 and 1.38 , respectively ) . The difference between these scores and those for the other two groups was statistically significant ( P < 0.001 ) . Pain perception during biopsy did not differ significantly among the DMSO/lidocaine , perianal , or periprostatic groups and was greatest in the lidocaine gel group ( 4.147 ; P < 0.001 ) . We did not observe any statistically significant correlation between the pain level during probe insertion and biopsy and pain tolerance ( P = 0.514 and P = 0.788 , respectively ) . The anesthesia type was the strongest single predictor of the pain level during biopsy ( P < 0.001 ) . CONCLUSIONS The use of 40 % DMSO with lidocaine instilled into the rectal vault for 10 minutes avoids any need for injection and is capable of decreasing the discomfort or pain experienced during probe insertion and prostate biopsy comparable to the perianal and periprostatic protocol AIM This study was design ed to compare the effectiveness of intrarectal lidocaine gel versus periprostatic lidocaine injection during transrectal ultrasound (TRUS)-guided prostate biopsy . METHODS Ninety men undergoing transrectal prostate biopsy from July through December 2004 were r and omized into three groups of 30 patients each . Before the biopsy , patients in Group 1 received 20 mL of 2 % lidocaine gel intrarectally ; patients in Group 2 received 5 mL ( 2.5 mL per side ) of 2 % lidocaine solution injected near the junction of the seminal vesicle with the base of the prostate ( along the neurovascular bundles ) , and patients in Group 3 ( control group ) received 5 mL ( 2.5 mL per side ) of normal saline injected along the neurovascular bundles . Pain level after the biopsy was assessed using a 10-point linear visual analog scale ( VAS ) . Results were statistically compared by the Wilcoxon Rank Sum test . RESULTS Patients in Group 2 had significantly lower VAS scores than those in Group 3 ( 3.6 + /- 2.1 vs 5.8 + /- 1.9 , P < 0.0001 ) , but those in Group 1 did not ( 5.5 + /- 2.7 vs 5.8 + /- 1.9 , P = 0.67 ) . Gross hematuria , rectal bleeding , and hemospermia occurred in 36 ( 40.0 % ) , 6 ( 7 % ) and 5 ( 6 % ) patients . One patient had temporary vasovagal syncope . No patient reported febrile urinary tract infection or urinary retention . CONCLUSIONS Periprostatic injection of local anaesthetic is a safe technique that significantly reduces pain during prostate biopsy , whereas intrarectal lidocaine injection did not reduce pain . This safe , simple technique should be applied in men undergoing TRUS-guided prostate biopsy to limit patient discomfort OBJECTIVE To compare the level of pain experienced by patients during transrectal ultrasound-guided prostatic biopsy using intrarectal 2 % lidocaine gel versus plain lubricant gel . DESIGN Prospect i ve double-blind r and omised controlled trial . SETTING Regional hospital , Hong Kong . PATIENTS From March 2002 to December 2003 , patients who underwent ultrasound-guided prostate biopsy at a Geriatric Urology Centre . MAIN OUTCOME MEASURES Pain and discomfort scores measured by horizontal visual analogue scales . RESULTS A total of 338 consecutive patients were r and omised to lidocaine gel or plain lubricant gel groups . The two groups were statistically similar in demographic and disease characteristics . There were no significant statistical differences in pain or discomfort score in the lidocaine gel and plain lubricant groups -- pain score : 1.75 versus 1.79 ( P=0.66 ) on day 0 and 0.21 versus 0.15 ( P=0.97 ) on day 1 ; discomfort score : 0.79 versus 0.77 ( P=0.86 ) on day 0 and 0.12 versus 0.12 ( P=0.76 ) on day 1 . No major complications were recorded in this cohort . CONCLUSIONS Transrectal ultrasound-guided trucut biopsy of the prostate can be safely performed with no anaesthesia in Chinese patients . Pain and discomfort are minimal . It was found that 2 % lidocaine gel has no statistical therapeutic or analgesic benefit over plain lubricant gel INTRODUCTION Studies have demonstrated the need for pain control during multiple transrectal prostate biopsies . Due to encountered published results on periprostatic nerve block , we prospect ively evaluated the efficacy and safety of periprostatic local anaesthesia at the apex in comparison to intrarectal lidocaine gel . METHODS From January 2001 to January 2002 110 patients underwent prostate biopsy . Patients were r and omized to receive 10 cc of either 2 % lidocaine gel intrarectally ( Group 1 ) or 10 cc of 1 % lidocaine solution injected under ultrasound guidance for bilateral periprostatic nerve block at the apex ( Group 2 ) . Pain during biopsy was assessed using a 10-point linear visual analog pain scale and a 5-point digital visual pain scale ( continuous variables ) . Statistical analysis of pain scores was performed using the Student t-test . RESULTS 96 patients fitted the inclusion and presented no exclusion criteria . 43 patients composed group 1 , and 53 patients group 2 . The mean pain score was 2.76+/-1.69 and 1.73+/-1.26 for group 1 and 2 , respectively for the 10-point linear visual analog pain scale ( p=0.001 ) . The mean pain score was 2.26+/-0.82 and 1.62+/-0.56 for groups 1 and 2 , respectively for the 5-point digital visual pain scale ( p<0.001 ) . There was no difference in mean patient age ( p=0.348 ) , prostate size ( p=0.899 ) , serum PSA ( p=0.932 ) , and complications when comparing both groups . The number of biopsies per patient was significantly higher in group 2 ( p=0.006 ) , but pain scores in each scale were significantly less . CONCLUSIONS Periprostatic nerve block at the apex is superior to intrarectal lidocaine gel for controlling pain during transrectal prostate biopsy , with no increased complications . This technique should be recommended for those patients without anal or rectal inflammatory diseases Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more PURPOSE We evaluated the effect of intracapsular anesthesia and periprostatic nerve block during transrectal ultrasound guided prostate biopsy . MATERIAL S AND METHODS In a prospect i ve , r and omized , double-blind , placebo controlled study 152 consecutive patients were r and omized into 3 groups . Group 1 of 41 patients was administered intraprostatic local anesthesia into the right and left sides with a total of 2 ml 1 % lidocaine and a periprostatic injection of 2 ml saline later . Group 2 of 49 patients was administered intraprostatic injection of 2 ml saline , followed by periprostatic local anesthesia with 2 ml 1 % lidocaine . Group 3 of 62 patients received intraprostatic and periprostatic local anesthesia with 2 ml 1 % lidocaine . Patients were asked to grade the pain level using a 10-point linear visual analog pain scale 1 ) when the transrectal ultrasound probe was inserted , 2 ) during anesthesia , 3 ) during biopsy and 4 ) 20 minutes after biopsy . One-way ANOVA and the Kruskal-Wallis test with the Tukey post hoc test were used to compare patient characteristics and pain scale responses among the 3 groups . RESULTS No major complications , including sepsis and severe rectal bleeding , were noted in any patient . There were statistically significant differences in pain scores among groups 1 to 3 during anesthesia ( mean + /- SD 5.6 + /- 2.5 , 6.7 + /- 2.3 and 4.9 + /- 2.1 , p = 0.003 ) and during biopsy ( 4.3 + /- 2.7 , 4.5 + /- 2.6 and 2.7 + /- 2.1 , respectively , p = 0.032 ) . There were no differences in pain scores among the 3 groups during probe insertion ( p = 0.39 ) . CONCLUSIONS A combination of intracapsular anesthesia and periprostatic nerve block is an effective and useful technique that is well tolerated by the patient . It decreases the level of pain and discomfort associated with the prostatic biopsy procedure Prostate biopsy is usually performed without anesthesia . We evaluated the patient ’s perception of pain/discomfort experienced during the procedure in terms of the type of anesthesia used : periprostatic infiltration with 2 % lidocaine , or intrarectal instillation of lidocaine-prilocain cream . A total of 198 patients were divided into three groups : group 1 ( control group , n=40 ) received sonographic gel intrarectally prior to biopsy , group 2 ( n=75 ) were given intrarectal instillation of lidocaine-prilocain cream , and group 3 ( n=80 ) received periprostatic anesthesia by injecting 10 ml of 2 % lidocaine . Pain after each biopsy was assessed using an 11-point linear visual analog pain scale . The mean pain scores were 5.1 in group 1 , 4.8 in group 2 , and 2.5 in group 3 , result ing in a significant difference between group 3 and both groups 1 and 2 , but not between groups 1 and 2 . The incidence of biopsy-related adverse events did not differ among groups . Transrectal ultrasonographic guided periprostatic anesthesia is superior to intarectal instillation of lidocaine-prilocain cream Purpose Prostate biopsy for diagnosing cancer can be painful . The efficacy and safety of combination perianal-intrarectal lidocaine-prilocaine ( PILP ) cream and periprostatic nerve block were compared with nerve block alone during transrectal ultrasound guided prostate biopsy ( TRUS-Bx ) . Material s and Methods From October 2007 to August 2009 , 74 men undergoing a transrectal prostate biopsy were r and omized into two groups . In group 1 , 36 patients received a combination of PILP cream and a periprostatic nerve block ; and in group 2 , 38 patients received lubricant jelly and a periprostatic nerve block . Thirty minutes later , the TRUS-Bx was performed . Pain was evaluated by a 10-point visual analogue scale ( VAS ) after the biopsy . Results Patients in group 1 showed a significantly lower VAS score than patients in group 2 ( mean score 2.22±0.89 vs. 3.02±1.15 , p<0.001 ) . In addition , there was a difference in the number of patients that had a pain score of three or more , 44 % in group 1 , and 65 % in group 2 . The overall complication rate was similar in both groups ( p=0.45 ) . Conclusions A combination of PILP cream and periprostatic nerve block reduced pain compared to the periprostatic nerve block alone . This safe , simple technique can be considered prior to TRUS-Bx to reduce patient discomfort OBJECTIVE To assess the benefit of the periprostatic administration of lidocaine previously to ultrasound-guided prostate biopsy . MATERIAL S AND METHODS In the period from April to October 2002 , forty patients underwent ultrasound-guided prostate biopsy due to increased PSA or abnormal digital rectal examination . A r and omized double-blind study was performed , where the patients received an injection of lidocaine 2 % or saline solution , in a total of 10 ml periprostatic . Immediately following the biopsy , the pain associated to the procedure was assessed , using a visual analogical scale from 0 to 10 . The mean number of fragments collected per patient in the biopsies was 11.3 . The statistical analysis used for assessment of pain was the Student 's t , with p < 0.05 being significant . RESULTS The groups were homogeneous concerning the anthropometrical data . In relation to pain , those patients in the groups that underwent biopsy with the use of lidocaine presented a maximum score of 6 , while in the group that underwent biopsy with the use of saline solution , 4 patients presented score 7 ou 8 . The mean score and st and ard deviation with lidocaine were 2.55 + /- 2.34 ( CI 95 % = 1.53 to 3.57 ) and with saline solution were 3.75 + /- 2.52 ( CI 95 % = 2.66 + /- 4.84 ) with no statistical significant difference between the groups . CONCLUSION The lidocaine injection did not show statistical difference when compared with saline solution in the periprostatic blockade during echo-guided prostate biopsy Abstract Objective . To evaluate the pain score during transrectal ultrasound (TRUS)-guided prostate biopsy using three different anaesthetic applications and no anaesthesia . Material and methods . One-hundred men undergoing TRUS-guided prostate biopsy were prospect ively enrolled in this study . Patients were r and omized to four groups . Group 1 ( n = 25 ) received no anaesthesia , group 2 ( n = 25 ) was administered a perianal lidocaine injection , group 3 ( n = 25 ) was administered a periprostatic lidocaine injection , and group 4 ( n = 25 ) was administered a combination of perianal – intrarectal lidocaine – prilocaine cream . The anaesthetic application was given 5 min before the procedure . All patients were asked to indicate the level of pain experienced on a visual analogue scale ( VAS ) during three situations , including when the TRUS probe was inserted and 15 min and 2 weeks after biopsy . Results . Mean pain scores were similar in all groups at the time of probe insertion . Mean pain scores showed statistically significant differences between group 1 and the other groups , except for group 4 , 15 min after the procedure . Group 3 showed better pain control 15 min after biopsy and this difference was statistically significant ( p < 0.043).The VAS scores were similar 2 weeks after the procedure in all groups . Conclusions . Anaesthetic application before TRUS-guided prostate biopsy may be advocated . The application of periprostatic lidocaine seems to be the most advantageous method for lowering the perception of pain Objective : To determine the efficacy of intrarectal lidocaine gel alone and a combination of lidocaine gel with 2 different longer-acting local anesthetic ( LA ) agents that were injected into the periprostatic area before transrectal ultrasound-guided prostate biopsy . Patients and Methods : One hundred patients undergoing transrectal prostate biopsy were r and omized into 4 groups of 25 patients each . Before the biopsy , group 1 received no local anesthesia , group 2 received 2 % lidocaine gel intrarectally , group 3 received intrarectal lidocaine gel and 5 ml bupivacaine ( 0.25 % ) injected into periprostatic area , and group 4 received lidocaine gel intrarectally and a 5-ml ropivacaine injection ( 0.25 % ) in the same location as group 3 . Pain levels during and after the biopsy were assessed by using a 10-point linear visual analog scale ( VAS ) . Results : Patients in groups 3 and 4 had significantly lower VAS scores than those in groups 1 and 2 , both during and 1 h after biopsy . There were no differences in the pain scores between groups 1 and 2 . Conclusion : The combination of intrarectal lidocaine gel and periprostatic longer-acting LA agents significantly reduces the pain related to prostate biopsy , whereas intrarectal lidocaine gel administration alone does not reduce pain . Thus , administration of the periprostatic longer-acting LA agents alone is adequate OBJECTIVES To compare pain control results between periprostatic nerve block alone and combined with topical prilocaine-lidocaine cream as local anesthesia of prostate biopsy . METHODS Three hundred patients were r and omized to receive PNB ( group 1 ) , topical anesthesia of the anal ring , anal canal , and anterior rectal wall combined with PNB ( group 2 ) and placebo ( group 3 ) . Patients were asked to use scale of 0 - 10 to complete a visual analogue scale question naire about pain during probe insertion ( VAS1 ) , periprostatic infiltration ( VAS2 ) , and cores ( VAS3 ) . RESULTS Pain during probe insertion in group 2 was significantly less than in groups 1 and 3 ( VAS1 , 0.29 vs. 1.46 and 1.48 ; p<0.0001 ) . Pain during periprostatic infiltration was also reduced in group 2 compared with group 1 ( VAS2 , 1.06 vs. 2.39 ; p<0.0001 ) . Pain control was similar during biopsy in the PNB and combined groups ( VAS3 , 0.43 vs. 0.37 ; p=0.77 ) and was superior to group 3 ( VAS3 , 3.02 ; p<0.0001 ) . In younger patients ( cut off , median age 67 yr ) these differences were still significant between groups 1 and 2 ( VAS1 , 1.95 vs.0.31 ; p<0.0001 and VAS2 , 2.97 vs. 1,15 ; p<0.0001 ) , but not in older patients ( VAS1 , 0.91 vs. 0.28 ; p=0.06 ; VAS2 , 1.52 vs. 0,92 ; p=0.06 ) . Vagal symptoms were registered in 36 ( 12 % ) patients in all groups . Sepsis occurred in one group 1 patient and in one group 2 patient . Rectal bleeding was observed in one group 2 patient . CONCLUSION Combined prilocaine-lidocaine cream topically placed with PNB is superior to PNB alone and may be of maximum benefit for younger patients OBJECTIVES To report a new method to block pelvic plexus and compare its efficacy with widely used periprostatic nerve block ( PPNB ) for transrectal ultrasonography-guided prostate biopsy . Pelvic plexuses were localized with the aid of color Doppler ultrasonography to create the pelvic block . METHODS This study was a single-center , prospect i ve r and omized trial . A total of 80 patients were recruited in 2 groups , with 40 patients in each . In group 1 ( PPNB group ) , 2 mL of 2 % lidocaine was injected between the prostate base and seminal vesicle on each side , using ultrasonic guidance . In group 2 ( pelvic plexus block group ) , 2 mL of 2 % lidocaine was injected into the region of the pelvic plexus lateral to the tip of vesicula seminalis on each side , using ultrasonic guidance . Color Doppler ultrasonography was used to identify injection sites . Patients were given an 11-point visual analog scale ( VAS ) to evaluate the level of pain encountered during probe insertion , injection of local anesthetic , and biopsy procedure . RESULTS In both groups , probe insertion was the least painful stage . With regard to local anesthetic injection , VAS pain score was significantly lower in group 2 ( 2.05 vs 3.12 , P = .0007 ) . Sampling the prostate was the most painful stage in both groups and group 2 had significantly lower biopsy VAS pain scores ( 2.7 vs 4.97 , P < .0001 ) . There were no major complications . CONCLUSIONS Administration of lidocaine in the area of the pelvic plexus under Doppler ultrasonographic guidance provides superior analgesia to PPNB , with limited morbidity during transrectal ultrasonography-guided biopsy of the prostate We have evaluated objective ly pain tolerance in transrectal ultrasound-guided prostate biopsy ( TRUS ) using local periprostatic per rectal anesthesia as compared to the conventional method . From November 2008 to May 2009 , 90 patients underwent transrectal ultrasound-guided prostate biopsy at Department of Urology , Clinical Center University Sarajevo . 90 patients who fulfilled the inclusion criteria were r and omized into 3 groups of 30 patients each . Group 1 received periprostatic local anesthesia with 2 % lidocaine , group 2 received Voltaren supp placed in rectum an hour before biopsy while group 3 received no local anesthesia . Pain scale responses were analyzed for each aspect of the biopsy procedure with a visual analog scale of 0-none to 10-maximal . There was no difference between the 3 groups in pain scores during digital rectal examination , intrarectal injection and probe insertion . The mean pain scores during needle insertion in group 1 receiving periprostatic nerve block and in group 2 receiving Voltaren supp were 3,10 + /- 2,32 and 5,15 + /- 2,01 respectively . In group 3 ( no local anesthesia ) , mean pain scores were 6,06 + /- 2,95 which was found to be significantly different ( p < 0,001 ) . However , morbidity after the biopsy was not statistically different between all 3 groups . TRUS-guided prostate biopsy is a traumatic and painful experience , but the periprostatic blockage use is clearly associated with more tolerance and patient comfort during the exam . It is an easy , safe , acceptable and reproducible technique and should be considered for all patients undergoing TRUS biopsy regardless of age or number of biopsies PURPOSE Prostate biopsy is an invasive procedure that may be painful and require some form of anesthesia . We compared the pain control results of periprostatic nerve block alone vs periprostatic nerve block with intraprostatic anesthesia as local anesthesia for prostate biopsy . MATERIAL S AND METHODS A total of 300 patients who underwent transrectal ultrasound guided prostate biopsy were r and omized into 3 groups . Group 1 of 100 patients received periprostatic nerve block and intraprostatic local anesthesia with 5 ml 2 % lidocaine . Group 2 of 100 patients received periprostatic nerve block and the same amount of 0.9 % NaCl by intraprostatic injection . Group 3 of 100 patients received no anesthesia . Patients were asked to use a scale of 0 to 10 to complete a visual analog scale question naire about pain during probe insertion , anesthesia and biopsy . RESULTS Pain control was similar during probe insertion and anesthesia in the 3 groups ( p = 0.885 and 0.227 , respectively ) . Pain during biopsy in group 1 was significantly less than in groups 2 and 3 ( p < 0.0001 ) . In patients with a smaller prostate volume ( 48 ml or less ) these differences were still significant between group 1 and 2 ( p < 0.0001 ) , although not in patients with a larger prostate volume ( greater than 48 ml ) ( p = 0.185 ) . In patients 66 years old or younger these differences were also significant in groups 1 and 2 ( p < 0.0001 ) but not in older patients ( p = 0.155 ) . CONCLUSIONS Combining periprostatic nerve block and intraprostatic local anesthesia provided significantly better pain control than periprostatic nerve block alone . The combination may be of maximum benefit in patients with a smaller prostate volume or younger patients OBJECTIVE To assess the efficacy and safety of periprostatic lignocaine injection in trans-rectal ultrasound ( TRUS ) -guided biopsy of the prostate gl and . METHODS Ninety-six men ( mean age 65 years , range 47 - 74 ) undergoing TRUS biopsy were r and omised into the local anaesthetic ( LA ) or placebo group . Six to twelve biopsy cores were taken , the majority being 10 cores . Patients were asked to fill in the expected pain score on a visual analogue scale ( VAS ) prior to the procedure . They also completed the actual pain experienced on VAS after the biopsy . The incidence of complications was documented . RESULTS The age , mean prostate specific antigen ( PSA ) were comparable in both groups . The expected pain score was also comparable ( 5.2 + /- 1.6 in LA , 5.0 + /- 1.4 in Placebo ) . In the LA group , the mean actual pain score was 3.0 + /- 1.8 and in the placebo group it was 6.5 + /- 2.2 ( P = 0.0001 ) . When patients were asked whether they would undergo the procedure again in the same way , 100 % of the LA group and only 64 % of the placebo group responded ' yes ' ( P = 0.002 using Fisher 's test ) . The complication rates were not significantly different between the two groups . CONCLUSION Peri-prostatic injection of local anaesthetic is safe and reduces discomfort significantly , and should be routinely offered to patients PURPOSE To our knowledge the optimal analgesia during prostate biopsy remains undetermined . We tested the efficacy and safety of combined perianal-intrarectal lidocaine-prilocaine cream and periprostatic nerve block during transrectal ultrasound guided prostate biopsy . MATERIAL S AND METHODS A total of 280 patients were r and omized to receive combined perianal-intrarectal lidocaine-prilocaine cream and periprostatic nerve block ( group 1 ) , perianal-intrarectal lidocaine-prilocaine cream alone ( group 2 ) , periprostatic nerve block alone ( group 3 ) or no anesthesia ( group 4 ) before transrectal ultrasound guided prostate biopsy . Pain was evaluated with a 10-point visual analog scale at subsequent procedural steps , including perianal-intrarectal substance administration , prostate transrectal ultrasound , periprostatic nerve block and sampling . Complications were assessed by self-administered question naire and telephone interview . RESULTS The groups were comparable in patient age , prostate volume , pathology results and visual analog scale perianal-intrarectal substance administration . Visual analog scale results for transrectal ultrasound were lower in groups 1 and 2 vs 3 and 4 ( mean 1.5 and 1.41 vs 5.37 and 5.31 , p < 0.001 ) and results for periprostatic nerve block were lower in group 1 vs 3 ( mean 1.03 vs 3.74 , p < 0.001 ) . Results for sampling were lower in groups 1 to 3 vs 4 ( mean 0.77 , 1.27 and 1.27 vs 4.33 , p < 0.001 ) and in group 1 vs 2 and 3 ( p < 0.001 ) . Stratified analysis showed that visual analog scale sampling was lower in group 1 vs 2 and 3 in patients 65 years old or younger , those with a prostate greater than 49 cc and those with lower anorectal compliance ( visual analog scale results for perianal-intrarectal substance administration greater than 2 ) ( p = 0.006 , < 0.001 and 0.003 , respectively ) . The overall complication rate was similar in all 4 groups ( p = 0.87 ) . CONCLUSIONS Our findings suggest that the combination of perianal-intrarectal lidocaine-prilocaine cream and periprostatic nerve block provides better pain control than the 2 modalities alone during the sampling part of transrectal ultrasound guided prostate biopsy with no increase in the complication rate . The magnitude of this effect is higher in younger men , men with a larger prostate and men with lower anorectal compliance OBJECTIVE To compare the efficacy and tolerability of spinal saddle block vs periprostatic lignocaine injection for anesthesia during transrectal prostate biopsy . METHODS A total of 75 patients were r and omized to undergo prostate biopsy in 3 groups ( n = 25 ) . Group 1 had no anesthesia , group 2 had periprostatic lignocaine injection , and group 3 had spinal saddle block . All patients had sextant biopsy . The groups were assessed for pain , level of cooperativeness , willingness to have a repeat biopsy , complication rate , and the duration of the procedure . RESULTS The mean age in the groups were , respectively , 65.0 ( ±5.7 ) ( group 1 ) , 65.5 ( ±9.3 ) ( group 2 ) , and 68.6 ( ±6.3 ) ( group 3 ) years . There was no statistical difference between the groups with respect to age , prostate volume , number of biopsies taken , and the prostate-specific antigen . The mean visual analog score in the groups was , respectively , 5.7 ( ±2.3 ) , 4.6 ( ±2.3 ) and 0.7 ( ±1.6 ) for groups 1 - 3 . The difference between groups 1 and 2 was not statistically significant ( P = .181 ) , whereas the difference between groups 2 and 3 and groups 1 and 3 was highly statistically significant ( P = .000 ) . There were also highly statistically significant differences in levels of cooperativeness and duration of the procedure between group 3 and groups 1 and 2 . The differences between the groups with respect to complication rates and willingness to have a repeat biopsy were not statistically significant . CONCLUSIONS Spinal saddle block was a more effective method of anesthesia than periprostatic lignocaine . It did not sacrifice the current outpatient/day case setting for prostate biopsy . It could be offered routinely to patients undergoing prostate biopsy PURPOSE Since the introduction of prostate specific antigen ( PSA ) screening , asymptomatic men often undergo transrectal ultrasound guided prostate biopsy . This procedure may cause significant discomfort , which may limit the number of biopsies . We performed a r and omized prospect i ve study to compare periprostatic infiltration with 1 % lidocaine with intrarectal instillation of 2 % lidocaine gel before prostate biopsy . MATERIAL S AND METHODS From October 1999 to July 2000 , 150 men underwent prostate biopsy at the Miami Veterans Administration and Jackson Memorial Hospital . Experienced senior residents performed all biopsies . Patients were r and omized into 2 groups depending on the method of anesthetic delivery . A visual analog scale was used to assess the pain score . Statistical analysis of pain scores was performed using the Student t test . RESULTS Ultrasound guided prostate biopsy was done in 150 cases . There was a statistical difference in the mean pain score after periprostatic infiltration and intrarectal instillation ( 2.4 versus 3.7 , p = 0.00002 ) with patients receiving periprostatic infiltration reporting significantly less pain . CONCLUSIONS Men should have the opportunity to receive local anesthesia before ultrasound guided prostate biopsy with the goal of decreasing the discomfort associated with this procedure . Our prospect i ve r and omized study indicates that ultrasound guided periprostatic nerve block with 1 % lidocaine provides anesthesia superior to the intrarectal placement of lidocaine gel BACKGROUND In the present study , we assessed the efficacy and morbidity of periprostatic local anesthesia before transrectal ultrasound (TRUS)-guided biopsy of the prostate . METHODS From August 2001 to February 2002 , 98 patients underwent TRUS-guided prostate biopsy at the Department of 2nd Urology , Ankara Numune Education and Research Hospital , Ankara , Turkey . Ninety patients who fulfilled the inclusion criteria were r and omized into three groups of 30 patients each . Group 1 received no local anesthesia , while group 2 received a periprostatic saline injection 5 min before the biopsy and group 3 received periprostatic local anesthesia with 1 % lidocaine . Pain-scale responses were analyzed for each aspect of the biopsy procedure using a visual analog scale . RESULTS There were no differences in pain scores between the three groups during digital rectal examination , intramuscular injection and probe insertion . Mean pain scores during needle insertion in groups 1 , 2 and 3 were 5.65 + /- 2.35 , 6.25 + /- 2.04 and 3.16 + /- 2.14 , respectively . There was no significant difference between the pain scores of groups 1 and 2 , whereas pain scores decreased significantly in group 3 . CONCLUSION Periprostatic local anesthesia before prostate biopsy is a safe and easy method to increase patient comfort during the procedure OBJECTIVE Although transrectal ultrasound-guided prostatic biopsies are associated with significant discomfort and pain , most urologists do not use any kind of anaesthesia . We therefore compared the efficacy of two local anaesthetics , namely , the rectal administration of lidocaine gel and lidocaine periprostatic infiltration prior to biopsies . DESIGN AND METHODS Three hundred and fifty-six r and omized patients received either 15 mL of 2 % lidocaine gel administered intrarectally ten minutes before prostate biopsies in group 1 ( 180 patients ) or 10 mL of 1 % lidocaine given under ultrasound guidance in two periprostatic injections of 5 mL , four minutes before the biopsies in group 2 ( 176 patients ) . A visual analogue scale ( VAS ) was used to assess the pain score during anaesthesia ( VAS 1 ) , during the biopsies ( VAS 2 ) and 30 minutes after them ( VAS 3 ) . RESULTS Patients receiving lidocaine gel experienced statistically less pain than the lidocaine injection group for mean VAS 1 ( 0.1 vs 1.4 , p < 0.0001 ) and mean VAS 3 ( 0.8 vs 1.4 , p < 0 . 001 ) but VAS 2 showed no statistically significant difference ( 2.0 vs 2.1 ) . No major morbidity was noted with either anaesthetic . CONCLUSION Rectal administration of lidocaine gel is both safe , simple and effective and results are more satisfactory than with lidocaine periprostatic infiltration Introduction : Controversy exists over the pain during prostate biopsy . Periprostatic nerve block ( PNB ) is a gold st and ard anesthetic technique during transrectal ultrasound (TRUS)-guided prostate biopsy . Recent studies showed that PNB alone is insufficient as analgesic . We compared the efficacy of tramadol and intraprostatic nerve block ( INB ) in addition to PNB . Material s and Methods : We conducted a prospect i ve double blinded placebo controlled study at our institute in 150 consecutive patients . Patients were r and omized into three groups . Group A received PNB with INB with 1 % lignocaine . Group B received oral tramadol with PNB . Group C patients were administered PNB only with 1 % lignocaine . Patients were asked to grade the pain level using 11 point linear visual analog scale ( VAS ) at the time of ultrasound probe insertion , at time of anesthesia , during biopsy , and 30 min after biopsy . Results : The study groups were comparable in demographic profile , prostate-specific antigen ( PSA ) levels , and prostate size . Group A recorded the minimum mean pain score of 2.66 during prostate biopsy which was significantly lower than group 3 ( P < 0.001 ) . Group B recorded significantly lower pain score at time of probe insertion and at anesthetic needle insertion than other two groups . Conclusions : PNB provides better pain control in TRUS-guided prostate biopsy but still there is need of additional analgesic in the form of tramadol or INB . Tramadol has advantage of oral intake and analgesic effect at time of probe insertion and at nerve block . Both tramadol and INB may be used in combination along with PNB OBJECTIVES One of the long-term consequences of estrogen deficiency in postmenopausal women is an increased risk of osteoporosis . Fractures of the hip and lumbar spine are associated with considerable morbidity and mortality . Estrogen replacement therapy reduces the risk of osteoporosis , but there is no clear agreement on the most appropriate doses to be used . The aim of this study was to compare changes in bone mineral density ( BMD ) measurements using conventional and lower dose estradiol . METHODS A prospect i ve , r and omized , placebo-controlled 12-month study of the effect of 1 and 2 mg estradiol on BMD in 152 hysterectomized postmenopausal Chinese women with no contraindication to the use of estrogen replacement therapy . RESULTS Over 12 months , spinal BMD in placebo treated patients decreased by a mean of 2 % from baseline ( -0.02+/-0.03 g/cm(2 ) ) while it increased by 2 % in the 1 mg ( 0.02+/-0.03 g/cm(2 ) ) and 3 % in the 2 mg group ( 0.03+/-0.03 g/cm(2 ) ) . Mean changes in BMD over 12 months in the hip were -0.02+/-0.02 g/cm(2 ) ( -2 % ) , 0.01+/-0.02 g/cm(2 ) ( + 1 % ) and 0.01+/-0.03 g/cm(2 ) ( + 1 % ) in the placebo , 1 and 2 mg estradiol groups , respectively ( P<0.05 ) . Relative to placebo , increases in BMD in both 1 and 2 mg groups were statistically significant for both spine and hip ( P<0.05 ) . However , there was no significant difference in the increase in BMD between the 1 and 2 mg doses for either lumbar spine or hip ( P=0.82 , 0.53 , respectively ) . CONCLUSION The results of our study show that a 1 mg dose of oral estradiol is effective in preventing bone loss in postmenopausal Chinese women INTRODUCTION AND OBJECTIVES Transrectal ultrasound guided biopsy is an essential part in the diagnosis of prostate cancer . Although this procedure is well tolerated by most patients , sometimes it can result in some uneasiness . In this r and omised double-blind placebo controlled study , we evaluated the effectiveness of intrarectal lidocaine during TRUS guided biopsy . MATERIAL S AND METHODS 100 consecutive eligible patients who had elevated total prostate specific antigen ( tPSA ) and /or abnormal digital rectal examination ( DRE ) were included into this study . Patients were r and omised into two groups . Group I received 20 cc of 2 % intrarectal lidocaine 20 minutes before transrectal ultrasound guided biopsy and Group II received same amount of serum physiologic . Pain was assessed using a 10 point modified visual analog scale . RESULTS Mean patient age was 65.5+/-2.5 and 64.5+/-11.5 years , mean tPSA was 12.3+/-3.6 and 11.3+/-1.7 ng/ml , mean biopsy duration was 6.8+/-2.5 and 6.6+/-2.2 minutes , mean pain score during transrectal ultrasound guided biopsy was 4.8+/-2.2 and 4.4+/-2.1 in Groups I and II , respectively . No statistically significant difference was observed with respect to age , tPSA , mean biopsy duration and pain score between these groups . There was only one patient who could not tolerate the procedure at all , and he was paradoxically in the lidocaine group . CONCLUSION The use of intrarectal lidocaine is not superior to placebo during transrectal prostate biopsy for pain control Introduction Currently , the use of local anesthetic at the time of transrectal ultrasound-guided biopsy of the prostate is not universally accepted , as the needle injection itself causes pain . In prior studies , lidocaine was compared to placebo in separate patient groups . We present the first study to evaluate both lidocaine and placebo injected in each patient . Material s and methods Fifty patients received periprostatic injections of both lidocaine and placebo , r and omized to separate sides of the prostate , in a r and omized , double-blind , placebo-controlled trial design . Injections were delivered at the angle between the seminal vesicle and prostate on each side . Patients grade d pain on a visual analog scale ( VAS ) ( 0–10 ) after injections and after each biopsy . Patients were surveyed to evaluate overall pain and discomfort before discharge . We used Student ’s t-test to compare the mean VAS scores between lidocaine and placebo . Results The mean ( SD ) VAS after biopsy was 1.9 ( 1.4 ) on the lidocaine side and 2.3 ( 1.4 ) on the placebo side ( P = 0.202 ) . Pain after the injection itself was similar to pain after biopsy , with the mean ( SD ) VAS of 2.4 ( 1.6 ) and 2.2 ( 1.7 ) after lidocaine and placebo injections , respectively ( P = 0.546 ) . None of the differences were statistically significant . Twenty-nine ( 59.2 % ) patients reported no pain at the time of discharge . Conclusions Pain experienced during transrectal biopsy of the prostate is mild and is not significantly lowered with periprostatic nerve block . Pain from injection itself is similar to pain from core biopsies . Pain from transrectal ultrasound-guided biopsy of the prostate is well tolerated with no anesthesia PURPOSE We assessed the effect of transrectal ultrasound guided prostatic nerve blockade on the discomfort associated with systematic needle biopsy of the prostate . MATERIAL S AND METHODS A prospect i ve r and omized double-blind study was performed of 64 patients requiring systematic biopsy of the prostate . Patients were r and omly assigned to receive an injection of 5 ml . 1 % lidocaine or 5 ml . saline ( 0.9 % sodium chloride ) at the vascular pedicle on 1 side of the prostate only . They were then asked to score the severity of discomfort of the injection and subsequent biopsies on each side . RESULTS Mean pain scores were significantly lower on the side with than the side without lidocaine injection ( 1.6 + /- 0.9 versus 2.4 + /- 1.2 , p < 0.0001 ) and not significantly different when saline was injected ( 2.9 + /- 1.2 versus 3.0 + /- 1.1 , p = 0.52 ) . Pain scores were significantly different when the lidocaine injected side was compared to the saline solution injected side ( p < 0.0001 ) but the difference was not significant between the noninjected sides of the 2 groups ( p = 0.076 ) . Of the patients in the lidocaine group 68 % reported that they would prefer to undergo biopsy with the injection compared to only 41 % in the placebo group ( p = 0.037 ) . During the study no patient in either group had any adverse effect from the injection . CONCLUSIONS Transrectal ultrasound guided nerve blockade before prostatic biopsy results in a more comfortable procedure for the patient Purpose : The aim of this study was to evaluate the efficacy of a combined topical and local anesthesia consisting of a transrectal lidocaine suppository followed by periprostatic nerve block ( PNB ) in comparison to the combination of transrectally applied lidocaine gel followed by PNB and PNB alone as methods of reducing pain during transrectal prostate biopsy . Patients and Methods : 100 patients were r and omized to four groups and received either a placebo suppository or 10 ml of 2 % lidocaine gel or a suppository containing 60 or 120 mg of lidocaine 1 h before biopsy . Additionally , every patient received a PNB using 5 ml 2 % lidocaine . After performing an extensive transrectal ultrasound-guided biopsy , pain was evaluated using a visual pain scale . Results : The mean pain score in the placebo group was 3.4 , in the lidocaine gel group it was 3.7 , and in the 60 or 120 mg lidocaine suppository groups it was 2.4 and 2.5 , respectively . No patient showed vegetative symptoms like sweating or symptomatic hypotonia and no patient had severe pain . Conclusion : The addition of lidocaine suppositories to PNB as a form of combined anesthesia showed a significantly better pain reduction than the addition of lidocaine gel to PNB or PNB alone PURPOSE We investigated the effectiveness of a new method , intraprostatic administration of local anesthesia vs traditional periprostatic injection for decreasing the discomfort caused by transrectal ultrasound guided , 10 core biopsy of the prostate . MATERIAL S AND METHODS We studied 71 patients who received intraprostatic anesthesia between October 2002 and March 2003 , and 99 who received periprostatic anesthesia between October 2001 and September 2002 before prostate biopsy . After biopsy patients were given a question naire , which consisted of 5 questions about pain and 3 about morbidity , and were asked to complete it and mail it to our department . RESULTS The mean score + /- SD for the degree of pain during biopsy in the periprostatic groups was 2.6 + /- 1.1 and that in the intraprostatic group was 1.9 + /- 1.1 , which was significantly different ( p < 0.001 ) . Other items , including the degree of pain after biopsy , duration and location of pain , and medicine intake for pain , were not significantly different between the 2 groups . There was no significant difference in morbidity , including hematuria , hemospermia and rectal bleeding , between the 2 groups . CONCLUSIONS Intraprostatic administration of local anesthesia significantly decreases the pain associated with prostate biopsy compared with periprostatic nerve block . It is a simple , safe and rapid technique that should be considered in all patients undergoing transrectal ultrasound guided prostate biopsy PURPOSE Recent reports have indicated the benefit of anesthesia during prostate biopsy . To assess this finding objective ly we performed a prospect i ve r and omized double-blind study to compare patient pain with and without local anesthesia during transrectal ultrasound guided prostate biopsies . MATERIAL S AND METHODS Between August 2000 and March 2001 , 108 men undergoing transrectal ultrasound guided biopsy of the prostate were r and omized in double-blind fashion to receive intrarectal 2 % lidocaine gel or intrarectal lubricant alone . No patient received pre-procedure narcotics or sedation . Pain associated with biopsy was determined using a horizontal linear visual analog pain scale . Pain scores in the 2 treatment groups were compared and possible predictors of increased pain were examined . RESULTS The 2 groups were similar in demographic characteristics . There was no significant difference in pain score in the 2 % lidocaine and lubricant alone groups ( 28.3 versus 28.9 mm . , p = 0.88 ) . Previous biopsy , time since previous biopsy , physician , number of biopsies and prostate volume did not correlate with pain score , while age correlated negatively with the score ( r = -0.27 , p = 0.005 ) . A single complication involving a vasovagal episode resolved spontaneously . CONCLUSIONS Intrarectal lidocaine gel provides no significant therapeutic or analgesic benefit compared with lubricant alone for transrectal ultrasound guided biopsy of the prostate . In younger patients more discomfort is associated with this procedure PURPOSE We assessed the analgesic effect of additional intrarectal lidocaine gel instillation during transrectal ultrasound guided prostate biopsy and identified the procedural steps that benefit from lidocaine gel instillation . MATERIAL S AND METHODS A total of 250 consecutive patients scheduled for prostate biopsy were r and omized into 2 groups . In the 125 group 1 patients lidocaine gel was instilled intrarectally before periprostatic neurovascular bundle block . The 125 patients in group 2 underwent only periprostatic neurovascular bundle block without lidocaine gel instillation . Of the 250 patients 90 in group 1 and 113 in group 2 , in whom 12 systematic cores were obtained , were enrolled for data analysis . Pain was assessed using a visual analog scale during periprostatic neurovascular bundle block ( visual analog scale 1 ) , during biopsy ( visual analog scale 2 ) and 20 minutes after biopsy ( visual analog scale 3 ) . Differences between the visual analog scale scores of the 2 groups at each procedural step were evaluated using the unpaired t test with p<0.05 considered significant . RESULTS In terms of pain experienced during the 3 procedural steps scores were significantly different during biopsy ( p<0.01 ) . Visual analog scale scores of patients in group 1 showed a tendency to be lower than the scores of patients in group 2 during periprostatic neurovascular bundle block and 20 minutes after biopsy ( p=0.11 and 0.20 , respectively ) . CONCLUSIONS Intrarectal lidocaine gel instillation before periprostatic neurovascular bundle block produces a significant additional analgesic effect during biopsy . The procedure is simple , safe and rapid , and it should be considered in all patients undergoing transrectal ultrasound guided prostate biopsy PURPOSE We compared intrarectal local anesthesia plus pelvic plexus block vs intrarectal local anesthesia plus periprostatic nerve block during transrectal ultrasound guided prostate biopsy . MATERIAL S AND METHODS Patients were r and omized 1:1 by a computer generated schedule into group 1 - 90 who received intrarectal local anesthesia ( lidocaine 1.5%-nifedipine 0.3 % cream ) plus pelvic plexus block ( 2.5 ml lidocaine 1 % plus naropine 0.75 % injected on each side into the pelvic neurovascular plexus lateral to the seminal vesicle tip ) and group 2 - 90 who received intrarectal local anesthesia plus periprostatic nerve block ( 2.5 ml of the same mixture injected on each side into the neurovascular bundles at the prostate-bladder-seminal vesicle angle ) before transrectal ultrasound guided prostate biopsy . After the procedure patients were instructed to rate the level of pain/discomfort from 0 to 10 on the visual analog scale at certain time points , including during the introduction and presence of the probe in the rectum , during pelvic plexus block or periprostatic nerve block , during biopsy and 30 minutes after biopsy . RESULTS The 2 groups were similar in age , serum prostate specific antigen and total prostate volume . There was no difference in pain perception during probe introduction and pelvic plexus or periprostatic nerve block . Pain during prostate biopsy was significantly lower in group 1 than in group 2 ( p < 0.001 ) . The same trend was recorded for pain perception 30 minutes after biopsy ( p = 0.001 ) . There were no major complications . CONCLUSIONS Pelvic plexus block under Doppler ultrasound guidance provides better analgesia than periprostatic nerve block during office based transrectal ultrasound guided prostate biopsy Objective : To compare caudal block with intrarectal local anesthesia plus periprostatic nerve block for transrectal ultrasound guided prostate biopsy . Methods : One hundred and ninety patients scheduled for transrectal ultrasound guided prostate biopsy were r and omized equally into Group-A who received caudal block ( 20 ml 1.2 % lidocaine ) and Group-B who received intrarectal local anesthesia ( 0.3 % oxybuprocaine cream ) plus periprostatic nerve block ( 10 ml 1 % lidocaine plus 0.5 % ropivacaine ) before biopsy . During and after the procedure , the patients rated the level of pain/discomfort at various time points . Complications during the whole study period and the patient overall satisfaction were also evaluated . Results : More pain and discomfort was detected during periprostatic nerve block than during caudal block . Pain and discomfort was significantly lower during prostate biopsy and during the manipulation of the probe in the rectum in Group-A than in Group-B. No significant differences were detected in the pain intensity after biopsy and side effects between the two groups . Conclusions : Caudal block provides better anesthesia than periprostatic nerve block plus intrarectal local anesthesia for TRUS guided prostate biopsy without an increase of side effects BACKGROUND Despite being highly efficient for the relief of patient discomfort due to transrectal ultrasound ( TRUS ) guided prostate biopsy , periprostatic anesthesia is occasionally reported to be of limited use . We aim ed to evaluate the efficacy of conscious sedation , an accepted method for lessening patient discomfort due to interventional radiological procedures and compare it with periprostatic anesthesia . METHODS 93 c and i date s for biopsy were r and omised to three groups : group 1 ( n = 31 ) received intravenous midazolam , group 2 ( n = 31 ) received periprostatic lidocaine injection , whereas group 3 ( n = 31 ) received no anesthetic before the procedure . After the biopsy patients were asked to express discomfort by visual anologue scale ( VAS ) . RESULTS The mean scores for groups 1 and 2 were significantly lower than that of group 3 ( 1.4 + /- 1.1 and 2.0 + /- 1.5 versus 4.7 + /- 1.6 , respectively ; p < 0.05 for both ) . For patients with VAS scores exceeding 4 ( moderate to severe discomfort ) , a significant difference was calculated between groups 1 and 2 ( 3 % versus 29 % , p < 0.05 ) and between each and group 3 ( 3 % and 29 % versus 80 % , respectively ; p < 0.05 for each ) . CONCLUSIONS Sedation is an alternative for increasing patient comfort during TRUS-guided prostate biopsy , especially in clinical situations like patient anxiety , young age , repeat biopsies or inflammatory anal diseases Transrectal Ultrasound ( TRUS ) guided prostate biopsy is regarded as the gold st and ard for prostate cancer diagnosis . The majority of patients perceive TRUS-guided prostate biopsy as a physically and psychologically traumatic experience . We aim ed to compare in this paper the efficacy of three different anesthesia techniques to control the pain during the procedure . MATERIAL S AND METHODS 150 patients who underwent transrectal ultrasound ( TRUS ) guided prostate biopsy were r and omly divided into three groups . Group A included 50 patients who received one hour before the procedure a mixture of 2.5 % lidocaine and 2.5 % prilocaine , Group B : 50 patients who received intrarectal local anesthetic administration ( lidocaine 5 ml 10 % ) and lidocaine local spray 15 % and Group C included 50 patients who received periprostatic block anesthesia ( lidocaine 10 ml 10 % ) . Visual analogue scale ( VAS ) of patients in different groups was evaluated at the end of the biopsy and 30 minutes after the procedure . RESULTS The VAS of patients in Group A was 1.32 ± 0.65 ( VAS I ) and 2.47 ± 0.80 ( VAS II ) . In group B the VAS of patients was 1.09 ± 0.47 ( VAS I ) and 1.65 ± 0.61 ( VAS II ) . In group C the VAS of patients was 2.63 ± 0.78 ( VAS I ) and 1.70 ± 0.85 ( VAS II ) . There was no statistically significant difference in term of VAS I between group A and B. A statistically significant difference was determined in terms of VAS II between group A and B. There was no statistically significant difference in term of VAS between group B and C. CONCLUSIONS The most effective of the three methods for pain control we used was intrarectal local anesthetic administration and lidocaine local spray 15 % that enables an ideal patient comfort OBJECTIVES To assess the efficacy of tramadol and lidocaine in reducing pain using the periprostatic nerve block technique with a spinal needle , guided by transrectal ultrasound ( TRUS ) before the biopsy application . METHODS Of the 112 eligible c and i date s who were asked to participate in the study , 90 agreed and provided informed consent . These 90 men were r and omized into 3 groups . Group 1 ( n = 30 ) received lidocaine , group 2 ( n = 29 ) received tramadol , and group 3 ( n = 31 ) received saline solution . Within 10 minutes of biopsy procedure completion , the patients were presented with visual pain scales and asked to rate the pain . The patients also asked whether they would be to return for this procedure if it became medically necessary . RESULTS The postprocedural mean pain scores of lidocaine , tramadol , and placebo groups were found to be 1.73 , 2.89 , and 4.32 , respectively . The mean pain scores were significantly lower in both the lidocaine and the tramadol groups compared with the placebo group ( P < .001 ) . In addition , statistically significant differences were found among the 3 groups regarding how willing they would be to return for the procedure if necessary . CONCLUSIONS In this study , we showed that the local anesthetic effect of tramadol in decreasing pain in periprostatic nerve block during TRUS-guided biopsy . The use of tramadol for pain relief in transrectal ultrasound-guided prostate biopsy is a practical , effective , and comfortable method compared with the results of the control group PURPOSE To evaluate the role of intrarectal EMLA , a new topical anesthetic cream , and lidocaine gel as local anesthesia during transrectal prostate biopsy and to observe whether gel temperature can improve pain control . PATIENTS AND METHODS A series of 210 consecutive patients were r and omized . Group 1 ( N = 60 ) underwent intrarectal instillation of EMLA cream , group 2 ( N = 50 ) 2.5 % lidocaine gel , group 3 ( N = 40 ) placebo , and group 4 ( N = 60 ) no treatment . Patients in groups 2 and 3 were subdivided into subgroups according to instillation of warm or cooled gel . Pain control was assessed by a 10-point visual analog scale . RESULTS The median pain scores were 2.6 in group 1 , 3.8 in group 2 , 3.9 in group 3 , and 3.6 in group 4 . In 16 patients ( 7.6 % ) , the procedure was suspended because of pain : none group 1 , 6.0 % in group 2 , 10 % in group 3 , and 15 % ing group 4 . The temperature of the lidocaine gel did not affect tolerability . CONCLUSION Intrarectal instillation of EMLA cream is a simple , safe , and effective method of local anesthesia during transrectal prostate biopsy , superior to lidocaine gel , placebo , and no treatment OBJECTIVES To determine the analgesic efficacy of local anesthetics injected lateral to the seminal vesicles before prostate biopsy , during and immediately after the procedure , because pain is a common side effect of transrectal ultrasound-guided prostate biopsy . METHODS Patients were r and omized to receive 5 mL of either 1 % lidocaine or sterile normal saline injected ( under ultrasound guidance ) lateral to the seminal vesicles bilaterally before performance of the prostate biopsies , with the patient and physician unaware of the treatment group . Five minutes after the injection , a series of 12 prostate biopsies were performed . A visual analog scale ( VAS ) for pain at rest and with activity was obtained before the biopsy ( preprocedure VAS ) and immediately ( intraprocedure VAS ) and 30 minutes ( postprocedure VAS ) after the biopsy . Surveys examining the patients ' expectations for biopsy pain were administered before and immediately after the biopsy . RESULTS No significant differences were found between the groups with regard to demographic data , VAS pain scores at rest and with activity , and survey results . CONCLUSIONS Injection of lidocaine lateral to the seminal vesicles before prostate biopsy did not diminish biopsy-associated pain Background : Transrectal ultrasound-guided prostate biopsy ( TRUSPB ) is considered the procedure of choice for the diagnosis of prostate cancer . Men undergoing this biopsy experience high psychological stress . Different studies recommend techniques as sedation , lidocaine gel intrarectally , periprostatic nerve block alone , or nitrous oxide inhalation as effective methods of analgesia during procedural-related pain or discomfort . We evaluated three techniques for pain relief during TRUSPB and evaluated if there was any increase in the incidence of complications when employing either technique . Setting : Assiut University Hospital , Assiut , Egypt . Methods : Three hundred patients of age 43–92-year-old underwent TRUSPBs . Patients were allocated r and omly into three equal groups to receive intravenous ( IV ) diazepam 5 mg slowly ( Group I ) , bilateral periprostatic nerve block by 10 ml of 1 % lidocaine solution injected under ultrasound guidance ( Group II ) , or combined IV diazepam and the periprostatic nerve block ( Group III ) . Results : The mean pain score was 4.95 for patients in Group I , 4.15 for patients in Group II , and 2.18 for patients in Group III with statistically significant findings ( F = 120.27 , P < 0.001 ) . TRUSPB under combined IV sedation and local anesthesia had no significant increase in the incidence of complications . Conclusions : Patients should have analgesia during TRUSPB to decrease the procedure pain and to improve tolerance permitting proper aim ing for biopsy cores without increasing the patient distress . The combined IV sedation and local periprostatic nerve block are efficient in controlling and limiting pain better than employing each technique alone with no significant increase in complications incidence |
13,265 | 21,154,354 | None of the six trials of vitamin A or beta-carotene supplementation in adults demonstrated any significant reduction in HIV disease progression .
No significant adverse effects of vitamin A in adults or children have been reported .
Zinc supplements reduced diarrhoeal morbidity and had no adverse effects on disease progression in a single safety trial in South African children .
No significant clinical benefits were found from zinc supplementation of pregnant Tanzanian women or Peruvian adults with persistent diarrhoea .
Vitamin A supplementation is beneficial and safe in HIV-infected children , but further evidence is needed to establish if supplementation confers similar benefits in HIV-infected adults .
Zinc is safe in HIV-infected adults and children .
It may have similar benefits in HIV-infected children and adults , and uninfected children with diarrhoea , as it does in HIV-uninfected children . | BACKGROUND Micronutrient deficiencies are widespread and compound the effects of HIV disease ; micronutrient supplements may be effective and safe in reducing this burden .
OBJECTIVES To assess whether micronutrient supplements are effective and safe in reducing mortality and morbidity in adults and children with HIV infection . | RATIONALE Vitamin D has been shown to be involved in the host immune response toward Mycobacterium tuberculosis . OBJECTIVES To test whether vitamin D supplementation of patients with tuberculosis ( TB ) improved clinical outcome and reduced mortality . METHODS We conducted a r and omized , double-blind , placebo-controlled trial in TB clinics at a demographic surveillance site in Guinea-Bissau . We included 365 adult patients with TB starting antituberculosis treatment ; 281 completed the 12-month follow-up . The intervention was 100,000 IU of cholecalciferol or placebo at inclusion and again 5 and 8 months after the start of treatment . MEASUREMENTS AND MAIN RESULTS The primary outcome was reduction in a clinical severity score ( TBscore ) for all patients with pulmonary TB . The secondary outcome was 12-month mortality . No serious adverse effects were reported ; mild hypercalcemia was rare and present in both arms . Reduction in TBscore and sputum smear conversion rates did not differ among patients treated with vitamin D or placebo . Overall mortality was 15 % ( 54 of 365 ) at 1 year of follow-up and similar in both arms ( 30 of 187 for vitamin D treated and 24 of 178 for placebo ; relative risk , 1.19 [ 0.58 - 1.95 ] ) . HIV infection was seen in 36 % ( 131 of 359 ) : 21 % ( 76 of 359 ) HIV-1 , 10 % ( 36 of 359 ) HIV-2 , and 5 % ( 19 of 357 ) HIV-1 + 2 . CONCLUSIONS Vitamin D does not improve clinical outcome among patients with TB and the trial showed no overall effect on mortality in patients with TB ; it is possible that the dose used was insufficient . Clinical trial registered with www.controlled-trials.com/is rct n ( IS RCT N35212132 ) BACKGROUND Results from observational studies suggest that micronutrient status is a determinant of the progression of human immunodeficiency virus ( HIV ) disease . METHODS We enrolled 1078 pregnant women infected with HIV in a double-blind , placebo-controlled trial in Dar es Salaam , Tanzania , to examine the effects of daily supplements of vitamin A ( preformed vitamin A and beta carotene ) , multivitamins ( vitamins B , C , and E ) , or both on progression of HIV disease , using survival models . The median follow-up with respect to survival was 71 months ( interquartile range , 46 to 80 ) . RESULTS Of 271 women who received multivitamins , 67 had progression to World Health Organization ( WHO ) stage 4 disease or died -- the primary outcome --as compared with 83 of 267 women who received placebo ( 24.7 percent vs. 31.1 percent ; relative risk , 0.71 ; 95 percent confidence interval , 0.51 to 0.98 ; P=0.04 ) . This regimen was also associated with reductions in the relative risk of death related to the acquired immunodeficiency syndrome ( 0.73 ; 95 percent confidence interval , 0.51 to 1.04 ; P=0.09 ) , progression to WHO stage 4 ( 0.50 ; 95 percent confidence interval , 0.28 to 0.90 ; P=0.02 ) , or progression to stage 3 or higher ( 0.72 ; 95 percent confidence interval , 0.58 to 0.90 ; P=0.003 ) . Multivitamins also result ed in significantly higher CD4 + and CD8 + cell counts and significantly lower viral loads . The effects of receiving vitamin A alone were smaller and for the most part not significantly different from those produced by placebo . Adding vitamin A to the multivitamin regimen reduced the benefit with regard to some of the end points examined . CONCLUSIONS Multivitamin supplements delay the progression of HIV disease and provide an effective , low-cost means of delaying the initiation of antiretroviral therapy in HIV-infected women OBJECTIVES We have previously investigated the role of either : aspirin and micronutrients or aspirin , micronutrients and chloroquine ( CQ ) in the management of asymptomatic HIV infected individuals . In this paper , we report the use of these combinations in the management of patients with AIDS , defined as CD4 count < 200 cells Background : Iron deficiency is common among female injection drug users , but it is unclear whether iron supplementation can reduce anemia and improve iron status without increasing plasma hepatitis C virus ( HCV ) or HIV RNA levels . Methods : We conducted a phase 3 , double-blind , r and omized , controlled clinical trial of daily micronutrients with 18 mg of iron ( iron group ) versus micronutrients without iron ( control group ) for 12 months among hepatitis C-positive female injection drug users in Baltimore , Maryl and . The main outcome measures were hemoglobin , markers of iron status , plasma HCV RNA , plasma HIV RNA , and liver enzymes at 6 and 12 months of follow-up . Results : Four hundred fifty-eight women ( 320 HIV-negative and 138 HIV-positive ) enrolled in the trial . There were no significant differences in the proportion of women with anemia , ferritin < 30 ng/mL , log10 plasma HCV RNA , or log10 plasma HIV RNA between treatment groups at enrollment . The proportion with anemia in the iron and control groups , respectively , was 20.7 % versus 31.3 % ( P = 0.026 ) at 6 months and 26.2 % versus 30.4 % ( P = 0.5 ) at 12 months ; with ferritin < 30 ng/mL , the proportion was 29.2 % versus 55.5 % ( P < 0.0001 ) at 6 months and 26.2 % versus 46.9 % ( P = 0.0018 ) at 12 months . In the iron and control groups , respectively , mean log10 plasma HCV RNA ( IU/mL ) was 5.2 versus 5.2 ( P = 0.86 ) at 6 months and 5.4 versus 5.3 ( P = 0.6 ) at 12 months . Among HIV-positive subjects , mean log10 plasma RNA ( copies/mL ) in the iron and placebo groups , respectively , was 3.8 versus 3.7 ( P = 0.75 ) at 6 months and 3.7 versus 4.1 ( P = 0.19 ) at 12 months . There were no significant differences in liver enzyme levels between the treatment groups at enrollment , 6 months , and 12 months . Conclusions : A daily micronutrient supplement with iron can reduce anemia and improve iron status in female injection drug users without increasing plasma HCV or HIV RNA levels or altering liver enzymes BACKGROUND Evidence has accumulated from observational studies that people eating more fruits and vegetables , which are rich in beta-carotene ( a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver ) and retinol ( an alcohol chemical form of vitamin A ) , and people having higher serum beta-carotene concentrations had lower rates of lung cancer . The Beta-Carotene and Retinol Efficacy Trial ( CARET ) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate ( vitamin A ) taken daily against placebo in 18314 men and women at high risk of developing lung cancer . The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm ; there were 28 % more lung cancers and 17 % more deaths in the active intervention group ( active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate ) . Promptly after the January 18 , 1996 , announcement that the CARET active intervention had been stopped , we published preliminary findings from CARET regarding cancer , heart disease , and total mortality . PURPOSE We present for the first time results based on the pre-specified analytic method , details about risk factors for lung cancer , and analyses of subgroups and of factors that possibly influence response to the intervention . METHODS CARET was a r and omized , double-blinded , placebo-controlled chemoprevention trial , initiated with a pilot phase and then exp and ed 10-fold at six study centers . Cigarette smoking history and status and alcohol intake were assessed through participant self-report . Serum was collected from the participants at base line and periodically after r and omization and was analyzed for beta-carotene concentration . An Endpoints Review Committee evaluated endpoint reports , including pathologic review of tissue specimens . The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence , with weighting linearly to hypothesized full effect at 24 months after r and omization . Relative risks ( RRs ) were estimated by use of Cox regression models ; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake . O'Brien-Fleming boundaries were used for stopping criteria at interim analyses . Statistical significance was set at the .05 alpha value , and all P values were derived from two-sided statistical tests . RESULTS According to CARET 's pre-specified analysis , there was an RR of 1.36 ( 95 % confidence interval [ CI ] = 1.07 - 1.73 ; P = .01 ) for weighted lung cancer incidence for the active intervention group compared with the placebo group , and RR = 1.59 ( 95 % CI = 1.13 - 2.23 ; P = .01 ) for weighted lung cancer mortality . All subgroups , except former smokers , had a point estimate of RR of 1.10 or greater for lung cancer . There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake ( RR = 1.99 ; 95 % CI = 1.28 - 3.09 ; test for heterogeneity of RR among quartiles of alcohol intake has P = .01 , unadjusted for multiple comparisons ) and with large-cell histology ( RR = 1.89 ; 95 % CI = 1.09 - 3.26 ; test for heterogeneity among histologic categories has P = .35 ) , but not with base-line serum beta-carotene concentrations . CONCLUSIONS CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality . The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finl and BACKGROUND In observational studies , the zinc status of HIV-infected persons has been associated with both positive and adverse clinical outcomes . Such endpoints may affect the risk of adverse birth outcomes among HIV-infected women . OBJECTIVE We examined the effects of zinc supplements on birth outcomes , hematologic indicators , and counts of T lymphocyte subsets among 400 HIV-infected pregnant women . DESIGN Eligible women between 12 and 27 wk of gestation were r and omly assigned to daily oral supplementation with either 25 mg Zn or placebo between recruitment and 6 wk after delivery . All women received iron , folic acid , and multivitamin supplements irrespective of the experimental assignment . RESULTS We observed no significant differences in birth weight , duration of gestation , or fetal and neonatal mortality between women in the zinc and placebo groups . Hemoglobin concentrations increased between baseline and 6 wk postpartum in both groups . However , the rise in hemoglobin over this period was significantly lower ( P = 0.03 ) in the zinc group ( x + /- SD : 11.5 + /- 17.9 g/L ) than in the placebo group ( 15.2 + /- 18.6 g/L ) . Similarly , the changes in red blood cell count and in packed cell volume over the same period were significantly lower in the zinc group ( P < 0.01 and P = 0.01 , respectively ) . Zinc had no effect on CD4(+ ) , CD8(+ ) , or CD3(+ ) cell counts during the follow-up period . CONCLUSION Because of the lack of beneficial effects of zinc on adverse pregnancy outcomes and the likelihood of negative effects on hemoglobin concentrations , no compelling evidence exists to support the addition of zinc to prenatal supplements intended for pregnant HIV-infected women Iron deficiency is one of the main causes of anemia during pregnancy , although other micronutrient deficiencies may play a role . We examined the effects of daily antenatal and postnatal supplementation with four combinations of micronutrients on maternal hematologic indicators in a double-masked r and omized controlled community trial . Communities , called sectors , were r and omly assigned to supplementation with folic acid ( 400 microg ) , folic acid plus iron ( 60 mg ) , folic acid plus iron and zinc ( 30 mg ) and folic acid plus iron , zinc and 11 other micronutrients , each at the approximate recommended daily allowance for pregnancy all given with vitamin A as retinol acetate ( 1000 microg retinol equivalent ) , or vitamin A alone as the control group . Hemoglobin ( Hb ) and indicators of iron status were assessed at baseline and at 32 wk of gestation . At 6-wk postpartum , Hb assessment was repeated using a finger stick . Severely anemic women ( Hb < 70 g/L ) were treated according to WHO recommendations . Folic acid alone had no effect on maternal anemia or iron status . Hb concentrations were 14 g/L , [ 95 % confidence limits ( CL ) , 8.3 - 19.2 ] , 10.0 g/L ( CL , 5.2 - 14.8 ) and 9.4 g/L ( CL , 4.7 - 14.1 ) higher in the groups receiving folic acid plus iron , folic acid plus iron and zinc and folic acid plus iron , zinc and multiple micronutrients , respectively , relative to the control . Anemia in the third trimester was reduced by 54 % with folic acid plus iron , by 48 % with folic acid plus iron and zinc and by 36 % with folic acid plus iron , zinc and multiple micronutrients supplementation , relative to the control ( P < 0.05 ) . Thus , the combinations of folic acid plus iron and zinc and folic acid plus iron , zinc and multiple micronutrients provided no additional benefit in improving maternal hematologic status during pregnancy compared with folic acid plus iron . The level of compliance and baseline Hb concentrations modified the effect of iron The impact of iron-only supplements ( FE ) versus multiple micronutrient supplements containing iron ( MM ) during pregnancy on iron status was assessed in a sub sample ( n = 453 ) of women who participated in a r and omized double-blind trial in Mexico . Compliance , monitored by observation , was high ( > 85 % ) . The two groups were similar at recruitment ( < 13 wk gestation ) for various sociodemographic characteristics and for mean hemoglobin ( Hb ) concentrations and prevalence of anemia ( Hb < 110 g/L ; 11 % ) . However , mean serum ferritin was higher ( P < 0.05 ) in the MM group ( n = 142 ) compared to the FE group ( n = 148 ) and the prevalence of iron deficiency ( serum ferritin < 12 micro g/L ) was lower in the MM group ( 44.4 % ) compared to the FE group ( 57.4 % ) . By the third trimester , almost half the women were anemic in both groups , and mean Hb ( g/L ) was lower for the MM group ( 104.2 ; 95 % CI : 102.5 , 106.0 ) compared to the FE group ( 108.1 ; 95 % CI : 106.4 , 109.8 ) after adjusting for baseline serum ferritin . In contrast , there were no differences in Hb concentrations at 1 mo postpartum or in mean ferritin and prevalence of iron deficiency at 32 wk gestation and 1 mo postpartum ( 90.9 and 45.1 % for the MM group ; 92.6 and 47.3 % for the FE group , respectively ) . In conclusion , rather than improve Hb or iron status relative to FE-only supplements as hypothesized , MM supplements may have slightly reduced Hb concentrations during pregnancy . Neither supplement was able to meet iron needs as evidence d by dramatic increases in anemia and iron deficiency by the end of pregnancy BACKGROUND Multiple micronutrient deficiencies may contribute to low birth weight , which is a major global determinant of mortality . OBJECTIVE We assessed the effect of prenatal multimicronutrient supplementation on gestational length and birth size . DESIGN We conducted a r and omized , placebo-controlled , double-blind effectiveness trial among antenatal care attendees in Harare , Zimbabwe . Pregnant women ( 22 - 35 wk of gestation ) were r and omly allocated to receive a multimicronutrient or placebo supplement daily until delivery . Supplementation with iron and folic acid was part of antenatal care . RESULTS Of 1669 women , birth data were available from 1106 ( 66 % ) , of whom 360 ( 33 % ) had HIV infection . The mean gestational length was 39.1 wk , and 16.6 % of the women had a gestational length < 37 wk . The mean birth weight was 3030 g , and 10.5 % of the infants had a birth weight < 2500 g. Multimicronutrient supplementation was associated with tendencies for increased gestational length ( 0.3 wk ; 95 % CI : -0.04 , 0.6 wk ; P = 0.06 ) , birth weight ( 49 g ; -6 , 104 g ; P = 0.08 ) , and head circumference ( 0.2 cm ; -0.02 , 0.4 cm ; P = 0.07 ) but was not associated with low birth weight ( birth weight < 2500 g ) ( relative risk : 0.84 ; 0.59 , 1.18 ; P = 0.31 ) . The effect of multimicronutrient supplementation on birth weight was not significantly different between HIV-uninfected ( 26 g ; -38 , 91 g ) and HIV-infected ( 101 g ; -3 , 205 g ) subjects ( interaction , P > 0.10 ) . CONCLUSION Antenatal multimicronutrient supplementation may be one strategy to increase birth size BACKGROUND The pattern of weight gain during pregnancy among HIV-infected women is largely unknown . Multivitamin supplementation was shown to be effective in preventing adverse pregnancy outcomes among HIV-positive women . These protective effects could be mediated in part by an improvement in the pattern of gestational weight gain . OBJECTIVE We examined the effects of multivitamin and vitamin A supplements on weight gain during the second and third trimesters of pregnancy among HIV-infected women . DESIGN We enrolled 1075 pregnant , HIV-1-positive women from Dar es Salaam , Tanzania , in a r and omized , placebo-controlled trial . Using a 2-by-2 factorial design , we assigned each woman to 1 of 4 regimens : multivitamins ( thiamine , riboflavin , niacin , folic acid , and vitamins B-6 , B-12 , C , and E ) , vitamin A , multivitamins including vitamin A , or placebo . The women took these oral supplements daily and were weighed monthly until the end of pregnancy . RESULTS The mean rate of weight gain was 306 g/wk during the second trimester and 247 g/wk during the third trimester . During the third trimester , average weight gain was significantly greater ( by 304 g ; 95 % CI : 17 , 590 ; P = 0.04 ) and the risk of low rate of weight gain ( < or= 100 g/wk ) was significantly lower ( relative risk : 0.73 ; 95 % CI : 0.58 , 0.93 ) in women who received multivitamins than in women who did not . Multivitamins including vitamin A were protective against low weight gain during the second trimester compared with multivitamins alone . CONCLUSION Multivitamin supplementation during pregnancy improves the pattern of weight gain among HIV-infected women BACKGROUND Linear growth retardation and wasting are common in children born to HIV-infected women . Inexpensive interventions that could improve the postnatal growth pattern of such children are needed . OBJECTIVE The objective was to examine the effect of supplementing HIV-infected women with multivitamins or vitamin A and beta-carotene , during and after pregnancy , on the growth of their children during the first 2 y of life . DESIGN We conducted a r and omized placebo-controlled trial in 886 mother-infant pairs in Tanzania . At the first prenatal visit , HIV-infected women were r and omly assigned to 1 of 4 daily oral regimens in a 2 x 2 factorial fashion : multivitamins ( MV : thiamine , riboflavin , vitamin B-6 , niacin , vitamin B-12 , vitamin C , vitamin E , and folic acid ) , preformed vitamin A + beta-carotene ( VA/BC ) , MV including VA/BC , or placebo . Supplementation continued during the first 2 y postpartum and thereafter . Children were weighed and measured monthly , and all received vitamin A supplements after 6 mo of age per the st and ard of care . RESULTS Multivitamins had a significant positive effect on attained weight ( 459 g ; 95 % CI : 35 , 882 ; P = 0.03 ) and on weight-for-age ( 0.42 ; 95 % CI : 0.07 , 0.77 ; P = 0.02 ) and weight-for-length ( 0.38 ; 95 % CI : 0.07 , 0.68 ; P = 0.01 ) z scores at 24 mo . VA/BC seemed to reduce the benefits of MV on these outcomes . No significant effects were observed on length , midupper arm circumference , or head circumference . CONCLUSION Supplementation of HIV-infected women with multivitamins ( vitamin B complex , vitamin C , and vitamin E ) during pregnancy and lactation is an effective intervention for improving ponderal growth in children Hypertension during pregnancy increases fetal growth retardation , preterm deliveries , and perinatal deaths , and yet its causes remain unclear . In HIV-infected women , preterm birth additionally increases the risk of HIV transmission to the infant . Oxidative stress and endothelial cell dysfunction of the placenta have been implicated in the development of hypertension during pregnancy . Vitamin intake can reduce oxidative stress and improve endothelial function . We therefore evaluated the effect of multivitamin ( 20 mg thiamine , 20 mg riboflavin , 25 mg B-6 , 50 microg B-12 , 500 mg C , 30 mg E , and 0.8 mg folic acid ) and vitamin A supplements ( 30 mg beta-carotene plus 5000 IU preformed vitamin A ) in relation to hypertension during pregnancy ( systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg at any time during pregnancy ) . In a double-blind , placebo-controlled , r and omized , clinical trial , conducted among 1078 HIV-positive pregnant Tanzanian women , those who received multivitamins were 38 % less likely to develop hypertension during pregnancy than those who did not [ relative risk ( RR ) = 0.62 , 95 % CI 0.40 - 0.94 , P = 0.03 ] . There was no overall effect of vitamin A on hypertension during pregnancy ( RR = 1.00 , 95 % CI 0.66 - 1.51 , P = 0.98 ) . Hypertension during pregnancy was more likely in women with high baseline systolic blood pressure ( > 120 vs. < or = 120 mm Hg ) ( RR = 6.02 , 95%CI 2.59 - 13.97 , P < 0.001 ) , and those with higher mid-upper arm circumference ( RR = 1.12 , 95 % CI 1.04 - 1.19 , P = 0.002 ) . Taking multivitamins containing vitamins B , C , and E during pregnancy may be an inexpensive and effective strategy to improve the health of the mother and baby To investigate the effects of selenium or beta-carotene supplementation in human immunodeficiency virus (HIV)-infected patients , who are known to have deficiencies of selenium and vitamin A , we evaluated the blood enzymatic antioxidant system , including superoxide dismutase ( SOD ) , selenodependent glutathione peroxidase ( GPX ) , and catalase ( Cat ) ; glutathione ( GSH ) status ; and plasma selenium concentration . The placebo group consisted of 18 HIV-infected patients with no supplementation , the selenium group was composed of 14 patients receiving oral selenium treatment , and the beta-carotene group comprised 13 patients receiving oral beta-carotene supplementation . All groups were studied for 1 y. At the beginning of the study , a significantly higher SOD activity ( P < 0.001 ) was observed in all HIV-infected patients compared with uninfected control subjects , and GPX activity at baseline was higher in the placebo ( P < 0.004 ) and selenium ( P < 0.014 ) groups than in the control subjects . These higher enzyme activities could be related to an increased synthesis of these enzymes in erythrocyte precursors under oxidative stress . Moreover , we observed significantly lower GSH values in all HIV-infected patients than in control subjects at the beginning of the study ( P < 0.001 ) . After selenium or beta-carotene supplementation , no significant difference was observed for SOD activity compared with baseline . On the contrary , GPX activity increased significantly after selenium treatment ( P < 0.04 between 3 and 6 mo ) , whereas a slight increase was found after beta-carotene treatment . Similarly , a significant increase in GSH values was observed at 12 mo compared with baseline both after selenium supplementation ( P < 0.001 ) and beta-carotene supplementation ( P < 0.01 ) . Because GPX and GSH play an important role in the natural enzymatic defense system in detoxifying hydrogen peroxide in water , selenium supplementation could be of great interest in protecting cells against oxidative stress . The lower efficiency of beta-carotene could be attributed to the seriousness of the pathology at the time of recruitment into the beta-carotene group BACKGROUND In observational studies , adequate selenium status has been associated with better pregnancy outcomes and slowed HIV disease progression . OBJECTIVE We investigated the effects of daily selenium supplements on CD4 cell counts , viral load , pregnancy outcomes , and maternal and infant mortality among 913 HIV-infected pregnant women . DESIGN In this r and omized , double-blind , placebo-controlled trial , eligible women between 12 and 27 wk of gestation were given daily selenium ( 200 mug as selenomethionine ) or placebo as supplements from recruitment until 6 mo after delivery . All women received prenatal iron , folic acid , and multivitamin supplements irrespective of experimental assignment . RESULTS The selenium regimen had no significant effect on maternal CD4 cell counts or viral load . Selenium was marginally associated with a reduced risk of low birth weight [ relative risk ( RR ) = 0.71 ; 95 % CI : 0.49 , 1.05 ; P = 0.09 ] and increased risk of fetal death ( RR = 1.58 ; 95 % CI = 0.95 , 2.63 ; P = 0.08 ) , but had no effect on risk of prematurity or small-for-gestational age birth . The regimen had no significant effect on maternal mortality ( RR = 1.02 ; 95 % CI = 0.51 , 2.04 ; P = 0.96 ) . There was no significant effect on neonatal or overall child mortality , but selenium reduced the risk of child mortality after 6 wk ( RR = 0.43 ; 95 % CI = 0.19 , 0.99 ; P = 0.048 ) . CONCLUSION Among HIV-infected women from Dar es Salaam , Tanzania , selenium supplements given during and after pregnancy did not improve HIV disease progression or pregnancy outcomes , but may improve child survival . This trial was registered at clinical trials.gov as NCT00197561 BACKGROUND Wasting is a strong independent predictor of mortality in HIV-infected persons . Vitamin supplements delay the disease progression , but their effect on wasting is not known . Data are lacking on the risk factors for wasting in African HIV-infected persons . OBJECTIVES The objectives were to examine the effect of vitamin supplements on wasting in HIV-infected women and to assess the effects of sociodemographic characteristics , morbidity events , and immunologic progression on the risk of wasting . DESIGN HIV-infected women ( n = 1078 ) from Tanzania were r and omly assigned to receive 1 of 4 daily oral regimens : multivitamins ( B complex , C , and E ) , vitamin A plus beta-carotene , multivitamins that included vitamin A plus beta-carotene , or placebo . The endpoints of the study included first episodes of a midupper arm circumference < 22 cm or a body mass index ( BMI ; in kg/m2 ) < 18 and the incidence of weight loss episodes during a median 5.3 y of follow-up . RESULTS Multivitamins alone significantly reduced the risk of a first episode of a midupper arm circumference < 22 cm ( relative risk : 0.66 ; 95 % CI : 0.47 , 0.94 ; P = 0.02 ) . In multivariate-adjusted Cox models , the woman 's age , education level , and height were inversely related to the incidence of wasting . Episodes of diarrhea , nausea or vomiting , lower respiratory tract infections , oral ulcers , thrush , severe anemia , and low CD4 + cell counts were each significantly related to an increased risk of wasting . CONCLUSIONS Vitamins C and E and the vitamin B complex have a protective effect on wasting in HIV-infected women . Prevention of diarrhea , severe respiratory tract infections , and anemia are likely to decrease the burden of wasting OBJECTIVE To evaluate the impact of 4 months of daily zinc supplementation on the incidence of severe and recurrent diarrhea in children 6 to 30 months of age . METHODS A double-blind , r and omized , placebo-controlled trial was conducted on children who were identified by a door-to-door survey to be aged 6 to 30 months and residing in the urban slum of Dakshinpuri , New Delhi . They were r and omized to receive daily zinc gluconate ( elemental zinc 10 mg to infants and 20 mg to older children ) or placebo . A field attendant administered the syrup daily at home for 4 months except on Sundays , when the mother did so . One bottle that contained 250 mL was kept in the child 's home and replaced monthly . Field workers visited households every seventh day during the 4-month follow-up period . At each visit , information was obtained for the previous 7 days on history of fever , number and consistency of stools , and presence of cough . When the child was ill , illness characteristics and treatment seeking outside the home were determined . If the child had diarrhea or vomiting , then dehydration was assessed . At household visits , 2 packets of oral rehydration salts were given when a child had diarrhea . Children who visited the study clinic spontaneously for illness or were referred by the field workers were treated according to the st and ard national program guidelines . Antibiotics were advised only for diarrhea with bloody stools or for associated illnesses . For using generalized estimating equations for longitudinal analysis of a recurring event such as diarrhea , the follow-up data for each child was divided into 17 child-periods of 7 days each and presence or absence of an incident episode of diarrhea or severe diarrhea within each 7-day period was coded . This method of analysis does not assume independence of events and therefore prevents underestimation of variance that results because of correlation of morbidity within the same child . A logistic generalized estimating equations model with exchangeable correlation covariance-variance matrix was then used to estimate the effect size . RESULTS Zinc or placebo doses were administered on 88.8 % and 91.2 % , respectively , of study days during the 4 months of follow-up . There was a small but significant increase in the average number of days with vomiting in the zinc group ( 4.3 [ st and ard deviation ( SD ) : 5.8 ] vs 2.6 [ SD 3.9 ] days ; difference in means : 1.7 [ 95 % confidence interval ( CI ) : 1.3 - 2.1 ] days ) . At the baseline , mean plasma zinc was 62.0 microg/dL ( SD : 14.3 microg/dL ) in the zinc and 62.0 microg/dL ( SD : 11.2 microg/dL ) in the placebo group ; 45.8 % and 42 % , respectively , had low plasma zinc levels below 60 microg/dL. At the end of the study , plasma zinc levels were substantially higher in the zinc group ( ratio of geometric means : 1.94 [ 95 % CI : 1.86 - 2.03 ] ) and the proportion with low plasma zinc was lower ( difference in proportions : -46.7 % [ 95 % CI : -41.8 % to -51.4 % ] ) . The incidence of diarrhea during follow-up was lower in the zinc-supplemented as compared with the placebo group ( odds ratio [ OR ] : 0.88 ; 95 % CI : 0.82 - 0.95 ) . The beneficial impact of zinc was greater on the incidence of diarrhea with progressively increasing duration : episodes of diarrhea that lasted 1 to 6 days ( OR : 0.92 ; 95 % CI : 0.85 - 1.00 ) , 7 to 13 days ( OR : 0.79 ; 95 % CI : 0.65 - 0.95 ) , and > or = 14 days ( OR : 0.69 ; 95 % CI : 0.48 - 0.98 ) . The impact was also greater on the incidence of episodes with progressively higher stool frequency : 3 to 5 stools per day ( OR : 0.90 ; 95 % CI : 0.83 - 0.98 ) , 6 to 9 stools per day ( OR : 0.87 ; 95 % CI : 0.77 - 0.98 ) , and > or = 10 per day ( OR : 0.77 ; 95 % CI : 0.63 - 0.94 ) . In the zinc group , significantly more children experienced no diarrheal episode during the study period ( risk ratio [ RR ] : 1.22 ; 95 % CI : 1.02 - 1.44 ) . Furthermore , substantially fewer children ( RR : 0.51 ; 95 % CI : 0.36 - 0.73 ) experienced recurrent diarrhea , defined as > 6 diarrheal episodes in the follow-up period as compared with children in the placebo group . The number of children who were hospitalized for any cause tended to be lower in the zinc group , but the difference was not statistically significant ( 1.79 % vs 2.43 % ; RR : 0.74 ; 95 % CI : 0.43 - 1.27 ) . The baseline mean plasma copper ( microg/dL ) was similar in the 2 groups ( difference in means : 1.6 ; 95 % CI : -2.9 to 6.1 ) . The end study plasma copper levels were significantly lower in the zinc group ( difference in means : -15.5 ; 95 % CI : -19.9 to - 11.1 ) . CONCLUSIONS Zinc supplementation substantially reduced the incidence of severe and prolonged diarrhea , the 2 important determinants of diarrhea-related mortality and malnutrition . This intervention also substantially reduced the proportion of children who experienced recurrent diarrhea . Prompt measures to improve zinc status of deficient population s are warranted . The potential approaches to achieve this goal include food fortification , dietary diversification , cultivation of plants that are zinc dense or have a decreased concentration of zinc absorption inhibitors , and supplementation of selected groups of children . Future studies should assess the impact of increased zinc intakes on childhood mortality in developing countries . For facilitating intervention , there is a need to obtain reliable estimates of zinc deficiency , particularly in developing countries . The functional consequences of the effect of various doses of zinc on plasma copper levels merits additional study Vitamin A administered to children infected with the human immunodeficiency virus before influenza vaccination in a double-blind r and omized study did not enhance vaccine serologic responses but did dampen the increase in the human immunodeficiency virus viral load 14 days after immunization ( vitamin A , decrease of 0.13 + /- 0.09 log(10 ) copies/mL ; placebo , increase of 0.14 + /- 0.08 , P = .02 ) BACKGROUND Epidemiologic evidence indicates that diets high in carotenoid-rich fruits and vegetables , as well as high serum levels of vitamin E ( alpha-tocopherol ) and beta carotene , are associated with a reduced risk of lung cancer . METHODS We performed a r and omized , double-blind , placebo-controlled primary -prevention trial to determine whether daily supplementation with alpha-tocopherol , beta carotene , or both would reduce the incidence of lung cancer and other cancers . A total of 29,133 male smokers 50 to 69 years of age from southwestern Finl and were r and omly assigned to one of four regimens : alpha-tocopherol ( 50 mg per day ) alone , beta carotene ( 20 mg per day ) alone , both alpha-tocopherol and beta carotene , or placebo . Follow-up continued for five to eight years . RESULTS Among the 876 new cases of lung cancer diagnosed during the trial , no reduction in incidence was observed among the men who received alpha-tocopherol ( change in incidence as compared with those who did not , -2 percent ; 95 percent confidence interval , -14 to 12 percent ) . Unexpectedly , we observed a higher incidence of lung cancer among the men who received beta carotene than among those who did not ( change in incidence , 18 percent ; 95 percent confidence interval , 3 to 36 percent ) . We found no evidence of an interaction between alpha-tocopherol and beta carotene with respect to the incidence of lung cancer . Fewer cases of prostate cancer were diagnosed among those who received alpha-tocopherol than among those who did not . Beta carotene had little or no effect on the incidence of cancer other than lung cancer . Alpha-tocopherol had no apparent effect on total mortality , although more deaths from hemorrhagic stroke were observed among the men who received this supplement than among those who did not . Total mortality was 8 percent higher ( 95 percent confidence interval , 1 to 16 percent ) among the participants who received beta carotene than among those who did not , primarily because there were more deaths from lung cancer and ischemic heart disease . CONCLUSIONS We found no reduction in the incidence of lung cancer among male smokers after five to eight years of dietary supplementation with alpha-tocopherol or beta carotene . In fact , this trial raises the possibility that these supplements may actually have harmful as well as beneficial effects OBJECTIVE We investigated whether vitamin A supplementation would decrease mortality and morbidity rates in children infected with the human immunodeficiency virus ( HIV ) . METHODS We conducted a r and omized , double-blind , placebo-controlled clinical trial at Mulago Hospital , a large hospital that serves the urban and semiurban population s of Kampala , Ug and a. One hundred eighty-one HIV-infected children were enrolled at 6 mo and r and omized to receive vitamin A supplementation , 60 mg retinol equivalent , or placebo every 3 mo from ages 15 to 36 mo . Morbidity was assessed through a 7-d morbidity history every 3 mo , and vital events were measured . Children received daily trimethoprim-sulfamethoxazole prophylactic therapy . RESULTS After age 15 mo , children were followed for a median of 17.8 mo ( interquartile range = 11.1 to 21.0 mo ) . The trial was stopped when there was a new policy to implement a program of mass supplementation of vitamin A in the country . Mortality rates among 87 children in the vitamin A group and 94 children in the control group were 20.6 % and 32.9 % , respectively , yielding a relative risk of 0.54 ( 95 % confidence interval , 0.30 to 0.98 ; P = 0.044 ) after adjusting for baseline weight-for-height Z score . Children who received vitamin A had lower modified point prevalences of persistent cough ( odds ratio , 0.47 ; 95 % confidence interval , 0.23 to 0.96 ; P = 0.038 ) and chronic diarrhea ( odds ratio , 0.48 ; 95 % confidence interval , 0.19 to 1.18 ; P = 0.11 ) and a shorter duration of ear discharge ( P = 0.03 ) . Vitamin A supplementation had no significant effect on modified point prevalences of fever , ear discharge , bloody stools , or hospitalizations . CONCLUSIONS Vitamin A supplementation decreases mortality rate in HIV-infected children and should be considered in the care for these children in developing countries UNLABELLED Intervention trials have shown that zinc is efficacious in treating acute diarrhea in children of developing countries . In a r and omized , placebo-controlled trial , we assessed the effectiveness and efficacy of giving 3 Recommended Daily Allowances of elemental zinc to 6- to 35-month-old children with acute diarrhea . METHODS Seventeen hundred ninety-two cases of acute diarrhea in Nepalese children were r and omized to 4 study groups . Three groups were blinded and the children supplemented daily by field workers with placebo syrup , zinc syrup , or zinc syrup and a massive dose of vitamin A at enrollment . The fourth group was open and the caretaker gave the children zinc syrup daily . Day-wise information on morbidity was obtained by household visits every fifth day . RESULTS The relative hazards for termination of diarrhea were 26 % ( 95 % confidence interval [ CI ] : 8 % , 46 % ) , 21 % ( 95 % CI : 4 % , 38 % ) , and 19 % ( 95 % CI : 2 % , 40 % ) higher in the zinc , zinc-vitamin A , and zinc-caretaker groups , respectively , than in the placebo group . The relative risks of prolonged diarrhea ( duration > 7 days ) in these groups were 0.57 ( 95 % CI : 0.38 , 0.86 ) , 0.53 ( 95 % CI : 0.35 , 0.81 ) , and 0.55 ( 0.37 , 0.84 ) ; zinc accordingly reduced the risk of prolonged diarrhea with 43 % to 47 % . Five percent and 5.1 % of all syrup administrations were followed by regurgitation in the zinc and zinc-vitamin A group , respectively , whereas this occurred after only 1.3 % of placebo administrations . Vomiting during diarrhea was also more common in children receiving zinc . CONCLUSIONS Three Recommended Daily Allowances of zinc given daily by caretakers or by field workers substantially reduced the duration of diarrhea . The effect of zinc was not dependent on or enhanced by concomitant vitamin A administration Background Prophylactic zinc supplementation has been shown to reduce diarrhea and respiratory illness in children in many developing countries , but its efficacy in children in Africa is uncertain . Objective To determine if zinc , or zinc plus multiple micronutrients , reduces diarrhea and respiratory disease prevalence . Design R and omized , double-blind , controlled trial . Setting Rural community in South Africa . Participants Three cohorts : 32 HIV-infected children ; 154 HIV-uninfected children born to HIV-infected mothers ; and 187 HIV-uninfected children born to HIV-uninfected mothers . Interventions Children received either 1250 IU of vitamin A ; vitamin A and 10 mg of zinc ; or vitamin A , zinc , vitamins B1 , B2 , B6 , B12 , C , D , E , and K and copper , iodine , iron , and niacin starting at 6 months and continuing to 24 months of age . Homes were visited weekly . Outcome Measures Primary outcome was percentage of days of diarrhea per child by study arm within each of the three cohorts . Secondary outcomes were prevalence of upper respiratory symptoms and percentage of children who ever had pneumonia by maternal report , or confirmed by the field worker . Results Among HIV-uninfected children born to HIV-infected mothers , median percentage of days with diarrhea was 2.3 % for 49 children allocated to vitamin A ; 2.5 % in 47 children allocated to receive vitamin A and zinc ; and 2.2 % for 46 children allocated to multiple micronutrients ( P = 0.852 ) . Among HIV-uninfected children born to HIV-uninfected mothers , median percentage of days of diarrhea was 2.4 % in 56 children in the vitamin A group ; 1.8 % in 57 children in the vitamin A and zinc group ; and 2.7 % in 52 children in the multiple micronutrient group ( P = 0.857 ) . Only 32 HIV-infected children were enrolled , and there were no differences between treatment arms in the prevalence of diarrhea . The prevalence of upper respiratory symptoms or incidence of pneumonia did not differ by treatment arms in any of the cohorts . Conclusion When compared with vitamin A alone , supplementation with zinc , or with zinc and multiple micronutrients , did not reduce diarrhea and respiratory morbidity in rural South African children . Trial Registration Clinical Trials.gov Background Micronutrient deficiencies compromise the survival of HIV-infected children in low-income countries . We assessed the effect of multiple micronutrient supplementation on the mortality of HIV-infected children in Ug and a. Methods In a r and omized , controlled trial , 847 children aged one to five years and attending HIV clinics in Ug and a were stratified by antiretroviral therapy ( ART , n = 85 versus no ART , n = 762 ) . The children were r and omized to six months of either : twice the recommended dietary allowance of 14 micronutrients as the intervention arm ( vitamins A , B1 , B2 , niacin , B6 , B12 , C , D and E , folate , zinc , copper , iodine and selenium ) ; or the st and ard recommended dietary allowance of six multivitamins ( vitamins A , D2 , B1 , B2 , C and niacin ) as a comparative " st and ard-of-care " arm . Mortality was analyzed at 12 months of follow up using Kaplan Meier curves and the log rank test . Results Mortality at 12 months was 25 out of 426 ( 5.9 % ) children in the intervention arm and 28 out of 421 ( 6.7 % ) in the comparative arms : risk ratio 0.9 ( 95 % CI 0.5 - 1.5 ) . Two out of 85 ( 2.4 % ) children in the ART stratum died compared with 51 out of 762 ( 6.7 % ) in the non-ART stratum . Of those who died in the non-ART stratum , 25 of 383 ( 6.5 % ) were in the intervention arm and 26 of 379 ( 6.9 % ) in the comparative arm ; risk ratio 1.0 ( 95 % CI 0.6 - 1.6 ) . There was no significant difference in survival at 12 months ( p = 0.64 , log rank test ) . In addition , there was no significant difference in mean weight-for-height at 12 months ; 0.70 ± 1.43 ( 95 % CI 0.52 - 0.88 ) for the intervention versus 0.59 ± 1.15 ( 95 % CI 0.45 - 0.75 ) in the comparative arm . The mean CD4 cell count ; 1024 ± 592 ( 95 % CI 942 - 1107 ) versus 1060 ± 553 ( 95 % CI 985 - 1136 ) was also similar between the two groups . Conclusions Twice the recommended dietary allowance of 14 micronutrients compared with a st and ard recommended dietary allowance of six multivitamins for six months was well tolerated , but it did not significantly alter mortality , growth or CD4 counts . Future intervention studies should carefully consider : ( 1 ) the composition and dosing of the supplements ; and ( 2 ) the power needed to detect a difference between arms . Trial Registration Clinical Trials.gov Identifier : OBJECTIVE To assess the impact on mortality related to pregnancy of supplementing women of reproductive age each week with a recommended dietary allowance of vitamin A , either preformed or as beta carotene . DESIGN Double blind , cluster r and omised , placebo controlled field trial . SETTING Rural southeast central plains of Nepal ( Sarlahi district ) . SUBJECTS 44 646 married women , of whom 20 119 became pregnant 22 189 times . INTERVENTION 270 wards r and omised to 3 groups of 90 each for women to receive weekly a single oral supplement of placebo , vitamin A ( 7000 micrograms retinol equivalents ) or beta carotene ( 42 mg , or 7000 micrograms retinol equivalents ) for over 31/2 years . MAIN OUTCOME MEASURES All cause mortality in women during pregnancy up to 12 weeks post partum ( pregnancy related mortality ) and mortality during pregnancy to 6 weeks postpartum , excluding deaths apparently related to injury ( maternal mortality ) . RESULTS Mortality related to pregnancy in the placebo , vitamin A , and beta carotene groups was 704 , 426 , and 361 deaths per 100 000 pregnancies , yielding relative risks ( 95 % confidence intervals ) of 0 . 60 ( 0.37 to 0.97 ) and 0.51 ( 0.30 to 0.86 ) . This represented reductions of 40 % ( P<0.04 ) and 49 % ( P<0.01 ) among those who received vitamin A and beta carotene . Combined , vitamin A or beta carotene lowered mortality by 44 % ( 0.56 ( 0.37 to 0.84 ) , P<0.005 ) and reduced the maternal mortality ratio from 645 to 385 deaths per 100 000 live births , or by 40 % ( P<0.02 ) . Differences in cause of death could not be reliably distinguished between supplemented and placebo groups . CONCLUSION Supplementation of women with either vitamin A or beta carotene at recommended dietary amounts during childbearing years can lower mortality related to pregnancy in rural , undernourished population s of south Asia OBJECTIVE Evidence from animal experiments and observational studies in humans suggests that vitamin A plays a fundamental role in physical growth . However , results from vitamin A supplementation trials in children are inconsistent ; whereas some did not find an overall effect on growth , others found benefits only among specific groups , including children with low concentrations of serum retinol or short duration of breastfeeding . The apparent lack of an overall effect of vitamin A on growth could be attributed to context -specific distribution of conditions that affect both growth and the response to supplementation , eg , baseline vitamin A status , deficiency of other nutrients ( fat , zinc ) , and the presence of infectious diseases . Human immunodeficiency virus ( HIV ) infection , malaria , and diarrheal disease adversely affect growth and are associated with increased prevalence of vitamin A deficiency . We hypothesize that vitamin A supplementation could ameliorate the adverse effect of these infections on child growth . METHODS We conducted a r and omized , clinical trial among 687 Tanzanian children who were 6 to 60 months of age and admitted to the hospital with pneumonia . Children were assigned to oral doses of 200 000 IU vitamin A ( half that dose if < 12 months ) or placebo on the day of admission , a second dose on the following day , and third and fourth doses at 4 and 8 months after discharge from the hospital , respectively . Anthropometric measurements were obtained at baseline and at monthly visits to the study clinics during 12 months after the initial hospitalization . Surveillance on the incidence and severity of diarrhea and respiratory infections was conducted during biweekly visits , alternately at a study clinic and the child 's home , using a pictorial diary that the mothers were trained to use . A blood specimen was drawn at baseline for determination of HIV status , malaria infection , and hemoglobin levels . We used mixed effects models to compare estimated total weight and height increases after 1 year of follow-up between treatment arms , overall and within levels of HIV status , malaria , and other possible baseline effect modifiers . We also assessed the potential modulating effect of vitamin A on the risk of stunting ( height-for-age < -2 st and ard deviations of the gender-specific National Center for Health Statistics median reference ) attributable to diarrheal and respiratory infections during follow-up , in the subset of children who were not stunted at baseline . A similar approach was followed for wasting ( weight-for-height < -2 st and ard deviations of the reference median ) . Cox regression models were used to estimate relative risks and 95 % confidence intervals ( CI ) , treating episodes of infection as time-dependent covariates . RESULTS A total of 554 children had at least 2 follow-up measurements of height or weight and constituted the study base . Baseline characteristics did not differ significantly by treatment arm . Seventy-three percent of the children were < 2 years of age , and 37 % were < 12 months ; 31 % were stunted at baseline and 9 % were wasted . Malaria ( Plasmodium falciparum ) and HIV infection were found in 24 % and 9 % of the children , respectively . Median duration of follow-up was 351 days , with 10 measurements /child , on average , irrespectively of treatment assignment . Supplementation with vitamin A among children who had HIV infection and were < 18 months of age result ed in a significant length increase . Four months after the first dose , infants who were HIV positive in the vitamin A arm had gained , on average , 2.8 cm ( 95 % CI : 1.0 - 4.6 ) more than children who received placebo , whereas no effect was observed among infants who were HIV negative ( difference at 4 months : -0.2 cm ; 95 % CI : -0.8 - 0.5 ) . Children who were < 12 months of age and had malaria at enrollment experienced a 747-g ( 95 % CI : 71 - 1423 ) higher yearly weight gain attributable to vitamin A ; among children without malaria , however , the supplements did not have a significant effect ( -57 g ; 95 % CI : -461 - 348 ) . These results remained unchanged after controlling for indicators of the socioeconomic and nutritional status at baseline . Linear growth was also improved by vitamin A among children from households with poor water supply ( 0.8 cm/year ; 95 % CI : 0 - 1.5 ) but not in children with tap water in the house or compound ( -1.0 cm/year ; 95 % CI : -1.9 - 0 ) . Weight gain was greater among children with mid-upper arm circumference below the 25th percentile of the age-specific distribution at baseline ( 458 g/year ; 95 % CI : 1 - 905 ) , but no benefit was evident among children with higher mid-upper arm circumference . The risk of stunting associated with episodes of persistent diarrhea ( lasting 14 or more days ) during follow-up was virtually eliminated by vitamin A supplements . Among children in the placebo group , the average risk of stunting associated with 1 or more episodes of persistent diarrhea between 2 consecutive visits was 5.2 times higher ( 95 % CI : 2.4 - 11.2 ) than that of children without diarrhea or with acute episodes . In contrast , among children who received vitamin A , there was virtually no risk of stunting associated with persistent diarrhea ( relative risk : 1.0 ; 95 % CI : 0.3 - 1.3 ) . This effect was slightly attenuated after controlling for the number of household possessions , gender , baseline low arm circumference , HIV infection , and presence of malaria parasites in blood . Vitamin A supplements did not modify the associations between respiratory infections and the risk of stunting or wasting . CONCLUSIONS Vitamin A supplementation improves linear and ponderal growth in infants who are infected with HIV and malaria , respectively , and decreases the risk of stunting associated with persistent diarrhea . Supplementation could constitute a low-cost , effective intervention to decrease the burden of growth retardation in setting s where infectious diseases are highly prevalent The effect of zinc supplementation on intestinal permeability changes and protein loss was studied in 32 children aged between 1 and 12 years during bouts of acute shigellosis and after recovery . An intestinal permeability test and then a 48 hour balance study were performed on all patients . They were then blindly assigned to receive vitamin B syrup either with or without zinc acetate ( 15 mg/kg per day ) for a month . All patients received a five day course of nalidixic acid . The balance study was repeated during convalescence and follow up , but a permeability test was done only at follow up after one month . Intestinal permeability , expressed as a urinary lactulose : mannitol excretion ratio , improved significantly ( p = 0.001 ) along with a significant increase ( p = 0.005 ) in mannitol excretion in the zinc supplemented children , suggesting a resolution of small bowel mucosal damage . The latter was associated with a higher coefficient of nitrogen absorption ( p = 0.03 ) , suggesting a possible role of zinc in the treatment of shigellosis . Enteric protein loss , as assessed by faecal alpha 1 antitrypsin clearance , was not influenced by zinc supplementation BACKGROUND Experimental and epidemiologic investigations suggest that alpha-tocopherol ( the most prevalent chemical form of vitamin E found in vegetable oils , seeds , grains , nuts , and other foods ) and beta-carotene ( a plant pigment and major precursor of vitamin A found in many yellow , orange , and dark-green , leafy vegetables and some fruit ) might reduce the risk of cancer , particularly lung cancer . The initial findings of the Alpha-Tocopherol , Beta-Carotene Cancer Prevention Study ( ATBC Study ) indicated , however , that lung cancer incidence was increased among participants who received beta-carotene as a supplement . Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial ( CARET ) , which tested a combination of beta-carotene and vitamin A. PURPOSE We examined the effects of alpha-tocopherol and beta-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics ( e.g. , age , number of cigarettes smoked , dietary or serum vitamin status , and alcohol consumption ) , by study compliance , and in relation to clinical factors , such as disease stage and histologic type . Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other population s. METHODS A total of 29,133 men aged 50 - 69 years who smoked five or more cigarettes daily were r and omly assigned to receive alpha-tocopherol ( 50 mg ) , beta-carotene ( 20 mg ) , alpha-tocopherol and beta-carotene , or a placebo daily for 5 - 8 years ( median , 6.1 years ) . Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry , along with measurements of serum levels of alpha-tocopherol and beta-carotene . Incident cases of lung cancer ( n = 894 ) were identified through the Finnish Cancer Registry and death certificates . Each lung cancer diagnosis was independently confirmed , and histology or cytology was available for 94 % of the cases . Intervention effects were evaluated by use of survival analysis and proportional hazards models . All P values were derived from two-sided statistical tests . RESULTS No overall effect was observed for lung cancer from alpha-tocopherol supplementation ( relative risk [ RR ] = 0.99 ; 95 % confidence interval [ CI ] = 0.87 - 1.13 ; P = .86 , logrank test ) . beta-Carotene supplementation was associated with increased lung cancer risk ( RR = 1.16 ; 95 % CI = 1.02 - 1.33 ; P = .02 , logrank test ) . The beta-carotene effect appeared stronger , but not substantially different , in participants who smoked at least 20 cigarettes daily ( RR = 1.25 ; 95 % CI = 1.07 - 1.46 ) compared with those who smoked five to 19 cigarettes daily ( RR = 0.97 ; 95 % CI = 0.76 - 1.23 ) and in those with a higher alcohol intake ( > or = 11 g of ethanol/day [ just under one drink per day ] ; RR = 1.35 ; 95 % CI = 1.01 - 1.81 ) compared with those with a lower intake ( RR = 1.03 ; 95 % CI = 0.85 - 1.24 ) . CONCLUSIONS Supplementation with alpha-tocopherol or beta-carotene does not prevent lung cancer in older men who smoke . beta-Carotene supplementation at pharmacologic levels may modestly increase lung cancer incidence in cigarette smokers , and this effect may be associated with heavier smoking and higher alcohol intake . IMPLICATION S While the most direct way to reduce lung cancer risk is not to smoke tobacco , smokers should avoid high-dose beta-carotene supplementation Objective : To determine the impact of nutritional ( selenium ) chemo-prevention on levels of psychological burden ( anxiety , depression , and mood state ) in HIV/AIDS . Method : A r and omized , double-blind , placebo-controlled selenium therapy ( 200 μ/day ) trial was conducted in HIV+ drug users from 1998–2000 . Psychosocial measures ( STAI-State and Trait anxiety , BDI-depression , and POMS- mood state ) , clinical status ( CD4 cell count , viral load ) , and plasma selenium levels were determined at baseline and compared with measurements obtained at the 12-month evaluation in 63 participants ( 32 men , 31 women ) . Results : The majority of the study participants reported elevated levels of both State ( 68 % ) and Trait ( 70 % ) anxiety . Approximately 25 % reported overall mood distress ( POMS > 60 ) and moderate depression ( BDI > 20 ) . Psychological burden was not influenced by current drug use , antiretroviral treatment , or viral load . At the 12-month evaluation , participants who received selenium reported increased vigor ( p = 0.004 ) and had less anxiety ( State , p = 0.05 and Trait , p = 0.02 ) , compared to the placebo-treated individuals . No apparent selenium-related affect on depression or distress was observed . The risk for state anxiety was almost four times higher , and nearly nine times greater for trait anxiety in the placebo-treated group , controlling for antiretroviral therapy , CD4 cell decline ( > 50 cells ) and years of education . Conclusions : Selenium therapy may be a beneficial treatment to decrease anxiety in HIV+ drug users who exhibit a high prevalence of psychological burden Effects of vitamin A supplementation during pregnancy and early lactation on maternal weight among HIV-1-seropositive South African women were examined . Three hundred twelve HIV-seropositive pregnant women between 28 and 32 weeks gestation were studied as part of a r and omized , double-blind , placebo-controlled trial at the King Edward VIII Hospital in Durban , South Africa . Patients were r and omized to receive placebo or 5,000 IU of retinyl palmitate and 30 mg of beta-carotene daily during pregnancy . At delivery , patients received placebo or 200,000 IU of retinyl palmitate . The main outcome measures were prenatal and postnatal maternal weight and weight loss at three months after delivery as measured in body mass index ( BMI ) . Supplementation of vitamin A was not associated with improvements in prepartum weight gain but was significantly associated with improved weight retention three to six months after delivery ( p = 0.02 ) . The benefit of vitamin A supplementation appeared to be confined to subgroups with baseline CD4 + count < 200 cells/microL and serum retinol 0 - 20 micrograms/dL. Similar trends were observed in maintenance of postpartum BMI . However , no statistically significant associations were observed . Although there was no benefit of vitamin A supplementation on prepartum weight gain , a benefit on maintenance of postnatal weight was observed . The benefit was highest among those who were vitamin A-deficient or whose CD4 + count was < 200 cells/microL presupplementation . In population s for whom antiretroviral therapy is not readily available or accessible , the finding that vitamin A may improve postpartum weight lends some hope to a relatively inexpensive treatment which could be used for helping ameliorate some weight loss which is common during HIV infection The duration of pneumonia and of diarrhea is reported to be longer in HIV-infected than in uninfected children . We assessed the effect of a multi-micronutrient supplement on the duration of hospitalization in HIV-infected children . In a double-blind , r and omized trial , HIV-infected children ( 4 - 24 mo ) who were hospitalized with diarrhea or pneumonia were enrolled ( n = 118 ) and given a daily dose of a multi-micronutrient supplement ( containing vitamins A , B complex , C , D , E , and folic acid , as well as copper , iron , and zinc at levels based on recommended daily allowances ) or a placebo until discharge from the hospital . Children 's weights and heights were measured after enrollment and micronutrient concentrations were measured before discharge . On recovery from diarrhea or pneumonia , the children were discharged and the duration of hospitalization was noted . Anthropometric indices and micronutrient concentrations did not differ between children who received supplements and those who received placebos . Overall , the duration of hospitalization was shorter ( P < 0.05 ) among children who were receiving supplements ( 7.3 + /- 3.9 d ) ( mean + /- SD ) than in children who were receiving placebos ( 9.0 + /- 4.9 ) ; this was independent of admission diagnosis . In children admitted with diarrhea , the duration of hospitalization was 1.6 d ( 19 % ) shorter among children receiving supplements than in those receiving placebos , and hospitalization for pneumonia was 1.9 d ( 20 % ) shorter among children receiving supplements . Short-term multi-micronutrient supplementation significantly reduced the duration of pneumonia or diarrhea in HIV-infected children who were not yet receiving antiretroviral therapy and who remained alive during hospitalization BACKGROUND Adequate zinc is critical for immune function ; however , zinc deficiency occurs in > 50 % of human immunodeficiency virus (HIV)-infected adults . We examined the safety and efficacy of long-term zinc supplementation in relation to HIV disease progression . METHODS A prospect i ve , r and omized , controlled clinical trial was conducted involving 231 HIV-infected adults with low plasma zinc levels ( < 0.75 mg/L ) , who were r and omly assigned to receive zinc ( 12 mg of elemental zinc for women and 15 mg for men ) or placebo for 18 months . The primary end point was immunological failure . HIV viral load and CD4(+ ) cell count were determined every 6 months . Question naires , pill counts , and plasma zinc and C-reactive protein levels were used to monitor adherence to study supplements and antiretroviral therapy . Intent-to-treat analysis used multiple-event analysis , treating CD4(+ ) cell count < 200 cells/mm(3 ) as a recurrent immunological failure event . Cox proportional hazard models and the general-linear model were used to analyze morbidity and mortality data . RESULTS Zinc supplementation for 18 months reduced 4-fold the likelihood of immunological failure , controlling for age , sex , food insecurity , baseline CD4(+ ) cell count , viral load , and antiretroviral therapy ( relative rate , 0.24 ; 95 % confidence interval , 0.10 - 0.56 ; P<.002 ) . Viral load indicated poor control with antiretroviral therapy but was not affected by zinc supplementation . Zinc supplementation also reduced the rate of diarrhea by more than half ( odds ratio , 0.4 ; 95 % confidence interval , 0.183 - 0.981 ; P=.019 ) , compared with placebo . There was no significant difference in mortality between the 2 groups . CONCLUSIONS This study demonstrated that long-term ( 18-month ) zinc supplementation at nutritional levels delayed immunological failure and decreased diarrhea over time . This evidence supports the use of zinc supplementation as an adjunct therapy for HIV-infected adult cohorts with poor viral control . Trial registration . Clinical Trials.gov identifier : NCT00149552 BACKGROUND In HIV-1-infected women , poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes . We assessed the effects of vitamin A and multivitamins on birth outcomes in such women . METHODS In Tanzania , 1075 HIV-1-infected pregnant women at between 12 and 27 weeks ' gestation received placebo ( n=267 ) , vitamin A ( n=269 ) , multivitamins excluding vitamin A ( n=269 ) , or multivitamins including vitamin A ( n=270 ) in a r and omised , double-blind , placebo-controlled trial with a 2x2 factorial design . We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets . We did analyses by intention to treat . RESULTS 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins ( relative risk 0.61 [ 95 % CI 0.39 - 0.94 ] p=0.02 ) . Multivitamin supplementation decreased the risk of low birthweight ( < 2500 g ) by 44 % ( 0.56 [ 0.38 - 0.82 ] p=0.003 ) , severe preterm birth ( < 34 weeks of gestation ) by 39 % ( 0.61 [ 0.38 - 0.96 ] p=0.03 ) , and small size for gestational age at birth by 43 % ( 0.57 [ 0.39 - 0.82 ] p=0.002 ) . Vitamin A supplementation had no significant effect on these variables . Multivitamins , but not vitamin A , result ed in a significant increase in CD4 , CD8 , and CD3 counts . INTERPRETATION Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women . The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained Abstract Objective : To evaluate the effect on morbidity and mortality of providing daily zinc for 14 days to children with diarrhoea . Design : Cluster r and omised comparison . Setting : Matlab field site of International Center for Diarrhoeal Disease Research , Bangladesh . Participants : 8070 children aged 3 - 59 months contributed 11 881 child years of observation during a two year period . Intervention : Children with diarrhoea in the intervention clusters were treated with zinc ( 20 mg per day for 14 days ) ; all children with diarrhoea were treated with oral rehydration therapy . Main outcome measures : Duration of episode of diarrhoea , incidence of diarrhoea and acute lower respiratory infections , admission to hospital for diarrhoea or acute lower respiratory infections , and child mortality . Results : About 40 % ( 399/1007 ) of diarrhoeal episodes were treated with zinc in the first four months of the trial ; the rate rose to 67 % ( 350/526 ) in month 5 and to > 80 % ( 364/434 ) in month 7 and was sustained at that level . Children from the intervention cluster received zinc for about seven days on average during each episode of diarrhoea . They had a shorter duration ( hazard ratio 0.76 , 95 % confidence interval 0.65 to 0.90 ) and lower incidence of diarrhoea ( rate ratio 0.85 , 0.76 to 0.96 ) than children in the comparison group . Incidence of acute lower respiratory infection was reduced in the intervention group but not in the comparison group . Admission to hospital of children with diarrhoea was lower in the intervention group than in the comparison group ( 0.76 , 0.59 to 0.98 ) . Admission for acute lower respiratory infection was lower in the intervention group , but this was not statistically significant ( 0.81 , 0.53 to 1.23 ) . The rate of non-injury deaths in the intervention clusters was considerably lower ( 0.49 , 0.25 to 0.94 ) . Conclusions : The lower rates of child morbidity and mortality with zinc treatment represent substantial benefits from a simple and inexpensive intervention that can be incorporated in existing efforts to control diarrhoeal disease . What is already known on this topic Zinc deficiency is highly prevalent in children in developing countries Zinc supplements given during diarrhoea reduce the duration and severity of treated episodes If given for 14 days during and after diarrhoea , zinc reduces the incidence of diarrhoea and pneumonia in the subsequent two to three months What this study adds Zinc used as a treatment for diarrhoea reduces mortality in children Zinc reduces admissions to hospital for diarrhoea The impact of zinc on mortality and morbidity can be achieved in a realistic large scale public health Background The period of complementary feeding , starting around 6 months of age , is a time of high risk for growth faltering and morbidity . Low micronutrient density of locally available foods is a common problem in low income countries . Children of HIV-infected women are especially vulnerable . Although antiretroviral prophylaxis can reduce breast milk HIV transmission in early infancy , there are no clear feeding guidelines for after 6 months . There is a need for acceptable , feasible , affordable , sustainable and safe ( AFASS by WHO terminology ) foods for both HIV-exposed and unexposed children after 6 months of age . Methods and Findings We conducted in Lusaka , Zambia , a r and omised double-blind trial of two locally made infant foods : porridges made of flour composed of maize , beans , bambaranuts and groundnuts . One flour contained a basal and the other a rich level of micronutrient fortification . Infants ( n = 743 ) aged 6 months were r and omised to receive either regime for 12 months . The primary outcome was stunting ( length-for-age Z<−2 ) at age 18 months . No significant differences were seen between trial arms overall in proportion stunted at 18 months ( adjusted odds ratio 0.87 ; 95 % CI 0.50 , 1.53 ; P = 0.63 ) , mean length-for-age Z score , or rate of hospital referral or death . Among children of HIV-infected mothers who breastfed < 6 months ( 53 % of HIV-infected mothers ) , the richly-fortified porridge increased length-for-age and reduced stunting ( adjusted odds ratio 0.17 ; 95 % CI 0.04 , 0.84 ; P = 0.03 ) . Rich fortification improved iron status at 18 months as measured by hemoglobin , ferritin and serum transferrin receptors . Conclusions In the whole study population , the rich micronutrient fortification did not reduce stunting or hospital referral but did improve iron status and reduce anemia . Importantly , in the infants of HIV-infected mothers who stopped breastfeeding before 6 months , the rich fortification improved linear growth . Provision of such fortified foods may benefit health of these high risk infants . Trial registration Controlled-Trials.com IS RCT Observational studies have associated vitamin A deficiency with vaginal shedding of human immunodeficiency virus ( HIV ) type 1-infected cells and mother-to-child HIV-1 transmission . To assess the effect of vitamin A supplementation on vaginal shedding of HIV-1 , a r and omized , double-blind , placebo-controlled trial of 6 weeks of daily oral vitamin A ( 10,000 IU of retinyl palmitate ) was conducted among 400 HIV-1-infected women in Mombasa , Kenya . At follow-up , there was no statistically significant difference in the prevalence of HIV-1 DNA ( 18 % vs. 21 % , P=.4 ) or the quantity of HIV-1 RNA ( 3.12 vs. 3.00 log(10 ) copies/swab , P=1.0 ) in vaginal secretions of women receiving vitamin A , compared with women receiving placebo . No significant effect of supplementation on plasma HIV-1 load or CD4 or CD8 cell counts was observed , and no effect was seen among women who were vitamin A deficient at baseline . Vitamin A supplementation is unlikely to decrease the infectivity of women infected with HIV-1 A total of 1078 human immunodeficiency virus ( HIV ) type 1-infected women from Tanzania were r and omized in a placebo-controlled trial using a factorial design to examine the effects of supplementation with vitamin A ( preformed vitamin A and beta carotene ) and /or multivitamins ( vitamins B , C , and E ) . Supplements were given during pregnancy and lactation . Children of women in the multivitamin arms had a significantly lower risk of diarrhea than did those in the no-multivitamin arm ( P=.03 ) . The mean CD4 + cell count was 151 cells/microL higher among children in the multivitamin arms than among those in the no-multivitamin arm ( P=.0006 ) . HIV-positive children experienced a benefit apparently similar to that in HIV-negative children ( P=.34 , by test for interaction ) . Maternal receipt of vitamin A significantly reduced the risk that the child would have cough with a rapid respiratory rate , a proxy for pneumonia ( P=.03 ) , but receipt of vitamin A had no effect on diarrhea or CD4 + cell count . Provision of multivitamin supplements ( including those with vitamins B , C , and E ) to HIV-infected , lactating women may be a low-cost intervention to improve their children 's health Malnutrition is common in pulmonary tuberculosis ( TB ) , and may impair survival . The objective of this study was to assess effects of multi-vitamin/mineral ( MVM ) and zinc ( Zn ) supplementation during TB treatment on mortality . Patients diagnosed with sputum-positive pulmonary TB in Mwanza , Tanzania , were r and omised , using a two-by-two factorial design , to Zn ( 45 mg ) or placebo , and MVM ( vitamins A , B , C , D , E , and selenium and copper ) or placebo . Survival status was ascertained at the end of the 8-month TB treatment and supplementation period . Of 499 TB patients , 213 ( 43 % ) had HIV . The mean weight gain at 7 months was 6.88 kg ( 95 % CI 6.36 , 7.41 ) . Zn and MVM combined , but neither alone ( interaction , P=0.03 ) , increased weight gain by 2.37 kg ( 95 % CI 0.91 , 3.83 ) , irrespective of HIV status . Survival status at 8 months was determined for 422 patients ( 84.6 % ) , of which fifty-two ( 12.3 % ) had died . Among fifty-two deaths , there were no effects of MVM ( relative risk ( RR ) 0.73 ; 95 % CI 0.43 , 1.23 ) and Zn ( RR 0.76 ; 95 % CI 0.46 , 1.28 ) . However , among HIV co-infected patients , marginally significant effects of both MVM ( RR 0.60 ; 95 % CI 0.34 , 1.05 ) and Zn ( RR 0.63 , 95 % CI 0.37 , 1.08 ) were seen , and MVM and Zn combined reduced mortality ( RR 0.29 ; 95 % CI 0.10 , 0.80 ; interaction ratio 0.52 ) . In conclusion , supplementation with MVM , including Zn , during treatment of pulmonary TB may reduce mortality in those co-infected with HIV . A r and omised trial of the effect of the combined intervention used in this study should be conducted in a different setting to confirm the finding Vitamin A supplementation has been suggested for treatment and prevention of HIV infection . However , some in vitro data indicate that vitamin A may activate HIV . R and omly , 40 HIV-seropositive women of reproductive age were allocated to receive a single oral dose of 9900 micromol ( 300,000 IU ) vitamin A or placebo . Plasma HIV-1 RNA concentration , total lymphocytes , selected lymphocyte subsets and activation markers , and in vitro lymphocyte proliferation to phytohemagglutinin ( PHA ) and C and ida were measured before dosing and at various time points over an 8-week follow-up period . No differences were found between treatment groups in the frequency of signs or symptoms of acute vitamin A toxicity , nor were differences evident in any lymphocyte subset or activation marker at any time during follow-up . Mean and median viral load concentration at each time point and change in viral load from baseline to each follow-up point did not differ between treatment groups . No difference was measured between treatment groups in the proportion of women who responded to PHA or C and ida . This study provides no evidence that high dose vitamin A supplementation of HIV-infected women is associated with significant clinical or immunologic adverse effects Background / Objective : The efficacy of zinc combined with vitamin A or multiple micronutrients in preventing diarrhoea is unclear in African countries with high prevalence of human immunodeficiency virus (HIV)-exposed children . Potential modifying factors , such as stunting , need to be addressed . The objective of this study was to determine whether adding zinc or zinc plus multiple micronutrients to vitamin A reduces diarrhoea incidence , and whether this differs between the strata of stunted or HIV-infected children . Methods : We analyzed data from a r and omized , controlled , double-blinded trial ( Clinical Trials.gov NCT00156832 ) of prophylactic micronutrient supplementation to children aged 6–24 months . Three cohorts of children : 32 HIV-infected children , 154 HIV-uninfected children born to HIV-infected mothers and 187 uninfected children born to HIV-uninfected mothers , received vitamin A , vitamin A plus zinc or multiple micronutrients , which included vitamin A and zinc . The main outcome was incidence of diarrhoea . Poisson regression was used in intent-to-treat analyses . Stratified analyses followed testing for statistical interaction between intervention and stunting . Results : We observed no significant differences in overall diarrhoea incidence among treatment arms . Stunting modified this effect with stunted HIV-uninfected children having significantly lower diarrhoea incidence when supplemented with zinc or multiple micronutrients compared with vitamin A alone ( 2.04 and 2.23 vs 3.92 episodes/year , respectively , P=0.024 ) . No meaningful subgroup analyses could be done in the cohort of HIV-infected children . Conclusions : Compared with vitamin A alone , supplementation with zinc and with zinc and multiple micronutrients , reduced diarrhoea morbidity in stunted rural South African children . Efficacy of zinc supplementation in HIV-infected children needs confirmation in studies that represent the spectrum of disease severity and age groups Vitamin A is essential for immunity and growth . A controlled clinical that involved 697 human immunodeficiency virus (HIV)-infected pregnant women was conducted to determine whether vitamin A prevents anemia , low birth weight , growth failure , HIV transmission , and mortality . Women received daily doses of iron and folate , either alone or combined with vitamin A ( 3 mg retinol equivalent ) , from 18 - 28 weeks ' gestation until delivery . In the vitamin A and control groups , respectively , the mean ( + /-SE ) birth weights were 2895+/-31 g and 2805+/-32 g ( P=.05 ) , the proportions of low-birth-weight infants were 14.0 % and 21.1 % ( P=.03 ) , the proportions of anemic infants at 6 weeks postpartum were 23.4 % and 40.6 % ( P<.001 ) , and the respective cumulative proportions of infants who were HIV infected at 6 weeks and 24 months of age were 26.6 % and 27.8 % ( P=.76 ) and 27.7 % and 32.8 % ( P=.21 ) . Receipt of vitamin A improved birth weight and neonatal growth and reduced anemia , but it did not affect perinatal HIV transmission OBJECTIVE To determine the effect of vitamin A supplementation on the risk of diarrhea and of acute respiratory infection . DESIGN Double-blind , r and omized , placebo-controlled trial . SETTING Dar-es-Salaam , Tanzania . SUBJECTS Six hundred eighty-seven children , 6 to 60 months old , hospitalized with pneumonia , who received vitamin A or placebo at baseline and at 4 and 8 months after discharge from hospital . MAIN OUTCOME VARIABLES Incidence and duration of episodes of diarrhea and respiratory tract infections during the year after discharge from the hospital . RESULTS Relative to those receiving placebo , children receiving vitamin A had a significantly smaller risk of severe watery diarrhea ( multivariate odds ratio = 0.56 , 95 % CI = 0.32 - 0.99 , P = .04 ) but a higher risk of cough and rapid respiratory rate ( multivariate odds ratio = 1.67 , 95 % CI = 1.17 - 2.36 , P = .004 ) . Vitamin A supplementation was also associated with increased risk of acute diarrhea among normally nourished children or children with stunted growth but was relatively protective among children with wasting disease ( P value for interaction = .01 ) . The apparently increased risk of respiratory tract infection was limited to children who were seronegative for human immunodeficiency virus ( HIV ) ( P value for interaction = .07 ) . CONCLUSIONS Vitamin A supplements provide a low-cost intervention against morbidity in HIV-infected and undernourished children . Supplements may also have serious non-lethal adverse outcomes in well-nourished individuals . Whether these apparent detrimental effects of vitamin A are transient or long-term needs to be examined OBJECTIVE The effects of vitamin A supplementation on morbidity of children born to human immunodeficiency virus (HIV)-infected women were evaluated in a population where vitamin A deficiency is not endemic . METHODS A r and omized , placebo-controlled trial of vitamin A supplementation was carried out in 118 offspring of HIV-infected women in Durban , South Africa . Those assigned to receive a supplement were given 50,000 IU of vitamin A at 1 and 3 months of age ; 100,000 IU at 6 and 9 months ; and 200,000 IU at 12 and 15 months . Morbidity in the past month was then recalled at each follow-up visit . Analysis was based on 806 child-months . RESULTS Among all children , the supplemented group had lower overall morbidity than the placebo group ( OR = 0.69 ; 95 % confidence interval [ CI ] = 0.48 , 0.99 ) . Among the 85 children of known HIV status ( 28 infected , 57 uninfected ) , morbidity associated with diarrhea was significantly reduced in the supplemented infected children ( OR = 0.51 ; 95 % CI = 0.27 , 0.99 ) , whereas no effect of supplementation on diarrheal morbidity was noted among the uninfected children . CONCLUSION In a population not generally vitamin A deficient , vitamin A supplementation for children of HIV-infected women appeared to be beneficial , reducing morbidity . The benefit was observed particularly for diarrhea among HIV-infected children BACKGROUND Tuberculosis ( TB ) often coincides with nutritional deficiencies . The effects of micronutrient supplementation on TB treatment outcomes , clinical complications , and mortality are uncertain . METHODS We conducted a r and omized , double-blind , placebo-controlled trial of micronutrients ( vitamins A , B complex , C , and E , as well as selenium ) in Dar es Salaam , Tanzania . We enrolled 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months . RESULTS Micronutrients decreased the risk ofTB recurrence by 45 % overall ( 95 % confidence interval [ CI ] , 7 % to 67 % ; P = .02 ) and by 63 % in HIV-infected patients ( 95 % CI , 8 % to 85 % ; P = .02 ) . There were no significant effects on mortality overall ; however , we noted a marginally significant 64 % reduction of deaths in HIV-negative subjects ( 95 % CI , -14 % to 88 % ; P = .08 ) . Supplementation increased CD3 + and CD4 + cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients . Micronutrients reduced the incidence of peripheral neuropathy by 57 % ( 95 % CI , 41 % to 69 % ; P < .001 ) , irrespective of HIV status . There were no significant effects on weight gain , body composition , anemia , or HIV load . CONCLUSIONS Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania Summary : Among HIV‐1‐infected individuals , vitamin A deficiency has been associated with faster disease progression and greater infectivity in observational studies , but r and omized clinical trials have shown no effect of vitamin A supplementation . We conducted a cross‐sectional study of 400 HIV‐1‐infected and 200 HIV‐1‐uninfected women in Mombasa , Kenya to examine the relations between vitamin A deficiency ( serum retinol < 30 μg/dL ) and HIV‐1 status , HIV‐1 disease stage , and the acute phase response ( serum C‐reactive protein ≥10 mg/L and /or & agr;1‐acid glycoprotein ≥1.2 g/L ) . Among the HIV‐1‐infected women , the effect of vitamin A supplementation was examined in a r and omized trial . Vitamin A deficiency was independently associated with HIV‐1 infection ( OR = 2.7 , 95 % CI : 1.9‐4.0 ) and the acute phase response ( OR = 2.8 , 95 % CI : 1.9‐4.1 ) . Among HIV‐1‐infected women , vitamin A deficiency and the acute phase response were associated with each other and were both independently associated with higher HIV‐1 plasma viral load and lower CD4 count . HIV‐1‐infected women having an acute phase response had no increase in serum vitamin A levels after supplementation . Serum levels increased significantly among women without an acute phase response , although not to normal levels among women who were deficient at baseline . Among HIV‐1‐infected individuals , it is likely that low serum vitamin A concentrations reflect more active infection and the acute phase response . These results provide possible explanations for the disparity between observational studies and r and omized trials of vitamin A for HIV‐1 infection BACKGROUND Low maternal serum retinol level is a risk factor for mother-to-child transmission ( MTCT ) of human immunodeficiency virus ( HIV ) . Multiple-large-dose vitamin A supplementation of HIV-positive children reduces mortality . The World Health Organization recommends single-large-dose vitamin A supplementation for postpartum women in areas of prevalent vitamin A deficiency ; neonatal dosing is under consideration . We investigated the effect that single-large-dose maternal/neonatal vitamin A supplementation has on MTCT , HIV-free survival , and mortality in HIV-exposed infants . METHODS A total of 14,110 mother-infant pairs were enrolled < or = 96 h after delivery , and both mother and infant , mother only , infant only , or neither received vitamin A supplementation in a r and omized , placebo-controlled trial with a 2 x 2 factorial design . All but 4 mothers initiated breast-feeding . A total of 4495 infants born to HIV-positive women were included in the present analysis . RESULTS Neither maternal nor neonatal vitamin A supplementation significantly affected postnatal MTCT or overall mortality between baseline and 24 months . However , the timing of infant HIV infection modified the effect that supplementation had on mortality . Vitamin A supplementation had no effect in infants who were polymerase chain reaction ( PCR ) positive [ corrected ] for HIV at baseline . In infants who were PCR negative at baseline and PCR positive at 6 weeks , neonatal supplementation reduced mortality by 28 % ( P=.01 ) , but maternal supplementation had no effect . In infants who were PCR negative at 6 weeks , all 3 vitamin A regimens were associated with ~2-fold higher mortality ( P < or = .05 ) . CONCLUSIONS Targeted vitamin A supplementation of HIV-positive children prolongs their survival . However , postpartum maternal and neonatal vitamin A supplementation may hasten progression to death in breast-fed children who are PCR negative at 6 weeks . These findings raise concern about universal maternal or neonatal vitamin A supplementation in HIV-endemic areas PURPOSE To evaluate the impact of selenium chemoprevention ( 200 microg/day ) on hospitalizations in HIV-positive individuals . METHOD Data were obtained from 186 HIV+ men and women participating in a r and omized , double-blind , placebo-controlled selenium clinical trial ( 1998 - 2000 ) . Supplements were dispensed monthly , and clinical evaluations were conducted every 6 months . Inpatient hospitalizations , hospitalization costs , and rates of hospitalization were determined 2 years before and during the trial . RESULTS At enrollment , no significant differences in CD4 cell counts or viral burden were observed between the two study arms . Fewer placebo-treated participants were using antiretrovirals ( p < .05 ) . The total number of hospitalizations declined from 157 before the trial to 103 during the 2 year study . A marked decrease in total admission rates ( RR = 0.38 ; p = .002 ) and percent of hospitalizations due to infection/100 patients for those receiving selenium was observed ( p = .01 ) . As a result , the cost for hospitalization decreased 58 % in the selenium group , compared to a 30 % decrease in the placebo group ( p = .001 ) . In the final analyses , selenium therapy continued to be a significant independent factor associated with lower risk of hospitalization ( p = .001 ) . CONCLUSION Selenium supplementation appears to be a beneficial adjuvant treatment to decrease hospitalizations as well as the cost of caring for HIV-1-infected patients There is evidence suggesting that patients infected with human immunodeficiency virus ( HIV ) are under chronic oxidative stress . In the present study , the level of oxidatively modified bases in lymphocyte DNA and some other parameters of oxidative stress were measured in HIV-infected patients ( n = 30 ) , as well as in control groups ( 10 healthy volunteers and 15 HIV-seronegative injected drug users ) . Additional experiments were conducted using lymphocyte DNA sample s from asymptomatic seropositive , HIV-infected patients who were supplemented with antioxidant vitamins A , C , and E or received placebo . Significant increases in the amount of the modified DNA bases were observed in HIV-infected patients when compared with the control group . The concentration of thiobarbituric acid reactive substances ( TBARS ) was higher and activities of antioxidant enzymes ( superoxide dismutase and catalase ) were lower in the group of HIV-infected patients in comparison to the control group . Vitamin supplementation result ed in the significant decrease in the levels of all modified DNA bases when compared to the patients who received placebo . The reduction of TBARS and the restoration of the activity of the enzymes were also observed . Our data suggest that people infected with HIV can benefit from treatment with antioxidant vitamins SETTING Zomba and Blantyre , Malawi , Africa . OBJECTIVES To determine whether daily micronutrient supplementation reduces the mortality of human immunodeficiency virus ( HIV ) infected adults with pulmonary tuberculosis ( TB ) . DESIGN A r and omised , controlled clinical trial of micronutrient supplementation for HIV-positive and HIV-negative adults with pulmonary TB . Participants were enrolled at the commencement of chemotherapy for sputum smear-positive pulmonary TB and followed up for 24 months . RESULTS A total of 829 HIV-positive and 573 HIV-negative adults were enrolled . During follow-up , 328 HIV-positive and 17 HIV-negative participants died . The proportion of HIV-positive participants who died in the micronutrient and placebo groups was 38.7 % and 40.4 % , respectively ( P = 0.49 ) . Micronutrient supplementation did not reduce mortality ( hazard ratio [ HR ] 0.93 , 95%CI 0.75 - 1.15 ) among HIV-positive adults . CONCLUSIONS Micronutrient supplementation at the doses used in this study does not reduce mortality in HIV-positive adults with pulmonary TB in Malawi Objective : To investigate the effect of antioxidant supplementation on viral load and the antioxidant/reactive oxygen species system in people with HIV . Design : Single centre , prospect i ve , dose comparison study . Setting : Outpatient clinic specializing in HIV care . Subjects : Sixty-six participants were sequentially recruited by advertisement , and 48 subjects completed the study . Interventions : A recommended dose antioxidant regimen ( 5450 IU vitamin A as β-carotene , 250 mg vitamin C , 100 IU vitamin E , 100 µg selenium , 50 mg coenzyme Q10 ) or a high-dose antioxidant regimen ( 21 800 IU vitamin A as β-carotene , 1000 mg vitamin C , 400 IU vitamin E , 200 µg selenium , 200 mg coenzyme Q10 ) for a 12 week period . Results : Using repeated measures analysis of variance , the changes over treatment time were significant for selenium , glutathione , glutathione peroxidase and lipid peroxides ( P<0.03 ) . Changes in allantoin , uric acid and viral load were not significant ( P>0.05 ) . The main effects for group and the interaction effects were not significant for any of the parameters measured ( P≥0.05 ) . Conclusion : Antioxidant supplementation significantly improved some measures of oxidative defence . There was no benefit in using a high-dose supplement in this study .Sponsorship : Blackmores Ltd supplied the antioxidant supplements . European Journal of Clinical Nutrition ( 2001 ) 55 , Background : Vitamin A deficiency is common among women in re source -poor countries and is associated with greater mortality during HIV . Methods : Fourteen thous and one hundred ten mothers were tested for HIV and r and omly administered 400,000 IU vitamin A or placebo at less than 96 hours postpartum . The effects of vitamin A and HIV status on mortality , health care utilization , and serum retinol were evaluated . Results : Four thous and four hundred ninety-five ( 31.9 % ) mothers tested HIV positive . Mortality at 24 months was 2.3 per 1000 person-years and 38.3 per 1000 person-years in HIV-negative and HIV-positive women , respectively . Vitamin A had no effect on mortality . Tuberculosis was the most common cause of death , and nearly all tuberculosis-associated deaths were among HIV-positive women . Among HIV-positive women , vitamin A had no effect on rates of hospitalization or overall sick clinic visits , but did reduce clinic visits for malaria , cracked and bleeding nipples , pelvic inflammatory disease , and vaginal infection . Among HIV-negative women , serum retinol was responsive to vitamin A , but low serum retinol was rare . Among HIV-positive women , serum retinol was largely unresponsive to vitamin A , and regardless of treatment group , the entire serum retinol distribution was shifted 25 % less than that of HIV-negative women 6 weeks after dosing . Conclusions : Single-dose postpartum vitamin A supplementation had no effect on maternal mortality , perhaps because vitamin A status was adequate in HIV-negative women and apparently unresponsive to supplementation in HIV-positive women BACKGROUND HIV contributes substantially to child mortality , but factors underlying these deaths are inadequately described . With individual data from seven r and omised mother-to-child transmission ( MTCT ) intervention trials , we estimate mortality in African children born to HIV-infected mothers and analyse selected risk factors . METHODS Early HIV infection was defined as a positive HIV-PCR test before 4 weeks of age ; and late infection by a negative PCR test at or after 4 weeks of age , followed by a positive test . Mortality rate was expressed per 1000 child-years . We investigated the effect of maternal health , infant HIV infection , feeding practice s , and age at acquisition of infection on mortality assessed with Cox proportional hazards models , and allowed for r and om effects for trials grouped geographically . FINDINGS 378 ( 11 % ) of 3468 children died . By age 1 year , an estimated 35.2 % infected and 4.9 % uninfected children will have died ; by 2 years of age , 52.5 % and 7.6 % will have died , respectively . Mortality varied by geographical region , and was associated with maternal death ( adjusted odds ratio 2.27 , 95 % CI 1.62 - 3.19 ) , CD4 + cell counts < 200 per microL ( 1.91 , 1.39 - 2.62 ) , and infant HIV infection ( 8.16 , 6.43 - 10.33 ) . Mortality was not associated with either ever breastfeeding and never breastfeeding in either infected or uninfected children . In infected children , mortality was significantly lower for those with late infection than those with early infection ( 0.52 , 0.39 - 0.70 ) . This effect was also seen in analyses of survival from the age at infection ( 0.74 , 0.55 - 0.99 ) . INTERPRETATION These findings highlight the necessity for timely antiretroviral care , for support for HIV-infected women and children in developing countries , and for assessment of prophylactic programmes to prevent MTCT , including child mortality and infection averted Objective : To examine the effect of zinc supplementation to HIV-1-infected pregnant women on viral load , early mother-to-child transmission of HIV ( MTCT ) , and wasting . Design : Double-blind placebo-controlled r and omized clinical trial . Setting : Antenatal clinic in Dar es Salaam , Tanzania . Subjects : Four hundred HIV-1-infected pregnant women . Methods : Women 12–27 weeks of gestation were r and omly assigned to receive a daily oral dose of 25 mg zinc or placebo from the day of the first prenatal visit until 6 weeks postdelivery . Weight and mid-upper arm circumference ( MUAC ) were measured monthly . HIV status of the babies was assessed at birth and at 6 weeks postpartum . Viral load was assessed in a r and om sample of 100 women at baseline and at the end of the study . Results : Zinc had no effects on maternal viral load or early MTCT . Supplementation was related to a significant threefold increase in the risk of wasting ( reaching a MUAC value < 22 cm ) during an average 22 weeks of observation ( RR=2.7 , 95%CI=1.1 , 6.4 , P=0.03 ) , and to a 4 mm decline in MUAC during the second trimester ( P=0.02 ) . Conclusions : Zinc supplementation to HIV-infected pregnant women offers no benefits on viral load or MTCT . The clinical relevance of an apparent decrease in MUAC associated with zinc supplementation is yet to be ascertained . These findings together with the lack of effect on fetal outcomes ( reported previously ) do not provide support for the addition of zinc supplements to the st and ard of prenatal care among HIV-infected women . Sponsorship : The US National Institute of Child Health and Human Development ( NICHD R01 32257 ) Summary Zinc has been shown to enhance intestinal mucosal repair in patients suffering from acrodermatitis enteropathica ; but the impact on mucosal integrity during acute ( AD ) or persistent ( PD ) diarrhoea is unknown . One hundred eleven children with AD and 190 with PD aged between 3 and 24 months received , r and omly and blind to the investigators , either an elemental zinc supplement of 5 mg/kg body wt/day or placebo in multivitamin syrup for 2 weeks while intestinal permeability and , biochemical and anthropometric markers were serially monitored . The permeability test was administered as an oral dose of 5 g lactulose/1 g mannitol in a 20-ml solution followed by a 5-h urine collection . The ratio of the urinary probe sugars was correlated to clinical , biochemical , and microbiological parameters . At presentation , lactulose excretion was increased and mannitol excretion decreased in both AD and PD as compared with age-matched asymptomatic children . The lactulose/mannitol ratio ( L/M ) was higher in subjects with mucosal invasive pathogens ( rotavirus and enteropathogenic Escherichia coli ) compared with children excreting Vibrio cholera and enterotoxigenic . coli . Two-week zinc supplementation significantly reduced lactulose excretion in both AD and PD , whereas the change in mannitol excretion and L/M was similar between study groups in both studies . Changes in lactulose excretion were significantly influenced by zinc supplementation in children with E. coli , Shigella sp. , and Campylobacter jejuni stool isolates . The greatest reduction in total lactulose excretion was seen in supplemented children who on presentation were lighter ( wt/age < 80 % ) , thinner ( wt/ht < 85 % ) , and undernourished [ middle upper arm circumference ( MUAC ) < 12.5 cm ] or with hypozincaemia ( < 14 μmlmol/L ) . The results suggest zinc supplementation improves intestinal permeability in certain groups of children with AD or PD syndrome and contributes to their recovery . This effect may indirectly reflect enhanced mucosal recovery . Further studies on the mechanisms of mucosal repair following zinc supplementation are recommended Objective : This clinical trial aims to evaluate if natural mixed carotenoids supplementation can improve the health and survival of acquired immunodeficiency syndrome ( AIDS ) patients . Design : A placebo-controlled , prospect i ve , r and omized , double-blind , multicenter clinical trial . Setting : Community , tertiary care human immunodeficiency virus ( HIV ) clinics of the Canadian HIV Trials Network ( CTN ) . Participants : Three hundred and thirty-one adults with advanced AIDS on conventional management were recruited during routine clinic visits . Interventions : All participants , including 166 controls , received daily oral specially formulated multivitamins including vitamin A and trace elements ; 165 treatment group participants received additional daily oral natural mixed carotenoids , equivalent to 120 000 IU ( 72 mg ) of β-carotene daily . Follow-up was quarterly at routine clinic visits . Results : Mean ( s.d . ) follow-up was for 13 ( 6 ) months . Thirty-six participants died by 18 months . Serum carotene concentration < 1.0 μmol/l was present in 16 % participants at baseline . Despite variation in carotene content of the treatment medication , serum carotene concentrations increased significantly to twice the baseline levels to 18 months follow-up in participants who received carotenoids treatment compared with controls ( P<0.0001 ) . Although not statistically significant , mortality was increased in participants who did not receive carotenoids treatment compared with those who did ( HR time to death 1.76 , 95 % CI 0.89 , 3.47 , P=0.11 ) . In multivariate analysis , survival was significantly and independently improved in those with higher baseline serum carotene concentrations ( P=0.04 ) or higher baseline CD4 T-lymphocyte counts ( P=0.005 ) . Adjusted mortality was also significantly and independently increased in those who did not receive carotenoids treatment compared with those who did ( HR time to death 3.15 , 95 % CI 1.10 , 8.98 , P=0.03 ) . Conclusions : Low serum carotene concentration is common in AIDS patients and predicts death . Supplementation with micronutrients and natural mixed carotenoids may improve survival by correction of a micronutrient deficiency . Further studies are needed to corroborate findings and eluci date mechanism of action . Sponsorship : CTN and Community Research Initiative of Toronto ( CRIT ) BACKGROUND The aim of this work was to study the effects of combined oral administration of N-acetylcysteine ( NAC ) and sodium selenite ( Se ) on plasma glutathione ( GSH ) , lymphocyte sub population s and viral load in asymptomatic human immunodeficiency virus (HIV)-infected patients . METHODS We used a prospect i ve , r and omized and controlled therapy trial with partial crossover . Twenty-four antiretroviral-naive HIV-infected out patients at Centers for Disease Control (CDC)'93 stages I and II were r and omized to receive the antioxidant combination NAC 600 mg t.i.d . and Se 500 micrograms per day for either 24 weeks ( group A , n = 13 ) or from the end of week 12 ( group B , n = 11 ) until the end of week 24 . Thus , group B served as untreated control during the first 12 weeks . RESULTS There was ( a ) a trend towards an increase in the percentage of CD4 + lymphocytes after 6 weeks ( P = 0.08 ) ; ( b ) an increase in the CD4/CD8 ratio after 6 and 12 weeks ( P = 0.02 and P = 0.04 respectively ) ; and ( c ) a decrease in the absolute CD8/CD38 count and percentage of lymphocytes after 6 weeks ( P = 0.002 and P = 0.033 respectively ) and 12 weeks ( P = 0.033 , P = 0.1 respectively ) in group A compared with the control period of group B. The effects observed in group A were , however , not paralleled to the same extent by group B after crossing-over to treatment after 12 weeks . In addition , erythrocyte glutathione peroxidase ( GSH-Px ) activity and GSH , glutathionedisulphide ( GSSG ) concentrations and the reduced/total GSH ratio were not affected by the treatment . Serum selenium levels increased significantly ( P < 0.001 ) upon treatment . Viral load was not altered . CONCLUSIONS The changes in lymphocyte subsets after NAC/Se treatment were not comparable to those after st and ard antiretroviral drug therapy . This , however , does not preclude per se possible benefits of antioxidant supplementation in HIV disease Abstract In HIV-infected patients , an increase in the production of oxygen-reactive species ( ROS ) is observed , with a consequent reduction of plasma levels of antioxidants such as α-tocopherol . The nuclear transcription factor-κB ( NF-κB ) is activated by a prooxidant state in the infected T cells through the release of its inhibitory subunit I-κB. The aim of the present work was to evaluate the behavior of hematological parameters and markers of anemia in HIV-infected patients who underwent antiretroviral therapy associated with 800 mg/day αtocopherol supplementation . Blood sample s were collected from supplemented ( n=9 ) and not-supplemented ( n=9 ) HIV-seropositive patients ( n=18 ) . We observed a decreased viral load in the α-tocopherol-supplemented group ( p<0.05 ) ; other changes , such as an increase in the CD4/CD8 ratio , in the hematocrit and in the hemoglobin concentration were also observed , though lacking statistical significance . We conclude that antiretroviral therapy in association with αtocopherol ( 800 mg/day ) supplementation is more effective in reducing viral load levels and also , possibly , in recovering other hematological parameters after a 60-day period of use Objective : We examined whether supplementation with vitamin A and /or vitamins B , C , and E to HIV-infected women during pregnancy and lactation is related to increased concentrations of vitamins A , B12 , and E in their infants during the first 6 months of life . Design : We carried out a r and omized clinical trial among 716 mother – infant pairs in Dar-es-Salaam , Tanzania . Women were r and omly allocated to receive a daily oral dose of one of four regimens : vitamin A , multivitamins ( B , C , and E ) , multivitamins including A , or placebo . Supplementation started at first prenatal visit and continued after delivery throughout the breastfeeding period . The serum concentration of vitamins A , E and B12 was measured in infants at 6 weeks and 6 months postpartum . Results : Maternal vitamin A supplementation increased serum retinol in the infants at 6 weeks ( mean difference=0.09 μmol/l , P<0.0001 ) and 6 months ( mean difference=0.06 μmol/l , P=0.0002 ) , and decreased the prevalence of vitamin A deficiency , but had no impact on serum vitamins E or B12 . Multivitamins increased serum vitamin B12 at 6 weeks and 6 months ( mean differences=176 pmol/l , P<0.0001 and 127 pmol/l , P<0.0001 , respectively ) and vitamin E ( mean differences=1.8 μmol/l , P=0.0008 and 1.1 μmol/l , P=0.004 , respectively ) and decreased the prevalence of vitamin B12 deficiency . Conclusions : Vitamin supplementation to HIV-1-infected women is effective in improving the vitamin status of infants during the first 6 months of age OBJECTIVE To determine whether plasma vitamin A levels are associated with immunologic status and clinical outcome during human immunodeficiency virus type 1 ( HIV-1 ) infection . PATIENTS AND METHODS Analysis of vitamin A levels , CD4 T cells , complete blood cell count , and serologic markers for liver disease in a r and om sub sample of 179 subjects from a cohort of more than 2000 intravenous drug users with longitudinal follow-up to determine survival . RESULTS Mean ( + /- SE ) follow-up time was 22.8 + /- 1.1 months , and 15 subjects died during follow-up . More than 15 % of the HIV-1-seropositive individuals had plasma vitamin A levels less than 1.05 mumol/L , a level consistent with vitamin A deficiency . The HIV-1-seropositive individuals had lower mean plasma vitamin A levels than HIV-1-seronegative individuals ( P < .001 ) . Vitamin A deficiency was associated with lower CD4 levels among both seronegative individuals ( P < .05 ) and seropositive individuals ( P < .05 ) . In the HIV-seropositive participants , vitamin A deficiency was associated with increased mortality ( relative risk = 6.3 ; 95 % confidence interval , 2.1 to 18.6 ) . CONCLUSION Vitamin A deficiency may be common during HIV-1 infection , and vitamin A deficiency is associated with decreased circulating CD4 T cells and increased mortality . Vitamin A is an essential micronutrient for normal immune function , and vitamin A deficiency seems to be an important risk factor for disease progression during HIV-1 infection BACKGROUND Despite findings that selenium supplementation may improve immune functioning , definitive evidence of its impact on human immunodeficiency virus ( HIV ) disease severity is lacking . METHODS High selenium yeast supplementation ( 200 mug/d ) was evaluated in a double-blind , r and omized , placebo-controlled trial . Intention-to-treat analyses assessed the effect on HIV-1 viral load and CD4 count after 9 months of treatment . Unless otherwise indicated , values are presented as mean + /- SD . RESULTS Of the 450 HIV-1-seropositive men and women who underwent screening , 262 initiated treatment and 174 completed the 9-month follow-up assessment . Mean adherence to study treatment was good ( 73.0 % + /- 24.7 % ) with no related adverse events . The intention-to-treat analyses indicated that the mean change ( Delta ) in serum selenium concentration increased significantly in the selenium-treated group and not the placebo-treated group ( Delta = 32.2 + /- 24.5 vs 0.5 + /- 8.8 microg/L ; P<.001 ) , and greater levels predicted decreased HIV-1 viral load ( P<.02 ) , which predicted increased CD4 count ( P<.04 ) . Findings remained significant after covarying age , sex , ethnicity , income , education , current and past cocaine and other drug use , HIV symptom classification , antiretroviral medication regimen and adherence , time since HIV diagnosis , and hepatitis C virus coinfection . Follow-up analyses evaluating treatment effectiveness indicated that the nonresponding selenium-treated subjects whose serum selenium change was less than or equal to 26.1 microg/L displayed poor treatment adherence ( 56.8 % + /- 29.8 % ) , HIV-1 viral load elevation ( Delta = + 0.29 + /- 1.1 log(10 ) units ) , and decreased CD4 count ( Delta = -25.8 + /- 147.4 cells/microL ) . In contrast , selenium-treated subjects whose serum selenium increase was greater than 26.1 microg/L evidence d excellent treatment adherence ( 86.2 % + /- 13.0 % ) , no change in HIV-1 viral load ( Delta = -0.04 + /- 0.7 log(10 ) units ) , and an increase in CD4 count ( Delta = + 27.9 + /- 150.2 cells/microL ) . CONCLUSIONS Daily selenium supplementation can suppress the progression of HIV-1 viral burden and provide indirect improvement of CD4 count . The results support the use of selenium as a simple , inexpensive , and safe adjunct therapy in HIV spectrum disease . Trial Registration is rct n.org Identifier : IS RCT N22553118 INTRODUCTION Although studies suggest that vitamin A or its metabolites influence the synthesis of erythropoietin in vitro and in animal models , it is unclear whether vitamin A supplementation increases plasma erythropoietin concentrations in humans . OBJECTIVE To determine whether daily vitamin A supplementation increases plasma erythropoietin concentrations in pregnant women with a high prevalence of anaemia . METHODS A r and omized , double-blind , controlled clinical trial was conducted to examine the effect of daily vitamin A ( 3000 microg retinol equivalent ) , iron ( 30 mg ) , and folate ( 400 microg ) versus iron ( 30 mg ) and folate ( 400 microg ) ( control ) on haemoglobin and plasma erythropoietin concentrations in 203 pregnant women in Malawi , Africa . RESULTS Mean gestational age at enrollment was 23 wk , at which time 50 % of the women were anaemic ( haemoglobin < 110 g/L ) . Mean ( + /-SEM ) change in haemoglobin from enrollment to 38 wk was 4.7+/-1.6 g/L ( p=0.003 ) and 7.3+/-2.3 g/L ( p=0.003 ) in the vitamin A and control groups , respectively . Mean change in plasma erythropoietin concentrations from enrollment to 38 wk was 2.39+/-5.00 ( p=0.63 ) and -2.87+/-3.92 IU/L ( p=0.46 ) in the vitamin A and controls groups , respectively . There were no significant differences between vitamin A and control groups in the slope of the regression line between log10 erythropoietin and haemoglobin at enrollment or 38 wk , and between enrollment and follow-up within either group . CONCLUSIONS Vitamin A supplementation does not appear to increase haemoglobin and plasma erythropoietin concentrations among pregnant women with a high prevalence of anaemia in Malawi Sub clinical mastitis , defined as raised milk sodium/potassium ( Na/K ) ratio is common and associated with poor infant growth and increased mother-to-child HIV transmission . In 1996 - 97 , we conducted a r and omized controlled trial of multiple micronutrient supplementation , at recommended daily allowance levels , from 22 to 35 weeks gestation until 3 months post-partum , on the prevalence and severity of sub clinical mastitis among 84 HIV-infected and 83 HIV-uninfected lactating Zimbabwean women and on their infants ' growth . Spot milk sample s collected before 4.5 months post-partum were analysed for Na/K ratio by flame photometry . There was no significant difference in prevalence of sub clinical mastitis between HIV-infected and HIV-uninfected women . After controlling for infant age at time of sampling , micronutrient-supplemented HIV-infected women had non-significantly ( P = 0.08 ) lower geometric mean Na/K ratio ( 0.43 , 95 % CI 0.35 - 0.51 ) than HIV-infected women given placebo ( 0.51 , 95 % CI 0.42 - 0.61 ) . Micronutrient supplementation had no effect on the prevalence of sub clinical mastitis among HIV-uninfected women ( odds ratio [ OR ] = 1.26 , 95 % CI 0.45 - 3.51 , P = 0.80 ) but induced a borderline decrease in prevalence ( OR = 2.82 , 95 % CI 0.96 - 8.26 , P = 0.07 ) among HIV-infected women . Infant weight between 1.5 and 4.5 months was lower in women with higher milk Na/K ratio . Thus , the importance of sub clinical mastitis for infant growth suggests that further investigations to decrease the condition , perhaps using higher micronutrient doses , are warranted Background : Observational studies suggest that poor nutritional status among HIVinfected pregnant women is associated with a higher risk of vertical transmission of HIV . Methods : We r and omized 1083 pregnant women infected with HIV‐1 in a doubleblind , placebo‐controlled trial to examine the effects of supplements of vitamin A and /or multivitamins ( excluding vitamin A ) using a 2‐x‐2 factorial design . We report the effects of the supplements on HIV infection defined using polymerase chain reaction ( PCR ) , or death up to 6 weeks postpartum . Results : Of babies in the multivitamin arm 38 , ( 10.1 % ) were HIV‐positive at birth compared with 24 ( 6.6 % ) in the no‐multivitamin arm ( relative risk [ RR ] = 1.54 ; 95 % CI , 0.94‐2.51 ; p = .08 ) . Of babies born to mothers in the vitamin A arm , 38 ( 10.0 % ) were HIV‐positive at birth compared with 24 ( 6.7 % ) in the no‐vitamin A arm ( RR , 1.49 ; 95 % CI , 0.91‐2.43 ; p = 0.11 ) . Neither multivitamins nor vitamin A had an effect on HIV status at 6 weeks among those who were HIV‐negative at birth ( RR = 1.04 ; 95 % CI , 0.65‐1.66 ; p = 0.88 ) and ( RR = 1.30 ; 95 % CI , 0.80‐2.09 ; p = .29 , respectively ) . Similarly , neither supplement was associated with being either HIVinfected or dead at birth ( RR , 0.98 ; 95 % CI , 0.76‐1.27 ; p = .89 and RR , 1.01 ; 95 % CI , 0.78‐1.31 ; p = .95 , respectively . A beneficial effect of multivitamins on birth weight was limited to babies who were HIV‐negative at birth ; babies in the multivitamin arm weighed + 94 g more compared with those in the no‐multivitamin arm ( p = .02 ) . Among babies who were HIV‐positive at birth , the corresponding difference was ‐31 g ( p = .82 ) . Conclusions : Vitamin A and multivitamins did not affect the risk of vertical transmission of HIV in utero nor during the intrapartum and early breastfeeding periods . Multivitamins result ed in a significant improvement in birth weight of babies who were HIV‐negative at birth but had no effect among those who were HIV‐positive . The effect of vitamin supplements on HIV transmission through breastfeeding and on clinical progression of HIV disease is yet to be ascertained Background : HIV-1 transmission through breastfeeding is a global problem and has been associated with poor maternal micronutrient status . Methods : A total of 1078 HIV-infected pregnant women from Tanzania were r and omly assigned to vitamin A or multivitamins excluding A from approximately 20 weeks ’ gestation and throughout lactation . Results : Multivitamins excluding A had no effect on the total risk of HIV-1 transmission ( RR 1.04 , 95 % CI 0.82–1.32 , P = 0.76 ) . Vitamin A increased the risk of transmission ( RR 1.38 , 95 % CI 1.09–1.76 , P = 0.009 ) . Multivitamins were associated with non-statistically significant reductions in transmission through breastfeeding , and mortality by 24 months among those alive and not infected at 6 weeks . Multivitamins significantly reduced breastfeeding transmission in infants of mothers with low baseline lymphocyte counts ( RR 0.37 ; 95 % CI 0.16–0.85 , P = 0.02 ) compared with infants of mothers with higher counts ( RR 0.99 , 95 % CI 0.68–1.45 , P = 0.97 ; P-for-interaction 0.03 ) . Multivitamins also protected against transmission among mothers with a high erythrocyte sedimentation rate ( P-for-interaction 0.06 ) , low hemoglobin ( P-for-interaction 0.06 ) , and low birthweight babies ( P-for-interaction 0.04 ) . Multivitamins reduced death and prolonged HIV-free survival significantly among children born to women with low maternal immunological or nutritional status . Vitamin A alone increased breastfeeding transmission but had no effect on mortality by 24 months . Conclusion : Vitamin A increased the risk of HIV-1 transmission . Multivitamin ( B , C , and E ) supplementation of breastfeeding mothers reduced child mortality and HIV-1 transmission through breastfeeding among immunologically and nutritionally compromised women . The provision of these supplements to HIV-infected lactating women should be considered BACKGROUND Zinc deficiency is associated with impaired immune function and an increased risk of infection . Supplementation can decrease the incidence of diarrhoea and pneumonia in children in re source -poor countries . However , in children with HIV-1 infection , the safety of zinc supplementation is uncertain . We aim ed to assess the role of zinc in HIV-1 replication before mass zinc supplementation is recommended in regions of high HIV-1 prevalence . METHODS We did a r and omised double-blind placebo-controlled equivalence trial of zinc supplementation at Grey 's Hospital in Pietermaritzburg , South Africa . 96 children with HIV-1 infection were r and omly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for 6 months . Baseline measurements of plasma HIV-1 viral load and the percentage of CD4 + T lymphocytes were established at two study visits before r and omisation , and measurements were repeated 3 , 6 , and 9 months after the start of supplementation . The primary outcome measure was plasma HIV-1 viral load . Analysis was per protocol . FINDINGS The mean log(10 ) HIV-1 viral load was 5.4 ( SD 0.61 ) for the placebo group and 5.4 ( SD 0.66 ) for the zinc-supplemented group 6 months after supplementation began ( difference 0.0002 , 95 % CI -0.27 to 0.27 ) . 3 months after supplementation ended , the corresponding values were 5.5 ( SD 0.77 ) and 5.4 ( SD 0.61 ) , a difference of 0.05 ( -0.24 to 0.35 ) . The mean percentage of CD4 + T lymphocytes and median haemoglobin concentrations were also similar between the two groups after zinc supplementation . Two deaths occurred in the zinc supplementation group and seven in the placebo group ( p=0.1 ) . Children given zinc supplementation were less likely to get watery diarrhoea than those given placebo . Watery diarrhoea was diagnosed at 30 ( 7.4 % ) of 407 clinic visits in the zinc-supplemented group versus 65 ( 14.5 % ) of 447 visits in the placebo group ( p=0.001 ) . INTERPRETATION Zinc supplementation of HIV-1-infected children does not result in an increase in plasma HIV-1 viral load and could reduce morbidity caused by diarrhoea . RELEVANCE TO PRACTICE Programmes to enhance zinc intake in deficient population s with a high prevalence of HIV-1 infection can be implemented without concern for adverse effects on HIV-1 replication . In view of the reductions in diarrhoea and pneumonia morbidity , zinc supplementation should be used as adjunct therapy for children with HIV-1 infection Background Vitamin A is important for protection against diarrhea , and supplements may benefit gut function of infants of HIV-infected mothers . Methods We studied 238 infants of HIV-infected South African women participating in a r and omized , double-blind , placebo-controlled trial of vitamin A during pregnancy ( 1.5 mg retinyl palmitate and 30 mg & bgr;-carotene daily ) plus 60 mg retinyl palmitate at delivery . The placebo group received identical placebo capsules at the same times . When infants were 1 , 6 , and 14 weeks of age , lactulose/mannitol dual sugar intestinal permeability tests were performed . Results Maternal vitamin A supplementation did not significantly affect infant gut permeability in the group as a whole at any time . By multiple regression analysis , HIV infection of the infant by 14 weeks was significantly associated with increased gut permeability at both 6 and 14 weeks . After controlling for birth weight , gestational age , current weight , feeding mode and recent morbidity , there was a trend toward an interaction between vitamin A supplementation and HIV infection ( P = 0.086 ) at 14 weeks . Vitamin A made no difference to gut permeability of uninfected infants ( lactulose/mannitol ratio for vitamin A group : 0.11 , 95 % confidence interval [ CI ] 0.08 , 0.15 , n = 73 and for placebo group : 0.09 , 95 % CI 0.06 , 0.12 , n = 76 ) , but largely prevented the increase in the ratio of HIV-infected infants ( vitamin A group : 0.17 , 95 % CI 0.13 , 0.23 , n = 23 ; placebo group : 0.50 , 95 % CI 0.37 , 0.68 , n = 20 ) . The effects on the lactulose/mannitol ratio were related to changes in lactulose , not mannitol , excretion . Vitamin A supplementation was associated with significantly lower lactulose excretion at 1 and 14 weeks , suggesting the major effect of vitamin A was on maintaining the integrity of gut tight junctions . Conclusions Vitamin A supplementation of HIV-infected pregnant women may prevent the deterioration in gut integrity in the subgroup of their infants who themselves become infected . Improving vitamin A status of HIV-infected infants may decrease their gastrointestinal morbidity BACKGROUND Vitamin D is a strong immunomodulator and may protect against adverse pregnancy outcomes , mother-to-child transmission ( MTCT ) of human immunodeficiency virus ( HIV ) , and child mortality . METHODS A total of 884 HIV-infected pregnant women who were participating in a vitamin supplementation trial in Tanzania were monitored to assess pregnancy outcomes and child mortality . The association of these outcomes with maternal vitamin D status at enrollment was examined in an observational analysis . RESULTS No association was observed between maternal vitamin D status and adverse pregnancy outcomes , including low birth weight and preterm birth . In multivariate models , a low maternal vitamin D level ( < 32 ng/mL ) was associated with a 50 % higher risk ( 95 % confidence interval [ CI ] , 2%-120 % ) of MTCT of HIV at 6 weeks , a 2-fold higher risk of MTCT of HIV through breast-feeding among children who were HIV uninfected at 6 weeks ( 95 % CI , 1.08 - 3.82 ) , and a 46 % higher overall risk of HIV infection ( 95 % CI , 11%-91 % ) . Children born to women with a low vitamin D level had a 61 % higher risk of dying during follow-up ( 95 % CI , 25%-107 % ) . CONCLUSIONS If found to be efficacious in r and omized trials , vitamin D supplementation could prove to be an inexpensive method of reducing the burden of HIV infection and death among children , particularly in re source -limited setting Objectives : To examine the impact of high-dose multiple micronutrient supplementation on survival and disease progression among HIV-infected individuals in Thail and . Design : R and omized placebo-controlled trial . Methods : Four-hundred and eighty-one HIV-infected men and women living in and around Bangkok with CD4 cell counts in the range 50 × 106– 550 × 106/l were r and omized to receive micronutrients or placebo for a period of 48 weeks . Trial participants were examined clinical ly 12-weekly and tested for CD4 cell count 24-weekly . A subset were tested for HIV plasma viral load at 48 weeks . Results : Seventy-nine ( 16 % ) trial participants were lost to follow-up and 23 ( 5 % ) died . The death rate was lower in the micronutrients arm with the mortality hazard ratios [ 95 % confidence interval ( CI ) ] of 0.53 ( 0.22–1.25 ; P = 0.1 ) overall and 0.37 ( 0.13–1.06 ; P = 0.052 ) and 0.26 ( 0.07–0.97 ; P = 0.03 ) among those with CD4 cell counts < 200 × 106/l and < 100 × 106/l respectively . There was no impact on CD4 cell count or plasma viral load . Conclusions : Multiple micronutrient supplementation may enhance the survival of HIV-infected individuals with CD4 cell counts < 200 × 106/l . This could have important public health implication s in the developing world where access to antiretrovirals remains poor . The clinical findings need to be reproduced in other setting s and the mechanism , which appears to be independent of change in CD4 cell count , merits further investigation A r and omized , unblinded study compared aerosolized pentamidine , 300 mg every month , and dapsone , 50 mg/day , for secondary prophylaxis of pneumocystosis in 196 AIDS patients . The study was prematurely discontinued due to excess mortality in the dapsone group . After a mean follow-up of 13 + /- 6.4 months , 22 ( 21 % ) of 103 patients in the pentamidine group were dead compared with 39 ( 42 % ) of 93 receiving dapsone ; the estimated mortality rates at 18 months were 24.6 % and 53.1 % , respectively ( P < .003 , log-rank test ) . A negative interaction was observed between zidovudine and dapsone ( P < .049 , interaction test of Cox model ) , and the mean CD4 cell count during the study was lower in the dapsone ( 49 + /- 61/mm3 ) than in the pentamidine group ( 83 + /- 88/mm3 ; P < .002 , t test ) . The lower survival might also be related to the oxidative effect of dapsone or to the addition of iron protoxalate to dapsone in this study . These results suggest caution in using dapsone as long-term therapy in advanced human immunodeficiency virus infection , especially in those receiving zidovudine OBJECTIVE . Vitamin D insufficiency occurs commonly in HIV-infected youth in the United States . In light of the importance of vitamin D for skeletal and nonskeletal health , including innate immunity , developing methods for improving vitamin D status in HIV-infected children and adolescents is an important area of clinical research . The objective of this study was to evaluate the effect of administration of oral cholecalciferol , 100000 IU every 2 months , and 1 g/day calcium on serum 25-hydroxyvitamin D concentrations , serum and urine calcium , and HIV disease progression during a 12-month period . METHODS . HIV-infected children and adolescents who were aged 6 to 16 years were r and omly assigned to receive vitamin D ( 100000 IU bimonthly ) and calcium ( 1 g/day ; n = 29 ) or double placebo ( n = 27 ) . Serum 25-hydroxyvitamin D concentrations as measured by radioimmunoassay , albumin-corrected calcium concentrations , and spot urinary calcium-creatinine ratios were determined monthly . RESULTS . No abnormalities in serum calcium concentration were observed . One participant who received placebo developed hypercalciuria . No group differences were seen in the change in CD4 count or CD4 % or viral load during 12 months . The overall mean monthly serum 25-hydroxyvitamin D concentrations were higher in the group that received vitamin D and calcium than in the placebo group , as was the monthly serum 25-hydroxyvitamin D area under the curve . After completing 12 months of study , 2 ( 6.7 % ) participants in the group that received vitamin D and calcium had a trough serum 25-hydroxyvitamin D concentration < 20 ng/mL compared with 14 ( 50 % ) in the placebo group . Twelve ( 44.4 % ) in the group that received vitamin D and calcium had a trough serum 25-hydroxyvitamin D concentration of ≥30 ng/mL compared with 3 ( 11.1 % ) in the placebo group . CONCLUSIONS . Administration of oral cholecalciferol to HIV-infected children and adolescents at a dosage of 100000 IU every 2 months , together with 1 g/day calcium , is safe and results in significant increases in serum 25-hydroxyvitamin D concentrations The use of vitamin A therapy during human immunodeficiency virus ( HIV ) infection is under clinical investigation , and vitamin A could potentially modulate HIV replication because the virus genome contains a retinoic acid response element . A r and omized , double-masked , placebo-controlled clinical trial was conducted to determine the impact of single high-dose vitamin A supplementation , 60-mg retinol equivalent ( 200,000 IU ) , on HIV load and CD4 lymphocyte count . HIV-infected injection drug users ( 120 ) were r and omly allocated to receive vitamin A or placebo . Plasma vitamin A level , CD4 lymphocyte count , and HIV load were measured at baseline and 2 and 4 weeks after treatment . Vitamin A supplementation had no significant impact on HIV load or CD4 lymphocyte count at 2 and 4 weeks after treatment . This study suggests that high-dose vitamin A supplementation does not influence HIV load Objectives : The HIV-infected population is known to be oxidatively stressed and deficient in antioxidant micronutrients . Since in vitro replication of HIV is increased with oxidative stress , this study assessed the effect of antioxidant vitamin supplementation on lipid peroxidation , a measure of oxidative stress , and viral load in humans . Design : A r and omized placebo-controlled , double-blind study . Methods : Forty-nine HIV-positive patients were r and omized to receive supplements of both DL-α-tocopherol acetate ( 800 IU daily ) and vitamin C ( 1000 mg daily ) , or matched placebo , for 3 months . Plasma antioxidant micronutrient status , breath pentane output , plasma lipid peroxides , malondialdehyde and viral load were measured at baseline and at 3 months . New or recurrent infections for the 6-month period after study entry were also recorded . Results : The vitamin group ( n = 26 ) had an increase in plasma concentrations of α-tocopherol ( P < 0.0005 ) and vitamin C ( P < 0.005 ) and a reduction in lipid peroxidation measured by breath pentane ( P < 0.025 ) , plasma lipid peroxides ( P < 0.01 ) and malondialdehyde ( P < 0.0005 ) when compared with controls ( n = 23 ) . There was also a trend towards a reduction in viral load ( mean ± SD changes over 3 months , −0.45 ± 0.39 versus + 0.50 ± 0.40 log10 copies/ml ; P = 0.1 ; 95 % confidence interval , −0.21 to −2.14 ) . The number of infections reported was nine in the vitamin group and seven in the placebo group . Conclusion : Supplements of vitamin E and C reduce oxidative stress in HIV and produce a trend towards a reduction in viral load . This is worthy of larger clinical trials , especially in HIV-infected persons who can not afford new combination therapies Vitamin deficiencies are frequent in children suffering from malaria . The effects of maternal multivitamin supplementation on the risk of malaria in children are unknown . We examined the impact of providing multivitamins or vitamin A/beta-carotene supplements during pregnancy and lactation to HIV-infected women on their children 's risk of malaria up to 2 years of age , in a r and omized , placebo-controlled trial . Tanzanian women ( N = 829 ) received one of four daily oral regimens during pregnancy and after delivery : 1 ) vitamins B , C , and E ( multivitamins ) ; 2 ) vitamin A and beta-carotene ( VA/BC ) ; 3 ) multivitamins including VA/BC ; or 4 ) placebo . After 6 months of age , all children received 6-monthly oral vitamin A supplements irrespective of treatment arm . The incidence of childhood malaria was assessed through three-monthly blood smears and at monthly and interim clinic visits from birth to 24 months of age . Compared with placebo , multivitamins excluding VA/BC reduced the incidence of clinical malaria by 71 % ( 95 % CI = 11 - 91 % ; P = 0.02 ) , whereas VA/BC alone result ed in a nonsignificant 63 % reduction ( 95 % CI = -4 % to 87 % ; P = 0.06 ) . Multivitamins including VA/BC significantly reduced the incidence of high parasitemia by 43 % ( 95 % CI = 2 - 67 % ; P = 0.04 ) . The effects did not vary according to the children 's HIV status . Supplementation of pregnant and lactating HIV-infected women with vitamins B , C , and E might be a useful , inexpensive intervention to decrease the burden of malaria in children born to HIV-infected women in sub-Saharan Africa OBJECTIVES To determine whether vitamin A supplements result in reduced mortality among HIV-infected and uninfected children . DESIGN R and omized , double blind , placebo-controlled trial . METHODS Starting in April , 1993 , we r and omized 687 children age 6 months to 5 years who were admitted to the hospital with pneumonia . Children who were severely malnourished or had clinical signs of vitamin A deficiency were excluded . At baseline children received placebo or 400 000 IU ( or half that for infants ) of vitamin A , in addition to st and ard treatment for pneumonia . They received further doses of the same regimen 4 and 8 months after hospital discharge . Sera from children were tested for HIV antibodies by enzyme-linked immunosorbent assay and Western blot tests . For positive children < 15 months of age , HIV infection was confirmed by amplified heat-denatured HIV-p24 antigen assays with confirmatory neutralization assays . HIV status was ascertained for 648 of 687 enrolled children . The mean duration of follow-up was 24.4 months ( SD = 12.1 ) . RESULTS Of 648 children 58 ( 9 % ) were HIV-infected . Compared with uninfected children , all-cause mortality was higher among HIV-infected children , as was mortality caused by pneumonia or diarrhea ( P < 0.001 for each ) . Overall vitamin A supplements result ed in a 49 % reduction in mortality [ relative risk ( RR ) , 0.51 ; 95 % confidence interval ( CI ) , 0.29 to 0.90 , P = 0.02 ] . Vitamin A supplements reduced all-cause mortality by 63 % among HIV-infected children ( RR 0.37 ; CI 0.14 to 0.95 , P = 0.04 ) and by 42 % among uninfected children ( RR 0.58 , CI 0.28 to 1.19 , P = 0.14 ) . Vitamin A supplements were also associated with a 68 % reduction in AIDS-related deaths ( P = 0.05 ) and a 92 % reduction in diarrhea-related deaths ( P = 0.01 ) . CONCLUSION Vitamin A deficiency , which is common among children in many developing countries , is particularly severe among HIV-infected children . Our findings indicate that vitamin A supplements , a low cost intervention , reduce mortality of HIV-infected children OBJECTIVE As HIV has spread through sub-Saharan Africa , persistent diarrhoea has emerged as a major problem in hospitals and in the community in severely affected areas . We have previously demonstrated that antiprotozoal therapy with albendazole reduces diarrhoea in AIDS patients in urban Zambia . This trial was design ed to test the hypothesis that the clinical response to albendazole might be improved by oral micronutrient supplementation . DESIGN R and omized , placebo-controlled trial . SETTING Home care service of Ndola Central Hospital , Zambia . PATIENTS HIV-seropositive patients with persistent diarrhoea . INTERVENTION Patients were r and omized to albendazole plus vitamins A , C and E , selenium and zinc orally or albendazole plus placebo , for 2 weeks . MAIN OUTCOME MEASURES Time with diarrhoea following completion of treatment ; mortality ; adverse events . RESULTS Serum vitamin A and E concentrations before treatment were powerful predictors of early mortality , but supplementation did not reduce time with diarrhoea or mortality during the first month , even after taking into account initial vitamin A or E concentrations , CD4 cell count or clinical markers of illness severity . Serum concentrations of vitamins A and E did not increase significantly in supplemented patients compared with those given placebo , and there were no changes in CD4 cell count or haematological parameters . No adverse events were detected except those attributable to underlying disease . CONCLUSIONS Although micronutrient deficiency is predictive of early death in Zambian patients with the diarrhoea-wasting syndrome , short-term oral supplementation does not overcome it nor influence morbidity or mortality OBJECTIVE Poor vitamin A status has been associated with a higher risk for mother-to-child transmission of HIV-1 and there is contradictory evidence on the impact of vitamin A on perinatal outcome . We therefore assessed the effect of vitamin A supplementation to mothers on birth outcome and mother-to-child transmission of HIV-1 . DESIGN AND METHODS In Durban , South Africa 728 pregnant HIV infected women received either vitamin A ( 368 ) or placebo ( 360 ) in a r and omized , double-blind trial . The vitamin A treatment consisted of a daily dose of 5000 IU retinyl palmitate and 30 mg beta-carotene during the third trimester of pregnancy and 200000 IU retinyl palmitate at delivery . HIV infection results were available on 632 children who were included in the Kaplan-Meier transmission analysis . Results are reported on mother-to-child transmission rates up to 3 months of age . RESULTS There was no difference in the risk of HIV infection by 3 months of age between the vitamin A [ 20.3 % ; 95 % confidence interval ( CI ) , 15.7 - 24.9 ] and placebo groups ( 22.3 % ; 95 % CI , 17.5 - 27.1 ) , nor were there differences in foetal or infant mortality rates between the two groups . Women receiving vitamin A supplement were , however , less likely to have a preterm delivery ( 11.4 % in the vitamin A and 17.4 % in the placebo group ; P = 0.03 ) and among the 80 preterm deliveries , those assigned to the vitamin A group were less likely to be infected ( 17.9 % ; 95 % CI , 3.5 - 32.2 ) than those assigned to the placebo group ( 33.8 % ; 95 % CI , 19.8 - 47.8 ) . CONCLUSION Vitamin A supplementation , a low-cost intervention , does not appear to be effective in reducing overall mother-to-child transmission of HIV ; however , its potential for reducing the incidence of preterm births , and the risk of mother-to-child transmission of HIV in these infants needs further investigation |
13,266 | 25,188,210 | Other outcome measures ( blood pressure , body mass index , self-efficacy and empowerment ) also showed neutral effects compared with control groups .
Culturally appropriate health education has short- to medium-term effects on glycaemic control and on knowledge of diabetes and healthy lifestyles . | BACKGROUND Ethnic minority groups in upper-middle-income and high-income countries tend to be socioeconomically disadvantaged and to have a higher prevalence of type 2 diabetes than is seen in the majority population .
OBJECTIVES To assess the effectiveness of culturally appropriate health education for people in ethnic minority groups with type 2 diabetes mellitus . | Eighty-five diabetic patients who were proficient in English were studied to assess the impact of educational material of varying literacy levels on patient comprehension . Two sample s of available diabetes foot care material of Grade 11 and 9 readability ( measured by SMOG formula ) and purpose ly written in-house material of Grade 6 readability were used . Patients were r and omized to read information of either Grade 6 and Grade 11 or Grade 6 and Grade 9 readability . Socio-demographic data and reading habits were collected to allow for identification of literacy markers . The mean CLOZE score ( a measure of comprehension ) was better in patients who read the Grade 6 information than for both the Grade 11 and Grade 9 information ( 59.5 + /- 11.8 , 46.8 + /- 22.0 , 45.8 + /- 22.2 respectively , p < 0.001 ) . When evaluated in terms of percent of patients that could independently underst and the material , Grade 6 information outperformed the Grade 11 and Grade 9 information ( 60 % , 19 % , 21 % , respectively , p < 0.001 ) . For the Grade 11 and Grade 9 information , poorer comprehension was associated with a non-English speaking background , early school leaving age , infrequent reading habits , and preference for tabloids ( p < 0.02 ) . Comprehension when patients read the Grade 6 information was no longer dependent on two of the four identified literacy markers . We conclude that reducing literacy dem and s of health literature improves patients ' comprehension . Attention to socio-demographic data and reading habits can assist educators in assessing patients ' literacy status and ensuring patients are given literature of compatible readability OBJECTIVE To test whether a theory-based , literacy , and culturally tailored self-management intervention , Latinos en Control , improves glycemic control among low-income Latinos with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 252 patients recruited from community health centers were r and omized to the Latinos en Control intervention or to usual care . The primarily group-based intervention consisted of 12 weekly and 8 monthly sessions and targeted knowledge , attitudes , and self-management behaviors . The primary outcome was HbA1c . Secondary outcomes included diet , physical activity , blood glucose self-monitoring , diabetes knowledge and self-efficacy , and other physiological factors ( e.g. , lipids , blood pressure , and weight ) . Measures were collected at baseline and at 4- and 12-month follow-up . Change in outcomes over time between the groups and the association between HbA1c and possible mediators were estimated using mixed-effects models and an intention-to-treat approach . RESULTS A significant difference in HbA1c change between the groups was observed at 4 months ( intervention −0.88 [ −1.15 to −0.60 ] versus control −0.35 [ −0.62 to 0.07 ] , P < 0.01 ) , although this difference decreased and lost statistical significance at 12 months ( intervention −0.46 [ −0.77 to −0.13 ] versus control −0.20 [ −0.53 to 0.13 ] , P = 0.293 ) . The intervention result ed in significant change differences in diabetes knowledge at 12 months ( P = 0.001 ) , self-efficacy ( P = 0.001 ) , blood glucose self-monitoring ( P = 0.02 ) , and diet , including dietary quality ( P = 0.01 ) , kilocalories consumed ( P < 0.001 ) , percentage of fat ( P = 0.003 ) , and percentage of saturated fat ( P = 0.04 ) . These changes were in turn significantly associated with HbA1c change at 12 months . CONCLUSIONS Literacy-sensitive , culturally tailored interventions can improve diabetes control among low-income Latinos ; however , strategies to sustain improvements are needed BACKGROUND Type 2 diabetes is up to four times more common in British Asians , but they know little about its management and complications . AIM To design and evaluate a structured pictorial teaching programme for Pakistani Moslem patients in Manchester with type 2 diabetes . METHOD A r and omized controlled trial of pictorial flashcard one-to-one education in 201 patients attending a hospital outpatient clinic or diabetic clinics in ten general practice s in Manchester . Patients ' knowledge , self-caring skills and attitudes to diabetes were measured on four topics before the structured teaching , and compared with results six months later . RESULTS All parameters of knowledge were increased in the study group ; for example , percentage scores for correctly identifying different food values increased from 57 % to 71 % ( Analysis of Variance ( ANOVA ) adjusted difference + 11.8 % ) and knowledge of one diabetic complication from 18 % to 78 % . Self-caring behaviour improved , with 92 % of patients doing regular glucose tests at six months compared with 63 % at the start . Attitudinal views were more resistant to change , with patients still finding it hard to choose suitable foods at social occasions . Haemoglobin A1c control improved by 0.34 % over six months ( ANOVA adjusted difference , 95 % CI -0.8 % to + 0.1 % ) . CONCLUSION It is concluded that this health education programme can empower Asian diabetics to take control of their diets , learn to monitor and interpret glucose results , and underst and the implication s of poor glycaemic control for diabetic complications BACKGROUND Cardiovascular disease ( CVD ) and diabetes account for one-third of the mortality difference between African American and white patients . We evaluated the effect of a CVD risk reduction intervention in African Americans with diabetes . METHODS We r and omized 359 African Americans with type 2 diabetes to receive usual care or a nurse telephone intervention . The 12-month intervention provided monthly self-management support and quarterly medication management facilitation . Co primary outcomes were changes in systolic blood pressure ( SBP ) , hemoglobin A1c ( HbA1c ) , and low-density lipoprotein cholesterol ( LDL-C ) over 12 months . We estimated between-intervention group differences over time using linear mixed-effects models . The secondary outcome was self-reported medication adherence . RESULTS The sample was 72 % female ; 49 % had low health literacy , and 37 % had annual income < $ 10,000 . Model-based estimates for mean baseline SBP , HbA1c , and LDL-C were 136.8 mm Hg ( 95 % CI 135.0 - 138.6 ) , 8.0 % ( 95 % CI 7.8 - 8.2 ) , and 99.1 mg/dL ( 95 % CI 94.7 - 103.5 ) , respectively . Intervention patients received 9.9 ( SD 3.0 ) intervention calls on average . Primary providers replied to 76 % of nurse medication management facilitation contacts , 18 % of these result ed in medication changes . There were no between-group differences over time for SBP ( P = .11 ) , HbA1c ( P = .66 ) , or LDL-C ( P = .79 ) . Intervention patients were more likely than those receiving usual care to report improved medication adherence ( odds ratio 4.4 , 95 % CI 1.8 - 10.6 , P = .0008 ) , but adherent patients did not exhibit relative improvement in primary outcomes . CONCLUSIONS This intervention improved self-reported medication adherence but not CVD risk factor control among African Americans with diabetes . Further research is needed to determine how to maximally impact CVD risk factors in African American patients Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged BACKGROUND AND AIM The risk of death from coronary heart disease ( CHD ) in women with diabetes is more than three times that of non-diabetic women . We assessed the difference in CHD risk levels of Afro-Caribbean diabetic women provided with facilities for self-monitoring of blood glucose and their counterparts without such facilities MATERIAL S AND METHODS Forty-nine patients who never used gluco-meters were studied as intervention ( 23 ) and control ( 26 ) groups . The intervention group was trained on self-monitoring of blood glucose . At baseline , BP , anthropometric indices , and fasting blood glucose of all patients were measured . Subsequently , the intervention patients were provided with gluco-meters , testing strips , and advised to self-monitor fasting and postpr and ial blood glucose every other day for 6 months . CHD risk was determined with the United Kingdom Prospect i ve Diabetes Study risk engine calculator . RESULTS The age , duration of diagnosis of diabetes , BP , and anthropometric indices were similar in the two groups ( all , P > 0.05 ) . The majority of the patients were unemployed or retired with only primary education . After 3 months , the HbA 1c levels of the control patients did not change ( 8.3 ± 0.4 % vs. 7.8 ± 0.4 % , P > 0.05 ) whereas the HbA 1c levels of the intervention patients reduced significantly from the baseline at 3 ( 9.2 ± 0.4 % vs. 7.4 ± 0.3 % , P < 0.001 ) and 6 ( 9.2 ± 0.4 % vs. 7.3 ± 0.3 % , P < 0.001 ) months . The 10-year CHD risk level of the intervention group was remarkably reduced from the baseline level after 6 months ( 7.4 ± 1.3 % vs. 4.5 ± 0.9 % ) of the study . CONCLUSION Provision of facilities for self-monitoring of blood glucose in Afro-Caribbean women with type 2 diabetes improves both their glycemic control and CHD risk profile The promotion of regular physical activity for people with type 2 diabetes poses a challenge for public health authorities . The purpose of this study was to evaluate the efficiency of a computer-tailoring print-based intervention to promote the adoption of regular physical activity among people with type 2 diabetes . An experimental design was used ; 325 participants between the age of 35 and 55 years old were r and omized in one of two experimental conditions : the computer-tailoring intervention and the generic intervention . The two dependant variables were the frequency of participation and the intention to participate in leisure-time physical activities . Among the research hypotheses , only one was confirmed : the first computer-tailoring print on the practice of physical activity was more efficient than the first generic intervention at 1-month follow-up . Other similar studies will be necessary to determine the real potential of this type of approach for people with type 2 diabetes in a real-life setting Purpose The purpose of the study was to test the feasibility and efficacy of a diabetes self-management and education program for Chinese Americans in a support group format . The rationale for the study was to create culturally appropriate diabetes education and management programs in response to the growing diabetes prevalence among Chinese Americans . The investigators hypothesized that participants will have improved diabetes knowledge and practice s , hemoglobin A1C , and social support . The study objectives were at least : 50 % will have significant improvements in diabetes knowledge and practice activities , 30 % of participants will have significant improvements in A1C , and 50 % will report a gain in emotional support . Methods The program consisted of 12 90-minute diabetes education and support group sessions offered in a medical office setting . The sample included 23 Chinese Americans with either type 1 or type 2 diabetes . Using a single-group , pre-post test design , A1C and diabetes knowledge were assessed at baseline and 6 months . Data were collected through clinical assessment s and written question naires . Results The results indicated high attendance and statistically significant increases in glycemic control and diabetes knowledge . Statistically insignificant differences were shown in diabetes management practice s. Secondary outcomes assessed participants ’ perceived diabetes management and emotional and social support . Conclusions Diabetes Self-Management : A Cultural Approach ( DSMCA ) support group model demonstrates that a culturally tailored support group utilizing a community-based participatory research approach is an effective format to improve diabetes self-management skills among Chinese Americans . The program can be adapted for other ethnic population s. The efficacy of the intervention can be further tested in larger r and omized trials Purpose The purpose of this pilot study was to evaluate the effects of a culturally sensitive , empowerment-based diabetes self-management education program for Spanish-speaking Hispanic/Latinos . Methods A prospect i ve quasi-experimental repeated measures design tested the effectiveness of the ¡ Si , Yo Puedo Controlar Mi Diabetes ! diabetes self-management education program . In sum , 144 persons residing in 2 Texas counties at the Texas-Mexico border ( Starr and Hidalgo ) served as participants . Two groups were formed , an intervention and a control ( wait list ) . Clinical ( A1C ) , cognitive , attitudinal , behavioral , and cultural assessment s were collected at baseline and 3 months . Results Demographic characteristics for the intervention and control groups were similar . Both groups were predominately female , low income , older than 40 years , and minimally acculturated . Baseline and posttest findings showed that the intervention group had a significant reduction in A1C values ; median difference was 0.3 ( n = 45 ) , especially for those with higher baseline values . Participants in the intervention group also improved in their self-efficacy and self-care scores . Conclusions Findings from the study suggest that additional dissemination of a diabetes self-management education program for Spanish-speaking Hispanic/Latinos is warranted to improve clinical outcomes and associated diabetes self-efficacy and self-care behaviors Purpose This study explores the potential utility of a culturally tailored diabetes management intervention approach by testing associations between acculturation and diabetes-related beliefs among Mexican-American adults with type 2 diabetes . Methods Data from 288 Mexican-American adults with type 2 diabetes were obtained via a bilingual , telephone-administered survey . Participants were drawn from a stratified , r and om sample design ed to obtain maximum variability in acculturation . The survey assessed diabetes-related beliefs , intervention preferences , and the following three acculturation constructs from the Hazuda acculturation and assimilation scales : Spanish use , value for preserving Mexican culture , and interaction with Mexican Americans . Results Only one outcome —preference for a program for Mexican Americans — was associated with all three acculturation variables . Spanish use was positively associated with belief in susto as a cause of diabetes , preference for expert-driven health guidance , and involvement of others in taking care of diabetes . Value for preserving Mexican culture was related to a more holistic view of health , as evidence d by an increased likelihood of consulting a cur and ero , use of prayer , and interest in a diabetes program with religious content . Value for cultural preservation was also related to higher suspicion of free diabetes programs . Interaction with Mexican Americans was associated with a belief that insulin causes blindness . Conclusion Findings from this study suggest distinct relationships between acculturation constructs and diabetes-related beliefs and preferences , thus arguing against the use of a single acculturation construct to determine diabetes intervention design . Cultural tailoring may enhance the cultural appropriateness and ultimate effectiveness of diabetes interventions for Mexican American adults Purpose The purpose of this study was to assess dietary intake habits of Mexican American Hispanic adults participating in the En Balance diabetes education program . Methods En Balance is a 3-month culturally sensitive diabetes education intervention for Spanish-speaking Hispanics . Of the 46 participants enrolled , 39 mainly Mexican American Hispanic adults with type 2 diabetes completed the En Balance program . Participants lived in the Riverside and San Bernardino counties of California , and all participants completed the program by June 2008 . Dietary intake was assessed at baseline and at 3 months using the vali date d Southwest Food Frequency Question naire . Results Clinical ly important decreases in glycemic control and serum lipid levels were observed at the end of the 3-month program . The baseline diet was characterized by a high intake of energy ( 2478 ± 1140 kcal ) , total fat ( 87 ± 44 g/day ) , saturated fat ( 28 ± 15 g/day ) , dietary cholesterol ( 338 ± 217 mg/day ) , and sodium ( 4236 ± 2055 mg/ day ) . At 3 months , the En Balance group mean intake of dietary fat ( P = .045 ) and dietary cholesterol ( P = .033 ) decreased significantly . Low dietary intakes of docosahexaenoic acid , eicosapentaenoic acid , and vitamin E were also observed in these adults with type 2 diabetes . Conclusions The En Balance program improved glycemic control and lipid profiles in a group of Hispanic diabetic participants . En Balance also promoted decreases in dietary fat and dietary cholesterol intake Technology and improved care coordination models can help diabetes educators and providers meet national care st and ards and provide culturally sensitive diabetes education that may improve diabetes outcomes . The purpose of the study was to evaluate the clinical usefulness of a nurse-led diabetes care program ( Comprehensive Diabetes Management Program , CDMP ) for poorly controlled Hispanic type 2 diabetes ( T2DM ) patients in an urban community health center setting . Patients were r and omized to the intervention condition ( IC ; n = 21 ) or an attention control condition ( AC ; n = 18 ) . IC and AC conditions were compared on rates of adherence to national clinical practice guidelines ( blood glucose , blood pressure , foot exam , eye exam ) , and levels of diabetes distress , depression , and treatment satisfaction . IC patients had a significant improvement in A1C from baseline to 12-month follow-up compared with AC ( −1.6 % ± 1.4 % versus −0.6 % ± 1.1 % ; P = .01 ) . The proportion of IC patients meeting clinical goals at follow-up tended to be higher than AC for A1c ( IC = 45 % ; AC = 28 % ) , systolic blood pressure ( IC = 55 % ; AC = 28 % ) , eye screening ( IC = 91 % ; AC = 78 % ) , and foot screening , ( IC = 86 % ; AC = 72 % ) . Diabetes distress and treatment satisfaction also showed greater improvement for IC than AC ( P = .05 and P = .06 , respectively ) , with no differences for depression . The CDMP intervention was more effective than an attention control condition in helping patients meet evidence -based guidelines for diabetes care Purpose The purpose of this study was to examine whether integrating depression treatment into care for type 2 diabetes mellitus among older African Americans improved medication adherence , glycemic control , and depression outcomes . Methods Older African Americans prescribed pharmacotherapy for type 2 diabetes mellitus and depression from physicians at a large primary care practice in west Philadelphia were r and omly assigned to an integrated care intervention or usual care . Adherence was assessed at baseline , 2 , 4 , and 6 weeks using the Medication Event Monitoring System to assess adherence . Outcomes assessed at baseline and 12 weeks included st and ard laboratory tests to measure glycemic control and the Center for Epidemiologic Studies Depression Scale ( CES-D ) to assess depression . Results In all , 58 participants aged 50 to 80 years participated . The proportion of participants who had 80 % or greater adherence to an oral hypoglycemic ( intervention 62.1 % vs usual care 24.1 % ) and an antidepressant ( intervention 62.1 % vs usual care 10.3 % ) was greater in the intervention group in comparison with the usual care group at 6 weeks . Participants in the integrated care intervention had lower levels of glycosylated hemoglobin ( intervention 6.7 % vs usual care 7.9 % ) and fewer depressive symptoms ( CES-D mean scores : intervention 9.6 vs usual care 16.6 ) compared with participants in the usual care group at 12 weeks . Conclusion A pilot r and omized controlled trial integrating type 2 diabetes mellitus treatment and depression was successful in improving outcomes among older African Americans . Integrated interventions may be more feasible and effective in real-world practice s with competing dem and s for limited re sources Background : The prevalence of type 2 diabetes and diabetesrelated morbidity and mortality is higher among low-income Hispanics when compared to that of Whites . However , little is known about how to effectively promote self-management in this population . Purpose : The objectives were first to determine the feasibility of conducting a r and omized clinical trial of an innovative self-management intervention to improve metabolic control in low-income Spanish-speaking individuals with type 2 diabetes and second to obtain preliminary data of possible intervention effects . Methods : Participants for this pilot study were recruited from a community health center , an elder program , and a community-wide data base developed by the community health center , in collaboration with other agencies serving the community , by surveying households in the entire community . Participants were r and omly assigned to an intervention ( n = 15 ) or a control ( n = 10 ) condition . Assessment s were conducted at baseline and at 3 months and 6 months postr and omization . The intervention consisted of 10 group sessions that targeted diabetes knowledge , attitudes , and self-management skills through culturally specific and literacysensitive strategies . The intervention used a cognitivebehavioral theoretical framework . Results : Recruitment rates at the community health center , elder program , and community registry were 48 % , 69 % , and 8 % , respectively . Completion rates for baseline , 3-month , and 6-month assessment s were 100 % , 92 % , and 92 % , respectively . Each intervention participant attended an average of 7.8 out of 10 sessions , and as a group the participants showed high adherence to intervention activities ( 93 % turned in daily logs , and 80 % self-monitored glucose levels at least daily ) . There was an overall Group × Time interaction ( p = .02 ) indicating group differences in glycosylated hemoglobin over time . The estimated glycosylated hemoglobin decrease at 3 months for the intervention group was −0.8 % ( 95 % confidence intervals = −1.1 % , −0.5 % ) compared with the change in the control group ( p = .02 ) . At 6 months , the decrease in the intervention group remained significant , −0.85 % ( 95 % confidence intervals = −1.2 , −0.5 ) , and the decrease was still significantly different from that of the controls ( p = .005 ) . There was a trend toward increased physical activity in the intervention group as compared to that of the control group ( p = .11 ) and some evidence ( nonsignificant ) of an increase in blood glucose self-monitoring in the intervention participants but not the control participants . Adjusting for baseline depressive scores , we oberved a significant difference in depressive symptoms between intervention participants and control participants at the 3-month assessment ( p = .02 ) . Conclusions : Low-income Spanish-speaking Hispanics are receptive to participate in diabetes-related research . This study shows that the pilot-tested diabetes self-management program is promising and warrants the conduct of a r and omized clinical trial Background Culturally appropriate interventions are needed to assist Latinas in making multiple healthful lifestyle changes . Purpose The purpose of this study was to test a cultural adaptation of a successful multiple health behavior change program , ¡ Viva Bien ! Methods R and om assignment of 280 Latinas with type 2 diabetes to usual care only or to usual care + ¡ Viva Bien ! , which included group meetings for building skills to promote the Mediterranean diet , physical activity , stress management , supportive re sources , and smoking cessation . Results ¡ Viva Bien ! participants compared to usual care significantly improved psychosocial and behavioral outcomes ( fat intake , stress management practice , physical activity , and social – environmental support ) at 6 months , and some improvements were maintained at 12 months . Biological improvements included hemoglobin A1c and heart disease risk factors . Conclusions The ¡ Viva Bien ! multiple lifestyle behavior program was effective in improving psychosocial , behavioral , and biological/ quality of life outcomes related to heart health for Latinas with type 2 diabetes ( Clinical Trials.gov no : NCT00233259 ) Purpose The purpose of this pilot study was to test a dance intervention and explore the role of peer support to improve the diabetes outcomes of A1C , weight , body fat , and blood pressure in African American women with type 2 diabetes . Methods This study was conducted in a community-based outpatient clinic . A mixed methods design was used . A total of 46 women , 26 to 83 years of age , were r and omized to either the 12-week dance group or usual care group . Both between group and intraindividual group differences were analyzed from baseline to 12 weeks . Focus group interviews explored the role of peer support through semistructured discussion s for the women enrolled in the dance group . Results Results showed significant group mean differences in systolic blood pressure ( BP ) and body fat . Paired t tests showed significant reductions in all the diabetes outcomes for the dance group and significant increases in glycolated hemoglobin ( A1C ) and systolic BP for the usual care group . The emergent themes of the focus groups were that a diabetes diagnosis was devastating , and changing eating habits and taking medications was often difficult . Peer support in the dance group was expressed as camaraderie , enjoyment , and laughter , which fostered attendance . Conclusions Dancing 2 times per week for 12 weeks produced significant group differences in systolic BP and body fat and significant intraindividual changes . The implication s are that dancing in a supportive environment with peers may be an effective strategy for diabetes educators to help those with diabetes to become more physically active and improve diabetes outcomes and overall health Purpose This study developed and tested a culturally appropriate , church-based intervention to improve diabetes self-management . Research Design and Methods This was a r and omized trial conducted at 24 African American churches in central North Carolina . Churches were r and omized to receive the special intervention ( SI ; 13 churches , 117 participants ) or the minimal intervention ( MI ; 11 churches , 84 participants ) . The SI included an 8-month intensive phase , consisting of 1 individual counseling visit , 12 group sessions , monthly phone contacts , and 3 encouragement postcards , followed by a 4-month reinforcement phase including monthly phone contacts . The MI received st and ard educational pamphlets by mail . Outcomes were assessed at 8 and 12 months ; the primary outcome was comparison of 8-month A1C levels . Results At baseline , the mean age was 59 years , A1C 7.8 % , and body mass index 35.0 kg/m2 ; 64 % of participants were female . For the 174 ( 87 % ) participants returning for 8-month measures , mean A1C ( adjusted for baseline and group r and omization ) was 7.4 % for SI and 7.8 % for MI , with a difference of 0.4 % ( 95 % confidence interval [ CI ] , 0.1 - 0.6 , P = .009 ) . In a larger model adjusting for additional variables , the difference was 0.5 % ( 95 % CI , 0.2 - 0.7 , P < .001 ) . At 12 months , the difference between groups was not significant . Diabetes knowledge and diabetes-related quality of life significantly improved in the SI group compared with the MI group . Among SI participants completing an acceptability question naire , intervention components and material s were rated as highly acceptable . Conclusions The church-based intervention was well received by participants and improved short-term metabolic control Purpose The purpose of this study was to examine the impact of family and friends on the management of persons with diabetes and their willingness to be involved in a culturally tailored program . Methods This qualitative study was based within a larger quasi-experimental study that focused on the impact of a culturally tailored group intervention compared with individual st and ard diabetes education on the outcomes of self-management and glycemic control among rural African Americans with type 2 diabetes . Twenty-one participants were r and omly assigned to an individual education group or a culturally tailored intervention group . Family members/ peers ( n = 6 ) attended invited group sessions to obtain information about diabetes and family/peer support . The facilitator of the invited group sessions used a guide to help with group discussion s. The investigators used an iterative approach to enhance the examination of the responses from the discussion guide , thus identifying recurring themes within the participants ' responses . Results The data revealed that family and friends made a difference in the diabetes management of individuals with dia- betes . Although family and friends may have been helpful at times , they also created moments of problems and an environment that made it more difficult to care for diabetes . The data also revealed that diabetes is hard to manage and control . Participants reported that taking medications and being aware of types of foods to keep a well-maintained glucose level were often challenging . Conclusions These findings confirm that family and peers greatly influence diabetes management among rural African Americans . The study 's results will help health care providers underst and the importance of involving family members and friends in the treatment and diabetes management of individuals with type 2 diabetes , particularly within rural African American communities where re sources are limited Purpose The purpose of this study is to evaluate the impact of a promotores-led diabetes self-management program by comparing the outcomes ( knowledge , beliefs , and HbA1c level ) of Mexican American patients with type 2 diabetes who received usual diabetic care in a wait-list control group to those who received self-management education and follow-up by promotores in consultation with clinic providers and staff . Methods This r and omized control study compared the results of 63 patients who attended a promotores-led culturally sensitive diabetes self-management course at a commu- nity clinic with 68 patients in a wait-list , usual-care control group . Participants were Mexican Americans with type 2 diabetes who were patients at the clinic and at least 18 years of age . At baseline , 3 months , and 6 months , the Diabetes Knowledge Question naire ( DKQ ) , Health Beliefs Question naire ( HBQ ) , and HbA1c levels ( drawn by the clinic laboratory ) were collected . Results There was a significant improvement in the intervention group 's DKQ scores over time and in treatment by time . The baseline HbA1c level was 7.49 and did not change over time in either group . The DKQ , HBQ , and HbA1c results were significantly affected by age ; the DKQ and HbA1c were affected by years with diabetes . Conclusions The promotores-led diabetes self-management course improved the knowledge of patients with diabetes . Participant baseline HbA1c level was close to therapeutic level ( much lower than reported in previous studies ) , suggesting participants received good medical care within the community clinic Purpose The purpose of this study is to test the efficacy of a culturally tailored comprehensive type 2 diabetes management intervention for Korean American immigrants ( KAIs ) with type 2 diabetes . Methods A r and omized controlled pilot trial with 2 parallel arms ( intervention vs control ) with a delayed intervention design was used . A total of 79 KAIs , recruited from the Baltimore-Washington area , completed baseline , 18-week , and 30-week follow-ups ( intervention , n = 40 ; control , n = 39 ) . All participants had uncontrolled type 2 diabetes ( hemoglobin A1C ≥7.5 % ) at baseline . The authors ’ comprehensive , self-help intervention program for type 2 diabetes management ( SHIP-DM ) consisted of a 6-week structured psychobehavioral education , home glucose monitoring with teletransmission , and bilingual nurse telephone counseling for 24 weeks . The primary outcome of the study was A1C level , and secondary outcomes included an array of psychobehavioral variables . Results Using analysis of covariance , the findings support that the proposed intervention was effective in significantly lowering A1C and fasting glucose and also in improving psychosocial outcomes in the sample . Specifically , the amount of reduction in A1C among intervention group participants was 1.19 % at 18 weeks and 1.31 % at 30 weeks , with 10 % and 15.5 % of the participants achieving the suggested goal of A1C < 7 % at 18 and 30 weeks of follow-up , respectively . Conclusions The results highlight the clinical efficacy of the SHIP-DM intervention composed of a 6-week education program , self-monitoring , and follow-up counseling , in terms of maintaining the improved intervention effects obtained and in terms of glucose control PURPOSE The purpose of this study was to compare 2 culturally competent diabetes self-management interventions design ed for Mexican Americans : an original extended program ( 24 hours of education , 28 hours of support groups ) versus a shorter , more re source -efficient compressed strategy ( 16 hours of education , 6 hours of support groups ) . The effects of the interventions on health beliefs are compared . METHODS The authors recruited 216 persons between 35 and 70 years of age diagnosed with type 2 diabetes for at least 1 year . Intervention groups of 8 participants and 8 support persons were r and omly assigned to 1 of the interventions . RESULTS Mean health belief scores on each subscale improved for both intervention groups . Both intervention groups reported significant improvements in perceptions of control of their diabetes . Improvements in health beliefs were more sustained at 12 months for individuals in the longer , extended program . The health belief subscale control was the most significant predictor of HbA1c levels at 12 months . CONCLUSIONS Both culturally competent diabetes self-management education interventions were effective in promoting more positive health beliefs . These findings on health beliefs indicate a dosage effect of the intervention and support the importance of ongoing contact through support groups to attain more sustainable improvements in health beliefs Purpose The purpose of this pilot study was to evaluate a culturally tailored intervention for rural African Americans . Social Cognitive Theory provided the framework for the study . Methods Twenty-two participants were recruited and r and omly assigned to either Group or Individual diabetes self-management ( DSME ) . Group DSME included story-telling , h and s-on activities , and problem-solving exercises . Individual DSME sessions focused on goal - setting and problem-solving strategies . Sessions were offered in an accessible community center over a 10-week period . Results Outcomes included glycosylated hemoglobin ( A1C ) , self-care actions , self-efficacy level , goal attainment , and satisfaction with DSME . Participants in both Group and Individual DSME improved slightly over the 3-month period in self-care activities , A1C level , and goal attainment . Although differences were not statistically significant , trends indicate improved scores on dietary actions , foot care , goal attainment , and empowerment for those experiencing Group DSME . Conclusions The culturally tailored approach was well received by all participants . Improvements among those receiving Individual DSME may indicate that brief sessions using a culturally tailored approach could enhance self-care and glycemic control . Additional testing among more participants over a longer time period is recommended PURPOSE The purpose of this r and omized controlled trial is to determine the effectiveness of an intervention led by promotoras ( community lay workers ) on the glycemic control , diabetes knowledge , and diabetes health beliefs of Mexican Americans with type 2 diabetes living in a major city on the Texas-Mexico border . METHODS One hundred fifty Mexican American participants were recruited at a Catholic faith-based clinic and r and omized into 2 groups . Personal characteristics , acculturation , baseline A1C level , diabetes knowledge , and diabetes health beliefs were measured . The intervention was culturally specific and consisted of participative group education , telephone contact , and follow-up using inspirational faith-based health behavior change postcards . The A1C levels , diabetes knowledge , and diabetes health beliefs were measured 3 and 6 months postbaseline , and the mean change between the groups was analyzed . RESULTS The 80 % female sample , with a mean age of 58 years , demonstrated low acculturation , income , education , health insurance coverage , and strong Catholicism . No significant changes were noted at the 3-month assessment , but the mean change of the A1C levels , F(1 , 148 ) = 10.28 , P < .001 , and the diabetes knowledge scores , F(1 , 148 ) = 9.0 , P < .002 , of the intervention group improved significantly at 6 months , adjusting for health insurance coverage . The health belief scores decreased in both groups . CONCLUSIONS The intervention result ed in decreased A1C levels and increased diabetes knowledge , suggesting that using promotoras as part of an interdisciplinary team can result in positive outcomes for Mexican Americans who have type 2 diabetes . Clinical implication s and recommendations for future research are suggested PURPOSE The purpose of this study was to evaluate the effects of a culturally sensitive diabetes education program for Hispanics with type 2 diabetes . METHODS This study is a prospect i ve cohort study to test the impact of a comprehensive diabetes education program on blood glucose control on Hispanics with type 2 diabetes . The educational program focused on maintaining glycemic control and general aspects of managing diabetes and complications . The study participants were recruited by flyers placed in Hispanic markets and in ambulatory care clinics . A total of 34 Hispanic male and female subjects with type 2 diabetes participated in the study . The concentrations of glucose , insulin , hemoglobin A1c ( HbA1c ) , total cholesterol , triglycerides , low-density lipoprotein and high-density lipoprotein ( HDL ) cholesterol were analyzed at baseline and at 3 months . RESULTS A significant mean change was observed for HbA1c , fasting plasma glucose , cholesterol/HDL ratio , and HDL after 3 months of education compared with baseline . There were significant reductions in weight , total fat , percent fat , trunk fat , and waist-to-hip ratio compared with baseline . After 3 months , subjects showed a significant positive correlation between changes in body mass index and insulin and weight , total fat , trunk fat , and fat free mass and insulin . CONCLUSIONS A culturally sensitive program conducted in Spanish had a significant impact on important clinical parameters in Hispanic subjects with diabetes in a relatively short time period . The study demonstrates the importance of design ing education intervention studies that are sensitive to cultural diversity , particularly in at-risk diabetic subjects PURPOSE The purpose of this pilot study was to determine the effectiveness of an edited Diabetes Prevention Program ( DPP ) Lifestyle Re sources Core Teaching Plan for managing patients with type 2 diabetes in an urban underserved setting . Modifications were made to attempt to cut to the bare essentials to work within the constrained budgets of safety net providers . The primary aim was to achieve a mean absolute reduction in HbA1c level of 1 percentage point . METHODS The authors conducted a r and omized controlled trial of 9 months ' duration for patients with type 2 diabetes with an HbA1c > or=8.0 % . A total of 67 patients r and omized into usual-care and case management groups were evaluated with an intention-to-treat analysis . A modified DPP workbook was used during 7 monthly visits with a nurse case manager . RESULTS As compared with the usual-care group , those in the case management group experienced a greater reduction in HbA1c level ( -1.87 vs -0.54 ; P=.011 ) and weight ( -2.47 kg vs + 0.88 kg ; P=.011 ) . CONCLUSION Use of an edited version of the DPP workbook in an urban , low-income , minority population with type 2 diabetesproduced a significant absolute reduction in HbA1c percentage and weight Background Increased access to the Internet and the availability of efficacious eHealth interventions offer great promise for assisting adults with diabetes to change and maintain health behaviors . A key concern is whether levels of engagement in Internet programs are sufficient to promote and sustain behavior change . Objective This paper used automated data from an ongoing Internet-based diabetes self-management intervention study to calculate various indices of website engagement . The multimedia website involved goal setting , action planning , and self-monitoring as well as offering features such as “ Ask an Expert ” to enhance healthy eating , physical activity , and medication adherence . We also investigated participant characteristics associated with website engagement and the relationship between website use and 4-month behavioral and health outcomes . Methods We report on participants in a r and omized controlled trial ( RCT ) who were r and omized to receive ( 1 ) the website alone ( n = 137 ) or ( 2 ) the website plus human support ( n = 133 ) that included additional phone calls and group meetings . The website was available in English and Spanish and included features to enhance engagement and user experience . A number of engagement variables were calculated for each participant including number of log-ins , number of website components visited at least twice , number of days entering self-monitoring data , number of visits to the “ Action Plan ” section , and time on the website . Key outcomes included exercise , healthy eating , and medication adherence as well as body mass index ( BMI ) and biological variables related to cardiovascular disease risk . Results Of the 270 intervention participants , the average age was 60 , the average BMI was 34.9 kg/m2 , 130 ( 48 % ) were female , and 62 ( 23 % ) self-reported Latino ethnicity . The number of participant visits to the website over 4 months ranged from 1 to 119 ( mean 28 visits , median 18 ) . Usage decreased from 70 % of participants visiting at least weekly during the first 6 weeks to 47 % during weeks 7 to 16 . There were no significant differences between website only and website plus support conditions on most of the engagement variables . In total , 75 % of participants entered self-monitoring data at least once per week . Exercise action plan pages were visited more often than medication taking and healthy eating pages ( mean of 4.3 visits vs 2.8 and 2.0 respectively , P < .001 ) . Spearman nonparametric correlations indicated few significant associations between patient characteristics and summary website engagement variables , and key factors such as ethnicity , baseline computer use , age , health literacy , and education were not related to use . Partial correlations indicated that engagement , especially in self-monitoring , was most consistently related to improvement in healthy eating ( r = .20 , P = .04 ) and reduction of dietary fat ( r = -.31 , P = .001 ) . There was also a significant correlation between self-monitoring and improvement in exercise ( r = .20 , P = .033 ) but not with medication taking . Conclusions Participants visited the website fairly often and used all of the theoretically important sections , but engagement decreased over 4 months . Usage rates and patterns were similar for a wide range of participants , which has encouraging implication s for the potential reach of online interventions . Trial Registration NCT00987285 ; http:// clinical trials.gov/show/NCT00987285 ( Archived by WebCite at http://www.webcitation.org/5vpe4RHTV BACKGROUND Although African American adults bear a disproportionate burden from diabetes mellitus ( DM ) , few r and omized controlled trials have tested culturally appropriate interventions to improve DM care . METHODS We r and omly assigned 542 African Americans with type 2 DM enrolled in an urban managed care organization to either an intensive or minimal intervention group . The intensive intervention group consisted of all components of the minimal intervention plus individualized , culturally tailored care provided by a nurse case manager ( NCM ) and a community health worker ( CHW ) , using evidence -based clinical algorithms with feedback to primary care providers ( eg , physicians , nurse practitioners , or physician assistants ) . The minimal intervention consisted of mailings and telephone calls every 6 months to remind participants about preventive screenings . Data on diabetic control were collected at baseline and at 24 months by blind observers ; data emergency department ( ER ) visits and hospitalizations were assessed using administrative data . RESULTS At baseline , participants had a mean age of 58 years , 73 % were women , and 50 % were living in poverty . At 24 months , compared with the minimal intervention group , those in the intensive intervention group were 23 % less likely to have ER visits ( rate difference [ RD ] , -14.5 ; adjusted rate ratio [ RR ] , 0.77 ; 95 % confidence interval [ CI ] , 0.59 - 1.00 ) . In on-treatment analyses , the rate reduction was strongest for patients who received the most NCM and CHW visits ( RD , -31.0 ; adjusted RR , 0.66 ; 95 % CI , 0.43 - 1.00 ; rate reduction downward arrow 34 % ) . CONCLUSION These data suggest that a culturally tailored intervention conducted by an NCM/CHW team reduced ER visits in urban African Americans with type 2 DM . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00022750 AIMS To determine whether an extended pharmacy service would improve glycaemic control and cardiovascular risks in diabetic Muslims . METHODS Ambulatory literate adult diabetic Muslims with A1C > 7 % were r and omly assigned to either a study group ( usual care plus added pharmacist input , N=63 ) or a control group ( usual care only , N=67 ) . On four consecutive visits , at 2-month intervals , the study group met a pharmacist who educated and discussed with each patient regarding medication uses and diabetic treatment . This was accompanied by providing a diabetic pamphlet . Changes in A1C ( mg/dL ) , lipid parameters ( mg/dL ) , medication adherence ( % pill count ) and diabetic knowledge scores were measured . RESULTS There was no difference in A1C reduction between the study and the control groups ( -0.8 vs. -0.6 , p=0.56 ) . Total cholesterol and LDL-C improvements were greater in the study group than in the control group ( -31.6 vs. -1.2 , p=0.000 ; -15.0 vs. + 9.1 , p=0.002 , respectively ) . The percent pill count ( + 6.8 vs. -2.8 , p=0.004 ) and diabetic knowledge scores ( + 2.1 vs. + 0.6 , p=0.002 ) were increased in the study group but not in the control group . CONCLUSION The pharmacist ' s one-on-one education on diabetes accompanied by its pamphlet , in Muslim patients with diabetes did not affect glycaemic outcome but reduction in cardiovascular risks through lowering total cholesterol and LDL-C was found . The strategies may also improve diabetic knowledge and medication adherence AIMS AND OBJECTIVES To examine the effect of a hospital-based clinic intervention on glycaemic control self-efficacy and glycaemic control behaviour of Chinese patients with type 2 diabetes mellitus ( DM ) . BACKGROUND Self-efficacy expectations are related to self-management of diabetes and , in conjunction with environmental support , are better predictors of behaviour than are knowledge and skills . Enhancing self-efficacy in patients with DM has been shown to have a positive effect on behavioural change and positively influence long-term glycaemic control . DESIGN A r and omised controlled trial study consisting of two-group pretest-post-test . METHODS One hundred and fifty-seven patients with type 2 DM were r and omly divided into two groups : ( 1 ) the experimental group ( 77 patients ) receiving one-month hospital-based clinic intervention and ( 2 ) the control group ( 80 patients ) receiving usual care . Data collection instruments used in this study were Diabetes Management Self-Efficacy Scale and Summary of Diabetes Self-Care Activities Measure . Outcomes were determined by changes in glycaemic control self-efficacy and glycaemic control behaviour of patients with type 2 DM . RESULTS The findings revealed that the experimental group showed statistically significant improvement in glycaemic control self-efficacy and glycaemic control behaviour immediately and four months after the intervention ( F = 26.888 , df = 1 , 155 , p < 0.05 and F = 18.619 , df = 1 , 155 , p < 0.05 , respectively ) . CONCLUSIONS One-month hospital-based clinic intervention could be useful in improving glycaemic control self-efficacy and glycaemic control behaviour . RELEVANCE TO CLINICAL PRACTICE Nurses can learn and use the sources of self-efficacy to enhance patients ' self-efficacy on their glycaemic control in clinical care . The health education is most important in nursing care and should be considered while organising the hospital-based clinic intervention Background Lower socioeconomic status is associated with excess disease burden from diabetes . Diabetes self-management support interventions are needed that are effective in engaging lower income patients , addressing competing life priorities and barriers to self-care , and facilitating behavior change . Objective To pilot test feasibility , acceptability , and effect on disease control of a problem-based diabetes self-management training adapted for low literacy and accessibility . Design Two-arm r and omized controlled trial powered to detect a 0.50 % change in A1C at follow-up with a 2-sided alpha of 0.05 in a pooled analysis . Participants Fifty-six urban African-American patients with type 2 diabetes and suboptimal blood sugar , blood pressure , or cholesterol control recruited from a diabetes registry within a university-affiliated managed care organization . Interventions A group , problem-based diabetes self-management training design ed for delivery in an intensive and a condensed program format . Three intensive and three condensed program groups were conducted during the trial . Main Measures Clinical ( A1C , systolic blood pressure [ SBP ] , diastolic blood pressure [ DBP ] , LDL and HDL cholesterol ) and behavioral ( knowledge , problem solving , self-management behavior ) data were measured at baseline , post-intervention , and 3 months post-intervention ( corresponding with 6–9 months following baseline ) . Results Adoption of both programs was high ( > 85 % attendance rates , 95 % retention ) . At 3 months post-intervention , the between-group difference in A1C change was −0.72 % ( p = 0.02 ) , in favor of the intensive program . A1C reduction was partially mediated by problem-solving skill at follow-up ( ß = −0.13 , p = 0.04 ) . Intensive program patients demonstrated within-group improvements in knowledge ( p < 0.001 ) , problem-solving ( p = 0.01 ) , and self-management behaviors ( p = 0.04 ) . Among the subsets of patients with suboptimal blood pressure or lipids at baseline , the intensive program yielded clinical ly significant individual improvements in SBP , DBP , and LDL cholesterol . Patient satisfaction and usability ratings were high for both programs . Conclusions A literacy-adapted , intensive , problem-solving-based diabetes self-management training was effective for key clinical and behavioral outcomes in a lower income patient sample PURPOSE Rural low-income African American patients with diabetes have traditionally poorer clinical outcomes and limited access to state-of-the-art diabetes care . We determined the effectiveness of a re design ed primary care model on patients ’ glycemic , blood pressure , and lipid level control . METHODS In 3 purposively selected , rural , fee-for-service , primary care practice s , African American patients with type 2 diabetes received point-of-care education , coaching , and medication intensification from a diabetes care management team made up of a nurse , pharmacist , and dietitian . In 5 r and omly selected control practice s matched for practice and patient characteristics , African American patients received usual care . Using univariate and multivariate adjusted models , we evaluated the effects of the intervention on intermediate ( median 18 months ) and long-term ( median 36 months ) changes in glycated hemoglobin ( hemoglobin A1c ) levels , blood pressure , and lipid levels , as well as the proportion of patients meeting target values . RESULTS Among 727 r and omly selected rural African American diabetic patients ( 368 intervention , 359 control ) , intervention patients had a significantly greater reduction in mean hemoglobin A1c levels at intermediate ( −0.5 % vs −0.2 % ; P < .05 ) and long-term ( −0.5 % vs −0.10 % ; P < .005 ) follow-up in univariate and multivariate models . The proportion of patients achieving a hemoglobin A1c level of less than 7.5 % ( 68 % vs 59 % , P < .01 ) and /or a systolic blood pressure of less than 140 mm Hg ( 69 % vs 57 % , P < .01 ) was also significantly greater in intervention practice s in multivariate models . CONCLUSION Re design ing care strategies in rural fee-for-service primary care practice s for African American patients with established diabetes results in significantly improved glycemic control relative to usual care Background US Latinos have greater prevalence of type 2 diabetes ( diabetes ) , uncontrolled diabetes and diabetes co-morbidities compared to non-Latino Whites . They also have lower literacy levels and are more likely to live in poverty . Interventions are needed to improve diabetes control among low-income Latinos . Methods and design This r and omized clinical trial tested the efficacy of a culturally- and literacy-tailored diabetes self-management intervention ( Latinos en Control ) on glycemic control among low-income Latinos with diabetes , compared to usual care ( control ) . Participants were recruited from five community health centers ( CHCs ) in Massachusetts . The theory-based intervention included an intensive phase of 12 weekly sessions and a follow-up maintenance phase of 8 monthly sessions . Assessment s occurred at baseline , and at 4 and 12 months . The primary outcome was glycosylated hemoglobin ( HbA1c ) . Secondary outcomes were self-management behaviors , weight , lipids and blood pressure . Additional outcomes included diabetes knowledge , self-efficacy , depression and quality of life . The study was design ed for recruitment of 250 participants ( estimated 20 % dropout rate ) to provide 90 % power for detecting a 7 % or greater change in HbA1c between the intervention and control groups . This is a difference in change of HbA1c of 0.5 to 0.6 % . Discussion Low-income Latinos bear a great burden of uncontrolled diabetes and are an understudied population . Theory-based interventions that are tailored to the needs of this high-risk population have potential for improving diabetes self-management and reduce health disparities . This article describes the design and methods of a theory driven intervention aim ed at addressing this need . Trial registration http://www . clinical trials.gov # OBJECTIVE —In an underserved Latino area , we established a disease-management program and proved its effectiveness . However , many patients still remained above target . This study was design ed to evaluate which factors are associated with reaching program goals . RESEARCH DESIGN AND METHODS —This was a r and omized , prospect i ve , observational study in which patients enrolled in our program were followed for 2 years with outcomes , measures , and question naires assessed at baseline and at 6 , 12 , and 24 months . RESULTS —Overall , A1C fell by 1 % . Adherence to medication was the strongest predictor of reaching the target A1C of < 8 % ; baseline A1C was also predictive . Knowledge scores increased in those who reached target , but the measures of self-efficacy and empowerment did not change for either group . CONCLUSIONS —Diabetes management is effective in a lower-income Latino population . However , adherence was suboptimal even when medications were provided on-site for free . Further research into barriers associated with medication adherence is needed High prevalence of type 2 diabetes ( T2D ) is seen in some immigrant groups in Western countries , particularly in those from the Indian subcontinent . Our aims were to increase the physical activity ( PA ) level in a group of Pakistani immigrant men , and to see whether any increase was associated with reduced serum glucose and insulin concentrations . The intervention was developed in collaboration with the Pakistani community . It used a social cognitive theory framework and consisted of structured supervised group exercises , group lectures , individual counselling and telephone follow-up . One- hundred and fifty physically inactive Pakistani immigrant men living in Oslo , Norway , were r and omised to either a control group or an intervention group . The 5-month intervention focused on increasing levels of PA , which were assessed by use of accelerometer ( Actigraph MTI 7164 ) recordings . Risk of diabetes was assessed by serum glucose and insulin concentrations determined in a fasted state , and after an oral glucose tolerance test ( OGTT ) . ANCOVA was used to assess differences between groups . There was a mean difference in PA between the two groups of 49 counts per minute per day , representing a 15 % ( 95 % CI = 8.7–21.2 ; P = 0.01 ) higher increase in total PA level in the intervention group than in the control group . Insulin values taken 2 h after an OGTT were reduced in the intervention group by 27 % ( 95 % CI = 18.9–35.0 ; P = 0.02 ) more than those in the control group . There were no differences in fasting or postpr and ial glucose values between the groups at the follow-up test . This type of intervention can increase PA and reduce serum insulin in Pakistani immigrant men , thereby presumably reducing their risk of T2D Poor adjustment to diabetes in older African American women may result from uncertainty , stemming from a lack of information about self-care activities , a complexity of self-care activities , comorbid conditions , and a lack of re sources . This study evaluated a telephone intervention to reduce uncertainty ( through problem-solving strategies , information , cognitive reframing , and improved patient — provider communication)—namely , to measure its effects on diabetes self-care and psychosocial adjustment . Sixty-eight older African American women were r and omly assigned to an experimental group and a control group . The experimental group received the intervention for 4 weeks , and the control group received usual care . Psychosocial adjustment and self-care were measured in all participants at baseline and 6 weeks postbaseline . The experimental group reported increased participation in exercise ( self-care component ; p < .001 ) and improvement in psychosocial adjustment ( p < .001 ) . Thus , reducing the uncertainty related to diabetes self-care improves self-care exercise , as well as psychosocial adjustment OBJECTIVE To determine whether a culturally appropriate clinic- and community-based intervention for African-American women with type 2 diabetes will increase moderate-intensity physical activity ( PA ) . RESEARCH DESIGN AND METHODS In this r and omized controlled trial conducted at seven practice s in central North Carolina , 200 African-American women , > or = 40 years of age with type 2 diabetes , were r and omized to one of three treatment conditions : clinic and community ( group A ) , clinic only ( group B ) , or minimal intervention ( group C ) . The clinic-based intervention ( groups A and B ) consisted of four monthly visits with a nutritionist who provided counseling to enhance PA and dietary intake that was tailored to baseline practice s and attitudes ; the community-based intervention ( group A ) consisted of three group sessions and 12 monthly phone calls from a peer counselor and was design ed to provide social support and reinforce behavior change goals ; and the minimal intervention ( group C ) consisted of educational pamphlets mailed to participants . The primary study outcome was the comparison of PA levels between groups assessed at 6 and 12 months by accelerometer , which was worn while awake for 7 days . RESULTS Totals of 175 ( 88 % ) and 167 ( 84 % ) participants completed PA assessment at 6 and 12 months , respectively . For comparison of PA , the P value for overall group effect was 0.014 . Comparing group A with C , the difference in the average adjusted mean for PA was 44.1 kcal/day ( 95 % CI 13.1 - 75.1 , P = 0.0055 ) . Comparing group B with C , the difference in the average adjusted mean was 33.1 kcal/day ( 95 % CI 3.3 - 62.8 , P = 0.029 ) . The intervention was acceptable to participants : 88 % were very satisfied with clinic-based counseling to enhance PA , and 86 % indicated that the peer counselor 's role in the program was important . CONCLUSIONS The intervention was associated with a modest enhancement of PA and was acceptable to participants Background Regular physical activity is an important goal for elders with chronic health conditions . Context This report describes Physical Activity for a Lifetime of Success ( PALS ) , an attempt to translate a motivational support program for physical activity , Active Choices , for use by a group of diverse , low-income , community-dwelling elders with diabetes . Methods PALS linked physical activity assessment and brief counseling by primary care providers with a structured referral to a community-based motivational telephone support program delivered by older adult volunteers . People with diabetes aged 65 years or older who were receiving care at two community clinics were r and omized to receive either immediate or delayed intervention . The main intended outcome measure was physical activity level ; the secondary outcome measure was mean hemoglobin A1c . Consequences One-third of those offered referral to the PALS program in the clinic setting declined . Another 44 % subsequently declined enrollment or were unreachable by the support center . Only 14 ( 21 % ) of those offered referral enrolled in the program . Among these 14 , the percentage who were sufficiently active was higher at follow-up than at enrollment , though not significantly so . Using an intent-to-treat analysis , which included all r and omized clinic patients , we found no significant change in mean hemoglobin A1c for the intervention group compared with controls . Interpretation A community-based referral and support program to increase physical activity among elderly , ethnically diverse , low-income people with diabetes , many of whom are not English-speaking , may be thwarted by unforeseen barriers . Those who enroll and participate in the PALS program appear to increase their level of physical activity OBJECTIVE This study examined the impact of a 6-month , empowerment-based diabetes self-management support ( DSMS ) intervention on clinical outcomes , self-care behaviors , and quality of life ( QOL ) compared to a 6-month control period . METHODS This control-intervention cohort study recruited 77 African-American adults with type 2 diabetes . Baseline , 6-month , and 12-month assessment s measured A1C , weight , body mass index ( BMI ) , blood pressure , lipids , self-care behaviors , and QOL . During the control period , participants received weekly educational newsletters . During the intervention period , participants attended weekly DSMS groups as frequently as they needed . Sessions were guided by participants ' self-management questions and concerns , and also emphasized experiential learning , coping , problem-solving , and goal - setting . RESULTS The control period found significant improvements for diastolic BP ( p<0.05 ) , serum cholesterol ( p<0.001 ) , following a healthy diet ( p<0.01 ) , and monitoring blood glucose ( p<0.01 ) . The intervention period found significant additional improvements for A1C ( p<0.001 ) , weight ( p<0.05 ) , BMI ( p<0.05 ) , and LDL ( p<0.001 ) . Compared to the control period , participation in the intervention led to a significant reduction in A1C ( p<0.01 ) . CONCLUSION Findings suggest that an empowerment-based , DSMS intervention is promising for improving and /or maintaining diabetes-related health , particularly A1C . PRACTICAL IMPLICATION S Incorporating empowerment principles in DSMS interventions may be useful for supporting patients ' self-management efforts in " real-world " setting Uncontrolled diabetes is a major health problem in Thail and . The objective of this study was to determine the effects of a diabetes self-management program on glycemic control , coronary heart disease ( CHD ) risk , and quality of life in 147 diabetic patients ( aged 56.8 + /- 10.2 years ) . Type 2 diabetic patients who met the research criteria were r and omized into two groups for a period of 6 months : the experimental group received the diabetes self-management program and the control group received the usual nursing care . The findings indicated that the experimental group demonstrated a significant decrease in the hemoglobin A(1c ) level and CHD risk , with an increase in quality of life ( QOL ) compared to the control group . The diabetes self-management program was effective for improving metabolic control and the QOL for individuals with diabetes . Further studies should be replicated using larger groups over a longer time frame Evidence from varied community setting s has shown that the Group Lifestyle Balance ( GLB ) Program and other adaptations of the Diabetes Prevention Program ( DPP ) intervention are effective in lowering diabetes risk . Most DPP data originated from studies of pre-diabetic whites , with only sparse evidence of the effect of DPP in African Americans ( AAs ) in community setting s. This paper describes the design , methods , baseline characteristics and cost effective measures , of a single-blinded , cluster-r and omized trial of a faith-based adaptation of the GLB program , Fit Body and Soul ( FBAS ) . The major aims are to test efficacy and cost utility of FBAS in twenty AA churches . R and omization occurred at the church level and 604 AA overweight/obese ( BMI ≥25kg/m(2 ) ) adults with fasting plasma glucose range from normal to pre-diabetic received either FBAS or a health-education comparison program . FBAS is a group-based , multi-level intervention delivered by trained church health advisors ( health professionals from within the church ) , with the goal of ≥7 % weight loss , achieved through increasing physical activity , healthy eating and behavior modification . The primary outcome is weight change at 12weeks post intervention . Secondary outcomes include hemoglobin A1C , fasting plasma glucose , waist circumference , blood pressure , physical activity level , quality of life measures , and cost-effectiveness . FBAS is the largest known cohort of AAs enrolled in a faith-based DPP translation . Reliance on health professionals from within the church for program implementation and the cost analysis are unique aspects of this trial . The design provides a model for faith-based DPPs and holds promise for program sustainability and widespread dissemination OBJECTIVE Although the Diabetes Prevention Program ( DPP ) and the Finnish Diabetes Prevention Study ( FDPS ) demonstrated that weight loss from lifestyle change reduces type 2 diabetes incidence in patients with prediabetes , the translation into community setting s has been difficult . The objective of this study is to report the first-year results of a community-based translation of the DPP lifestyle weight loss ( LWL ) intervention on fasting glucose , insulin resistance , and adiposity . RESEARCH DESIGN AND METHODS We r and omly assigned 301 overweight and obese volunteers ( BMI 25–40 kg/m2 ) with fasting blood glucose values between 95 and 125 mg/dL to a group-based translation of the DPP LWL intervention administered through a diabetes education program ( DEP ) and delivered by community health workers ( CHWs ) or to an enhanced usual-care condition . CHWs were volunteers with well-controlled type 2 diabetes . A total of 42.5 % of participants were male , mean age was 57.9 years , 26 % were of a race/ethnicity other than white , and 80 % reported having an education beyond high school . The primary outcome is mean fasting glucose over 12 months of follow-up , adjusting for baseline glucose . RESULTS Compared with usual-care participants , LWL intervention participants experienced significantly greater decreases in blood glucose ( −4.3 vs. −0.4 mg/dL ; P < 0.001 ) , insulin ( −6.5 vs. −2.7 μU/mL ; P < 0.001 ) , homeostasis model assessment of insulin resistance ( −1.9 vs. −0.8 ; P < 0.001 ) , weight ( −7.1 vs. −1.4 kg ; P < 0.001 ) , BMI ( −2.1 vs. −0.3 kg/m2 ; P < 0.001 ) , and waist circumference ( −5.9 vs. −0.8 cm ; P < 0.001 ) . CONCLUSIONS This translation of the DPP intervention conducted in community setting s , administered through a DEP , and delivered by CHWs holds great promise for the prevention of diabetes by significantly decreasing glucose , insulin , and adiposity OBJECTIVE To compare the effectiveness of a telephonic and a print intervention over 1 year to improve diabetes control in low-income urban adults . RESEARCH DESIGN AND METHODS A r and omized trial in Spanish and English comparing a telephonic intervention implemented by health educators with a print intervention . Participants ( N = 526 ) had an A1C ≥7.5 % and were prescribed one or more oral agents . All were members of a union/employer jointly sponsored health benefit plan . Health coverage included medications . Primary outcomes were A1C and pharmacy cl aims data ; secondary outcomes included self-report of two medication adherence measures and other self-care behaviors . RESULTS Participants were 62 % black and 23 % Hispanic ; 77 % were foreign born , and 42 % had annual family incomes < $ 30 thous and . Baseline median A1C was 8.6 % ( interquartile range 8.0–10.0 ) . Insulin was also prescribed for 24 % of participants . The telephone group had mean ± SE decline in A1C of 0.23 ± 0.11 % over 1 year compared with a rise of 0.13 ± 0.13 % for the print group ( P = 0.04 ) . After adjusting for baseline A1C , sex , age , and insulin use , the difference in A1C was 0.40 % ( 95 % CI 0.10–0.70 , P = 0.009 ) . Change in medication adherence measured by cl aims data , but not by self-report measures , was significantly associated with change in A1C ( P = 0.01 ) . Improvement in medication adherence was associated ( P = 0.005 ) with the telephonic intervention , but only among those not taking insulin . No diabetes self-care activities were significantly correlated with the change in A1C . CONCLUSIONS A 1-year tailored telephonic intervention implemented by health educators was successful in significantly , albeit modestly , improving diabetes control compared with a print intervention in a low-income , insured , minority population Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The increasing prevalence of diabetes and obesity , growing health disparities , and shortage of bilingual and culturally trained health care professionals underscore the role of trained community health workers ( CHWs ) to provide economically sustainable and culturally relevant services . This prospect i ve r and omized design evaluated the relative effectiveness of a CHW intervention among Hispanic persons with newly diagnosed type 2 diabetes , as compared with usual clinic practice in three inner-city health centers . In sum , 189 Hispanic patients newly diagnosed with type 2 diabetes were r and omly assigned to one of three 6-month diabetes management approaches — CHW , case management , and st and ard provider care— and assessed for diabetes-related health measures and clinical indicators at baseline and postintervention . Participants in the CHW group achieved greater improvements than did the controls in program measures : health status , emergency department utilization , dietary habits , physical activity , and medication adherence . They also had 2.9 times greater odds of decreasing body mass index Objectives To describe the design and baseline population characteristics of an adapted lifestyle intervention trial aim ed at reducing weight and increasing physical activity in people of Indian and Pakistani origin at high risk of developing type 2 diabetes . Design Cluster , r and omised controlled trial . Setting Community-based in Edinburgh and Glasgow , Scotl and , UK . Participants 156 families , comprising 171 people with impaired glycaemia , and waist sizes ≥90 cm ( men ) and ≥80 cm ( women ) , plus 124 family volunteers . Interventions Families were r and omised into either an intensive intervention of 15 dietitian visits providing lifestyle advice , or a light ( control ) intervention of four visits , over a period of 3 years . Outcome measures The primary outcome is a change in mean weight between baseline and 3 years . Secondary outcomes are changes in waist , hip , body mass index , plasma blood glucose and physical activity . The cost of the intervention will be measured . Qualitative work will seek to underst and factors that motivated participation and retention in the trial and families ’ experience of adhering to the interventions . Results Between July 2007 and October 2009 , 171 people with impaired glycaemia , along with 124 family volunteers , were r and omised . In total , 95 % ( 171/196 ) of eligible participants agreed to proceed to the 3-year trial . Only 13 of the 156 families contained more than one recruit with impaired glycaemia . We have recruited sufficient participants to undertake an adequately powered trial to detect a mean difference in weight of 2.5 kg between the intensive and light intervention groups at the 5 % significance level . Over half the families include family volunteers . The main participants have a mean age of 52 years and 64 % are women . Conclusions Prevention of Diabetes & Obesity in South Asians ( PODOSA ) is one of the first community-based , r and omised lifestyle intervention trials in a UK South Asian population . The main trial results will be su bmi tted for publication during 2013 . Trial registration Current controlled trials IS RCT N25729565 ( http://www.controlled-trials.com/is rct n/ ) Background Yoga is a popular therapy for diabetes but its efficacy is contested . The aim of this study was to explore the feasibility of research ing community based yoga classes in Type 2 diabetes with a view to informing the design of a definitive , multi-centre trial Methods The study design was an exploratory r and omised controlled trial with in-depth process evaluation . The setting was two multi-ethnic boroughs in London , UK ; one with average and one with low mean socio-economic deprivation score . Classes were held at a sports centre or GP surgery . Participants were 59 people with Type 2 diabetes not taking insulin , recruited from general practice lists or opportunistically by general practice staff . The intervention group were offered 12 weeks of a twice-weekly 90-minute yoga class ; the control group was a waiting list for the yoga classes . Both groups received advice and leaflets on healthy lifestyle and were encouraged to exercise . Primary outcome measure was HbA1c . Secondary outcome measures included attendance , weight , waist circumference , lipid levels , blood pressure , UKPDS cardiovascular risk score , diabetes-related quality of life ( ADDQoL ) , and self-efficacy . Process measures were attendance at yoga sessions , self-reported frequency of practice between taught sessions , and qualitative data ( interviews with patients and therapists , ethnographic observation of the yoga classes , and analysis of documents including minutes of meetings , correspondence , and exercise plans ) . Results Despite broad inclusion criteria , around two-thirds of the patients on GP diabetic registers proved ineligible , and 90 % of the remainder declined to participate . Mean age of participants was 60 + /- 10 years . Attendance at yoga classes was around 50 % . Nobody did the exercises regularly at home . Yoga teachers felt that most participants were unsuitable for ' st and ard ' yoga exercises because of limited flexibility , lack of basic fitness , co-morbidity , and lack of confidence . There was a small fall in HbA1c in the yoga group which was not statistically significant and which was not sustained six months later , and no significant change in other outcome measures . Conclusion The benefits of yoga in type 2 diabetes suggested in some previous studies were not confirmed . Possible explanations ( apart from lack of efficacy ) include recruitment challenges ; practical and motivational barriers to class attendance ; physical and motivational barriers to engaging in the exercises ; inadequate intensity and /or duration of yoga intervention ; and insufficient personalisation of exercises to individual needs . All these factors should be considered when design ing future trials . Trial registration National Research Register ( 1410 ) and Current Controlled Trials ( IS RCT N63637211 ) OBJECTIVES We tested the effectiveness of a culturally tailored , behavioral theory-based community health worker intervention for improving glycemic control . METHODS We used a r and omized , 6-month delayed control group design among 164 African American and Latino adult participants recruited from 2 health systems in Detroit , Michigan . Our study was guided by the principles of community-based participatory research . Hemoglobin A1c ( HbA1c ) level was the primary outcome measure . Using an empowerment-based approach , community health workers provided participants with diabetes self-management education and regular home visits , and accompanied them to a clinic visit during the 6-month intervention period . RESULTS Participants in the intervention group had a mean HbA1c value of 8.6 % at baseline , which improved to a value of 7.8 % at 6 months , for an adjusted change of -0.8 percentage points ( P < .01 ) . There was no change in mean HbA1c among the control group ( 8.5 % ) . Intervention participants also had significantly greater improvements in self-reported diabetes underst and ing compared with the control group . CONCLUSIONS This study contributes to the growing evidence for the effectiveness of community health workers and their role in multidisciplinary teams engaged in culturally appropriate health care delivery Few r and omized trials attempt to improve insulin sensitivity and associated metabolic risks in overweight Latino youth . The purpose of this study is to examine the effects of a modified carbohydrate nutrition program combined with strength training on insulin sensitivity , adiposity , and other type 2 diabetes risk factors in overweight Latino adolescents . In a 16-week r and omized trial , 54 overweight Latino adolescents ( 15.5 + /- 1.0 years ) were r and omly assigned to : ( i ) Control ( C ; n = 16 ) , ( ii ) Nutrition ( N ; n = 21 ) , or ( iii ) Nutrition + Strength training ( N+ST ; n = 17 ) . The N group received modified carbohydrate nutrition classes ( once per week ) , while the N+ST received the same nutrition classes plus strength training ( twice per week ) . The following were measured at pre- and postintervention : strength by 1-repetition maximum , dietary intake by 3-day records , body composition by dual-energy X-ray absorptiometry , glucose/insulin indices by oral glucose tolerance test ( OGTT ) and intravenous glucose tolerance test with minimal modeling . Across intervention group effects were tested using analysis of covariance with post hoc pairwise comparisons . A significant overall intervention effect was found for improvement in bench press ( P < 0.001 ) and reductions in energy ( P = 0.05 ) , carbohydrate ( P = 0.04 ) and fat intake ( P = 0.03 ) . There were no significant intervention effects on insulin sensitivity , body composition , or most glucose/insulin indices with the exception of glucose incremental area under the curve ( IAUC ) ( P = 0.05 ) , which decreased in the N and N+ST group by 18 and 6.3 % compared to a 32 % increase in the C group . In conclusion , this intense , culturally tailored intervention result ed in no significant intervention effects on measured risk factors with the exception of a beneficial effect on glycemic response to oral glucose Background Epidemiologic data have shown that the prevalence of Type 2 diabetes varies with ethnic origin . Type 2 diabetes is up to four times more common in British South Asians than in the indigenous white population . The aim of this study was to develop a culturally appropriate educational intervention programme for South Asians with Type 2 diabetes . We then investigated whether this intervention could produce an improvement , and finally whether any improvement was greater than background changes in knowledge in comparison groups . Methods A multi-site prospect i ve , r and omised controlled study was conducted in all day care centres and three general practice registers with high proportion patients from different ethnic minority groups in Glasgow , Scotl and . The intervention consisted of 18 educational sessions in 6 separate programmes . A modified question naire was used to measure the knowledge , attitudes , and practice of diabetes before and after intervention . Results Baseline assessment showed that Indian and Pakistani subjects had less knowledge about diabetes , regarded the disease less seriously , and had a lesser underst and ing of the relationship between control and complications than the white population . No differences in initial responses were found between those who completed the second assessment and those who did not . The intervention group showed significant improvements in scores for Knowledge ( + 12.5 % ) ; Attitudes toward seriousness ( + 13.5 % ) , complications ( + 8.1 % ) , Practice ( + 20.0 % ) . However there were also changes in the ethnic control group scores ; respectively + 5.0 % , + 16.3 % ( significant P < 0.001 ) , + 1.5 % , + 1.7 % . The single white control group also showed some improvements ; respectively + 12.2 % , + 12.4 % ( P = 0.04 ) , + 6.0 % , + 25.0 % ( P = 0.007 ) , but the differences in improvement between these two control groups were not significant . Overall , the improvement seen was similar in both intervention and ethnic control groups and there was no significant difference in the amount of change ( P = 0.36 CI -0.9 to + 2.6 ) . Conclusion This study has shown that conducting a culturally-competent educational intervention in patients with Type 2 diabetes from ethnic minority groups is feasible and can improve their knowledge and attitudes and practice . However there was no net benefit compared with the control group Background African Americans with Type 2 diabetes ( T2DM ) have higher prevalence of diabetes , poorer metabolic control , and greater risk for complications and death compared to American Whites . Poor outcomes in African Americans with T2DM can be attributed to patient , provider , and health systems level factors . Provider and health system factors account for < 10 % of variance in major diabetes outcomes including hemoglobin A1c ( HbA1c ) , lipid control , and re source use . Key differences appear to be at the patient level . Of the patient level factors , consistent differences between African Americans and American Whites with T2DM have been found in diabetes knowledge , self-management skills , empowerment , and perceived control . A variety of interventions to improve diabetes self-management have been tested including : 1 ) knowledge interventions ; 2 ) lifestyle interventions ; 3 ) skills training interventions ; and 4 ) patient activation and empowerment interventions . Most of these interventions have been tested individually , but rarely have they been tested in combination , especially among African Americans who have the greatest burden of diabetes related complications . This study provides a unique opportunity to address this gap in the literature . Methods / Design We describe an ongoing four-year r and omized clinical trial , using a 2 × 2 factorial design , which will test the efficacy of separate and combined telephone-delivered , diabetes knowledge/information and motivation/behavioral skills training interventions in high risk African Americans with poorly controlled T2DM ( HbA1c ≥ 9 % ) . Two-hundred thirty-two ( 232 ) male and female African-American participants , 18 years of age or older and with an HbA1c ≥ 9 % , will be r and omized into one of four groups for 12-weeks of phone interventions : ( 1 ) an education group , ( 2 ) a motivation/skills group , ( 3 ) a combined group or ( 4 ) a usual care/general health education group . Participants will be followed for 12-months to ascertain the effect of the interventions on glycemic control . Our primary hypothesis is that among African Americans with poorly controlled T2DM , patients r and omized to the combined diabetes knowledge/information and motivation/behavioral skills training intervention will have significantly greater reduction in HbA1c at 12 months of follow-up compared to the usual care/general health education group . Discussion Results from this study will provide important insight into how best to deliver diabetes education and skills training in ethnic minorities and whether combined knowledge/information and motivation/behavioral skills training is superior to the usual method of delivering diabetes education for African Americans with poorly controlled T2DM.Trial registration National Institutes of Health Clinical Trials Registry ( Clinical Trials.gov identifier # NCT00929838 ) OBJECTIVE Multifaceted care has been shown to reduce mortality and complications in type 2 diabetes . We hypothesized that structured care would reduce renal complications in type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 205 Chinese type 2 diabetic patients from nine public hospitals who had plasma creatinine levels of 150–350 μmol/l were r and omly assigned to receive structured care ( n = 104 ) or usual care ( n = 101 ) for 2 years . The structured care group was managed according to a prespecified protocol with the following treatment goals : blood pressure < 130/80 mmHg , A1C < 7 % , LDL cholesterol < 2.6 mmol/l , triglyceride < 2 mmol/l , and persistent treatment with renin-angiotensin blockers . The primary end point was death and /or renal end point ( creatinine > 500 μmol/l or dialysis ) . RESULTS Of these 205 patients ( mean ± SD age 65 ± 7.2 years ; disease duration 14 ± 7.9 years ) , the structured care group achieved better control than the usual care group ( diastolic blood pressure 68 ± 12 vs. 71 ± 12 mmHg , respectively , P = 0.02 ; A1C 7.3 ± 1.3 vs. 8.0 ± 1.6 % , P < 0.01 ) . After adjustment for age , sex , and study sites , the structured care ( 23.1 % , n = 24 ) and usual care ( 23.8 % , n = 24 ; NS ) groups had similar end points , but more patients in the structured care group attained ≥3 treatment goals ( 61 % , n = 63 , vs. 28 % , n = 28 ; P < 0.001 ) . Patients who attained ≥3 treatment targets ( n = 91 ) had reduced risk of the primary end point ( 14 vs. 34 ; relative risk 0.43 [ 95 % CI 0.21–0.86 ] compared with that of those who attained ≤2 targets ( n = 114 ) . CONCLUSIONS Attainment of multiple treatment targets reduced the renal end point and death in type 2 diabetes . In addition to protocol , audits and feedback are needed to improve outcomes Background Studies have shown that lifestyle interventions are effective in preventing or delaying the onset of type 2 diabetes in high-risk patients . However , research on the effectiveness of lifestyle interventions in high-risk immigrant population s with different cultural and socioeconomic background s is scarce . The aim was to design a culturally adapted lifestyle intervention for an immigrant population and to evaluate its effectiveness and cost-effectiveness . Methods / design In this r and omized controlled trial , 308 participants ( born in Iraq , living in Malmö , Sweden and at high risk of type 2 diabetes ) will be allocated to either a culturally adapted intervention or a control group . The intervention will consist of 10 group counseling sessions focusing on diet , physical activity and behavioral change over 6 months , and the offer of exercise sessions . Cultural adaptation includes gender-specific exercise sessions , and counseling by a health coach community member . The control group will receive the information about healthy lifestyle habits provided by the primary health care center . The primary outcome is change in fasting glucose level . Secondary outcomes are changes in body mass index , insulin sensitivity , physical activity , food habits and health-related quality of life . Measurements will be taken at baseline , after 3 and 6 months . Data will be analyzed by the intention-to-treat approach . The cost-effectiveness during the trial period and over the longer term will be assessed by simulation modeling from patient , health care and societal perspectives . Discussion This study will provide a basis to measure the effectiveness of a lifestyle intervention design ed for immigrants from the Middle East in terms of improvement in glucose metabolism , and will also assess its cost-effectiveness . Results from this trial may help health care providers and policy makers to adapt and implement lifestyle interventions suitable for this population group that can be conducted in the community . Trial registration Clinical Trials.gov , Introduction This study evaluated the impact of a waiting room-administered , low-literacy , computer multimedia diabetes education program on patient self-management and provider intensification of therapy . Methods In this r and omized , controlled trial , 129 participants either viewed a computer multimedia education program ( intervention group ) or read an educational brochure ( control group ) while in the waiting room . Participants were uninsured , primarily ethnic minority adults with type 2 diabetes receiving care from a county clinic in Chicago , Illinois . Wilcoxon test , t-test , and linear mixed model analyses evaluated changes in diabetes knowledge , self-efficacy , behaviors , medications prescribed , hemoglobin A1c ( HbA1c ) , and blood pressure levels over 3 months . Results During the study period , there was an increase in the number of oral diabetes medications prescribed over three months to multimedia users compared with those in the control group ( P=0.017 ) . HbA1c declined by 1.5 in the multimedia group versus 0.8 in the control group ( P=0.06 ) . There were no differences between groups in changes in blood pressure levels , self-efficacy , and most diabetes-related behaviors . Self-reported exercise increased in the control group compared with the multimedia group ( 0.9 days/week vs. 0.1 days/week , P=0.016 ) . Conclusion Multimedia users received a greater intensification of diabetes therapy , but demonstrated no difference in self-management in comparison with those receiving educational brochures . The availability of a computer multimedia program in the waiting room appears to be a novel and acceptable approach in providing diabetes education for underserved population OBJECTIVE To determine the effects of a culturally competent diabetes self-management intervention in Mexican Americans with type 2 diabetes . RESEARCH DESIGN AND METHODS A prospect i ve , r and omized , repeated measures study was conducted on the Texas-Mexico border in Starr County . A total of 256 r and omly selected individuals with type 2 diabetes between 35 and 70 years of age , diagnosed with type 2 diabetes after 35 years of age , and accompanied by a family member or friend were included . The intervention consisted of 52 contact hours over 12 months and was provided by bilingual Mexican American nurses , dietitians , and community workers . The intervention involved 3 months of weekly instructional sessions on nutrition , self-monitoring of blood glucose , exercise , and other self-care topics and 6 months of biweekly support group sessions to promote behavior changes . The approach was culturally competent in terms of language , diet , social emphasis , family participation , and incorporation of cultural health beliefs . Outcomes included indicators of metabolic control ( HbA(1c ) and fasting blood glucose ) , diabetes knowledge , and diabetes-related health beliefs . RESULTS Experimental groups showed significantly lower levels of HbA(1c ) and fasting blood glucose at 6 and 12 months and higher diabetes knowledge scores . At 6 months , the mean HbA(1c ) of the experimental subjects was 1.4 % below the mean of the control group ; however , the mean level of the experimental subjects was still high ( > 10 % ) . CONCLUSIONS This study confirms the effectiveness of culturally competent diabetes self-management education on improving health outcomes of Mexican Americans , particularly for those individuals with HbA(1c ) levels > 10 % This article describes the design and implementation of an online diabetes self-management intervention for a sample of inner-city African Americans with diabetes . Study participants were r and omly assigned to the treatment ( 26 ) and control ( 21 ) conditions . The results indicate that treatment group participants were more likely to achieve positive outcomes in terms of lowered hemoglobin A1c and body mass index measurements than were control group members . These findings support the development of telehealth interventions to promote effective chronic disease management in medically underserved communities OBJECTIVE to examine the effects of the Informatics for Diabetes Education and Telemedicine ( IDEATel ) telemedicine intervention and pedometer use on physical activity ( PA ) and impairment in older adults with diabetes . DESIGN r and omised clinical trial . Subjects ethnically diverse medically underserved Medicare beneficiaries with diabetes ( n= 1,650 ) . METHODS participants received home videovisits with a diabetes educator every 4 - 6 weeks or usual care . All received a pedometer . Annual measurements included hemoglobin A1c , Comprehensive Assessment and Referral Evaluation Activities of Daily Living , Diabetes Self-Care Activities , Charlson Comorbidity Index , Luben Social Support and pedometer use . Mixed model analyses were performed using r and om effects to adjust for clustering within primary care physicians . RESULTS in the telemedicine group compared with the usual care group , the rate of decline in PA ( P= 0.0128 ) and physical impairment ( PI ) ( P= 0.0370 ) was significantly less over time . Significant mean endpoint differences were observed for PA ( P= 0.003 ) . Pedometer use was significantly associated with PA ( P= 0.0006 ) and PI ( P < 0.0001 ) . Baseline characteristics associated with greater PA included having fewer comorbid conditions ( P= 0.0054 ) , less depression ( P < 0.0001 ) , more social networking ( P < 0.0001 ) , lower BMI ( P < 0.0001 ) , male gender ( P < 0.0001 ) and lower hemoglobin A1c level ( P= 0.0045 ) . Similar predictors were observed for PI , except duration of diabetes also predicted increased impairment ( P < 0.0001 ) . Significant indirect effects were observed through use of the pedometer on reduced decline in PA ( P= 0.0024 , 0.0013 ) and PI ( P= 0.0024 , P < 0.0001 ) . CONCLUSIONS this telemedicine intervention reduced rates of decline in PA and impairment in older adults with diabetes . Pedometers may be a helpful inexpensive adjunct to diabetes initiatives delivered remotely with emerging technologies . Clinical Trials.gov identifier NCT 00271739 OBJECTIVE To evaluate the effect of a culturally sensitive diabetes self-management education program that uses a low-cost , peer-educator format ( Project Dulce ) on glucose control and metabolic parameters in low-income Mexican Americans with type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 207 Mexican-American patients recruited from federally funded community health centers in San Diego County with HbA1c > 8 % were r and omly assigned to the Project Dulce peer intervention or continuation of st and ard diabetes care . The primary outcome of interest was HbA1c . RESULTS The majority of subjects were born in Mexico , were female , were middle-aged , had less than an eighth- grade education , and had high baseline HbA1c levels . Significant time-by-group interaction effects for HbA1c ( P = 0.02 ) and diastolic blood pressure ( P = 0.04 ) indicated that the Project Dulce group exhibited greater improvement ( i.e. , decreases ) across time . Within-group analyses showed that the intervention group exhibited significant improvements from baseline to month 4 in absolute levels of HbA1c ( −1.7 % , P = 0.001 ) and HDL cholesterol ( + 1.4 mg/dL , P = 0.01 ) and from baseline to month 10 in absolute levels of HbA1c ( −1.5 % , P = 0.01 ) , total cholesterol ( −7.2 mg/dL , P = 0.04 ) , HDL cholesterol ( + 1.6 mg/dL , P = 0.01 ) , and LDL cholesterol ( −8.1 mg/dL , P = 0.02 ) . No significant changes were noted in the control group . CONCLUSIONS This r and omized trial , using the Project Dulce model of culturally sensitive , peer-led education , demonstrates improvement in glucose and metabolic control and suggests that this low-cost approach to self-management education for high-risk diabetic population s is effective CONTEXT Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions and lower access to care . OBJECTIVES To examine the effectiveness of a telemedicine intervention to achieve clinical management goals in older , ethnically diverse , medically underserved patients with diabetes . DESIGN , Setting , and Patients A r and omized controlled trial was conducted , comparing telemedicine case management to usual care , with blinded outcome evaluation , in 1,665 Medicare recipients with diabetes , aged > /= 55 years , residing in federally design ated medically underserved areas of New York State . Interventions Home telemedicine unit with nurse case management versus usual care . Main Outcome Measures The primary endpoints assessed over 5 years of follow-up were hemoglobin A1c ( HgbA1c ) , low density lipoprotein ( LDL ) cholesterol , and blood pressure levels . RESULTS Intention-to-treat mixed models showed that telemedicine achieved net overall reductions over five years of follow-up in the primary endpoints ( HgbA1c , p = 0.001 ; LDL , p < 0.001 ; systolic and diastolic blood pressure , p = 0.024 ; p < 0.001 ) . Estimated differences ( 95 % CI ) in year 5 were 0.29 ( 0.12 , 0.46)% for HgbA1c , 3.84 ( -0.08 , 7.77 ) mg/dL for LDL cholesterol , and 4.32 ( 1.93 , 6.72 ) mm Hg for systolic and 2.64 ( 1.53 , 3.74 ) mm Hg for diastolic blood pressure . There were 176 deaths in the intervention group and 169 in the usual care group ( hazard ratio 1.01 [ 0.82 , 1.24 ] ) . CONCLUSIONS Telemedicine case management result ed in net improvements in HgbA1c , LDL-cholesterol and blood pressure levels over 5 years in medically underserved Medicare beneficiaries . Mortality was not different between the groups , although power was limited . Trial Registration http:// clinical trials.gov Identifier : NCT00271739 OBJECTIVE —To determine 1 ) whether participants in the Spanish Diabetes Self-Management Program ( SDSMP ) , when compared at 6 months to r and omized control subjects , would demonstrate improvements in health status , health behaviors , and self-efficacy ; and 2 ) whether SDSMP participants receiving monthly automated telephone reinforcement would maintain improvements at 18 months better than those not receiving reinforcement . RESEARCH DESIGN AND METHODS —A total of 567 Spanish-speaking adults with type 2 diabetes were r and omized to a usual-care control group or 6-week community-based , peer-led SDSMP . SDSMP participants were re-r and omized to receive 15 months of automated telephone messages or no reinforcement . A1C was measured at baseline and 6 and 18 months . All other data were collected by self-administered question naires . RESULTS —At 6 months SDSMP participants compared with control subjects demonstrated improvements in A1C ( −0.4 % ) , health distress , symptoms of hypo- and hyperglycemia , and self-efficacy ( P < 0.05 ) . At 18 months all improvements persisted ( P < 0.05 ) . SDSMP participants also demonstrated improvements in self-rated health and communication with physicians , had fewer emergency room visits ( −0.18 visits in 6 months , P < 0.05 ) , and trended toward fewer visits to physicians . At 18 months the only difference between reinforced and nonreinforced participants was increased glucose monitoring for the reinforcement group . CONCLUSIONS —The SDSMP demonstrated effectiveness in lowering A1C and improving health status . Reinforcement did not add to its effectiveness . Given the high needs of the Spanish-speaking population , the SDSMP deserves consideration for implementation Background Given the increasing prevalence of diabetes and the lack of patients reaching recommended therapeutic goals , novel models of team-based care are emerging . These teams typically include a combination of physicians , nurses , case managers , pharmacists , and community-based peer health promoters ( HPs ) . Recent evidence supports the role of pharmacists in diabetes management to improve glycemic control , as they offer expertise in medication management with the ability to collaboratively intensify therapy . However , few studies of pharmacy-based models of care have focused on low income , minority population s that are most in need of intervention . Alternatively , HP interventions have focused largely upon low income minority groups , addressing their unique psychosocial and environmental challenges in diabetes self-care . This study will evaluate the impact of HPs as a complement to pharmacist management in a r and omized controlled trial . Methods / Design The primary aim of this r and omized trial is to evaluate the effectiveness of clinical pharmacists and HPs on diabetes behaviors ( including healthy eating , physical activity , and medication adherence ) , hemoglobin A1c , blood pressure , and LDL-cholesterol levels . A total of 300 minority patients with uncontrolled diabetes from the University of Illinois Medical Center ambulatory network in Chicago will be r and omized to either pharmacist management alone , or pharmacist management plus HP support . After one year , the pharmacist-only group will be intensified by the addition of HP support and maintenance will be assessed by phasing out HP support from the pharmacist plus HP group ( crossover design ) . Outcomes will be evaluated at baseline , 6 , 12 , and 24 months . In addition , program and healthcare utilization data will be incorporated into cost and cost-effectiveness evaluations of pharmacist management with and without HP support . Discussion The study will evaluate an innovative , integrated approach to chronic disease management in minorities with poorly controlled diabetes . The approach is comprised of clinic-based pharmacists and community-based health promoters collaborating together . They will target patient-level factors ( e.g. , lack of adherence to lifestyle modification and medications ) and provider-level factors ( e.g. , clinical inertia ) that contribute to poor clinical outcomes in diabetes . Importantly , the study design and analytic approach will help determine the differential and combined impact of adherence to lifestyle changes , medication , and intensification on clinical outcomes .Trial registration Clinical Trials.gov identifier : OBJECTIVE The Informatics for Diabetes Education and Telemedicine ( IDEATel ) project r and omized ethnically diverse underserved older adults with diabetes to a telemedicine intervention or usual care . Intervention participants had lower A1C levels over 5 years . New analyses were performed to help better underst and this difference . RESEARCH DESIGN AND METHODS IDEATel r and omized Medicare beneficiaries with diabetes ( n = 1,665 ) to receive home video visits with a diabetes educator and upload glucose levels every 4–6 weeks or usual care ( 2000–2007 ) . Annual measurements included BMI , A1C ( primary outcome ) , and completion of question naires . Mixed-model analyses were performed using r and om effects to adjust for clustering within primary care physicians . RESULTS At baseline , A1C levels ( mean ± SD ) were 7.02 ± 1.25 % in non-Hispanic whites ( n = 821 ) , 7.58 ± 1.78 % in non-Hispanic blacks ( n = 248 ) , and 7.79 ± 1.68 % in Hispanics ( n = 585 ) . Over time , lower A1C levels were associated with more glucose uploads ( P = 0.02 ) and female sex ( P = 0.002 ) . Blacks , Hispanics , and insulin-users had higher A1C levels than non-Hispanic whites ( P < 0.0001 ) . BMI was not associated with A1C levels . Blacks and Hispanics had significantly fewer uploads than non-Hispanic whites over time . Hispanics had the highest baseline A1C levels and showed the greatest improvement in the intervention , but , unlike non-Hispanic whites , Hispanics did not achieve A1C levels < 7.0 % at 5 years . CONCLUSIONS Racial/ethnic disparities were observed in this cohort of underserved older adults with diabetes . The IDEATel telemedicine intervention was associated with improvement in glycemic control , particularly in Hispanics , who had the highest baseline A1C levels , suggesting that telemedicine has the potential to help reduce disparities in diabetes management OBJECTIVE The Re sources for Health trial evaluates a social-ecologically based lifestyle ( physical activity and diet ) intervention targeting low-income , largely Spanish-speaking patients with multiple chronic conditions . DESIGN A r and omized controlled trial was conducted with 200 patients recruited from an urban community health center and assigned to intervention and usual care conditions . Intervention involved 2 face-to-face , self-management support and community linkage sessions with a health educator , 3 follow-up phone calls , and 3 tailored newsletters . MAIN OUTCOME MEASURES Primary outcomes measured at 6-months were changes in dietary behavior and physical activity . Changes in multilevel support for healthy living were evaluated as a secondary outcome . RESULTS After adjustment for age , sex , language , and number of chronic conditions , significant intervention effects were observed for dietary behavior and multilevel support for healthy lifestyles but not for physical activity . CONCLUSION The Re sources for Health intervention provides an effective and practical model for improving health behavior among low-income , Spanish-speaking patients with multiple chronic conditions Objective Hispanics in the USA are affected by the diabetes epidemic disproportionately , and they consistently have lower access to care , poorer control of the disease and higher risk of complications . This study evaluates whether a community health worker ( CHW ) intervention may improve clinical ly relevant markers of diabetes care in adult underserved Hispanics . Methods and analysis The Northern Manhattan Diabetes Community Outreach Project ( NOCHOP ) is a two-armed r and omised controlled trial to be performed as a community-based participatory research study performed in a Primary Care Setting in Northern Manhattan ( New York City ) . 360 Hispanic adults with poorly controlled type 2 diabetes mellitus ( haemoglobin A1c > 8 % ) , aged 35–70 years , will be r and omised at a 1:1 ratio , within Primary Care Provider clusters . The two study arms are ( 1 ) a 12-month CHW intervention and ( 2 ) enhanced usual care ( educational material s mailed at 4-month intervals , preceded by phone calls ) . The end points , assessed after 12 months , are primary = haemoglobin A1c and secondary = blood pressure and low-density lipoprotein-cholesterol levels . In addition , the study will describe the CHW intervention in terms of components and intensity and will assess its effects on ( 1 ) medication adherence , ( 2 ) medication intensification , ( 3 ) diet and ( 4 ) physical activity . Ethics and dissemination All participants will provide informed consent ; the study protocol has been approved by the Institutional Review Board of Columbia University Medical Center . CHW interventions hold great promise in improving the well-being of minority population s who suffer from diabetes mellitus . The NOCHOP study will provide valuable information about the efficacy of those interventions vis-à-vis clinical ly relevant end points and will inform policy makers through a detailed characterisation of the programme and its effects . Clinical trial registration number NCT00787475 at clinical trials.gov OBJECTIVE To evaluate the effectiveness of a culturally adapted , primary care – based nurse – community health worker ( CHW ) team intervention to support diabetes self-management on diabetes control and other biologic measures . RESEARCH DESIGN AND METHODS Two hundred sixty-eight Samoan participants with type 2 diabetes were recruited from a community health center in American Samoa and were r and omly assigned by village clusters to the nurse-CHW team intervention or to a wait-list control group that received usual care . RESULTS Participants had a mean age of 55 years , 62 % were female , mean years of education were 12.5 years , 41 % were employed , and mean HbA1c was 9.8 % at baseline . At 12 months , mean HbA1c was significantly lower among CHW participants , compared with usual care , after adjusting for confounders ( b = −0.53 ; SE = 0.21 ; P = 0.03 ) . The odds of making a clinical ly significant improvement in HbA1c of at least 0.5 % in the CHW group was twice the odds in the usual care group after controlling for confounders ( P = 0.05 ) . There were no significant differences in blood pressure , weight , or waist circumference at 12 months between groups . CONCLUSIONS A culturally adapted nurse-CHW team intervention was able to significantly improve diabetes control in the U.S. Territory of American Samoa . This represents an important translation of an evidence -based model to a high-risk population and a re source -poor setting Participants who received Pies Sanos , a 15-min intervention design ed to improve diabetes self-efficacy and foot self-care behaviors in adult patients with type 2 diabetes who lived in a predominantly Mexican American community , performed more-complete foot self-care 1 month later in their homes . Recruited when they presented for nonurgent care to the emergency department in two community hospitals near the U.S .— Mexico border , participants were r and omized into one of three groups . At follow-up , there was a significant difference in observed foot self-care behaviors between groups , F(2 , 135 ) = 2.99 , p < .05 , as well as a significant difference within the intervention , t ( 47 ) = −4.32 , p < .01 , and control group , t ( 46 ) = −2.06 , p < .05 , for baseline and follow-up self-reported foot self-care behaviors . Baseline diabetes self-efficacy was significantly and positively correlated with both baseline ( r = .335 , p < .001 ) and follow-up ( r = .174 , p < .05 ) foot self-care behaviors Background : With growing use of Community Health Workers ( CHWs ) to reach underserved population s , there is a need for more information on training methods to prepare CHWs , particularly in a health educator role . Objectives : To describe procedures used to recruit , train , and evaluate CHWs in Project Sugar 2 , a r and omized controlled trial of a nurse case manager and CHW team intervention design ed to improve diabetes care and control in a sample of 542 urban African Americans with type 2 diabetes . Methods : CHWs received a Core Training on guidelines and procedures , didactic diabetes self-management education , and research protocol training . However , barriers to CHW implementation of the intervention were encountered , including CHW attrition , job performance and satisfaction issues , low self-confidence in knowledge and skills as educators , difficulties with maintaining a large caseload , and inefficiencies experienced in conducting home visits . To address barriers , the initial training was modified and Results : The supplemental training result ed in CHW retention , satisfaction , confidence in skills , and feelings of ownership of the intervention . Participant satisfaction with care received from the CHWs and the Project Sugar 2 intervention was rated as high by 97 % and 93 % of responders , respectively . Conclusion : Core training in research intervention policies , procedures , and protocol s , combined with an extended participatory training , led to effective preparation of laypersons to serve as CHWs Healthy Living Partnerships to Prevent Diabetes ( HELP PD ) is a r and omized controlled trial design ed to translate the Diabetes Prevention Program ( DPP ) lifestyle intervention into a community setting using community health workers engaged through an existing Diabetes Care Center ( DCC ) . Overweight and obese ( BMI 25 - 40 kg/m² ) individuals with pre-diabetes ( fasting blood glucose 95 - 125 mg/dl ) with no medical contraindications to participate in a lifestyle intervention were recruited for participation in this study . St and ard recruitment strategies were employed , including mass mailing , direct provider referral , and community events . Participant recruitment and r and omization for this trial began in 2007 and was concluded in 2009 . 1818 screenings were conducted ; of these , 326 ( 17.9 % ) qualified and 301 ( 16.6 % ) participants were r and omized over a 21 month period . 23.8 % of potential participants were excluded during the initial telephone screening , primarily for BMI and recent history of CVD . The majority of participants ( 220 , 73.1 % ) reported mass mailing as their primary source of information about the study . Mass mailing was more effective with participants who identified themselves as white when compared to African-Americans . The cost of recruitment per r and omized participant was $ 816 , which includes direct costs and staff effort . 41 % of the r and omized participants were male and approximately 27 % reported a race or ethnicity other than white . In comparison to the DPP study cohort , the HELP PD population is older , more educated and predominately white . These differences , reflecting in part the community in which HELP PD was conducted , may have implication s for retention and adherence in the lifestyle intervention group Background Diabetes outcomes are worse for underserved patients from certain ethnic/racial minority population s. Telephonic disease management is a cost-effective strategy to deliver self-management services and possibly improve diabetes outcomes for such patients . Objective We conducted a trial to test the effectiveness of a supplemental telephonic disease management program compared to usual care alone for patients with diabetes cared for in a community health center . Design R and omized controlled trial . Participants All patients had type 2 diabetes , and the majority was Hispanic or African American . Most were urban-dwelling with low socioeconomic status , and nearly all had Medicaid or were uninsured . Measurements Clinical measures included glycemic control , blood pressure , lipid levels , and body mass index . Vali date d surveys were used to measure dietary habits and physical activity . Results A total of 146 patients were r and omized to the intervention and 149 to the control group . Depressive symptoms were highly prevalent in both groups . Using an intention to treat analysis , there were no significant differences in the primary outcome ( HbA1c ) between the intervention and control groups at 12 months . There were also no significant differences for secondary clinical or behavioral outcome measures including BMI , systolic or diastolic blood pressure , LDL cholesterol , smoking , or intake of fruits and vegetables , or physical activity . Conclusions A clinic-based telephonic disease management support for underserved patients with diabetes did not improve clinical or behavioral outcomes at 1 year as compared to patients receiving usual care alone Abstract Objective : To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes . Design : R and omised controlled trial comparing tight control of blood pressure aim ing at a blood pressure of < 150/85 mm Hg ( with the use of an angiotensin converting enzyme inhibitor captopril or a β blocker atenolol as main treatment ) with less tight control aim ing at a blood pressure of < 180/105 mm Hg . Setting : 20 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Subjects : 1148 hypertensive patients with type 2 diabetes ( mean age 56 , mean blood pressure at entry 160/94 mm Hg ) ; 758 patients were allocated to tight control of blood pressure and 390 patients to less tight control with a median follow up of 8.4 years . Main outcome measures : Predefined clinical end points , fatal and non-fatal , related to diabetes , deaths related to diabetes , and all cause mortality . Surrogate measures of microvascular disease included urinary albumin excretion and retinal photography . Results : Mean blood pressure during follow up was significantly reduced in the group assigned tight blood pressure control ( 144/82 mm Hg ) compared with the group assigned to less tight control ( 154/87 mm Hg ) ( P<0.0001 ) . Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24 % in diabetes related end points ( 95 % confidence interval 8 % to 38 % ) ( P=0.0046 ) , 32 % in deaths related to diabetes ( 6 % to 51 % ) ( P=0.019 ) , 44 % in strokes ( 11 % to 65 % ) ( P=0.013 ) , and 37 % in microvascular end points ( 11 % to 56 % ) ( P=0.0092 ) , predominantly owing to a reduced risk of retinal photocoagulation . There was a non-significant reduction in all cause mortality . After nine years of follow up the group assigned to tight blood pressure control also had a 34 % reduction in risk in the proportion of patients with deterioration of retinopathy by two steps ( 99 % confidence interval 11 % to 50 % ) ( P=0.0004 ) and a 47 % reduced risk ( 7 % to 70 % ) ( P=0.004 ) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study ( ETDRS ) chart . After nine years of follow up 29 % of patients in the group assigned to tight control required three or more treatments to lower blood pressure to achieve target blood pressures . Conclusion : Tight blood pressure control in patients with hypertension and type 2 diabetes achieves a clinical ly important reduction in the risk of deaths related to diabetes , complications related to diabetes , progression of diabetic retinopathy , and deterioration in visual acuity OBJECTIVE Effective behavioral diabetes interventions for Mexican Americans are needed . Our study focused on efforts to recruit Mexican American adults for a trial testing a diabetes community health worker ( CHW ) self-management intervention . DESIGN Behavioral r and omized controlled trial , community-based participatory research approach . SETTING Chicago . PARTICIPANTS Mexican American adults with type 2 diabetes . OUTCOME MEASURES Screening and r and omization . METHODS Initial eligibility criteria included Mexican heritage , treatment with oral diabetes medication , residence in design ated zip codes , planned residence in the area for two years , and enrollment in a specific insurance plan . RESULTS Recruitment through the insurer result ed in only one r and omized participant . Eligibility criteria were relaxed and subsequent efforts included bilingual advertisements , presentations at churches and community events , postings in clinics , partnerships with community providers , and CHW outreach . Zip codes were exp and ed multiple times and insurance criteria removed . CHW outreach result ed in 53 % of r and omized participants . CONCLUSIONS Despite strong ties with the target community , culturally appropriate recruitment strategies involving community representation , and a large pool of potential participants , significant challenges were encountered in recruitment for this diabetes intervention trial . Research ers identified three key barriers to participation : study intensity and duration , lack of financial incentives , and challenges in establishing trust . For future research to be successful , investigators need to recognize these barriers , offer adequate incentives to compensate for intervention intensity , and establish strong trust through community partnerships and the incorporation of community members in the recruitment process OBJECTIVE To evaluate a weight loss and exercise program design ed to improve diabetes management in older African-Americans . RESEARCH DESIGN AND METHODS Overweight African-Americans ( n = 64 ) ages 55–79 years with NIDDM were r and omized to either an intervention ( 12 weekly group sessions , 1 individual session , and 6 biweekly group sessions ) or usual care ( 1 class and 2 informational mailings ) . Clinical and behavioral variables were assessed at 0 , 3 , and 6 months of treatment . RESULTS Significant net differences in the intervention versus usual care were observed for weight ( −2.0 kg , P = 0.006 ) , physical activity , and dietary intake of fat , saturated fat , cholesterol , and nutrition knowledge at 3 months ( all P < 0.05 ) and for weight at 6 months ( −2.4 kg ; P = 0.006 ) and mean HbA1c values at 3 and 6 months ( respectively , −1.6 and −2.4 % , both P < 0.01 ) . After the adjustment for changes in weight and activity , the intervention participants were ∼ twice as likely to have a one unit decrease in HbA1c value as those in usual care . Blood pressure increase sin usual care participants result ed in net differences ( intervention minus control ) at 3 and 6 months of −3.3 ( P = 0.09 ) and −4.0 ( P = 0.05 ) mmHg diastolic , respectively , and −8.4 ( P = 0.06 ) and −5.9 ( P > 0.10 ) mmHg systolic , respectively . Blood lipid profiles improved more in intervention than usual care participants , but not significantly . CONCLUSIONS The intervention program was effective in improving glycemic and blood pressure control . The decrease in HbA1c values was generally independent of the relatively modest changes in dietary intake , weight , and activity and may reflect indirect program effects on other aspects of self-care CONTEXT Recruiting and retaining minorities from rural , community health centers is a challenge . Collaboration between the research ers and health center personnel and activities to enhance trust may improve results . PURPOSE To describe recruitment and retention strategies and report results of a 12-month clinical trial of a telemedicine-based diabetes self-management intervention , conducted within a rural community health center . METHODS Multi-level , multi-staged recruitment process including collaborative planning , data extraction , medical record review , telephone screen , 2 in-person enrollment visits and r and omization . Target sample was adults > or=35 years of age with type 2 diabetes , glycated hemoglobin (GHb)>7 % with no significant comorbidities to prevent safe participation . Follow-up visits occurred at 6 and 12 months post-r and omization . FINDINGS Of those eligible from medical record review , 65 % were African-American(AA)/other and female . Approximately 33 % of those successfully contacted by telephone were r and omized ( n=165 ) , yielding a predominately AA/other ( 73.9 % ) and female ( 74.5 % ) sample . Among those eligible at the Telephone Screen , a greater percentage of Non-Hispanic Whites ( NHW ) refused participation than AA/other ( 54.2 % vs 45.8 % ) , while a greater percentage of women refused compared to men ( 64.4 % vs 35.6 % ) . Significant baseline differences were found by ethnicity for education , insurance , transportation and diastolic blood pressure ; by gender for income , transportation , weight , and home monitoring of blood glucose . Overall 6 and 12 month retention rates were 90.9 % and 82.4 % , respectively , with a greater percentage of AA/Other and female participants retained . CONCLUSIONS Our collaborative approach was successful in recruiting and retaining ethnically diverse study participants who reside in a rural underserved area of South Carolina . Differences in baseline characteristics and retention by ethnicity and gender were found . Successful translational research must allow for a collaborative approach addressing factors at the level of the community health center , key personnel , and patients in an effort to build trust for the purpose of advancing the science of translating research to practice OBJECTIVE The objective of this study was to evaluate the impact of a problem-based empowerment patient education program specifically tailored for urban African Americans with type 2 diabetes . RESEARCH DESIGN AND METHODS The study used a r and omized controlled trial ( RCT ) pretest/post-test design with repeated measures . Patients were r and omly assigned to either a six-week intervention group or a six-week wait-listed control group . After completing the six sessions , patients were invited to participate in one of two follow-up conditions ; attend a monthly support group or receive a monthly phone call from a nurse . Assessment measures included HbA1C , lipids , blood pressure , weight , self-management behavior and psychosocial adaptation . RESULTS Both control and intervention patients showed a broad array of small-to-modest positive changes during the six-week RCT . These gains were maintained or improved upon during the one-year follow-up period . For patients in the two follow-up conditions , a positive correlation was seen between the number of follow-up contacts and their one-year HbA1C values . CONCLUSIONS We believe that results of this study can be attributed to volunteer bias , study effects ( ie , providing study data on several occasions to patients and their physicians during the one-year study period ) , and impact of the interventions . However , the study design does not allow us to examine the relative impact of these three factors on the patient improvements seen over the one-year study period Objective : This article describes design elements of the Multifaceted Depression and Diabetes Program ( MDDP ) r and omized clinical trial . The MDDP trial hypothesizes that a socioculturally adapted collaborative care depression management intervention will reduce depressive symptoms and improve patient adherence to diabetes self-care regimens , glycemic control , and quality -of-life . In addition , baseline data of 387 low-income , 96 % Hispanic , enrolled patients with major depression and diabetes are examined to identify study population characteristics consistent with trial design adaptations . Methods : The PHQ-9 depression scale was used to identify patients meeting criteria for major depressive disorder ( 1 cardinal depression symptom + a PHQ-9 score of > 10 ) from two community safety net clinics . Design elements included sociocultural adaptations in recruitment and efforts to reduce attrition and collaborative depression care management . Results : Of 1,803 diabetes patients screened , 30.2 % met criteria for major depressive disorder . Of 387 patients enrolled in the clinical trial , 98 % had Type 2 diabetes , and 83 % had glycated hemoglobin ( HbA1c ) levels ≥ 7 % . Study recruitment rates and baseline data analyses identified socioeconomic and clinical factors that support trial design and intervention adaptations . Depression severity was significantly associated with diabetes complications , medical comorbidity , greater anxiety , dysthymia , financial worries , social stress , and poorer quality -of-life . Conclusion : Low-income Hispanic patients with diabetes experience high prevalence of depressive disorder and depression severity is associated with socioeconomic stressors and clinical severity . Improving depression care management among Hispanic patients in public sector clinics should include intervention components that address self-care of diabetes and socioeconomic stressors BACKGROUND Delivery of high- quality , evidence -based health care to deprived sectors of the community is a major goal for society . We investigated the effectiveness of a culturally sensitive , enhanced care package in UK general practice s for improvement of cardiovascular risk factors in patients of south Asian origin with type 2 diabetes . METHODS In this cluster r and omised controlled trial , 21 inner-city practice s in the UK were assigned by simple r and omisation to intervention ( enhanced care including additional time with practice nurse and support from a link worker and diabetes-specialist nurse [ nine practice s ; n=868 ] ) or control ( st and ard care [ 12 practice s ; n=618 ] ) groups . All adult patients of south Asian origin with type 2 diabetes were eligible . Prescribing algorithms with clearly defined targets were provided for all practice s. Primary outcomes were changes in blood pressure , total cholesterol , and glycaemic control ( haemoglobin A1c ) after 2 years . Analysis was by intention to treat . This trial is registered , number IS RCT N 38297969 . FINDINGS We recorded significant differences between treatment groups in diastolic blood pressure ( 1.91 [ 95 % CI -2.88 to -0.94 ] mm Hg , p=0.0001 ) and mean arterial pressure ( 1.36 [ -2.49 to -0.23 ] mm Hg , p=0.0180 ) , after adjustment for confounders and clustering . We noted no significant differences between groups for total cholesterol ( 0.03 [ -0.04 to 0.11 ] mmol/L ) , systolic blood pressure ( -0.33 [ -2.41 to 1.75 ] mm Hg ) , or HbA1c ( -0.15 % [ -0.33 to 0.03 ] ) . Economic analysis suggests that the nurse-led intervention was not cost effective ( incremental cost-effectiveness ratio pound28 933 per QALY gained ) . Across the whole study population over the 2 years of the trial , systolic blood pressure , diastolic blood pressure , and cholesterol decreased significantly by 4.9 ( 95 % CI 4.0 - 5.9 ) mm Hg , 3.8 ( 3.2 - 4.4 ) mm Hg , and 0.45 ( 0.40 - 0.51 ) mmol/L , respectively , and we recorded a small and non-significant increase for haemoglobin A1c ( 0.04 % [ -0.04 to 0.13 ] ) , p=0.290 ) . INTERPRETATION We recorded additional , although small , benefits from our culturally tailored care package that were greater than the secular changes achieved in the UK in recent years . Stricter targets in general practice and further measures to motivate patients are needed to achieve best possible health-care outcomes in south Asian patients with diabetes OBJECTIVES We assessed whether community health workers ( CHWs ) could improve glycemic control among Mexican Americans with diabetes . METHODS We recruited 144 Mexican Americans with type 2 diabetes between January 2006 and September 2008 into the single-blinded , r and omized controlled Mexican American Trial of Community Health Workers ( MATCH ) and followed them for 2 years . Participants were assigned to either a CHW intervention , delivering self-management training through 36 home visits over 2 years , or a bilingual control newsletter delivering the same information on the same schedule . RESULTS Intervention participants showed significantly lower hemoglobin A1c levels than control participants at both year 1 Δ = -0.55 ; P = .021 ) and year 2 ( Δ = -0.69 ; P = .005 ) . We observed no effect on blood pressure control , glucose self-monitoring , or adherence to medications or diet . Intervention participants increased physical activity from a mean of 1.63 days per week at baseline to 2.64 days per week after 2 years . CONCLUSIONS A self-management intervention delivered by CHWs result ed in sustained improvements in glycemic control over 2 years among Mexican Americans with diabetes . MATCH adds to the growing body of evidence supporting the use of CHWs to reduce diabetes-related health disparities OBJECTIVE Numerous mobile health ( mHealth ) interventions are being developed to aid in management of complex chronic medical conditions . However , the acceptance of mHealth programs by low-income , bilingual population s has not yet been evaluated . The Trial to Examine Text-based mHealth for Emergency department patients with Diabetes ( TExT-MED ) program is a text message-based mHealth program design ed specifically for re source -poor patients with diabetes . We conducted a prospect i ve proof-of-concept trial to assess satisfaction and preliminary effectiveness of the TExT-MED program . RESEARCH DESIGN AND METHODS A consecutive sample of adult patients in the emergency department with diabetes and a text message-capable mobile phone was enrolled in the TExT-MED program . Participants received three text messages daily for 3 weeks in English or Spanish in the following domains : educational/motivational , medication reminders , healthy living challenges , diabetes trivia , and links to free diabetes management tools . RESULTS Twenty-three patients with diabetes ( median hemoglobin A1c , 8.9 % ) were enrolled in TExT-MED . In the week before TExT-MED , 56.5 % of subjects reported eating fruits/vegetables daily versus 83 % after , 43.5 % reported exercising before versus 74 % after , and 74 % reported performing foot checks before versus 85 % after . Self-efficacy , measured by the Diabetes Empowerment Scale-Short Form , improved from 3.9 to 4.2 . Scores on the Morisky Medication Adherence Scale improved more dramatically from 3.5 to 4.75 . Ninety percent of participants indicated they would like to continue the program , and 100 % would recommend the program to family or friends . CONCLUSIONS This pilot trial of the TExT-MED program demonstrated increased healthy behaviors , improved diabetes self-efficacy and medication adherence , and received excellent satisfaction scores in re source -poor , inner city patients with diabetes OBJECTIVES One out of four older African American women ( OAAW ) may develop diabetes . The disproportionate number of complications suffered by OAAW with diabetes may be due in part to uncertainty about how to manage diabetes and prevent or manage complications . The purpose of this study was to test the efficacy of an individualized psychoeducational diabetes uncertainty management intervention ( DM-UMI ) directed at managing diabetes-related uncertainties and delivered by a nurse via telephone to OAAW . METHODS Sixty-eight participants with diabetes were r and omly assigned to an experimental or a control group . Participants in the experimental group received the DM-UMI , which was delivered for four weeks . The DM-UMI was composed of four strategies ( intervention variables ) : improving diabetes knowledge , patient-provider communication , problem-solving and cognitive reframing , which were expected to reduce diabetes-related uncertainty ( outcome variable ) . The control group received their usual care . Measurement occurred at two time points for all participants : at Time 1 : baseline and at Time 2 : 6 weeks post baseline . RESULTS Despite improvement in all intervention variables only problem-solving ( P < .001 ) was significantly related to decrease in uncertainty ( P = .01 ) . CONCLUSION The study suggests that teaching problem-solving skills and assisting OAAW to apply these skills , via an individualized telephone intervention , may reduce ambiguities about diabetes care AIMS To determine whether tighter cardiovascular risk factor control with structured education in individuals with type 2 diabetes ( T2DM ) and microalbuminuria benefits cardiovascular risk factors . METHODS Participants from a multiethnic population , recruited from primary care and specialist clinics were r and omised to intensive intervention with structured patient ( DESMOND model ) education ( n=94 ) or usual care by own health professional ( n=95 ) . PRIMARY OUTCOME change in HbA1c at 18months . SECONDARY OUTCOMES changes in blood pressure ( BP ) , cholesterol , albuminuria , proportion reaching risk factor targets , modelled cardiovascular risk scores . RESULTS Mean ( SD ) age and diabetes duration of participants were 61.5 ( 10.5 ) and 11.5 ( 9.3 ) years , respectively . At 18months , intensive intervention showed significant improvements in HbA1c ( 7.1(1.0 ) vs. 7.8(1.4)% , p<0.0001 ) , systolic BP ( 129(16 ) vs. 139(17 ) mmHg , p<0.0001 ) , diastolic BP ( 70(11 ) vs. 76(12 ) mmHg , p<0.001 ) , total cholesterol ( 3.7(0.8 ) vs. 4.1(0.9 ) mmol/l , p=0.001 ) . Moderate and severe hypoglycaemia was 11.2 vs. 29.0 % ; p=0.001 and 0 vs. 6.3 % ; p=0.07 , respectively . More intensive participants achieved ≥3 risk factor targets with greater reductions in cardiovascular risk scores . CONCLUSIONS Intensive intervention showed greater improvements in metabolic control and cardiovascular risk profile with lower rates of moderate and severe hypoglycaemia . Intensive glycaemic interventions should be underpinned by structured education promoting self-management in T2DM Objectives . Adherence to diabetes self care is poor for Hispanic American and African-American patients . This study examined the change in adherence over time and in response to a telemedicine intervention for elderly diabetes patients in these groups compared to white diabetes patients . We also examined whether adherence mediated the effect of the intervention on glycemic control ( A1c ) . Design . The Informatics for Diabetes Education and Telemedicine project r and omized medically underserved Medicare patients ( n=1665 ) to telemedicine case management ( televideo educator visits , individualized goal - setting /problem solving ) or usual care . Hispanic and African-American educators delivered the intervention in Spanish if needed . Main outcome measures . Annual assessment included A1c and self-reported adherence ( Summary of Diabetes Self-Care Activities scale ) . A simple model ( only time and group terms ) and a model with covariates ( e.g. , age ) were examined for baseline and 5 years of follow-up . SAS PROC Mixed was used with non-linear terms to examine mediating effects of adherence on A1c , by performing tests of the mediating path coefficients . Results . Over time , self-reported adherence improved for the treatment group compared to usual care ( p<0.001 ) . There was no significant interaction with racial/ethnic group membership , i.e. , all groups improved . However , minority subjects were consistently less adherent than whites . Also , greater comorbidity and diabetes symptoms predicted poorer adherence , greater duration of diabetes and more years of education predicted better adherence . Adherence was a significant mediator of A1c ( p<0.001 ) . Conclusions . A unique , tailored telemedicine intervention was effective in achieving improved adherence to diabetes self care . However , African-American and Hispanic American participants were less adherent than white participants at all time points despite an individualized and accessible intervention . The finding that adherence did mediate glycemic control suggests that unique interventions for minority groups may be needed to overcome this disparity Background : Type 2 diabetes affects one in five African American women older than 60 years . These women face distinct challenges in managing diabetes self-care . Therefore , tailored self-care interventions for this population need to be developed and tested . Objectives : The effectiveness of a tailored , four-visit , in-home symptom-focused diabetes intervention with and without booster telephone calls was compared with an attentional control focused on skills training for weight management and diet . Methods : African American women ( n = 180 ; > 55 years old , Type 2 diabetes mellitus > 1 year , HbA1c > 7 % ) were r and omly assigned to the intervention or attentional control condition . Half the intervention participants were assigned to also receive a telephone-delivered booster intervention . Participants were evaluated at baseline and 3 , 6 , and 9 months . Results : Baseline HbA1 was 8.3 in the intervention group ( n = 60 ) , 8.29 in the intervention with booster group ( n = 55 ) , and 8.44 in the attentional control condition ( n = 59 ) . HbA1c declined significantly in the whole sample ( 0.57 % ) with no differences between study arms . Participants in the booster arm decreased HbA1c by 0.76 % . Symptom distress , perceived quality of life , impact of diabetes , and self-care activities also improved significantly for the whole sample with no significant differences between study arms . Discussion : Parsimonious interventions of four in-person visits yielded clinical ly significant decreases in HbA1c . Although the weight and diet program was intended as an attentional control , the positive effects suggest it met a need in this population . Because the contents of both the intervention and the attentional control were effective despite different approaches , a revised symptom-focused intervention that incorporates weight and diet skills training may offer even better results OBJECTIVE The public is increasingly aware of the importance of HbA(1c ) testing , yet the vast majority of patients with diabetes do not know their HbA(1c ) status or goal . We set forth to evaluate the impact of a system that provides uniquely formatted and personalized reports of diabetes status and goals on changes in HbA(1c ) levels . RESEARCH DESIGN AND METHODS A total of 150 patients with diabetes were r and omized to receive either st and ard care or intervention inclusive of a computer-generated 11 " x 17 " color poster depicting an individual 's HbA(1c ) status and goals along with personalized steps to aid in goal achievement . All patients enrolled received diabetes education during the 3 months before enrollment . HbA(1c ) was performed at baseline and 6 months . RESULTS At baseline , there were no significant differences between patient groups in terms of age , sex , education level , race , and HbA(1c ) or lipid levels . Among patients with baseline HbA(1c ) > or = 7.0 % , there was an 8.6 % ( 0.77 % absolute ) reduction in HbA(1c ) among control subjects compared with a 17.0 % ( 1.69 % absolute ) decline in the intervention group ( P = 0.032 ) . There were no differences between the control and intervention groups with respect to the frequency of patients experiencing any decline in HbA(1c ) ( 63 vs. 69 % , P = 0.87 ) ; among these patients experiencing a decline , the most substantial reductions were seen with the control group , which had a 13.3 % ( 1.15 % absolute ) decline compared with the intervention patients , who reduced their HbA(1c ) by 24.2 % ( 2.26 % absolute reduction ; P = 0.0048 ) . At study close , 77 % of the patients had their poster displayed on their refrigerator . CONCLUSIONS This unique and personalized computer-generated intervention result ed in HbA(1c ) lowering comparable to that of hypoglycemic agents Abstract Background . Type 2 diabetes is a growing concern among medically underserved Chinese Americans . However , very few interventions have been developed or adapted for Chinese Americans with diabetes . Objective . To use a participatory research approach to evaluate the effectiveness of a culturally tailored , linguistically appropriate model for diabetes care employing health coaches to improve A1C levels among Chinese-American patients in a federally qualified health center setting . Methods . We compared change in A1C between intervention participants ( n = 46 ) , who received a health coaching intervention , and control participants ( n = 46 ) , who received usual care over a period of ~ 6 months . Results . Intervention participants showed a decrease in mean A1C at follow-up ( −0.40 % ) compared to control subjects ( + 0.04 % ) , although this difference was not statistically significant . At the 6-month follow-up , a significantly higher percentage of intervention participants ( 45.7 % ) had well-controlled A1C levels compared to control subjects ( 23.9 % ) ( P = 0.048 ) . Conclusions . It is feasible to implement a culturally tailored , linguistically appropriate teamlet model of care for Chinese Americans with type 2 diabetes . Such a model may be helpful in reducing A1C levels . Given trends in A1C improvement during a 6-month pilot , future r and omized trials with a larger sample capable of providing adequate statistical power to detect improvements are warranted BACKGROUND Cardiovascular disease ( CVD ) and diabetes account for over one third of the mortality difference between African Americans and white patients . The increased CVD risk in African Americans is due in large part to the clustering of multiple CVD risk factors . OBJECTIVES The current study is aim ed at improving CVD outcomes in African-American adults with diabetes by addressing the modifiable risk factors of systolic blood pressure , glycosylated hemoglobin , and low-density lipoprotein cholesterol . METHODS A sample of African American patients with diabetes ( N = 400 ) will receive written education material at baseline and be r and omized to one of 2 arms : ( 1 ) usual primary care or ( 2 ) nurse-administered disease-management intervention combining patient self-management support and provider medication management . The nurse administered intervention is delivered monthly over the telephone . The nurses also interacts with the primary care providers at 3 , 6 , and 9 months to provide concise patient up date s and facilitate changes in medical management . All patients are followed for 12 months after enrollment . The primary outcomes are change in glycosylated hemoglobin , systolic blood pressure , and low-density lipoprotein cholesterol over 12-months . Secondary outcomes include change in overall cardiovascular risk , aspirin use , and health behaviors . CONCLUSION Given the continued racial disparities in CVD , the proposed study could result in significant contributions to cardiovascular risk reduction in African-American patients Objective . To examine the impact of two culturally competent diabetes education methods , individual counselling and individual counselling in conjunction with group education , on nutrition adherence and glycemic control in Portuguese Canadian adults with type 2 diabetes over a three-month period . Design . The Diabetes Education Centre is located in the urban multicultural city of Toronto , Ontario , Canada . We used a three-month r and omized controlled trial design . Eligible Portuguese-speaking adults with type 2 diabetes were r and omly assigned to receive either diabetes education counselling only ( control group ) or counselling in conjunction with group education ( intervention group ) . Of the 61 patients who completed the study , 36 were in the counselling only and 25 in the counselling with group education intervention . We used a per- protocol analysis to examine the efficacy of the two educational approaches on nutrition adherence and glycemic control ; paired t-tests to compare results within groups and analysis of covariance ( ACOVA ) to compare outcomes between groups adjusting for baseline measures . The Theory of Planned Behaviour was used to describe the behavioural mechanisms that influenced nutrition adherence . Results . Attitudes , subjective norms , perceived behaviour control , and intentions towards nutrition adherence , self-reported nutrition adherence and glycemic control significantly improved in both groups , over the three-month study period . Yet , those receiving individual counselling with group education showed greater improvement in all measures with the exception of glycemic control , where no significant difference was found between the two groups at three months . Conclusions . Our study findings provide preliminary evidence that culturally competent group education in conjunction with individual counselling may be more efficacious in shaping eating behaviours than individual counselling alone for Canadian Portuguese adults with type 2 diabetes . However , larger longitudinal studies are needed to determine the most efficacious education method to sustain long-term nutrition adherence and glycemic control AIM Our objective was to evaluate the effect of training in a patient-centred intervention for GPs and practice nurses on outcomes for patients with Type II diabetes . METHODS We carried out a r and omized controlled trial within general practice s as the basis for r and omization and a before- and -after design for measures of patient outcome . A parallel process study examined the use of the method by professionals . The study was carried out in 29 general practice s in South Glamorgan who had participated for at least 2 years in a local scheme of audit and CME in relation to Type II diabetes care . The subjects were 252 Type II diabetic patients recruited by 15 experimental and 14 control practice s. The main outcome measures were changes in glycosylated haemoglobin , patient satisfaction with care and treatment , functional health status and professional ability to apply the intervention . RESULTS Professionals adopted the innovative method with enthusiasm , but after 2 years only 19 % continued to apply the method systematic ally . The trial was , therefore , unable to demonstrate significant biochemical or functional improvements . This highlights the need to underst and the factors associated with professional uptake and subsequent ability to sustain changes in behaviour . CONCLUSIONS The efficacy of this behavioural intervention remains unproved , despite its acceptability to professional staff . Detailed and prolonged development and testing of behavioural interventions is an essential first step before embarking on r and omized controlled trials which involve complex behavioural changes in professionals or patients BACKGROUND Participation in diabetic retinopathy screening is suboptimal . The Vision is Precious study ( 2001 - 2005 ) tested the hypothesis that a tailored telephone intervention in urban minority diabetes population s , offered in English or Spanish , would result in greater screening for retinopathy than a st and ard print intervention . DESIGN R and omized controlled trial SETTING / PARTICIPANTS Subjects ( N=598 ) were adults with diabetes without a dilated fundus examination ( DFE ) in > 1 year from three healthcare centers in Bronx NY . INTERVENTION A tailored telephone intervention to promote retinopathy screening compared to a st and ard print intervention over a 6-month period . MAIN OUTCOME MEASURES Documentation of a DFE within 6 months was the main outcome . Data on risk perceptions using the Risk Perception Survey for Diabetes were collected pre- and post-intervention . Electronic data bases were used to obtain hemoglobin A1c information . RESULTS Subjects were 40 % men , mean age 57 years ; 39 % reported household incomes as < $ 15 K ; 45 % reported their race as black , and 42 % reported ethnicity as Hispanic/Latino ; 23 % chose Spanish as their preferred language . Data were analyzed in 2006 . There was a 74 % increase in retinopathy screening in the telephone versus print group ( p<0.0005 ) , with no differences by intervention language or by gender . Predictors of undergoing a DFE included : telephone intervention , baseline risk-perception scores indicating less worry and more realism about diabetes complications , and the interaction of self-reported worry and being in the telephone intervention . Subjects who had poor diabetes control responded with greater success to telephone interventions . CONCLUSIONS A limited telephone intervention can improve significantly participation in retinopathy screening in a minority , low-income population . This intervention influenced risk perceptions about diabetes complications . Further research is needed to develop effective risk communications to prevent the complications of diabetes The purpose of this pilot study was to test the effectiveness of an in-home , nurse-delivered , symptom-focused teaching/counseling intervention with older rural African American women who have type 2 diabetes . Forty-one participants were r and omly assigned to either the intervention or the comparison group . Participants in the intervention showed statistically significant improvement in their medication , diet , home glucose monitoring self-care practice s , perceptions of quality of life , and distress from symptoms . Both groups evidence d improvement of HbA(1c ) levels . The intervention group achieved greater improvement , but the difference was not statistically significant . Participant satisfaction was high . Further studies should look into the cost of the intervention , as compared with that of usual care , and its long-term effects AIMS In this r and omized controlled trial we evaluated the effectiveness of medical nutritional therapy on Arab patients with Type 2 diabetes in Oman delivered by a dietitian . METHODS Patients with Type 2 diabetes ( n = 170 ) were r and omly assigned to a group receiving usual nutritional care ( n = 85 ) or a group receiving practice guidelines nutritional care ( n = 85 ) . Anthropometric ( weight , height , BMI and waist circumference ) and biochemical ( fasting blood glucose , HbA1c ) variables were measured at baseline and after each appointment . Patients were given 1 - 3 appointments with a dietitian over 6 months . RESULTS Those in the group receiving practice guidelines nutritional care ( n = 85 ) had significant changes in HbA(1c ) ( -0.8 % , P = 0.001 ) , fasting plasma glucose ( -1.3 mmol\l , P = 0.003 ) and weight ( -5.1 kg , P = 0.05 ) , whereas the patients in the usual nutritional care group ( n = 85 ) had no significant improvements in either HbA(1c ) ( -0.4 % , P = 0.248 ) or fasting plasma glucose ( -0.2 mmol/l , P = 0.638 ) during the same period . We also found a significant difference between the group receiving practice guidelines nutritional care and the usual nutritional care group , respectively , in waist circumference ( 96.9 ± 7.9 vs. 100.0 ± 8.7 cm , P = 0.019 ) , triglycerides levels ( 1.42 ± 0.58 vs. 1.98 ± 0.96 mmol\l , P = 0.001 ) , cholesterol levels ( 5.1 ± 1.0 vs. 5.5 ± 0.9 mmol/l , P = 0.009 ) and LDL cholesterol levels ( 3.58 ± 0.98 vs. 3.89 ± 0.98 mmol/l , P = 0.046 ) . CONCLUSIONS Medical nutrition therapy provided by dietitians to Arab patients with Type 2 diabetes in Oman result ed in significant improvements in anthropometric and biochemical outcomes in both the usual nutritional care group and the group receiving practice guidelines nutritional care . Subjects with Type 2 diabetes tended to do better with practice guidelines nutritional care than with usual nutritional care . Ongoing medical counselling in nutrition by a trained dietitian is important for better long-term metabolic control OBJECTIVE The Northern Plains Indians of the Cheyenne River Sioux Tribe have experienced significant lifestyle and dietary changes over the past seven generations that have result ed in increased rates of diabetes and obesity . The objective of this study was to determine if Northern Plains Indians with type 2 diabetes mellitus who are r and omized to receive culturally adapted educational lessons based on the Medicine Wheel Model for Nutrition in addition to their usual dietary education will have better control of their type 2 diabetes than a nonintervention , usual care group who received only the usual dietary education from their personal providers . DESIGN A 6-month , r and omized , controlled trial was conducted January 2005 through December 2005 , with participants r and omized to the education intervention or usual care control group . The education group received six nutrition lessons based on the Medicine Wheel Model for Nutrition . The usual care group received the usual dietary education from their personal providers . PARTICIPANTS One hundred fourteen Northern Plains Indians from Cheyenne River Sioux Tribe aged 18 to 65 years , with type 2 diabetes . METHODS Weight , body mass index ( BMI ) , hemoglobin A1c , fasting serum glucose and lipid parameters , circulating insulin , and blood pressure were measured at the beginning and completion . Diet histories , physical activity , and dietary satiety surveys were measured at baseline and monthly through completion . Differences were determined using Student t tests , chi(2 ) tests , and analysis of variance . RESULTS The education group had a significant weight loss ( 1.4+/-0.4 kg , P < or=0.05 ) and decrease in BMI ( 1.0+/-0.1 , P < or=0.05 ) from baseline to completion . The usual care group had no change in weight ( 0.5+/-0.5 kg ) or BMI ( 0.5+/-0.2 ) . There were no between group differences due to intervention in energy , carbohydrate , protein , and fat intake and physical activity . CONCLUSIONS The culturally based nutrition intervention promoted small but positive changes in weight . Greater frequency and longer duration of educational support may be needed to influence blood glucose and lipid parameters Because Latinas experience a high prevalence of type 2 diabetes and its complications , there is an urgent need to reach them with interventions that promote healthful lifestyles . This article illustrates a sequential approach that took an effective multiple-risk-factor behavior-change program and adapted it for Latinas with type 2 diabetes . Adaptation stages include ( a ) information gathering from literature and focus groups , ( b ) preliminary adaptation design , and ( c ) preliminary adaptation test . In this third stage , a pilot study finds that participants were highly satisfied with the intervention and showed improvement across diverse outcomes . Key implication s for applications include the importance of a model for guiding cultural adaptations , and the value of procedures for obtaining continuous feedback from staff and participants during the preliminary adaptation test We describe a r and omized controlled trial , the Lakota Oyate Wicozani Pi Kte ( LOWPK ) trial , which was design ed to determine whether a Web-based diabetes and nutritional intervention can improve risk factors related to cardiovascular disease ( CVD ) among a group of remote reservation – dwelling adult American Indian men and women with type 2 diabetes who are at high risk for CVD . Enrollment on a rolling basis of 180 planned participants began during 2009 ; an average 18-month follow-up was completed by June 2011 . The primary outcome variable is change in glycosylated hemoglobin level after an average 18-month follow-up period . Secondary outcome variables include changes in low-density lipoprotein cholesterol , systolic blood pressure , body mass index , and smoking status , as well as an evaluation of intervention cost-effectiveness . If effective , the LOWPK trial may serve as a guide for future chronic disease intervention trials in remote , technologically challenged setting OBJECTIVES Community Health Workers ( CHWs ) have been recommended to reduce diabetes disparities , but few robust trials of this approach have been conducted . Limitations of prior studies include : unspecified a priori outcomes ; lack of blinded outcome assessment s ; high participant attrition rates ; and lack of attention to intervention fidelity . These limitations reflect challenges in balancing method ologic rigor with the needs of vulnerable population s. The Mexican-American Trial of Community Health workers ( MATCH ) was a blinded r and omized controlled trial testing CHW efficacy in improving physiologic outcomes and self-management behaviors among Mexican-Americans with type 2 diabetes . This paper describes methods used to overcome limitations of prior studies . RESEARCH DESIGN AND METHODS The primary aim was to determine if a CHW intervention would result in significant reductions in Hemoglobin A1c and rates of uncontrolled blood pressure . 144 Mexican-Americans with diabetes were r and omized . The intervention consisted of self-management training delivered by CHWs over a 24-month period ; the comparison population received identical information via bilingual newsletter . Blinded research assistants completed assessment s at baseline , 12 months , and 24 months post-r and omization . RESULTS The MATCH cohort was characterized by low acculturation and socioeconomic status . Study participants had low rates of medication adherence and glucose monitoring . 70 % had poor glycemic control with A1c levels over 7.0 , and 57.3 % had blood pressures worse than ADA target levels ( < 130/80 ) . CONCLUSIONS MATCH preserved community sensitivity and method ologic rigor . The study 's attention to intervention fidelity , behavioral attention control , blinded outcomes assessment , and strategies to enhance participant retention can be replicated by research ers testing culturally-tailored CHW interventions Aims We tested the hypothesis that enhanced care for diabetes , tailored to the needs of the South Asian community with Type 2 diabetes , would improve risk factors for diabetic vascular complications and ultimately reduce morbidity and mortality OBJECTIVES We evaluated a community-based , translational lifestyle program to reduce diabetes risk in lower-socioeconomic status ( SES ) and ethnic minority adults . METHODS Through an academic-public health department partnership , community-dwelling adults at risk for diabetes were r and omly assigned to individualized lifestyle counseling delivered primarily via telephone by health department counselors or a wait-list control group . Primary outcomes ( 6 and 12 months ) were fasting glucose level , triglycerides , high- and low-density lipoprotein cholesterol , weight , waist circumference , and systolic blood pressure . Secondary outcomes included diet , physical activity , and health-related quality of life . RESULTS Of the 230 participants , study retention was 92 % . The 6-month group differences for weight and triglycerides were significant . The intervention group lost 2 pounds more than did the control group ( P=.03 ) and had decreased triglyceride levels ( difference in change , 23 mg/dL ; P=.02 ) . At 6 months , the intervention group consumed 7.7 fewer grams per day of fat ( P=.05 ) and more fruits and vegetables ( P=.02 ) than did control participants . CONCLUSIONS Despite challenges design ing effective translational interventions for lower-SES and minority communities , this program modestly improved some diabetes risk factors . Thus , individualized , telephone-based models may be a promising alternative to group-based interventions OBJECTIVE To assess the effectiveness of a culturally sensitive , structured education programme ( CSSEP ) on biomedical , knowledge , attitude and practice measures among Arabs with type two diabetes . RESEARCH DESIGN S AND METHODS A total of 430 patients with type II diabetes mellitus living in Doha , Qatar were enrolled in the study . They were r and omized to either intervention ( n = 215 ) or a control group ( n = 215 ) . A baseline and one-year interval levels of biomedical variables including HbA1C , lipid profile , urine for microalbuminuria ; in addition to knowledge , attitude and practice ( KAP ) scores were prospect ively measured . The intervention was based on theory of empowerment , health belief models and was culturally sensitive in relation to language ( Arabic ) , food habits and health beliefs . It consisted of four educational sessions for each group of patients ( 10 - 20 patients per session ) , lasting for 3 - 4 h. The first session discussed diabetes pathophysiology and complications ; while the second session discussed healthy life style incorporating the Idaho plate method ; and the third session dealt with exercise benefits and goal setting and the fourth session concentrated enhancing attitude and practice using counselling techniques . Outcomes were assessed at base line and 12 months after intervention . RESULTS After 12 months participation in the intervention was shown to have led to a statistically significant reduction in HbA1C in the ( CSSEP ) group ( -0.55 mmol/L , P = 0.012 ) , fasting blood sugar ( -0.92 mmol/L , P = 0.022 ) , body mass index ( 1.70 , P = 0.001 ) and albumin/creatinine ratio ( -3.09 , P < 0.0001 ) but not in the control group . The intervention group also had improvement in Diabetes knowledge ( 5.9 % , P < 0.0001 ) , attitude ( 6.56 % , P < 0.0001 ) , and practice ( 6.52 % , P = 0.0001 ) . CONCLUSION This study demonstrates the effectiveness of culturally sensitive , structured , group-based diabetes education in enhancing biomedical and behavioural outcomes in Diabetic patients A low – glycemic index ( GI ) diet is effective in lowering A1C in diabetic patients ( 1–3 ) . However , most research is from Western countries , where potato and wheat are the main sources of carbohydrates . A GI-based nutrition education program , design ed for people who consume white rice ( a high-GI food ) as the staple , has not yet been studied . We developed a low-GI dietary regimen based on Japanese foods . This study aim ed to evaluate whether GI-based nutrition education improves blood glucose control more than a conventional nutrition education in participants with type 2 diabetes or impaired fasting glucose . We conducted a 3-month , r and omized , controlled , parallel-group trial . Participant inclusion criteria were as follows : 1 ) fasting plasma glucose ( FPG ) between 110 and 160 mg/dl or A1C between 5.8 and 8.0 % ( 4 ) and 2 ) nonusage of any hypoglycemic drugs . All participants attended one group session on conventional nutritional education at baseline . Each participant was then r and omly assigned to either GI-based or conventional nutrition education ; four individual sessions followed ( 2nd week and 1st , 2nd , and 3rd month ) . Conventional nutritional education was based on the Japan Diabetes Society guidelines ( 4 ) and focused on lowering total energy intake , mainly Background Patients with type 2 diabetes mellitus ( T2D ) have an increased risk of cardiovascular disease and mortality compared to the background population . Observational studies report an association between reduced blood glucose and reduced risk of both micro- and macrovascular complications in patients with T2D . Our previous systematic review of intensive glycaemic control versus conventional glycaemic control was based on 20 r and omised clinical trials that r and omised 29 , 986 participants with T2D . We now report our up date d review . Objectives To assess the effects of targeted intensive glycaemic control compared with conventional glycaemic control in patients with T2D . Search methods Trials were obtained from search es of The Cochrane Library , MEDLINE , EMBASE , Science Citation Index Exp and ed , LILACS , and CINAHL ( all until December 2012 ) . Selection criteria We included r and omised clinical trials that prespecified targets of intensive glycaemic control versus conventional glycaemic control targets in adults with T2D . Data collection and analysis Two authors independently assessed the risk of bias and extracted data . Dichotomous outcomes were assessed by risk ratios ( RR ) and 95 % confidence intervals ( CI ) . Health-related quality of life and costs of intervention were assessed with st and ardized mean differences ( SMD ) and 95 % Cl . Main results Twenty-eight trials with 34,912 T2D participants r and omised 18,717 participants to intensive glycaemic control versus 16,195 participants to conventional glycaemic control . Only two trials had low risk of bias on all risk of bias domains assessed . The duration of the intervention ranged from three days to 12.5 years . The number of participants in the included trials ranged from 20 to 11,140 . There were no statistically significant differences between targeting intensive versus conventional glycaemic control for all-cause mortality ( RR 1.00 , 95 % CI 0.92 to 1.08 ; 34,325 participants , 24 trials ) or cardiovascular mortality ( RR 1.06 , 95 % CI 0.94 to 1.21 ; 34,177 participants , 22 trials ) . Trial sequential analysis showed that a 10 % relative risk reduction could be refuted for all-cause mortality . Targeting intensive glycaemic control did not show a statistically significant effect on the risks of macrovascular complications as a composite outcome in the r and om-effects model , but decreased the risks in the fixed-effect model ( r and om RR 0.91 , 95 % CI 0.82 to 1.02 ; and fixed RR 0.93 , 95 % CI 0.87 to 0.99 ; P = 0.02 ; 32,846 participants , 14 trials ) . Targeting intensive versus conventional glycaemic control seemed to reduce the risks of non-fatal myocardial infa rct ion ( RR 0.87 , 95 % CI 0.77 to 0.98 ; P = 0.02 ; 30,417 participants , 14 trials ) , amputation of a lower extremity ( RR 0.65 , 95 % CI 0.45 to 0.94 ; P = 0.02 ; 11,200 participants , 11 trials ) , as well as the risk of developing a composite outcome of microvascular diseases ( RR 0.88 , 95 % CI 0.82 to 0.95 ; P = 0.0008 ; 25,927 participants , 6 trials ) , nephropathy ( RR 0.75 , 95 % CI 0.59 to 0.95 ; P = 0.02 ; 28,096 participants , 11 trials ) , retinopathy ( RR 0.79 , 95 % CI 0.68 to 0.92 ; P = 0.002 ; 10,300 participants , 9 trials ) , and the risk of retinal photocoagulation ( RR 0.77 , 95 % CI 0.61 to 0.97 ; P = 0.03 ; 11,212 participants , 8 trials ) . No statistically significant effect of targeting intensive glucose control could be shown on non-fatal stroke , cardiac revascularization , or peripheral revascularization . Trial sequential analyses did not confirm a reduction of the risk of non-fatal myocardial infa rct ion but confirmed a 10 % relative risk reduction in favour of intensive glycaemic control on the composite outcome of microvascular diseases . For the remaining microvascular outcomes , trial sequential analyses could not establish firm evidence for a 10 % relative risk reduction . Targeting intensive glycaemic control significantly increased the risk of mild hypoglycaemia , but substantial heterogeneity was present ; severe hypoglycaemia ( RR 2.18 , 95 % CI 1.53 to 3.11 ; 28,794 participants , 12 trials ) ; and serious adverse events ( RR 1.06 , 95 % CI 1.02 to 1.10 ; P = 0.007 ; 24,280 participants , 11 trials ) . Trial sequential analysis for a 10 % relative risk increase showed firm evidence for mild hypoglycaemia and serious adverse events and a 30 % relative risk increase for severe hypoglycaemia when targeting intensive versus conventional glycaemic control . Overall health-related quality of life , as well as the mental and the physical components of health-related quality of life did not show any statistical significant differences . Authors ' conclusions Although we have been able to exp and the number of participants by 16 % in this up date , we still find paucity of data on outcomes and the bias risk of the trials was mostly considered high . Targeting intensive glycaemic control compared with conventional glycaemic control did not show significant differences for all-cause mortality and cardiovascular mortality . Targeting intensive glycaemic control seemed to reduce the risk of microvascular complications , if we disregard the risks of bias , but increases the risk of hypoglycaemia and serious adverse events BACKGROUND In this study , our main goal was to determine whether an integrated , community-based model of care using culturally appropriate health-care assistants to manage hypertension in Māori and Pacific patients with diabetes and chronic kidney disease ( CKD ) is more effective than conventional care in achieving blood pressure ( BP ) targets and delaying progression of cardiac and renal end-organ damage . METHODS Sixty-five Māori and Pacific patients ( aged 47 - 75 years ) with type 2 diabetes , moderate CKD ( > 0.5 g proteinuria/day , serum creatinine 130 - 300 µmol/l ) and hypertension were r and omized to usual care ( n = 32 ) or community/intervention care ( n = 33 ) for 12 months . Community care patients were visited monthly by a nurse-led health-care assistant for BP measurement . Antihypertensives were adjusted using a stepwise protocol , aim ing for a BP < 130/80 mmHg . Office BP and renal and echocardiographic parameters were measured at baseline and 12 months . RESULTS Baseline characteristics including office BP , renal and echocardiographic parameters , and number of antihypertensives were well matched in both groups . By 12 months , the community care patients had achieved a significantly greater reduction in office systolic BP ( -21 ± 26 mmHg vs -12 ± 20 mmHg , P = 0.04 ) and in 24-h urine protein ( -1.4 ± 2.6 g vs + 0.1 ± 2.8 g , P = 0.04 ) . The number of prescribed antihypertensives was greater in these patients at 12 months ( 3.4 ± 1.1 vs 2.3 ± 1.0 , P < 0.01 ) . Left ventricular ( LV ) mass and left atrial ( LA ) volume progressed in the usual care group , but not in the intervention group ( P < 0.05 ) . CONCLUSION This novel model of care is more effective than conventional care in lowering systolic BP and reducing cardiac and renal end-organ damage in these high-risk patients OBJECTIVE To provide the specific weight loss outcomes for African-American , Hispanic , and white men and women in the lifestyle and metformin treatment arms of the Diabetes Prevention Program ( DPP ) by race-gender group to facilitate research ers translating similar interventions to minority population s , as well as provide realistic weight loss expectations for clinicians . METHODS AND PROCEDURES Secondary analyses of weight loss of 2,921 overweight participants ( 22 % black ; 17 % Hispanic ; 61 % white ; and 68 % women ) with impaired glucose tolerance r and omized in the DPP to intensive lifestyle modification , metformin or placebo . Data over a 30-month period are examined for comparability across treatment arms by race and gender . RESULTS Within lifestyle treatment , all race-gender groups lost comparable amounts of weight with the exception of black women who exhibited significantly smaller weight losses ( P < 0.01 ) . For example , at 12 months , weight losses for white men ( -8.4 % ) , white women ( -8.1 % ) , Hispanic men ( -7.8 % ) , Hispanic women ( -7.1 % ) , and black men ( -7.1 % ) were similar and significantly higher than black women ( -4.5 % ) . In contrast , within metformin treatment , all race-gender groups including black women lost similar amounts of weight . Race-gender specific mean weight loss data are provided by treatment arm for each follow-up period . DISCUSSION Diminished weight losses were apparent among black women in comparison with other race-gender groups in a lifestyle intervention but not metformin , underscoring the critical nature of examining sociocultural and environmental contributors to successful lifestyle intervention for black women AIMS To observe the effects of active glucose monitoring , alteration of drug dosage and timing , dietary counselling and patient education in the occurrence of acute diabetic complications in fasting individuals with diabetes during the month of Ramadan . METHODS This prospect i ve study was conducted at the outpatient department of the Baqai Institute of Diabetology and Endocrinology . Two educational sessions , one about drug dosage and timing alteration and glucose monitoring , and the other about dietary and lifestyle modifications , were given to the patients by a doctor and a dietician , respectively . Patients who had been recruited were advised to note their blood glucose readings on a chart for at least 15 fasting days , twice a day with at least one reading in the fasting state . RESULTS A total of 3946 readings were obtained in 110 subjects ; 82 readings were in the hypoglycaemic range , and there were 22 episodes of symptomatic hypoglycaemia and 60 episodes of biochemical hypoglycaemia observed in 27 patients . Seven patients experienced symptomatic hypoglycaemia , whereas 20 patients had biochemical hypoglycaemia . Symptomatic hypoglycaemic episodes showed a downward trend from weeks 1 to 4 . The highest frequencies of hypo- and hyperglycaemic episodes were observed pre-dawn . None of the patients developed diabetic ketoacidosis or hyperglycaemic hyperosmolar state . CONCLUSION We observed that , with active glucose monitoring , alteration of drug dosage and timing , dietary counselling and patient education , the majority of the patients did not have any serious acute complications of diabetes during Ramadan This study examines the validity of a Spanish- language dietary behaviors self-report question naire ( The Latino Dietary Behaviors Question naire [ LDBQ ] ) for Latinos with diabetes . The sample ( n=252 ) was Spanish-speaking , female ( 77 % ) , middle-aged ( mean age 55 years ) , low education ( 56 % < 8th grade education ) , and low income ( 50 % < $ 10,000 annual household income ) . Baseline and 12-month measures were collected as part of a r and omized clinical trial . LDBQ reliability , validity , and sensitivity to change over time were evaluated using exploratory factor analysis ; internal consistency analysis ; and correlation analysis using baseline and change scores for LDBQ , 3-day 24-hour dietary recall nutrient mean , and clinical measures . Cronbach 's αs were moderate . Four factors were identified at both time points . Significant baseline correlations ( r ) were found for LDBQ total scores ; factor scores ; and energy intake ( r=-0.29 to -0.34 ) , total dietary fiber ( r=0.19 ) , sodium ( r=-0.24 to -0.30 ) , percent energy from total fat ( r=-0.16 ) , fat subtypes ( r=-0.16 to 0.15 ) , and percent energy from protein ( r=0.17 ) . Twelve-month data produced a similar pattern . T tests of LDBQ change scores showed significantly greater change in dietary behaviors for the intervention group than for the control group , t(135)=-4.17 , P<0.01 . LDBQ change scores correlated significantly with mean 24-hour nutrient intake and a subset of clinical measures , but were not associated with clinical change scores ( except high-density lipoprotein cholesterol ) . The LDBQ is a useful tool to assess and target behaviors for change and assess intervention effects Purpose The purpose of this study was to evaluate the impact of an innovative intervention that utilized a certified medical assistant with specific diabetes training to work with a multidisciplinary diabetes care team to help provide basic diabetes education and self-care support in low-income minority population s with type 2 diabetes . Methods Enrolled participants were r and omized to either the medical assistant coaching ( MAC ) group ( N = 25 ) or the treatment as usual ( TAU ) group ( N = 25 ) . Deidentified data was obtained on a matched no contact control ( NCC ) group ( N = 50 ) . Results Analysis of covariance ( ANCOVA ) comparisons revealed no significant differences between the 3 groups on A1C , but a trend was observed . A1Cs decreased across time for the MAC group , while increasing for the TAU and NCC groups . ANCOVA comparisons also indicated that the MAC group experienced significantly greater increases in perceived empowerment and a larger , although non-significant , reduction in perceived diabetes related problems than the TAU group . Conclusions This r and omized controlled pilot study suggests that the inclusion of a medical assistant self-care coach as part of the diabetes care team holds promise in improving outcomes and should be further examined in a large-scale study Type 2 diabetes disproportionately affects American Indians and Alaska Natives ( AI/ANs ) . In the larger population , patient self-management has become an increasing focus of the health care system to help reduce the impact of diabetes . However , little is known about patient self-management programs design ed for AI/ANs . This study reports on the feasibility of implementing the Stanford Internet Diabetes Self-Management Workshop within the AI/AN population using a participatory research approach . This is a continuation of self-management studies to assist in meeting the needs of both patients and the health care system for health services that are effective ( evidence based ) , efficient , and culturally appropriate . To our knowledge , this is the first study examining the effectiveness of an Internet-based diabetes patient self-management program among AI/ANs . This article reports on a pilot for a larger r and omized study that is ongoing AIMS To analyze the effects of 8 weeks of aerobic walking using a heart rate monitor ( HRM ) and pedometer for monitoring exercise intensity on glycemic outcomes , fasting blood glucose ( FBG ) , cardiovascular fitness and well-being in type 2 diabetes patients . METHODS Forty adults with type 2 diabetes were r and omly allocated to an 8-week supervised program of walking using heart rate monitor and pedometer ( group A=20 ) and control group ( group B=20 ) . All outcomes were determined at baseline and after the 8-week training period . RESULTS The exercise training program result ed in a 9.7 % ( P<0.05 ) improvement in group A. Fasting blood glucose level decreased significantly by 37 % in group A ( P<0.05 ) . Body mass index ( BMI ) ratio decreased by 3.9 % in group A and increased by 2.2 % in group B. General well-being ( GWB ) improved by 28.8 % ( P<0.05 ) in the exercising group and there was an improvement in all parameters associated with cardiovascular health . CONCLUSION Monitoring an exercise program using a heart rate monitor and pedometer was effective and decreased the level of HbA1c , FBG , BMI and improved general well-being . Further using HRM helped us to attribute all improvements to the exercise intensity that we used in our study OBJECTIVE To inform the refinement of a culturally adapted diabetes intervention , we evaluated acculturation 's association with variables at several sequential steps : baseline measures of diet and physical activity , intervention engagement , putative mediators ( problem solving and social re sources ) , and outcomes ( fat consumption and physical activity ) . METHOD Latina women ( N = 280 ) recruited from health organizations were r and omly assigned to a culturally adapted lifestyle intervention ( ¡ Viva Bien ! ) or usual care . A brief version of the Acculturation Rating Scale for Mexican Americans-II ( ARSMA-II ) acculturation scales ( Anglo and Latina orientations ) was administered at baseline . Assessment s at baseline , 6 months , and 12 months included social supportive re sources for diet and exercise , problem solving , saturated fat consumption , and physical activity . RESULTS Latina orientation was negatively related to saturated fat intake and physical activity at baseline . Latina orientation also was positively related to session attendance during Months 6 - 12 of the intervention . Independent of 6-month intervention effects , Anglo orientation was significantly positively related to improvements in problem solving and dietary supportive re sources . Anglo orientation related negatively to improved physical activity at 6 and 12 months . There were no Acculturation × Intervention interactions on putative mediators or outcomes . CONCLUSION The cultural adaptation process was successful in creating an engaging and effective intervention for Latinas at all levels of acculturation . However , independent of intervention effects , acculturation was related to putative mediating variables ( problem solving and social re sources ) and an outcome variable ( physical activity ) , an indication of acculturation 's general influence on lifestyle and coping factors |
13,267 | 29,066,053 | The review clearly indicates that characteristics of insomnia may not be limited to sleep .
Reports suggest that at least some individuals with insomnia may deviate from people without sleep complaints with respect to demographics , mental and physical health , childhood trauma , life events , fatigue , sleepiness , hyperarousal , hyperactivity , other sleep disorders , lifetime sleep history , chronotype , depression , anxiety , mood , quality of life , personality , happiness , worry , rumination , self-consciousness , sensitivity , dysfunctional beliefs , self-conscious emotion regulation , coping , nocturnal mentation , wake resting-state mentation , physical activity , food intake , temperature perception and hedonic evaluation . | Meta-analyses and systematic review s have reported surprisingly few consistent insomnia-characteristics with respect to cognitions , mood , traits , history of life events and family history .
One interpretation of this limited consistency is that different subtypes of insomnia exist , each with its own specific multivariate profile of characteristics .
Because previously unrecognized subtypes will be differentially represented in individual studies and dilute effect sizes of subtype-dependent characteristics of importance , they are unlikely to be reported consistently in individual studies , let alone in meta-analyses .
This review therefore aims to complement meta-analyses by listing previously reported psychometric characteristics of insomnia , irrespective of the degree of consistency over studies . | This study consisted of secondary analyses of data from 2 r and omized clinical trials to test whether pretherapy cognitions predict CBT outcomes . The sample consisted of 155 primary insomnia patients with sleep maintenance complaints . Of these , 98 were r and omized to CBT , 23 were assigned to progressive muscle relaxation training ( PMR ) , and 34 were assigned to a control ( sham therapy or wait-list ) condition ( CON ) . All patients completed the Dysfunctional Beliefs and Attitudes about Sleep Scale ( DBAS ) , a sleep-related Self-Efficacy Scale ( SES ) and nightly sleep diaries for 2 weeks prior to receiving their assigned treatment . They then completed sleep diaries throughout an 8-week acute treatment period and during a 2-week period at a posttherapy follow-up . A subset of the sample ( n=67 ) also completed polysomnography immediately before and after completing their assigned treatment . Preliminary regression analyses conducted with a small subset ( n=15 ) of the patients receiving CBT showed those with relatively high levels of unhelpful sleep-related beliefs ( Type 1 patients ) , as reflected by their pretherapy responses to the DBAS and SES question naires , showed markedly greater reductions in nocturnal wakefulness in response to CBT than did those ( Type 2 patients ) reporting less pronounced sleep-related beliefs . Given these findings , we used the regression equation derived from our initial analyses to dichotomize our entire sample into Type 1 ( n=82 ; 52.9 % ) and Type 2 ( n=73 ; 47.1 % ) subgroups . Subsequent comparisons showed CBT-treated Type 1 patients had significantly less wake time after sleep onset during most of the 8-week treatment phase than did the Type 1 and 2 individuals assigned to either PMR or CON . Relative to patients assigned to the PMR and CON conditions , CBT-treated Type 1 patients showed better performance across multiple subjective and objective benchmarks of clinical ly significant improvement , whereas the CBT-treated Type 2 patients did not . Results suggest that insomnia patients ' pretherapy cognitive dispositions predict CBT outcome , and those with a pronounced sense of sleep-related helplessness are best suited for this treatment which targets this cognitive stance In a prospect ive-longitudinal study of a representative birth cohort , we tested why stressful experiences lead to depression in some people but not in others . A functional polymorphism in the promoter region of the serotonin transporter ( 5-HT T ) gene was found to moderate the influence of stressful life events on depression . Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms , diagnosable depression , and suicidality in relation to stressful life events than individuals homozygous for the long allele . This epidemiological study thus provides evidence of a gene-by-environment interaction , in which an individual 's response to environmental insults is moderated by his or her genetic makeup OBJECTIVE The purpose of this study was to examine whether there is a bidirectional relationship between , on one h and , anxiety and depression and , on the other h and , insomnia over the course of a year . METHODS A r and omly selected sample of 3000 participants from the general population filled out a baseline survey ( N=1812 ) and a 1-year follow-up survey ( N=1498 ) on anxiety , depression , and insomnia . RESULTS On cross-sectional analyses , bivariate correlations showed that anxiety , depression , and insomnia were significantly intercorrelated ( varphi=.31-.54 ) . On prospect i ve analyses , logistic regression analyses demonstrated that anxiety at baseline [ odds ratio (OR)=4.27 ( 8 % of variance ) ] and depression at baseline [ OR=2.28 ( 2 % of variance ) ] were related to new cases of insomnia on follow-up . Furthermore , insomnia at baseline was related to new episodes of high anxiety and high depression on follow-up [ OR=2.30 ( 2 % of variance ) and OR=3.51 ( 4 % of variance ) , respectively ] . CONCLUSION Evidence suggests that there is a bidirectional relationship between , on one h and , anxiety and depression and , on the other h and , insomnia . This suggests that anxiety , depression , and insomnia are intertwined over time , implying implication s for theoretical conceptualizations and interventions The aims of this study were to measure the error in sleep estimation in normal controls and subjects with primary insomnia to establish the minimum amount of sleep needed for reliable subjective estimation and to depict the distribution of the error in sleep estimation in both groups . A two-step retrospective ( study 1 ) and prospect i ve ( study 2 ) validation study was carried out . Study 1 included 288 normal subjects [ 176 females and 112 males , mean age 58.5 years , st and ard deviation ( SD ) 7.23 ] . Study 2 included 159 patients ( 98 females and 61 males ; mean age 49.1 years , SD 12.71 ) with primary insomnia . Participants underwent a full-night polysomnographic study , followed by a morning assessment of subjective sleep parameters . A misperception index ( MI ) was computed using the following formula : MI = [ objective total sleep time (oTST)-subjective total sleep time (sTST)]/oTST . The statistical properties of this index were analysed in detail in both groups . In controls , the Bl and -Altman test demonstrated the reliability of this index for values of oTST > 120 min . Healthy subjects estimated their sleep time correctly , while insomniacs largely underestimated their sleep time . Statistical analysis of the distribution of MI in insomnia patients disclosed the presence of two subgroups , one with moderate sleep misperception ( 132 patients ) and the other with high sleep misperception ( 27 patients ) . The latter presented MI values > or=0.9 , exhibiting statistical properties different from those with MI < 0.9 and from normal subjects . The MI gives a reliable and immediate description of sleep misperception in healthy and insomnia subjects . Its application supports the existence of the high misperception of insomnia as a separate pathological entity STUDY OBJECTIVE To examine the association between depression and three subtypes of insomnia , namely , difficulty initiating sleep ( DIS ) , early morning awakening ( EMA ) , and difficulty maintaining sleep ( DMS ) . DESIGN Cross-sectional and longitudinal study . SETTING Community dwellers in Japan . PARTICIPANTS Nationally representative sample s of adults aged 65 and over ( total N=4,997 ) were selected by a multistage stratified r and om sampling method in 1999 and were interviewed face-to-face in 1999 , 2001 , 2003 , and 2006 . Those who responded to the 3rd survey conducted in 2003 and the 4th survey conducted in 2006 were used in this study . MEASUREMENT AND RESULTS Depression was evaluated according to the 11-item short form of the CES-D scale at 2 points in time . Insomnia subtypes were assessed by self-reported measures . A logistic regression was employed to examine the association between insomnia subtypes and the presence of depression , controlling for relevant factors . A cross-sectional analysis based on the 2003 data demonstrated statistically significant odds ratios ( ORs ) for DIS and EMA . In the longitudinal study , DIS at the time of the 3rd survey was found to be significantly related to the presence of depression at the time of the 4th survey , with an odds ratio ( 95%CI ) of 1.592 ( 1.012 to 2.504 ) . EMA ( OR 1.070 ; 95 % CI , 0.664 to 1.723 ) and DMS ( OR 1.215 ; 95 % CI , 0.860 to 1.716 ) , however , were not found to be significantly related to the presence of depression . CONCLUSION The longitudinal study revealed a statistically significant relationship , controlling for other relevant factors , between DIS and the presence of depression three years later , but not between EMA or DMS and depression . Based on our findings , we recommend that the association between insomnia subtypes and depression be studied longitudinally in clinical setting Background Psychiatric distress and insomnia symptoms exhibit similar patterning by gender and socioeconomic position . Prospect i ve evidence indicates a bi-directional relationship between psychiatric distress and insomnia symptoms so similarities in social patterning may not be coincidental . Treatment for insomnia can also improve distress outcomes . We investigate the extent to which the prospect i ve patterning of distress over 20 years is associated with insomnia symptoms over that period . Methods 999 respondents to the Twenty-07 Study had been followed for 20 years from approximately ages 36–57 ( 73.2 % of the living baseline sample ) . Psychiatric distress was measured using the GHQ-12 at baseline and at 20-year follow-up . Gender and social class were ascertained at baseline . Insomnia symptoms were self-reported approximately every five years . Latent class analysis was used to classify patterns of insomnia symptoms over the 20 years . Structural Equation Models were used to assess how much of the social patterning of distress was associated with insomnia symptoms . Missing data was addressed with a combination of multiple-imputation and weighting . Results Patterns of insomnia symptoms over 20 years were classified as either healthy , episodic , developing or chronic . Respondents from a manual social class were more likely to experience episodic , developing or chronic patterns than those from non-manual occupations but this was mostly explained by baseline psychiatric distress . People in manual occupations experiencing psychiatric distress however were particularly likely to experience chronic patterns of insomnia symptoms . Women were more likely to experience a developing pattern than men , independent of baseline distress . Psychiatric distress was more persistent over the 20 years for those in manual social classes and this effect disappeared when adjusting for insomnia symptoms . Irrespective of baseline symptoms , women , and especially those in a manual social class , were more likely than men to experience distress at age 57 . This overall association for gender , but not the interaction with social class , was explained after adjusting for insomnia symptoms . Sensitivity analyses supported these findings . Conclusions Gender and socioeconomic inequalities in psychiatric distress are strongly associated with inequalities in insomnia symptoms . Treatment of insomnia or measures to promote healthier sleeping may therefore help alleviate inequalities in psychiatric distress BACKGROUND AND PURPOSE To estimate the prevalence of insomnia symptoms and syndrome in the general population , describe the types of self-help treatments and consultations initiated for insomnia , and examine help-seeking determinants . PATIENTS AND METHODS A r and omly selected sample of 2001 French-speaking adults from the province of Quebec ( Canada ) responded to a telephone survey about sleep , insomnia , and its treatments . RESULTS Of the total sample , 25.3 % were dissatisfied with their sleep , 29.9 % reported insomnia symptoms , and 9.5 % met criteria for an insomnia syndrome . Thirteen percent of the respondents had consulted a healthcare provider specifically for insomnia in their lifetime , with general practitioners being the most frequently consulted . Daytime fatigue ( 48 % ) , psychological distress ( 40 % ) , and physical discomfort ( 22 % ) were the main determinants prompting individuals with insomnia to seek treatment . Of the total sample , 15 % had used at least once herbal/dietary products to facilitate sleep and 11 % had used prescribed sleep medications in the year preceding the survey . Other self-help strategies employed to facilitate sleep included reading , listening to music , and relaxation . CONCLUSIONS These findings confirm the high prevalence of insomnia in the general population . While few insomnia sufferers seek professional consultations , many individuals initiate self-help treatments , particularly when daytime impairments such as fatigue become more noticeable . Improved knowledge of the determinants of help-seeking behaviors could guide the development of effective public health prevention and intervention programs to promote healthy sleep STUDY OBJECTIVES To determine whether the frequency spectrum of the sleep EEG is a physiologic correlate of 1 ) the degree to which individuals with persistent primary insomnia ( PPI ) underestimate their sleep time compared with the traditionally scored polysomnogram ( PSG ) and 2 ) the sleep complaints in PPI subjects who have relatively long traditionally scored PSG sleep times and relatively greater underestimation of sleep time . DESIGN We compared EEG frequency spectra from REM and NREM sleep in PPI subjects subtyped as subjective insomnia sufferers ( those with relatively long total sleep time and relative underestimation of sleep time compared with PSG ) , and objective insomnia sufferers ( those with relatively short PSG total sleep time ) with EEG frequency spectra in normals . We also studied the correlation between these indices and the degree of underestimation of sleep . Further , we determined the degree to which sleep EEG indexes related to sleep complaints . SETTING Duke University Medical Center Sleep Laboratory . PARTICIPANTS Normal ( N=20 ) , subjective insomnia ( N=12 ) , and objective insomnia ( N=18 ) subjects . INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Lower delta and greater alpha , sigma , and beta NREM EEG activity were found in the patients with subjective insomnia but not those with objective insomnia , compared with the normal subjects . These results were robust to changes in the subtyping criteria . No effects were found for REM spectral indexes . Less delta non- REM EEG activity predicted greater deviation between subjective and PSG estimates of sleep time across all subjects . For the subjective insomnia subjects , diminished low-frequency and elevated higher frequency non- REM EEG activity was associated with their sleep complaints . CONCLUSIONS NREM EEG frequency spectral indexes appear to be physiologic correlates of sleep complaints in patients with subjective insomnia and may reflect heightened arousal during sleep Objective Although stress is often presumed to cause sleep disturbances , little research has documented the role of stressful life events in primary insomnia . The present study examined the relationship of stress and coping skills , and the potential mediating role of presleep arousal , to sleep patterns in good sleepers and insomnia sufferers . Methods The sample was composed of 67 participants ( 38 women , 29 men ; mean age , 39.6 years ) , 40 individuals with insomnia and 27 good sleepers . Subjects completed prospect i ve , daily measures of stressful events , presleep arousal , and sleep for 21 consecutive days . In addition , they completed several retrospective and global measures of depression , anxiety , stressful life events , and coping skills . Results The results showed that poor and good sleepers reported equivalent numbers of minor stressful life events . However , insomniacs rated both the impact of daily minor stressors and the intensity of major negative life events higher than did good sleepers . In addition , insomniacs perceived their lives as more stressful , relied more on emotion-oriented coping strategies , and reported greater presleep arousal than good sleepers . Prospect i ve daily data showed significant relationships between daytime stress and nighttime sleep , but presleep arousal and coping skills played an important mediating role . Conclusions The findings suggest that the appraisal of stressors and the perceived lack of control over stressful events , rather than the number of stressful events per se , enhance the vulnerability to insomnia . Arousal and coping skills play an important mediating role between stress and sleep . The main implication of these results is that insomnia treatments should incorporate clinical methods design ed to teach effective stress appraisal and coping skills STUDY OBJECTIVES ( 1 ) To describe the prevalence and prospect i ve course of insomnia in a representative young-adult sample and ( 2 ) to describe the cross-sectional and longitudinal associations between insomnia and depression . DESIGN Longitudinal cohort study . SETTING Community of Zurich , Switzerl and . PARTICIPANTS Representative stratified population sample . INTERVENTIONS None . MEASUREMENTS AND RESULTS The Zurich Study prospect ively assessed psychiatric , physical , and sleep symptoms in a community sample of young adults ( n=591 ) with 6 interviews spanning 20 years . We distinguished 4 duration -based subtypes of insomnia : 1-month insomnia associated with significant distress , 2- to 3-week insomnia , recurrent brief insomnia , and occasional brief insomnia . The annual prevalence of 1-month insomnia increased gradually over time , with a cumulative prevalence rate of 20 % and a greater than 2-fold risk among women . In 40 % of subjects , insomnia developed into more chronic forms over time . Insomnia either with or without comorbid depression was highly stable over time . Insomnia lasting 2 weeks or longer predicted major depressive episodes and major depressive disorder at subsequent interviews ; 17 % to 50 % of subjects with insomnia lasting 2 weeks or longer developed a major depressive episode in a later interview . " Pure " insomnia and " pure " depression were not longitudinally related to each other , whereas insomnia comorbid with depression was longitudinally related to both . CONCLUSIONS This longitudinal study confirms the persistent nature of insomnia and the increased risk of subsequent depression among individuals with insomnia . The data support a spectrum of insomnia ( defined by duration and frequency ) comorbid with , rather than secondary to , depression Dysfunctional beliefs and attitudes about sleep are presumed to play an important mediating role in perpetuating insomnia . The present study evaluated the impact of cognitive-behavioral and pharmacological treatments for insomnia on sleep-related beliefs and attitudes and the relationship between those changes and sleep improvements . The participants were older adults with chronic and primary insomnia . They received cognitive-behavior therapy ( CBT ) , pharmacotherapy ( PCT ) , combined CBT+PCT ( COMB ) , or a medication placebo ( PLA ) . In addition to daily sleep diaries and sleep laboratory measures , the participants completed the dysfunctional beliefs and attitudes about sleep scale ( DBAS ) at baseline and posttreatment , and at 3- , 12- and 24-month follow-up assessment s. The results showed that CBT and COMB treatments produced greater improvements of beliefs and attitudes about sleep at posttreatment than PCT and PLA . Reductions of DBAS scores were significantly correlated with improvements of sleep efficiency as measured by daily sleep diaries and by polysomnography . In addition , more adaptive beliefs and attitudes about sleep at posttreatment were associated with better maintenance of sleep improvements at follow-ups . These findings highlight the importance of targeting sleep-related beliefs and attitudes in the treatment of insomnia OBJECTIVE The purpose of this study was to examine the role of perfectionism to pre-existing and future insomnia . METHODS Based on a r and om sample from the general population ( N=3600 ) , 1936 participants filled out a baseline and 1-year follow-up survey on perfectionism ( concern over mistakes and personal st and ards ) , emotional distress and insomnia . RESULTS The results from sequential logistic regression analyses showed that concern over mistakes was significantly related to pre-existing and future insomnia . When emotional distress was accounted for , none of the perfectionism subscales contributed significantly in explaining pre-existing and future insomnia . CONCLUSIONS The results indicate that though perfectionism seems to be related to both pre-existing and future insomnia , its role seems relatively weak Background : Insomnia is a prevalent health complaint that is often difficult to evaluate reliably . There is an important need for brief and valid assessment tools to assist practitioners in the clinical evaluation of insomnia complaints . Objective : This paper reports on the clinical validation of the Insomnia Severity Index ( ISI ) as a brief screening measure of insomnia and as an outcome measure in treatment research . The psychometric properties ( internal consistency , concurrent validity , factor structure ) of the ISI were evaluated in two sample s of insomnia patients . Methods : The first study examined the internal consistency and concurrent validity of the ISI in 145 patients evaluated for insomnia at a sleep disorders clinic . Data from the ISI were compared to those of a sleep diary measure . In the second study , the concurrent validity of the ISI was evaluated in a sample of 78 older patients who participated in a r and omized-controlled trial of behavioral and pharmacological therapies for insomnia . Change scores on the ISI over time were compared with those obtained from sleep diaries and polysomnography . Comparisons were also made between ISI scores obtained from patients , significant others , and clinicians . Results : The results of Study 1 showed that the ISI has adequate internal consistency and is a reliable self-report measure to evaluate perceived sleep difficulties . The results from Study 2 also indicated that the ISI is a valid and sensitive measure to detect changes in perceived sleep difficulties with treatment . In addition , there is a close convergence between scores obtained from the ISI patient 's version and those from the clinician 's and significant other 's versions . Conclusions : The present findings indicate that the ISI is a reliable and valid instrument to quantify perceived insomnia severity . The ISI is likely to be a clinical ly useful tool as a screening device or as an outcome measure in insomnia treatment research STUDY OBJECTIVE To study prospect ively the relations of insomnia to the development of anxiety disorders and depression in a population -based sample . DESIGN Cohort study based on data from 2 general health surveys of the adult population . SETTING Two general health surveys in the adult population in Nord-Trøndelag County of Norway , HUNT-1 performed in 1984 - 6 and HUNT-2 in 1995 - 7 PARTICIPANTS Participants without significant anxiety and depression in HUNT-1 were categorized according to the presence and absence of insomnia in the 2 surveys ( N=25,130 ) . MEASUREMENTS AND RESULTS Anxiety disorders and depression in HUNT-2 were assessed by the Hospital Anxiety and Depression Scale and analyzed using multivariate logistic regression analysis adjusted for age , gender , education , comorbid depression/anxiety , and history of insomnia . Anxiety disorders in HUNT-2 were significantly associated with the group with insomnia in HUNT-1 only ( OR 1.6 ; 95 % CI , 1.1 - 2.3 ) , the group with insomnia in HUNT-2 only ( OR 3.4 ; 95 % CI , 3.1 - 3.8 ) , as well as with the group with insomnia in both surveys ( OR 4.9 ; 95 % CI , 3.8 - 6.4 ) . Depression in HUNT-2 was significantly associated with the group with insomnia in HUNT-2 only ( OR 1.8 ; 95 % CI , 1.6 - 2.0 ) , but not with the groups with insomnia in HUNT-1 only or with insomnia in both surveys . CONCLUSIONS Only a state-like association between insomnia and depression was found . In addition to being a state marker , insomnia may be a trait marker for individuals at risk for developing anxiety disorders . Results are consistent with insomnia being a risk factor for the development of anxiety disorders STUDY OBJECTIVES To examine the rates of family history of insomnia in a population -based sample composed of self-defined good sleepers and individuals with insomnia and compare individuals with and without family history of insomnia on several characteristics presumably associated with insomnia . DESIGN Cross-sectional comparisons of self-defined good sleepers and individuals with insomnia selected from a larger epidemiologic study using a r and omly selected sample of 2001 adults of the province of Quebec in Canada . PARTICIPANTS Nine hundred fifty-three adults ( 60.3 % women ; mean age = 43.9 years ) completed several postal question naires , including a survey of past and current history of insomnia/sleep disorders for self and first-degree relatives . Participants were classified as good sleepers , individuals with insomnia symptoms , or individuals with an insomnia syndrome . INTERVENTIONS N/A. RESULTS Of the total sample , 34.9 % reported at least 1 first-degree relative with past or current insomnia . The mother was the most frequently afflicted first-degree relative with insomnia ( 19.7 % ) . Family history rates of insomnia were not significantly different when individuals with current insomnia symptoms or syndrome were compared with self-defined good sleepers . However , significant group differences emerged when good sleepers were subdivided according to the presence or absence of past personal history of insomnia . Individuals with past or current insomnia were significantly more likely to report a family history of insomnia than were good sleepers who had never experienced insomnia in the past ( 39.1 % vs 29.0 % ) . Participants with a family history of insomnia endorsed higher scores on measures of insomnia severity , anxiety symptomatology , and arousal predisposition . CONCLUSIONS These findings provide additional evidence about the potential role of both family and personal history of insomnia as predisposing factors to insomnia . Longitudinal family studies are needed to further examine the relative contribution of genetic and environmental factors in the genesis and heritability of insomnia STUDY OBJECTIVES To examine the joint effect of insomnia and objective short sleep duration on neuropsychological performance . DESIGN Representative cross-sectional study . SETTING Sleep laboratory . PARTICIPANTS 1,741 men and women r and omly selected from central Pennsylvania . INTERVENTIONS None . MEASUREMENTS Insomnia ( n = 116 ) was defined by a complaint of insomnia with a duration > or = 1 year and the absence of sleep disordered breathing ( SDB ) , while normal sleep ( n = 562 ) was defined as the absence of insomnia , excessive daytime sleepiness , and SDB . Both groups were split according to polysomnographic sleep duration into 2 categories : > or = 6 h of sleep ( " normal sleep duration ") and < 6 h of sleep ( " short sleep duration ") . We compared the groups ' performance on a comprehensive neuropsychological battery that measured processing speed , attention , visual memory , and verbal fluency , while controlling for age , race , gender , education , body mass index , and physical and mental health . RESULTS No significant differences were detected between insomniacs and controls . However , the insomnia with short sleep duration group compared to the control with normal or short sleep duration groups showed poorer neuropsychological performance in variables such as processing speed , set-switching attention , and number of visual memory errors and omissions . In contrast , the insomnia with normal sleep duration group showed no significant deficits . CONCLUSIONS Insomnia with objective short sleep duration is associated with deficits in set-switching attentional abilities , a key component of the " executive control of attention . " These findings suggest that objective sleep duration may predict the severity of chronic insomnia , including its effect on neurocognitive function Insomniacs often complain of memory deficits , yet objective measures have not consistently corroborated their subjective impressions . A possible explanation for the partial gap between self-report and behavioral measures of memory impairment is that insomniacs recruit extra effort to compensate for the consequences of poor sleep . The present study investigated whether subjective insomnia severity would predict objective effort mobilization , as indexed by cardiovascular measures , in an easy memory task . Seventy-seven university students , mostly women , with a mean age of 22 years were asked to memorize four strings of four r and om letters in 5 min while cardiovascular measures were obtained . After taking an immediate recall test , participants completed the Insomnia Severity Index , the Multidimensional Fatigue Inventory , and a question naire on last night 's sleep and today 's fatigue . Finally , they were given a surprise delayed recall test . Analyses indicated that self-reported insomnia severity was associated with an increase in systolic blood pressure during the learning phase . Regarding memory performance , insomnia severity was unrelated to immediate recall but related to a decrement in delayed recall . These findings reveal for the first time that subjective insomnia severity predicts objective effort mobilization in an easy memory task , suggesting that young poor sleepers recruit extra re sources to cope with everyday cognitive challenges While high levels of activity and exercise training have been associated with improvements in sleep quality , minimum levels of activity likely to improve sleep outcomes have not been explored . A two-armed parallel r and omized controlled trial ( N=41 ; 30 females ) was design ed to assess whether increasing physical activity to the level recommended in public health guidelines can improve sleep quality among inactive adults meeting research diagnostic criteria for insomnia . The intervention consisted of a monitored program of ≥150 min of moderate- to vigorous-intensity physical activity per week , for 6 months . The principal end-point was the Insomnia Severity Index at 6 months post-baseline . Secondary outcomes included measures of mood , fatigue and daytime sleepiness . Activity and light exposure were monitored throughout the trial using accelerometry and actigraphy . At 6 months post-baseline , the physical activity group showed significantly reduced insomnia symptom severity ( F(8,26 ) = 5.16 , P = 0.03 ) , with an average reduction of four points on the Insomnia Severity Index ; and significantly reduced depression and anxiety scores ( F(6,28 ) = 5.61 , P = 0.02 ; and F(6,28 ) = 4.41 , P = 0.05 , respectively ) . All of the changes were independent of daily light exposure . Daytime fatigue showed no significant effect of the intervention ( F(8,26 ) = 1.84 , P = 0.18 ) . Adherence and retention were high . Internationally recommended minimum levels of physical activity improve daytime and night-time symptoms of chronic insomnia independent of daily light exposure levels |
13,268 | 26,615,034 | However , there was no difference between antihistamines and placebo in the mid term ( three to four days ) to long term ( six to 10 days ) .
When evaluating individual symptoms such as nasal congestion , rhinorrhoea and sneezing , there was some beneficial effect of the sedating antihistamines compared to placebo ( e.g. rhinorrhoea on day three : mean difference ( MD ) -0.23 , 95 % CI -0.39 to -0.06 on a four- or five-point severity scale ; sneezing on day three : MD -0.35 , 95 % CI -0.49 to -0.20 on a four-point severity scale ) , but this effect is clinical ly non-significant .
Adverse events such as sedation were more commonly reported with sedating antihistamines although the differences were not statistically significant .
Antihistamines have a limited short-term ( days one and two of treatment ) beneficial effect on severity of overall symptoms but not in the mid to long term .
There is no clinical ly significant effect on nasal obstruction , rhinorrhoea or sneezing .
Although side effects are more common with sedating antihistamines , the difference is not statistically significant .
There is no evidence of effectiveness of antihistamines in children | BACKGROUND The common cold is an upper respiratory tract infection , most commonly caused by a rhinovirus .
It affects people of all age groups and although in most cases it is self limiting , the common cold still causes significant morbidity .
Antihistamines are commonly offered over the counter to relieve symptoms for patients affected by the common cold , however there is not much evidence of their efficacy .
OBJECTIVES To assess the effects of antihistamines on the common cold . | Between november 1993 and july 1995 60 patients with a common cold underwent r and omized and double-blind testing of 3 commercial nasal sprays-benzydamine , xylometazoline combined with the secretolytic S-carboxymethylcysteine , and phenylephrine combined with the antihistaminic dimethindene maleate . After prior active rhinomanometric measurement of the untreated nose , the test substance was applied . The change of nasal patency was registered after 3 and 10 minutes and then after 2 , 4 , 6 and 8 hours . At the end the patient gave a subjective evaluation of the used spray . There was no change in nasal obstruction following application of NaCl or benzydamine . Xylometazoline/S-carboxymethylcysteine ( + 87 % ) or phenylephrine/ dimethindene maleate ( + 113 % ) augmented nasal patency within minutes . Using phenylephrine/dimethindene maleate the effect lasted less than 2 hours , while after xylometazoline/S-carboxymethylcysteine decongestion lasted more than 6 hours . The patients also subjectively reported an increase in nasal patency after the use of benzydamine and placebo . But only phenylephrine/ dimethindene maleate or xylometazoline/S-carboxymethylcysteine were judged good . Using benzydamine or phenylephrine + dimethindene maleate , more side-effects ( mainly dryness and burning ) were mentioned . Considering the subjective assessment of side-effects and duration of action , as well as objective parameters , derivatives of imidazole ( oxymetazoline and xylometazoline ) are first choice in treatment of the common cold It is now possible for some allergy patients to breathe more easily and remain alert , as demonstrated by European clinical trials of a potent new antihistamine , terfenadine . The drug does not produce sedation or other adverse effects associated with older antihistamine preparations . In addition , there are no apparent contraindications for its use in adult allergy sufferers , nor have any carcinogenic , mutagenic , or teratogenic effects been seen in animals . Terfenadine , manufactured by Merrell Dow Pharmaceuticals , Inc , Cincinnati , is like other antihistamines — an H 1 receptor antagonist ; that is , it specifically blocks the chain of cellular events following the release of histamine that triggers the typical symptoms of acute and perennial rhinitis and allergic dermatitis . However , terfenadine does not affect the CNS , as indicated by a series of clinical trials reported at a Milan symposium to introduce the agent in Italy We used a rhinovirus challenge model to test the therapeutic efficacy of clemastine fumarate for reducing sneezing and nasal secretion in a double-blind , r and omized clinical trial . Clemastine fumarate ( 1.34 mg ) or placebo was administered at 8 A.M. and 8 P.M. for 4 days , beginning 24 hours , 36 hours , 48 hours , and 60 hours after viral challenge . Infected evaluable subjects who received clemastine ( n = 75 ) had reduced sneeze-severity scores compared with those who received placebo ( n = 75 ) on illness days 2 ( 0.3 vs. 0.5 ; P = .003 ) , 3 ( 0.4 vs. 0.8 ; P = .0003 ) , 4 ( 0.3 vs. 0.5 ; P = .025 ) , and 5 ( 0.1 vs. 0.3 ; P = .03 ) ; sneeze counts for infected evaluable subjects ( vs. counts for those who received placebo ) were reduced on illness days 2 ( 1.5 vs. 3.1 ; P = .01 ) , 3 ( 1.7 vs. 5.6 ; P = .0001 ) , and 5 ( 0.7 vs. 1.9 ; P = .03 ) . Infected evaluable subjects who received treatment had reduced rhinorrhea scores ( compared with those who received placebo ) on illness days 2 ( 0.7 vs. 1.0 ; P = .04 ) and 3 ( 0.6 vs. 0.9 ; P = .04 ) and had reduced nasal secretion weights on day 3 ( 3.6 g vs. 6.3 g ; P = .03 ) . Over 4 days of treatment , mean sneeze scores for infected evaluable subjects ( vs. scores for those who received placebo ) were reduced by 50 % , mean sneeze counts by 57 % , mean rhinorrhea scores by 27 % , and mean nasal secretion weights by 35 % . Other cold symptoms were unaffected by treatment . Treatment with clemastine was associated with an excess incidence of dry mouth ( 6 % ) , dry nose ( 19 % ) , and dry throat ( 17 % ) Two hundred and seventeen patients between 6 and 12 years of age suffering from acute cough took part in a r and omized , single-blind study comparing ' Pholcolix ' and ' Actifed ' Compound . No significant difference in efficacy was demonstrated but analysis of palatability components ( taste , smell , aftertaste and feeling in the mouth ) showed numerical superiority for ' Pholcolix ' for all parameters , with a high degree of significance for overall taste . ' Pholcolix ' caused significantly fewer side-effects , with ' Actifed ' Compound causing markedly more drowsiness after daytime dosage Antihistamines are widely used in common cold medications , although the role of histamine in the development of common cold symptoms is unclear and the use of antihistamines for the treatment of common cold is controversial . It is clear that antihistamines do not offer a cure for common cold but they may alleviate symptoms of sneezing and runny nose . The present study was design ed to investigate the efficacy of an antihistamine , doxylamine , on the symptoms of runny nose and sneezing associated with common cold . We conducted a r and omized double-blind study in cold sufferers . One thous and and one volunteers with cold symptoms were screened in four centres ( UK , Denmark , Belgium , Germany ) and 688 satisfied the entry criteria of the study . The main reasons for excluding subjects were a low nasal secretion weight ( secretion weight < 0.2 g , 72 % ) and a low subjective rhinorrhoea score ( 24 % ) . Volunteers were r and omized to receive either doxylamine succinate 7.5 mg by mouth four times a day up to nine doses ( n = 345 ) or placebo ( n = 343 ) . The principal measurements were prospect ively defined as runny nose and sneezing symptom scores . Data were analysed on an intention-to-treat basis , using Cochran-Mantel-Haenszel statistics controlling for baseline symptom scores . A between-group comparison showed that doxylamine-treated volunteers benefited from a significantly greater reduction in runny nose scores ( P < 0.01 ) and sneezing scores ( P < 0.001 ) , than those volunteers in the placebo group . Doxylamine therapy was well tolerated ; the incidence of unexpected side-effects was comparable with placebo . Of the expected side-effects , 13.3 % of doxylamine-treated patients reported drowsiness . The incidence of sedative effects was lower than has been reported for other commonly used first-generation antihistamines This study sought to investigate the efficacy of dextromethorphan ( DM ) , diphenhydramine ( DPH ) , and placebo ( PL ) for symptoms attributed to upper respiratory infections as determined by children , and to evaluate the concordance of perception of nocturnal symptoms between children and parents . A total of 37 children age 6 to 18 years of age were r and omized in a double-masked fashion to receive a single bedtime dose of DM , DPH , or PL . Children found no significant difference in the effect of DM , DPH , or PL for any study outcome , and responses by parents and children were significantly correlated To determine whether the cough of the common cold arises from upper respiratory stimuli and whether antihistamine-decongestant therapy is an effective treatment for this cough , we prospect ively evaluated volunteers with uncomplicated common colds in a r and omized , double-blind , placebo-controlled study . After completing a st and ardized question naire and undergoing a physical examination , throat-culturing , and pulmonary function testing , subjects took the active drug or identical-appearing placebo for 7 days while they kept a diary in which they ranked the severity of 17 symptoms for 14 days . Pulmonary function testing was repeated , on average , on Days 4 , 8 , and 14 . Forty-six percent of the variation in cough severity could be explained by throat-clearing and 47 % of the variation in throat-clearing severity by postnasal drip . FIF50 % , the only physiologic parameter that significantly correlated with cough , rose as cough severity fell . Antihistamine-decongestant therapy reduced postnasal drip and significantly decreased the severity of cough , nasal obstruction , nasal discharge , and throat-clearing during the first few days of the common cold . In addition , cough was 20 to 30 % less prevalent in the active drug group within 3 days of starting therapy . We conclude that the cough of the common cold arose from upper respiratory tract stimuli and that cough and other cardinal symptoms of the common cold were reduced with antihistamine-decongestant therapy when these symptoms were at their worst We tested the efficacy of brompheniramine maleate in a large r and omized , controlled trial of volunteers with experimental rhinovirus colds . Brompheniramine ( 12 mg ) or placebo was administered at 8:00 A.M. and 8:00 P.M. for < or = 4 days after the onset of symptoms ( 24 , 36 , or 48 hours after virus challenge ) . During the first 3 days of treatment ( the first 4 days after virus challenge ) , nasal secretion weights were lower for infected evaluable subjects receiving brompheniramine ( n = 113 ) than for controls ( day 1 : 4.3 g vs. 6.8 g ; day 2 : 4.8 g vs. 7.7 g ; and day 3 : 3.3 g vs. 5.3 g ) ( P < or = .03 ) , as were rhinorrhea scores ( day 1 : 0.6 vs. 0.8 ; day 2 : 0.5 vs. 0.8 ; and day 3 : 0.3 vs. 0.5 ) ( P < .03 ) , sneeze counts ( day 1 : 1.8 vs. 3.6 ; day 2 : 2.1 vs. 5.1 ; and day 3 : 1.3 vs. 3.3 ) ( P < or = .001 ) , and sneeze severity scores ( day 1 : 0.3 vs. 0.6 ; day 2 : 0.25 vs. 0.7 ; and day 3 : 0.2 vs. 0.4 ) ( P < .001 ) ( n = 112 ) . Cough counts were lower after day 1 of treatment for the brompheniramine group than for controls ( 4.7 vs. 7.9 ) ( P = .05 ) ( day 2 after virus challenge ) , and other symptoms were modestly reduced or were unaffected in the brompheniramine group . Total symptom scores were also lower for the brompheniramine group than for controls on treatment days 1 ( 4.8 vs. 6.0 ) ( P = .03 ) and 2 ( 4.1 vs. 5.6 ) ( days 2 and 3 after virus challenge ) ( P = .003 ) . Treatment with brompheniramine was associated with the adverse effects of somnolence ( n = 3 ) and confusion ( n = 1 ) . Brompheniramine was efficacious treatment for the sneezing , rhinorrhea , and cough associated with rhinovirus colds Limited data support the use of first-generation antihistamines for treatment of the common cold . The purpose of this study was to test the effectiveness of clemastine fumarate , a first-generation antihistamine , for treatment of sneezing and rhinorrhea associated with naturally occurring common colds . Four hundred three subjects ( 202 clemastine fumarate recipients and 201 placebo recipients ) who reported new onset ( < 24 hours ) of cold symptoms that included rhinorrhea or sneezing were studied . At baseline ( day 1 ) , the mean symptom-severity scores + /- SEM for the clemastine fumarate and placebo groups were not significantly different . The mean rhinorrhea-severity score + /- SEM was not different on day 2 ; however , on day 3 , the mean rhinorrhea-severity score + /- SEM was 1.02 + /- 0.07 for the clemastine fumarate group and 1.39 + /- 0.07 for the placebo group ( P < .001 ) . This treatment effect persisted on day 4 . A significant effect on sneezing was noted on days 2 - 4 . Sedation occurred in 14 % of the clemastine fumarate-treated subjects and 1.5 % of the placebo-treated subjects ( P < .0001 ) Abstract A r and omized , controlled , double-masked clinical trial was conducted with a combination antiviral-antimediator treatment for experimental rhinovirus colds . In all , 150 healthy men and women ( aged 18–51 years ) were r and omly assigned to 1 of 3 groups : intranasal interferon (IFN)–α2b ( 6 × 106 U every 12 h × 3 ) plus oral chlorpheniramine ( 12 mg extended release ) and ibuprofen ( 400 mg ) every 12 h for 4.5 days ( n=59 subjects ) ; intranasal placebo plus oral chlorpheniramine and ibuprofen ( n=61 subjects ) ; or intranasal and oral placebos ( n=30 subjects ) . Treatment was started 24 h after intranasal viral challenge . During the 4.5 days of treatment with IFN-α2b , chlorpheniramine , and ibuprofen , the daily mean total symptom score was reduced by 33%–73 % , compared with placebo . Treatment reduced the severity of rhinorrhea , sneezing , nasal obstruction , sore throat , cough , and headache and reduced nasal mucus production , nasal tissue use , and virus concentrations in nasal secretions . IFN-α2b added to the effectiveness of chlorpheniramine and ibuprofen and was well A total of 466 healthy adults from four different regions of Engl and entered a double-blind , r and omised trial to test the effectiveness of an antihistamine ( triprolidine ) and a decongestant ( pseudoephedrine ) , alone or in combination , in relieving symptoms of the common cold . During the study 199 subjects reported a total of 243 colds . Subjects recorded the severity of 12 symptoms during treatment and noted separately the severity of a further seven symptoms that represented unwanted effects of treatment or served as an index of suggestibility . They were then asked about their overall improvement in symptoms during treatment and whether they thought they had taken placebo . Sneezing , nasal obstruction , and overall response to treatment were significantly improved ( p < 0.01 ) with psuedoephedrine or pseudoephedrine and triprolidine compared with placebo A multicentric trial compared the effect of chlorpheniramine maleate with a placebo on the signs and symptoms of the common cold . Two hundred seventy-one patients were domiciled for 48 hours and evaluated during this period and for four days afterwards . Evaluations by both patients and physicians showed that chlorpheniramine maleate was superior to placebo in lessening the degree of symptoms of the common cold . Statistically significant differences were found both on the first day and as late as the seventh day . Significant differences and trends were shown in such measures as total objective score , physicians ' evaluation of symptoms . The overall incidence of side effects other than drowsiness did not differ between the treatment groups We tested the hypothesis that antihistamine-decongestant combinations cause no clinical ly significant relief of the symptoms of upper respiratory tract infections in young children by r and omly assigning 96 children to one of three treatment groups : antihistamine-decongestant , placebo , and no treatment . There were no differences among the three study groups in the proportion of children considered " better " overall by the parent 48 hours after the initial assessment ( drug , 67 % ; placebo , 71 % ; no treatment , 57 % ; p = 0.53 ) . There were no differences among groups in individual or composite symptom score changes . Two thirds of parents whose children were eligible for the drug trial believed that their child needed medicine for cold symptoms . In the proportion of parents believing that their child needed medicine , there was no difference between those who consented to participate and those who refused . Parents who wanted medicine at the initial visit reported more improvement at follow-up , regardless of whether the child received drug , placebo , or no treatment . We conclude that there is no clinical ly significant improvement in symptoms of upper respiratory tract infection , including no significant placebo effect , in young children for whom an antihistamine-decongestant is prescribed Although antihistamines are widely used for symptomatic treatment of seasonal ( allergic ) rhinitis , the role of histamines in the pathogenesis of infectious rhinitis is not clear . Two antihistamines , orally administered chlorpheniramine maleate ( CM ) and diphenhydramine hydrochloride ( DH ) administered by intranasal spray , were used under double-blinded , r and omized , placebo-controlled conditions to assess both tolerance and efficacy in volunteers with experimental rhinovirus ( RV ) colds . In the initial trial , CM ( 4.0 mg per treatment ) was ingested 4 times daily for 4 days beginning 24 h after intranasal inoculation of RV type 29 in susceptible volunteers . In the second trial , DH was sprayed intranasally 4 times daily ( 2 mg per treatment ) for 5 days beginning 24 h after inoculation of RV type 39 . Clinical colds occurred in 60 % of the CM group ( n = 13 ) and 73 % of the placebo ( n = 15 ) in the first study , and in 66 % of the DH group ( n = 12 ) compared with 81 % in the placebo group ( n = 11 ) in the second . Both CM and DH were well tolerated but had no significant effects on nasal symptoms or nasal mucus production . The findings provide additional evidence against an important role for histamine in the pathogenesis of nasal symptomatology in rhinovirus colds Abstract Treatment with first-generation antihistamines reduces sneezing , rhinorrhea , nasal mucus weight , and , in some instances , cough in subjects with experimental or natural colds ; however , treatment with second-generation antihistamines has not been effective for these complaints in trials in subjects with natural colds . This article reports the negative results of a clinical trial with loratadine , a second-generation antihistamine , in adults in the rhinovirus challenge model . This finding in the highly controlled setting of the challenge model confirms the earlier negative studies with second-generation antihistamines in natural colds . First-generation antihistamines block both histaminic and muscarinic receptors as well as passing the blood-brain barrier . Second-generation antihistamines mainly block histaminic receptors and do not pass the blood-brain barrier . The effectiveness of first-generation antihistamines in blocking sneezing in colds may be due primarily to neuropharmacological manipulation of histaminic and muscarinic receptors in the medulla Summary We have assessed the effects of terfenadine on rhinitis symptoms associated with the common cold in 91 patients in a double-blind placebo-controlled study . The patients received three doses of either terfenadine 60 mg ( n=44 ) or placebo ( n=47 ) at about 12-h intervals , starting in most patients within 48 h from the onset of symptoms . Because of deviations from the protocol , 28 cases were classified as not eligible for efficacy evaluation , but were nevertheless analysed . Excellent/good or moderate efficacy was reported by 63 % of eligible and 59 % of all patients who received terfenadine ( placebo 40 % and 51 % respectively , p=0.049 and 0.113 respectively ) . 68 % of eligible and 52 % of all patients indicated that they would take terfenadine again ( placebo 23 % , for bothp=0.002 ) . Two h after tablet intake mean nasal airflow was increased by 11 l·min−1 , SD 8 ( placebo −1 l·min−1 , SD 6,p=0.005 ) . Symptoms were improved and rhinoscopy showed reduced swelling and redness of the mucosa and reduced nasal secretion and obstruction ( basically unchanged in the placebo group).Therefore , terfenadine seems to act favourably on the acute rhinitis symptoms associated with the common cold . Since terfenadine is devoid of anticholinergic activity , nose symptoms during the initial stage of the common cold may be mediated to an important degree by histamine We studied the effectiveness of nasal decongestant-antihistamine in treating acute sinusitis in children . All subjects received oral amoxicillin for 14 days . Subjects r and omized to the decongestant-antihistamine group received nasal oxymetazolone and oral syrup containing brompheniramine and phenylpropanolamine . Controls received placebo nasal saline and oral syrup . In both groups symptoms resolved quickly , and radiographs improved significantly . Responses to treatment were similar between the two groups . Water 's radiographs of the maxillary sinuses proved reliable in the assessment of the degree of sinus involvement . We conclude that decongestant-antihistamine need not be given to the child with acute maxillary sinusitis This paper presents the results of a r and omized , double-blind , placebo-controlled study of the efficacy of chlorpheniramine in relieving the symptoms and attenuating the pathophysiologic correlates of a rhinovirus " common cold . " Forty healthy , adult , nonatopic subjects were r and omly assigned to one of two treatment groups : active drug and placebo . On study Day 0 , all subjects were challenged intranasally with rhinovirus type 39 ( dose = 100 TCID50 ) . Subjects were cloistered from Day 2 to Day 7 , at which time they were treated with either chlorpheniramine or placebo . From 3 days before challenge to study Day 19 , subjects had nasal patency assessed by rhinomanometry , eustachian tube function assessed by the 9-step test and sonotubometry , middle ear pressure assessed by tympanometry and nasal clearance assessed by the dyed-saccharin technique . Symptom diaries were maintained throughout the period of follow-up . During cloister , symptoms also were scored by interview , nasal secretions were quantified and nasal washings were performed for viral culture . Results showed that 19 ( 95 % ) subjects in the active-treatment group and 18 ( 90 % ) subjects in the placebo-treatment group shed virus . Symptomatic colds were observed in 63 % of the active-treated and 83 % of the placebo-treated subjects . Symptoms increased on Day 1 and peaked at Days 4 to 5 . Detrimental changes in other measured functions consistent with those previously reported were observed . During the period of treatment , significant differences in the average symptom scores favoring the active-treatment group were observed for sneezing . Also , weight of expelled secretions was greater and mucociliary clearance rate less on some cloister days for the placebo-treated group . No significant differences between treatment groups in the objective measures of nasal congestion or the response of the middle ear and eustachian tube were documented Second-generation Hi-receptor antagonists such as loratadine and terfenadine , which are relatively free from anticholinergic effects and from sedation and other adverse effects on the central nervous system ] are gradually replacing first-generation Hi-receptor antagonists in the treatment of chronic allergic rhinoconjunctivitis and chronic urticaria . Although these medications have been well studied in adults , 2"7 there are few rigorous , well- design ed , objective investigations in children , s , 9 We hypothesized that loratadine and terfenadine would have a prompt , potent Hi-receptor antagonist effect in children compared with the effect produced b y placebo . We evaluated loratadine and terfenadine with the use of an objective l relatively noninvasive bioassay , in which suppression of the wheal and flare produced by epicutaneous tests with histamine was assessed at regular intervals before and after ingestion of the Hi-receptor antagonist or placebo . This bioassay has been found to be ideal for determining the onset of action , potency , and duration of action of HIreceptor antagonists in children , s , 10 , 11 and to correlate with suppression of the symptoms of rhinoconjunctivitis . 1~ A total of 132 patients with symptoms associated with either upper respiratory allergies or the common cold was enrolled in this 5-day study . Azatadine maleatelpseudoephedrine sulfate syrup was compared to placebo using a double-blind design . Evaluation of efficacy was based on results in eighty patients and that of safety in 115 . Onset of relief was significantly better ( p = 0·03 ) with azatadine maleatel pseudoephedrine sulfate syrup than with placebo . However this was due mainly to the distribution of patients who indicated ‘ no relief ' : ten in the combination group as opposed to sixteen in the placebo group . Over-all evaluation of results indicated that a significantly greater degree of symptomatic relief was achieved with the active test formulation than with placebo on both Days 3 ( p = 0·03 ) and 5 ( p = 0·04 ) of therapy . Somnolence was the most frequently reported side-effect In a five-day , r and omized , double-blind study , the efficacy and safety of a syrup containing a combination of azatadine maleate , pseudoephedrine sulfate , and dextromethorphan hydrobromide ( SCH 399 syrup ) were compared with those of an expectorant containing the antihistamine diphenhydramine hydrochloride in 60 children with symptoms of the common cold and associated cough . One-half teaspoonful of assigned medication was administered three or four times daily . The severity of signs and symptoms was grade d on days 0 , 3 , and 5 . At days 3 and 5 , patients treated with SCH 399 experienced a significantly greater degree of relief ( P less than 0.001 ) than did patients treated with the expectorant product . Differences between treatment groups in overall therapeutic response , as evaluated by the physician , were statistically significant ( P less than 0.001 ) at each visit , favoring patients treated with SCH 399 . More than 75 % of the patients treated with SCH 399 demonstrated an excellent therapeutic response . Tolerance to both study medications was excellent A r and omized , double-blind , placebo-controlled study was done on 106 volunteers to assess the effectiveness of chlorpheniramine maleate against the common cold . The results suggest that this antihistamine is significantly effective in relieving the symptoms of a cold if used four times daily for one week , and that relief was gained with no significant increase in side effects Clinical trials of antihistamines combined with adrenergic substances showed a dccongestive effect on nasal mucosal congestion due to acute rhinitis . Double-blind technique combined with objective rhinomano-meiry over 9 hours in each individual trial showed complete absence of placebo effect ; the results were therefore conclusive . Tests on 85 subjects with acute rhinitis as well as tests on 50 normal subjects with histamine-pro-voked nasal blocking support the idea that an antihistamine and an adrenergic substance show synergism with regard to nasal decongestion . Of the drugs tested , clemastine combined with phenylpropanolamine gave the best result A rhinomanometric technique was used to evaluate the nasal decongestant effect of a single dose of Day Nurse ® over a 4-hour post-dosing period in human volunteers suffering from nasal congestion due to a common cold . A significant improvement in nasal congestion was obtained at the 1 hour , 2 hour , 3 Hour and 4 hour post-dosing interval , from initial values compared to a placebo group . The study therefore demonstrated by an objective technique that Day Nurse ® provides relief of nasal congestion and related symptoms in cold sufferers The role of histamine in the pathogenesis of infectious rhinitis is unclear , as is the efficacy of antihistaminic drugs in the treatment of the common cold . This study evaluated the short-term efficacy of oral terfenadine ( Seldane ) in the treatment of the common cold . Over a 5-week period , the authors recruited 250 adults who had developed cold symptoms within 6 to 48 hours prior to enrollment . Volunteers had a primary complaint of runny or stuffy nose ; at least one other respiratory symptom ; no fever or exudative pharyngitis ; and no history of atopy , sinusitis , or use of cold preparations within 1 week of enrollment . Out of the eligible subjects , 126 were r and omly assigned terfenadine ( 60 mg ) , and 124 received placebo . Volunteers self-administered either terfenadine or placebo twice a day on Days 1 , 2 and 3 , and a final dose on the morning of Day 4 . They also recorded the severity of their clinical symptoms ( runny nose , sniffles , sneezing , postnasal drip , cough and sore throat ) on symptom cards . Both groups reported similar severity scores throughout the treatment period . Average symptom burdens declined at almost identical rates for both groups . Terfenadine was well tolerated and had a low incidence of side effects . According to subject evaluation , terfenadine was no more effective than placebo . The mean + /- SD score of global efficacy was 2.2 + /- 1.1 in the terfenadine group and 2.1 + /- 1.3 in the placebo group ( P = NS ) . Slightly fewer terfenadine recipients ( 41 % ) than placebo recipients ( 48 % ) said they would use the study medication again for treating cold symptoms . ( ABSTRACT TRUNCATED AT 250 WORDS Seventy subjects suffering from the common cold were recruited at general practitioner surgeries and were treated with an evening dose of a syrup† containing 600 mg paracetamol , 15 mg dextromethorphan hydrobromide , 8 mg ephedrine sulphate , 7.5 mg doxylamine succinate per 30 ml or an identical-appearing and flavoured control syrup without the active ingredients , in a double-blind crossover design study , lasting two days . Subjects were r and omly allotted to two equal groups . One group took active formulation the first evening followed by the control formulation the second evening . The second group took the two formulations in the reverse order . Evaluation of symptomatic relief on a 6-point rating scale against eight major cold symptoms was carried out by each subject at 10 a.m. following the administration of active or control formulation the previous evening . Following combination of data for the two groups , results showed a significant degree of relief provided by the active formulation compared to control for the following symptoms , cough , nasal congestion , nasal discharge , sneezing , generally feeling unwell , headache , sore throat , disturbed sleep , the difference between the two preparations in relief of cough being highly significantly in favour of the “ active ” preparation . Additionally , a highly significant number of the subjects expressed a preference for the global symptomatic relief provided by the active formulation as compared to control . These results have demonstrated that the “ active ” formulation provides effective therapy for night-time symptomatic relief of the eight major symptoms of the common cold OBJECTIVE To determine whether an antihistamine-decongestant combination ( ADC ) is superior to placebo in temporarily relieving symptoms of upper respiratory tract infection ( URI ) in preschool children . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Four pediatric offices in the Seattle , Wash , area . PARTICIPANTS Children 6 months through 5 years of age with a URI of less than 7 days ' duration . METHODS Children were r and omly assigned to receive an ADC ( brompheniramine maleate-phenylpropanolamine hydrochloride ) or placebo as needed for URI symptoms . Two hours after each dose of study medication , changes in the child 's runny nose , nasal congestion , cough , and sleep status were assessed by means of a st and ardized question naire . RESULTS A total of 175 responses were recorded for 59 patients . There were no statistically significant differences in symptom improvement between the ADC and the placebo group ( runny nose , p = 0.48 ; nasal congestion , p = 0.94 ; cough , p = 0.66 ) . However , the proportion of children asleep 2 hours after receiving the ADC was significantly higher than the proportion receiving placebo ( 46.6 % vs 26.5 % ; p = 0.01 ) . Results were unchanged after control for the correlated nature of repeated responses , age , symptom duration , use of acetaminophen , time that the medication was given , and parental desire for medication . CONCLUSIONS The ADC was equivalent to placebo in providing temporary relief of URI symptoms in preschool children . However , the ADC did have significantly greater sedative effects than did placebo |
13,269 | 27,872,391 | Direct access to school nursing and other health services , as well as disease-specific education , improved health and academic outcomes among students with CHCs . | Children and adolescents in the United States spend many hours in school .
Students with chronic health conditions ( CHCs ) may face lower academic achievement , increased disability , fewer job opportunities , and limited community interactions as they enter adulthood .
School health services provide safe and effective management of CHCs , often for students with limited access to health care . | BACKGROUND Asthma is a serious problem for low-income preteens living in disadvantaged communities . Among the chronic diseases of childhood and adolescence , asthma has the highest prevalence and related health care use . School-based asthma interventions have proven successful for older and younger students , but results have not been demonstrated for those in middle school . METHODS This r and omized controlled study screened students 10 - 13 years of age in 19 middle schools in low-income communities in Detroit , Michigan . Of the 6,872 students who were screened , 1,292 students were identified with asthma . Schools were matched and r and omly assigned to Program 1 or 2 or control . Baseline , 12 , and 24 months data were collected by telephone ( parents ) , at school ( students ) and from school system records . Measures were the students ' asthma symptoms , quality of life , academic performance , self-regulation , and asthma management practice s. Data were analyzed using multiple imputation with sequential regression analysis . Mixed models and Poisson regressions were used to develop final models . RESULTS Neither program produced significant change in asthma symptoms or quality of life . One produced improved school grade s ( p = .02 ) . The other enhanced self-regulation ( p = .01 ) at 24 months . Both slowed the decline in self-regulation in undiagnosed preteens at 12 months and increased self-regulation at 24 months ( p = .04 ; p = .003 ) . CONCLUSION Programs had effects on academic performance and self-regulation capacities of students . More developmentally focused interventions may be needed for students at this transitional stage . Disruptive factors in the schools may have reduced both program impact and the potential for outcome assessment Pediatric asthma rates are reaching epidemic proportions , adversely affecting children 's quality of life , educational potential , and health care costs , especially those in the inner city . This study evaluated the effectiveness of a school-based asthma case management ( CM ) approach with medically underserved inner-city children attending Memphis City schools . Fourteen elementary schools with high rates of asthma-related hospital utilization were grouped according to school size , percentage of children with asthma enrolled , and percentage of children eligible for free or reduced-price lunch . Schools were r and omized to either a nurse CM intervention or a usual care ( UC ) condition . The CM group included 115 students ; 128 students were in the UC group . A longitudinal design was used to follow students ' progress . Students were primarily African-American children diagnosed with asthma . In CM schools , nurse case managers conducted weekly group sessions incorporating the Open Airways curriculum , followed up on students ' school absences , and coordinated students ' asthma care with families , school personnel , and medical providers . In UC schools , students received routine school nursing services . CM students had fewer school absences than their counterparts in UC schools ( mean 4.38 vs 8.18 days , respectively ) and experienced significantly fewer emergency department visits ( p < .0001 ) and fewer hospital days ( p < .05 ) than UC students . No such differences existed before program initiation . Replication and follow-up in year 2 showed continued significant improvements . School-based nurse CM can achieve significant improvements in school attendance and medical utilization OBJECTIVE To evaluate the impact of the School-Based Asthma Therapy trial on asthma symptoms among urban children with persistent asthma . DESIGN R and omized trial , with children stratified by smoke exposure in the home and r and omized to a school-based care group or a usual care control group . SETTING Rochester , New York . PARTICIPANTS Children aged 3 to 10 years with persistent asthma . INTERVENTIONS Directly observed administration of daily preventive asthma medications by school nurses ( with dose adjustments according to National Heart , Lung , and Blood Institute Expert Panel guidelines ) and a home-based environmental tobacco smoke reduction program for smoke-exposed children , using motivational interviewing . MAIN OUTCOME MEASURE Mean number of symptom-free days per 2 weeks during the peak winter season ( November-February ) , assessed by blinded interviews . RESULTS We enrolled 530 children ( 74 % participation rate ) . During the peak winter season , children receiving preventive medications through school had significantly more symptom-free days compared with children in the control group ( adjusted difference = 0.92 days per 2 weeks ; 95 % confidence interval , 0.50 - 1.33 ) and also had fewer nighttime symptoms , less rescue medication use , and fewer days with limited activity ( all P < .01 ) . Children in the treatment group also were less likely than those in the control group to have an exacerbation requiring treatment with prednisone ( 12 % vs 18 % , respectively ; relative risk = 0.64 ; 95 % confidence interval , 0.41 - 1.00 ) . Stratified analyses showed positive intervention effects even for children with smoke exposure ( n = 285 ; mean symptom-free days per 2 weeks : 11.6 for children in the treatment group vs 10.9 for those in the control group ; difference = 0.96 days per 2 weeks ; 95 % confidence interval , 0.39 - 1.52 ) . CONCLUSIONS The School-Based Asthma Therapy intervention significantly improved symptoms among urban children with persistent asthma . This program could serve as a model for improved asthma care in urban communities OBJECTIVE To test the feasibility and preliminary effectiveness of the School-Based Preventive Asthma Care Technology ( SB-PACT ) program , which includes directly observed therapy of preventive asthma medications in school facilitated by Web-based technology for systematic symptom screening , electronic report generation , and medication authorization from providers . STUDY DESIGN We conducted a pilot r and omized trial of SB-PACT versus usual care with 100 children ( aged 3 - 10 years ) from 19 inner-city schools in Rochester , New York . Outcomes were assessed longitudinally by blinded interviewers . Analyses included bivariate statistics and linear regression models , adjusting for baseline symptoms . RESULTS There were data for 99 subjects for analysis . We screened all children using the Web-based system , and 44 of 49 treatment group children received directly observed therapy as authorized by their providers . Treatment group children received preventive medications 98 % of the time they were in school . Over the school year , children in the treatment group experienced nearly 1 additional symptom-free day over 2 weeks versus the usual care group ( 11.33 vs 10.40 , P = .13 ) . Treatment children also experienced fewer nights with symptoms ( 1.68 vs 2.20 , P = .02 ) , days requiring rescue medications ( 1.66 vs 2.44 , P = .01 ) , and days absent from school due to asthma ( 0.37 vs 0.85 , P = .03 ) compared with usual care . Further , treatment children had a greater decrease in exhaled nitric oxide ( -9.62 vs -0.39 , P = .03 ) , suggesting reduction in airway inflammation . CONCLUSION The SB-PACT intervention demonstrated feasibility and improved outcomes across multiple measures in this pilot study . Future work will focus on further integration of preventive care delivery across community and primary care systems This study examines healthcare utilization over time in Bronx , New York schoolchildren with asthma who were previously identified via parent surveys in six elementary schools . Four of the schools have on-site school-based health centers ( SBHCs ) , and two do not have on-site health services ( control schools ) . At baseline , we reported an asthma prevalence of 20 % , and high rates of emergency department ( ED ) use ( 46 % ) in the previous year . To determine if asthma morbidity ( specifically , ED use , community provider use , and hospitalizations for asthma ) could be reduced by incorporating an aggressive intervention at two schools with SBHCs , we prospect ively followed children for up to 3 years . Parents were scheduled for interviews every 6 months , and were queried about their children 's use of health services for asthma in the prior 6 months . In multivariate models , children in the two intervention SBHC schools were less likely to have visited a community provider for asthma ( relative rate ratio , 0.52 ; 95 % confidence interval ( CI ) , 0.30 - 0.88 ) or an emergency department for asthma ( odds ratio , 0.44 ; 95 % CI , 0.14 - 1.38 ; P = 0.059 ) in the prior 6 months compared to children attending control schools . There was no difference in community provider use or emergency department use for asthma between children attending nonintervention SBHCs and control schools . However , school type did not affect asthma hospitalization rates , which declined in all groups . Our findings support the effectiveness of aggressive school-based asthma services provided by SBHCs to reduce asthma morbidity and complement community health services Abstract Objective : To present outcomes of an asthma self-management educational intervention delivered to children ( grade s 2–5 ) at school and to parents in a home visit . Methods : The intervention effectiveness was tested in a 12-month longitudinal study with r and omization by elementary schools into treatment and attention-control groups with 183 children who had a diagnosis of asthma . Data were collected at four time points . Change over time was examined with linear mixed models . Results : Quality of life ( QOL ) , hospitalizations , and emergency department visits improved significantly for all the children . African American and Mexican American children had worse asthma-related QOL than did White children . Asthma management behaviors , asthma self-efficacy , and coping likewise improved with girls improving significantly more than the boys . Significant improvements in inhaler skill and asthma severity were seen in the treatment group children when compared to the control group . Treatment group parents showed significant improvements in home asthma management and self-efficacy . Conclusions : The improvement in inhaler skill is an important finding for practitioners as this is a behavior that can be addressed in the clinical setting . The reduction in the treatment group ’s asthma severity scores may reflect the improvement in medication delivery as their inhaler skill improved . The differential improvement between boys and girls points to the need for testing other formats in asthma education that can address different learning styles . The individualized parent asthma education enabled the intervener to incorporate neighborhood and home environmental information thereby allowing for tailoring of parental instruction INTRODUCTION Asthma is the most prevalent chronic illness , affecting more than 7 million children younger than 17 years . Asthma has become a leading public health concern because of the dramatic rise in the incidence of this disease during the past 15 years , particularly in minority population s. This study tested a two-part intervention on selected psychosocial and health outcomes of 8- to 13-year-old inner city minority students with asthma . METHOD The intervention consisted of participation in an asthma education program ( Open Airways ) followed by 5 monthly visits with a nurse practitioner . The total sample of 52 children was composed of 28 children in the treatment group who received the intervention and 24 children who served as a control group . RESULTS Students in the treatment group scored significantly higher than the control group over time on measures of asthma knowledge , asthma self-efficacy , general self-care practice s , and asthma self-care practice s. No significant differences were found between the two groups on health outcomes . DISCUSSION A school-based intervention program can improve psychosocial outcomes for inner-city minority children with asthma . Recommendations for future research and clinical practice are discussed STUDY OBJECTIVE This study assessed the impact of a comprehensive school-based asthma program on symptoms , grade s , and school absences in children , and parents ' asthma management practice s. DESIGN R and omized controlled trial . SETTING Fourteen elementary schools in low-income neighborhoods in Detroit , MI . PARTICIPANTS Eight hundred thirty-five children with asthma in grade s 2 through 5 and their parents . INTERVENTION The intervention entailed six components for children , their parents , classmates , and school personnel to encourage and enable disease management . MEASUREMENTS AND RESULTS Parents completed telephone interviews and the schools provided data at baseline and 24 months after intervention . At follow-up , treatment children with persistent disease had significant declines in both daytime ( 14 % fewer , p < 0.0001 ) and nighttime ( 14 % fewer , p < 0.0001 ) symptoms . Among children with both mild intermittent and persistent disease , those in the treatment group had 17 % fewer daytime symptoms ( p < 0.0001 ) but 40 % more nighttime symptoms . Treatment children had higher grade s for science ( p < 0.02 ) but not reading , mathematics , or physical education . No differences in school absences for all causes between groups were noted in school records . However , parents of treatment group children reported fewer absences attributable to asthma in the previous 3 months ( 34 % fewer , p < 0.0001 ) and 12 months ( 8 % fewer , p < 0.05 ) . Parents of treatment children had higher scores ( 2.19 greater , p = 0.02 ) on an asthma management index . The program may have stimulated attention to symptoms at night by parents of children with mild intermittent disease . Overall , the intervention provided significant benefits , particularly for children with persistent asthma School-based asthma interventions delivered by nonschool staff have been successful but are limited in their reach because of the cost and effort of bringing in outside educators and their inability to establish improved communication about asthma between schools , families , and primary care providers ( PCPs ) . To address these problems , Columbia University and the New York City Department of Education and the New York City Department of Health and Mental Hygiene undertook a r and omized controlled trial to test the efficacy of a comprehensive school-based asthma program . In this intervention , school nurses were trained to facilitate the establishment of a preventive network of care for children with asthma by coordinating communications and fostering relationships between families , PCPs , and school personnel . PCPs also received training regarding asthma management . There was limited support for this model . While case detection helped nurses identify additional students with asthma and nurses increased the amount of time spent on asthma-related tasks , PCPs did not change their medical management of asthma . Few improvements in health outcomes were achieved . Relative to controls , 12-months posttest intervention students had a reduction in activity limitations due to asthma ( -35 % vs -9 % , p < .05 ) and days with symptoms ( 26 % vs 39 % , p = .06 ) . The intervention had no impact on the use of urgent health care services , school attendance , or caregiver 's quality of life . There were also no improvements at 24-months postintervention . We faced many challenges related to case detection , training , and implementing preventive care activities , which may have hindered our success . We present these challenges , describe how we coped with them , and discuss the lessons we learned Background . Low-income , minority teens have disproportionately high rates of asthma morbidity and are at high risk for nonadherence to preventive medications . Objective . To assess the feasibility and preliminary effectiveness of an innovative school-based asthma program to enhance the delivery of preventive care for 12–15 year olds with persistent asthma . We hypothesized that this intervention would ( 1 ) be feasible and acceptable among this population and ( 2 ) yield reduced asthma morbidity . Design / methods . Subjects/ setting : Teens with persistent asthma and a current preventive medication prescription in Rochester , NY . Design : Single group pre-post pilot study during the 2009–2010 school year . Intervention : Teens visited the school nurse daily for 6–8 weeks at the start of the school year to receive directly observed therapy ( DOT ) of preventive asthma medications ; 2–4 weeks following DOT initiation , they received three counseling sessions ( one in-home and two via telephone ) using motivational interviewing ( MI ) to explore attitudes about asthma management , build motivation for medication adherence , and support transition to independent preventive medication use . Primary outcome : Number of symptom-free days (SFDs)/2 weeks ; outcome data were collected 2 months after baseline and at the end of school year . Results . We enrolled 30 teens ; 28 participated in the intervention . All teens initiated a trial of school-based DOT . All in-home MI visits were completed successfully , and 89 % completed both follow-up sessions . Teens experienced an overall reduction of symptoms with more SFDs/2 weeks from baseline to 2-month and final ( end of school year ) assessment s ( 8.71 vs. 10.79 vs. 12.89 , respectively , p = .046 and p = .004 ) . Teens also reported fewer days with symptoms , less activity limitation , and less rescue medication use ( all p < .05 ) . Exhaled nitric oxide levels decreased ( p = .012 ) , suggesting less airway inflammation . At the final assessment , teens reported significantly higher motivation to take their preventive medication every day ( p = .043 ) . At the end of the study , 79 % of teens stated that they were better at managing asthma on their own , and 93 % said they would participate in a similar program again . Conclusions . This pilot study provides preliminary evidence of the feasibility and effectiveness of a novel school-based intervention to promote independence in asthma management and improve asthma outcomes in urban teens |
13,270 | 12,838,300 | In NSCLC , Bcl-2 expression was associated with a better prognosis .
The data on Bcl-2 expression in small cell lung cancer were insufficient to assess its prognostic value | The role of the anti-apoptotic protein Bcl-2 in lung cancer remains controversial . | This study was performed to determine the frequency of inactivation and clinical correlates in non-small cell lung cancer ( NSCLC ) of three known tumor suppressor genes [ TSGs ; RB , MTS1/CDKN2 ( p16 ) , and p53 ] and various regions of 3p loss of heterozygosity ( LOH ) as other major potential TSG sites . Paraffin sections from 103 resected NSCLCs were analyzed for expression of pRB , p16 , and p53 by immunohistochemistry , whereas DNA from tumor and normal tissue were tested for LOH at 3p25 - 26 , 3p21 , and 3p14 . Previously published LOH data for 5q , 11p , 17q , and 18q were also available . Loss of pRB or p16 expression and overexpression of p53 were considered abnormal . The immunohistochemical and LOH data were correlated with a variety of clinical parameters including stage , age , sex , smoking history , and survival . With respect to pRB , p16 , and p53 , the tumors could be grouped into four categories : normal for all three proteins ( 21 % ) ; abnormal for pRB or p16 and normal for p53 ( 30 % ) ; normal for pRB and p16 and abnormal for p53 ( 20 % ) ; and abnormal in both pathways ( 28 % ) . Aberrant expression of pRB , p16 , p53 , and 3p LOH , either individually or in combination , was not associated with survival differences or any other clinical parameters , with the exception that pRB/pl6 abnormalities were more common in older patients ( P = 0.0005 ) . pRB and p16 expression showed a strong inverse correlation ( P = 0.002 ) , whereas there was no correlation between expression of pRB , p16 , and p53 . Abnormal expression of any of the three genes inversely correlated with K-ras codon 12 mutations ( P = 0.004 ) , but not with 3p LOH or LOH at other TSG loci . We conclude that resectable NSCLCs show distinct patterns of TSG inactivation , but that no clear clinical correlates exist either alone or in combination for pRB , p16 , p53 , and 3p abnormalities The 5-year survival rate of non-small cell lung carcinoma ( NSCLC ) has only marginally improved during the past two decades , despite advances in surgery and chemoradiotherapy . Major efforts are currently directed toward biological characterization of these tumors to define biomarkers able to add further prognostic information , thus improving new therapeutic protocol s. We analyzed the predictive relevance of the microvessel count ( MC ) , bcl-2 and p53 proteins , proliferative activity , and usual postsurgical parameters on recurrence and overall survival in a series of 70 patients with NSCLC . The expression of biological parameters ( p53 , bcl-2 , proliferative activity , and MC ) was detected using immunohistochemistry on paraffin-embedded and frozen sections from the tumors treated with surgical resection alone until relapse . In the univariate analysis , the histotype , tumor status , node status , p53 , bcl-2 , and MC have been shown to significantly affect progression and death . In the multiple logistic regression analysis , the MC ( P < 0.000001 ) , tumor status ( P < 0.005 ) , and node status ( P < 0.0002 ) influenced the overall survival while prediction of relapse was strongly revealed by tumor status ( P < 0.005 ) , nodal metastatic involvement ( P < 0.000001 ) , and the assessment of the vascular count ( P < 0.0004 ) . These data have allowed the creation of a multivariate model which may add more information on risk of recurrence and death in patients with NSCLC and can form the basis for future r and omized clinical trials This study was design ed prospect ively to evaluate the development of anti-p53 antibodies ( Abs ) in lung cancer patients in relation to their clinical outcome . Sera , derived from 125 lung cancer patients , consisting of 14 small cell lung cancers ( SCLC ) and 111 non-SCLCs ( NSCLC ) , were surveyed . The p53-null human NSCLC cell line , NCI-H1299 , transfected with a human mutant p53 gene was prepared as the source of p53 antigen for immunoblotting analyses to detect the presence of serum anti-p53 Abs . The control group included sera from 10 healthy adults and 14 patients with benign pulmonary diseases . Clinical data including staging and survival were recorded for statistical analyses . The anti-p53 Abs were found in 8 % ( 10 of 125 ) of the lung cancer patients studied ( 8.1 % of NSCLC versus 7.1 % of SCLC patients ) , whereas none of the control sera had detectable anti-p53 Abs . The presence of anti-p53 Abs was closely associated with malignant pleural effusions ( P = 0.001 ) . The p53 Ab-positive patients had a worse prognosis than the p53 Ab-negative patients ( P < 0.02 ; median survival , 20 versus 41 weeks ) . In both univariate and multivariate analyses , the tumor extension and probably the presence of anti-p53 Abs were significant predictors for cancer death . The development of anti-p53 Abs ( n = 9 ) was also a predictor for poor survival in patients with malignant effusions ( n = 51 ) . In conclusion , the presence of serum anti-p53 Abs is closely associated with malignant pleural effusions in lung cancer patients . It may serve as a negative prognostic factor for survival independent of malignant pleural effusions and tumor staging PURPOSE This study attempted to determine the prognostic value for survival of various pretreatment characteristics in patients with nonresectable non-small-cell lung cancer in the context of more than 10 years of experience of a European Cooperative Group . PATIENTS AND METHODS We included in the analysis all eligible patients ( N = 1,052 ) with advanced non-small-cell lung cancer registered onto one of seven trials conducted by the European Lung Cancer Working Party ( ELCWP ) during one decade . The patients were treated by chemotherapy regimens based on platinum derivatives . We prospect ively collected 23 variables and analyzed them by univariate and multivariate methods . RESULTS The global estimated median survival time was 29 weeks , with a 95 % confidence interval of 27 to 30 weeks . After univariate analysis , we applied two multivariate statistical techniques . In a Cox regression model , the selected explanatory variables were disease extent , Karnofsky performance status , WBC and neutrophil counts , metastatic involvement of skin , serum calcium level , age , and sex . These results were confirmed by application of recursive partitioning and amalgamation algorithms ( RECPAM ) , which led to classification of the patients into four homogeneous subgroups . CONCLUSION We confirmed by our analysis the role of well-known independent prognostic factors for survival , but also identified the effect of the neutrophil count , rarely studied , with the use of two methods : a classical Cox regression model and a RECPAM analysis . The classification of patients into the four subgroups we obtained needs to be vali date d in other series Although postoperative adjuvant therapy for non‐small cell lung cancer ( NSCLC ) had not been reported to be effective , it has been reported recently that oral administration of tegafur ( 1‐[2‐tetrahydrofuryl]‐5‐fluorouracil , FT ) may improve the postoperative prognosis . In the present paper , to examine whether p53 status affects the efficacy of FT as postoperative adjuvant chemotherapy for NSCLC , a total of 236 consecutive patients with completely resected pathologic stage I – IIIa NSCLC were retrospectively review ed . p53 status was determined by immunohistochemical staining . For all patients , the 5‐year survival rate of patients with FT administration ( FT group ) was 78.1 % , being significantly higher than that ( 69.1 % ) of patients without FT administration ( control group ) ( P=0.046 ) . For patients without immunohistochemical evidence of p53 overexpression , the 5‐year survival rate in the FT group was 87.1 % , being significantly higher than that ( 74.0 % ) in the control group ( P=0.036 ) . This demonstrates an improvement of postoperative prognosis by FT administration . On the other h and , for patients with p53 overexpression , there was no significant difference in the postoperative prognosis between the FT group and the control group ( 5‐year survival rate 63.2 % and 60.1 % , respectively ; P=0.514 ) , demonstrating that FT administration was not effective for these patients . In conclusion , p53 status may be useful for predicting the efficacy of postoperative adjuvant chemotherapy using FT . A prospect i ve r and omized study stratified by p53 status is needed to clarify the effect of postoperative FT administration Historical information and pathological material from 150 consecutive patients with localized adenocarcinoma of the lung was collected to evaluate oncogene expression of erbB-2 and p53 , and erbB-2 gene amplification . Pathological material after resection was review ed to verify histological staging , and patient follow-up was complete in all cases for at least 68 months . Immunohistochemistry of erbB-2 ( HER-2/neu ) and p53 oncogene expression was performed on two separate paraffin tumor blocks for each patient with normal lung as control . Gene amplification of erbB-2 was measured after DNA extraction from 20-micrometer sections of erbB-2-positive and -negative tumors . All analyses were blinded and included Kaplan-Meier survival estimates with Cox proportional hazards regression modeling . Two adequate blocks of tumor and normal lung were available for 138 ( 92 % ) patients . Immunohistochemical identification of expression of p53 was observed in 49 ( 37 % ) patients and erbB-2 in 17 ( 13 % ) patients . DNA dot blot analyses were performed on 17 erbB-2-positive and 13 r and omly selected erbB-2-negative tumors . There was 1 ( 6 % ) of 17 erbB-2-positve tumors with 4-fold erbB-2 gene amplification . Actual 5-year survival was 63 % and actuarial 10-year survival was 59 % for the entire population of 150 patients . Significant univariate predictors ( P < 0.05 ) of cancer death were the presence of symptoms , tumor size > 3 cm , poor differentiation , visceral pleural invasion , and p53 expression . Multivariate analysis associated symptoms and p53 expression as independent factors with decreased survival . Thus , this project examined p53 and erbB-2 expression in patients with localized adenocarcinoma and associated p53 status with survival . Multicenter collection of data should allow the development of a model of cancer recurrence in this most common lung cancer BACKGROUND Pre clinical studies in animal models have demonstrated tumor regression following intratumoral administration of an adenovirus vector containing wild-type p53 complementary DNA ( Ad-p53 ) . Therefore , in a phase I clinical trial , we administered Ad-p53 to 28 patients with non-small-cell lung cancer ( NSCLC ) whose cancers had progressed on conventional treatments . METHODS Patients received up to six , monthly intratumoral injections of Ad-p53 by use of computed tomography-guided percutaneous fine-needle injection ( 23 patients ) or bronchoscopy ( five patients ) . The doses ranged from 10(6 ) plaque-forming units ( PFU ) to 10(11 ) PFU . RESULTS Polymerase chain reaction ( PCR ) analysis showed the presence of adenovirus vector DNA in 18 ( 86 % ) of 21 patients with evaluable posttreatment biopsy specimens ; vector-specific p53 messenger RNA was detected by means of reverse transcription-PCR analysis in 12 ( 46 % ) of 26 patients . Apoptosis ( programmed cell death ) was demonstrated by increased terminal deoxynucleotide transferase-mediated biotin uridine triphosphate nick-end labeling ( TUNEL ) staining in posttreatment biopsy specimens from 11 patients . Vector-related toxicity was minimal ( National Cancer Institute 's Common Toxicity Criteria : grade 3 = one patient ; grade 4 = no patients ) in 84 courses of treatment , despite repeated injections ( up to six ) in 23 patients . Therapeutic activity in 25 evaluable patients included partial responses in two patients ( 8 % ) and disease stabilization ( range , 2 - 14 months ) in 16 patients ( 64 % ) ; the remaining seven patients ( 28 % ) exhibited disease progression . CONCLUSIONS Repeated intratumoral injections of Ad-p53 appear to be well tolerated , result in transgene expression of wild-type p53 , and seem to mediate antitumor activity in a subset of patients with advanced NSCLC Drug resistance is a major problem in patients with small cell lung cancer ; in fact , most die of resistant disease , despite an initial response . Several markers of drug resistance have been described in pre clinical models , but the mechanism of drug resistance in lung cancer patients remains unknown . The objective of this study was to evaluate the role of the expression of a number of markers of drug resistance , proliferation , and apoptosis in relation to response to chemotherapy and survival in patients with small cell lung cancer . Tumor sample s were derived from 93 previously untreated patients who were r and omized in a Phase III study to receive cyclophosphamide , epirubicine , and etoposide or cyclophosphamide , epirubicine and vincristine alternating with carboplatin and etoposide . Paraffin-embedded sample s , derived from the primary tumor site prior to chemotherapy , were analyzed by immunohistochemistry for expression of markers implicated in drug resistance [ topoisomerase ( topo ) IIalpha , topo IIbeta , and multidrug resistance-associated protein ] , apoptosis ( p53 , p21 , and bcl-2 ) , or proliferation ( Ki67 ) . Response prediction was analyzed by chi2 test and logistic regression analysis ; overall and disease-free survival curves were compared by log-rank test and Cox regression analysis . Shorter survival was observed in patients with extensive disease ( P = 0.037 ) and poorer performance status ( P = 0.028 ) and in patients whose tumors expressed high topo IIalpha levels ( P = 0.01 ) and high Ki67 ( P = 0.024 ) . By multivariate analysis , the following factors were found to be predictive for worse survival : high expression levels of topo IIalpha , Ki67 , and bcl-2 ; male sex ; and extensive disease . High topo IIbeta expression was found to be predictive for lower overall and complete response rate . No relationship between apoptotic pathway markers or MRP and response to chemotherapy was observed . In conclusion , high expression of topo IIalpha was predictive of worse survival , and high expression of topo IIbeta was predictive of lower response rates . Furthermore , lower survival probability was observed in patients with bcl-2-positive tumors . Immunohistochemical assessment of these markers in diagnostic biopsies may give important prognostic information and may help selecting patients in the worse prognostic categories for new therapeutic strategies In order to ascertain the feasibility of detecting p53 gene mutations in patients with lung cancer in a nonsurgical diagnostic setting before starting treatment , we screened for p53 gene mutations in tumor specimens obtained using diagnostic methods such as fiberoptic bronchoscopy , thoracentesis , and percutaneous needle aspiration . We examined 206 specimens from 66 patients diagnosed with primary lung cancer at Hiroshima University Hospital between October 1991 and July 1993 using the polymerase chain reaction/denaturing gradient gel electrophoresis technique . p53 gene mutations were found in 64 of 159 ( 40 % ) cytologically positive specimens , but in none of 47 cytologically negative specimens . The PCR-based assay did not increase the sensitivity of the cytopathologic examination in detecting malignant cells . The type and location of the p53 gene mutation was the same in cytologically positive specimens obtained by different methods , but from the same patient . Of the 66 patients , p53 gene mutations were found in 27 ( 41 % ) at the time of the first nonsurgical diagnostic examination : 7 of 12 ( 58 % ) with small cell carcinoma , 9 of 20 ( 45 % ) with squamous cell carcinoma , and 11 of 34 ( 32 % ) with adenocarcinoma of the lung . The incidence of p53 gene mutation for each histologic subtype was comparable to previously published data examining surgically and /or autopsy-obtained specimens . These results indicate that detection of p53 gene mutations in a nonsurgical , diagnostic setting is feasible . This technique will make it possible to assess the significance of p53 gene mutations in relation to survival and response to therapy before starting treatment , in future prospect i ve studies BACKGROUND Some patients with cancer develop antibodies against the p53 tumor suppressor protein . The presence of these antibodies in serum has been associated with the expression of mutant p53 by the tumor and in some studies with a poorer survival . PURPOSE The goals of this study were to determine the prevalence of anti-p53 antibodies in the serum of patients with newly diagnosed small-cell lung cancer ( SCLC ) and to assess the clinical relevance of the presence of these antibodies in the serum , particularly their relationship with tumor response to treatment and with patient survival . METHODS In this prospect i ve study , serum was obtained from 170 patients at the time of diagnosis of SCLC who were to subsequently receive platinum- or doxorubicin-based chemotherapy at any one of four hospitals in Barcelona , Spain , from October 1991 through June 1994 . Normal human sera from blood bank donors ( n = 50 ) served as controls . The presence of anti-p53 antibodies was determined by western blot analysis with the use of purified recombinant p53 protein . As of January 1996 , 96.5 % of the patients had been treated and observed in the study , for a median follow-up time of 33.5 months . Survival was estimated by the Kaplan-Meier method . Cox proportional hazards regression and unconditional logistic regression analyses were conducted . All P values result ed from two-sided tests . RESULTS Anti-p53 antibodies were detected in the serum of 27 ( 16 % ) of the 170 patients studied . None of 50 serum sample s from normal individuals contained anti-p53 antibodies . Analysis of pretreatment clinical characteristics demonstrated that a weight loss of less than 5 % ( P = .025 ) , a serum lactic acid dehydrogenase ( LDH ) level of less than 450 U/L ( P = .002 ) , and limited stage disease ( i.e. , tumor confined to one hemithorax , with local and regional lymph node positivity for tumor cells and /or ipsilateral pleural effusion allowed ) ( P < .001 ) were associated with a statistically significant complete response to therapy . The presence of serum anti-p53 antibodies was not associated with clinical characteristics , such as age ( P = .622 ) , functional status ( P = 1.0 ) , disease stage ( P = .634 ) , complete response to treatment ( P = .572 ) , and survival ( P = .492 ) or with any laboratory parameters including known prognostic factors in SCLC , such as serum sodium or LDH concentration ( P values of .731 and .246 , respectively ) . CONCLUSIONS AND IMPLICATION S The presence of anti-p53 antibodies in the serum of patients with newly diagnosed SCLC was not associated with any clinical characteristics or prognostic markers , suggesting that , in this context , the measurement of anti-p53 antibodies is not a useful prognostic marker In patients with non-small cell lung cancer ( NSCLC ) , tumor expression of P21-Ras , HER2 , P53 , and Bcl-2 has been reported as independent predictors of prognosis . However , the prognostic information carried by these proteins has usually been determined separately , and their potential interaction has not been taken into account . We conducted immunostaining for P21-Ras , HER2 , P53 and Bcl-2 on 238 cases of NSCLC in a Korean population with 203 squamous cell carcinomas , and 35 adenocarcinomas . P21-Ras , HER2 , P53 or Bcl-2 was expressed at high levels in 54.6 , 42.0 , 18.1 and 71.8 % of the NSCLC studied , respectively . A total of 59 tumors ( 24.8 % ) expressed only one protein , while 70 ( 29.4 % ) expressed two , 59 ( 24.8 ) expressed three , and 17 tumors ( 7.1 % ) expressed all four proteins . Univariate analysis testing the association of marker expression with survival found Bcl-2 expression to be significantly associated with a poor prognosis , as well as the co-expression of Bcl-2 + HER2 , Bcl-2 + HER2 + P53 , and Bcl-2 + HER2 + P53 + P21-ras with an increasing hazard ratio . By multivariate analysis controlling for age , tumor stage and tumor type , only the combination of Bcl-2 + HER2 expression was an independent marker of poor prognosis ( hazard ratio = 1.91 , P = 0.003 ) . Thus , a prospect i ve analysis of the co-expression of Bcl-2 + HER2 in NSCLC patients may identify patients with a poor prognosis who may benefit from more aggressive therapy BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline . Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias OBJECTIVE Microvessel count ( MC ) , as a measure of tumor angiogenesis , has been shown to be significantly correlated with metastatic disease in cutaneous , mammary , prostatic , head and neck cancer . We have previously assessed the role of intensity of angiogenesis as predictor of metastasis in surgically resected T1N0M0 NSCLC . We needed to confirm its value , in a prospect i ve larger study on Stage I NSCLC , before its utilization as a prognostic tool for further clinical investigations . METHODS In the present report we prospect ively investigated 227 patients ( 206 males , 21 females ; median age 65 years ) with Stage I NSCLC treated only by radical surgery between March 1991 and December 1994 with utmost care for some biological characteristics ( proliferative activity , the blood vessel invasion , angiogenesis and the p53 protein expression ) . RESULTS The operative procedures consisted of 62 pneumonectomies , 148 lobectomies and 17 segmentectomies or wedge resections . With a median follow-up of 36 months ( range 15 - 60 ) , eighty patients have already experienced a local ( n = 22 ) or systemic ( n = 58 ) relapse . Univariate analysis revealed that T factor ( T1 versus T2)(P = 0.008 ) and angiogenesis count ( < or = versus > median , 17 ) ( P = 0.0006 ) were significant predictors of survival . The same variables were also significant predictors of long Disease Free Survival ( P = 0.006 and P = 0.004 , respectively ) . On multivariate analysis , however , only the microvessel count retained its level of prognostic significance as regards both overall ( P < 0.01 ) and disease-free survival ( P < 0.01 ) . CONCLUSIONS The present study corroborates the role of angiogenesis in the metastatic spread of NSCLC and emphasizes its value in the identification of patients in whom surgery should be supplemented by systemic treatment Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews BACKGROUND Prophylactic cranial irradiation in patients with small-cell lung cancer decreases the overall rate of brain metastases without an effect on overall survival . It has been suggested that this treatment may increase neuropsychological syndromes and brain abnormalities indicated by computed tomography scans . However , other retrospective data suggested a beneficial effect on overall survival for patients in complete remission . PURPOSE Our purpose was to evaluate the effects of prophylactic cranial irradiation on brain metastasis , overall survival , and late-occurring toxic effects in patients with small-cell lung cancer in complete remission . METHODS We conducted a prospect i ve study of 300 patients who had small-cell lung cancer that was in complete remission . The patients were r and omly assigned to receive either prophylactic cranial irradiation delivering 24 Gy in eight fractions during 12 days ( treatment group ) or no prophylactic cranial irradiation ( control group ) . A neuropsychological examination and a computed tomography scan of the brain were performed at the time of r and om assignment and repeatedly assessed at 6 , 18 , 30 , and 48 months . Patterns of failure were analyzed according to total event rates and also according to an isolated first site of relapse , using a competing-risk approach . RESULTS Two hundred ninety-four patients who did not have brain metastases at the time of r and om assignment were analyzed . The 2-year cumulative rate of brain metastasis as an isolated first site of relapse was 45 % in the control group and 19 % in the treatment group ( P < 10(-6 ) ) . The total 2-year rate of brain metastasis was 67 % and 40 % , respectively ( relative risk = 0.35 ; P < 10(-13 ) ) . The 2-year overall survival rate was 21.5 % in the control group and 29 % in the treatment group ( relative risk = 0.83 ; P = .14 ) . There were no significant differences between the two groups in terms of neuropsychological function or abnormalities indicated by computed tomography brain scans . CONCLUSIONS Prophylactic cranial irradiation given to patients with small-cell lung cancer in complete remission decreases the risk of brain metastasis threefold without a significant increase in complications . A possible beneficial effect on overall survival should be tested with a higher statistical power . IMPLICATION S The results of the trial favor , at present , the indication of prophylactic cranial irradiation for patients who are in complete remission . A longer follow-up and confirmatory trials are needed to fully assess late-occurring toxic effects . The possible effect on overall survival needs to be evaluated with a larger number of patients in complete remission , and a meta- analysis of similar trials is recommended |
13,271 | 19,880,914 | RESULTS Risperidone long-acting injection was the first licensed SGA-LAI compound and is effective in the long-term management of schizophrenia , with a safety profile similar to that of oral risperidone .
In terms of efficacy , at injection intervals of up to 4 weeks it appears comparable to oral olanzapine , although the potential for ; post-injection syndrome ' ( delirium ) calls for additional safety considerations . | BACKGROUND Second-generation antipsychotics ( SGAs ) represent an advance in the long-term management of schizophrenia .
AIMS To review the available evidence concerning SGA long-acting injections ( LAIs ) .
Olanzapine pamoate has recently been approved in Europe . | BACKGROUND Treatment with long-acting injectable risperidone was evaluated in young adults likely to be in the early stages of schizophrenia or schizoaffective disorder . METHOD An open-label 50-week trial included young adults ( men aged 18 - 25 years and women aged 18 - 30 years ) . RESULTS Sixty-six young adults received at least 1 injection of long-acting risperidone ( 25 or 50 mg ) every two weeks ; 64 % of the patients completed the 50-week trial . A mode dose of 25 mg/14 days was received by 23 patients and 50 mg/14 days by 43 patients . Mean PANSS scores improved significantly from baseline at each time point , with 64 % of the patients showing clinical improvement ( > or=20 % reduction in PANSS total scores ) at endpoint . Patient-rated quality of life ( SF-36 scores ) improved and patients ' attitudes toward the medication were positive ( DAI scores ) . Severity of movement disorders ( ESRS ) and injection-site pain ratings were low throughout the trial . Results were similar in the population of other ( older ) patients . CONCLUSIONS Long-acting risperidone was associated with clinical benefits in stable young adults with early schizophrenia or schizoaffective illness The pharmacokinetics and tolerability of long-acting risperidone ( Risperdal Consta ) were evaluated in a multicenter , prospect i ve , open-label , 15-week study of 86 patients with schizophrenia . Subjects stabilized on 2 , 4 or 6 mg of oral risperidone once daily for at least 4 weeks were assigned to receive i.m . injections of 25 , 50 or 75 mg of risperidone , respectively , every 2 weeks for 10 weeks . The 90 % confidence intervals for the i.m./oral ratios of the mean steady-state plasma-AUC , corrected for dosing interval , and of the average plasma concentration of the active moiety ( risperidone plus 9-hydroxyrisperidone ) were within the range of 80 - 125 % , indicating bioequivalence of the i.m . and oral formulations . However , mean steady-state peak concentrations of the active moiety were 25 - 32 % lower with i.m . than oral dosing ( P < 0.05 ) and fluctuations in plasma active-moiety levels were 32 - 42 % lower with the i.m . than oral regimen . Symptoms of schizophrenia continued to improve after switching from oral to i.m . dosing . Long-acting risperidone was well tolerated locally and systematic ally . Although overall bioequivalence of the two formulations was established , the differences in pharmacokinetic profiles between the two formulations indicate potential benefits for long-acting risperidone BACKGROUND The extent to which antipsychotics improve patients ' well-being is uncertain . AIMS To examine psychopathology and patient-rated functioning and well-being in patients treated with risperidone . METHOD In a 1-year , open-label , international multicentre trial of long-acting risperidone in 615 stable adult patients with schizophrenia , self-rated functioning and well-being were measured every 3 months using the Short Form 36-item question naire ( SF-36 ) . Psychopathology was quantified using the Positive and Negative Syndrome Scale ( PANSS ) . RESULTS Significant improvements were found on the SF-36 mental component summary score and vitality and social functioning scales . PANSS and mental component summary scores were moderately correlated . CONCLUSIONS Patient-reported functioning and well-being appear to differ from investigator-rated psychotic symptoms . Patient-rated well-being should be assessed with symptoms to help measure treatment outcomes BACKGROUND The use of risperidone long-acting injection ( RLAI ) is reasonably well supported by controlled studies . Little is known about treatment outcomes in patients receiving RLAI in clinical practice . METHOD All prescribers in the South London and Maudsley Trust , London , United Kingdom , were informed that RLAI could be ordered for suitable patients with a DSM-IV diagnosis of schizophrenia or schizo-affective disorder : those known to be noncompliant with oral atypical antipsychotics and those intolerant of the adverse effects of conventional depot antipsychotics . Prescribers provided treatment and clinical progress data at the time of each prescription . Data collected included reason for prescribing RLAI , Clinical Global Impressions scale ( CGI ) score , inpatient or out-patient status , and details of all medications prescribed . All treatment discontinuations were investigated . The study was conducted from August 2002 to August 2003 . RESULTS Outcome could be determined for 100 subjects . Seventy-nine subjects ( 79 % ) were hospitalized when RLAI was initially prescribed . Mean duration of stay before RLAI initiation was 97 days ( range , 0 - 1492 days ) . Most subjects were switched to RLAI from oral atypical ( 58 % ) or conventional depot ( 28 % ) antipsychotics . The main reason given for prescribing RLAI was poor patient acceptability of previous treatments ( 79 % ) . Overall , 51 % of the subjects discontinued RLAI . The main reason for discontinuation was lack of effect ( 24 subjects ) . No patient-related factor predicted outcome . CGI scores improved from a mean of 4.7 to 3.6 over the study period ( p < .001 ) . Overall , 61 subjects ( 61 % ) showed an improvement in CGI scores between baseline and endpoint . Antipsychotic coprescriptions were reduced from 71 % of subjects to 8 % . In completers , 23 ( 61 % ) of 38 subjects beginning RLAI as in patients were discharged . The modal dose of RLAI was 25 mg every 2 weeks . CONCLUSION RLAI was moderately effective in clinical practice as judged by attrition from treatment . CGI score changes and discharge rates also suggest moderate effectiveness . RLAI was well tolerated . Antipsychotic coprescription was infrequent OBJECTIVE This study examined the effects of 2 doses of long-acting risperidone injection in patients with schizophrenia or schizoaffective disorder . METHOD This 52-week , prospect i ve , r and omized , double-blind , multicenter , international study included clinical ly stable out patients with schizophrenia or schizoaffective disorder ( DSM-IV criteria ) . Setting s included physicians ' offices and clinics . Patients received a fixed dose of long-acting risperidone ( 25 or 50 mg ) every 2 weeks . Primary outcome was time to relapse , defined as either re-hospitalization or other exacerbation criteria . Other assessment s included the Positive and Negative Syndrome Scale , Clinical Global Impressions-Severity of Illness scale , and functional and quality -of-life measures . Safety was assessed via treatment-emergent adverse events , laboratory tests , and movement disorder rating scales . Data were collected from December 2002 to September 2004 . RESULTS A total of 324 patients were r and omized to 25 mg ( N = 163 ) or 50 mg ( N = 161 ) of long-acting risperidone . Time to relapse was comparable ( p = .131 ) for both groups . Projected median time to relapse was 161.8 weeks ( 95 % CI = 103.0 to 254.2 ) with 25 mg and 259.0 weeks ( 95 % CI = 153.6 to 436.8 ) with 50 mg . One-year incidences of relapse were 21.6 % ( N = 35 ) and 14.9 % ( N = 24 ) , respectively ( p = .059 ) . Psychiatric hospitalization was the reason for relapse for 16 ( 10 % ) in the 25-mg group and 10 ( 6 % ) in the 50-mg group . Patients experienced statistically significant but modest improvements at endpoint in most measures ( i.e. , psychotic symptoms , functioning , movement disorder severity ) with both doses , with no significant between-group differences . CONCLUSION In this 1-year study , long-acting risperidone was associated with low relapse and rehospitalization rates , indicating that doses of 25 to 50 mg are appropriate for long-term treatment in schizophrenia Long-acting injectable antipsychotic formulations of conventional antipsychotics were developed to address the problem of partial adherence among patients with schizophrenia . Injection site pain , other skin reactions and patient satisfaction with treatment were assessed in two large , multicentre studies of long-acting injectable risperidone ( Risperdal CONSTA ™ , Janssen Pharmaceutica Products , Titusville , New Jersey , USA ) , the first available long-acting atypical antipsychotic agent . Patients rated injection site pain using a 100-mm Visual Analogue Scale ( VAS ) , and investigators rated injection site pain , redness , swelling and in duration . Patient satisfaction with treatment was assessed with the Drug Attitude Inventory ( DAI ) . VAS pain ratings were low at all visits across all doses in both studies , and decreased from first to final injection . In the 12-week , double-blind study , mean±SD VAS scores at the first and final injections were 15.6±20.7 and 12.5±18.3 for placebo-treated patients , and 11.8±14.4 ( first ) and 10.0±12.4 ( final ) for 25 mg ; 16.3±21.9 ( first ) and 13.6±21.7 ( final ) for 50 mg ; and 16.0±17.9 ( first ) and 9.6±16.0 ( final , P<0.01 ) for 75 mg of long-acting risperidone . Mean VAS scores in the 50-week , open-label study at the first and final injection were : 17.9±22.2 ( first ) and 9.5±16.7 ( final , P<0.0001 ) for 25 mg ; 18.1±19.7 ( first ) and 10.4±14.8 ( final , P<0.0001 ) for 50 mg ; and 18.5±21.6 ( first ) and 13.6±19.9 ( final , P=0.0001 ) for 75 mg of long-acting risperidone . Overall , there was no or minimal injection site pain and skin reactions were rare . Mean DAI ratings were available for the 50-week study and indicated high patient satisfaction throughout the trial ( baseline=7.30 ; endpoint=7.70 ; P<0.0001 versus baseline ) . These findings may positively affect patient and clinician attitudes towards long-term therapy with long-acting injectable risperidone OBJECTIVE The authors assessed the efficacy and safety of the first long-acting atypical antipsychotic ( long-acting injectable risperidone ) in patients with schizophrenia . METHOD In a 12-week , multicenter , double-blind , r and omized study , patients received intramuscular injections every 2 weeks of placebo or long-acting risperidone ( 25 mg , 50 mg , or 75 mg ) . The primary measure of efficacy was the change in total score on the Positive and Negative Syndrome Scale . RESULTS Of the 554 patients who were enrolled , 400 entered the double-blind study , and 370 received at least one postbaseline assessment . Mean changes in score of -6.2 , -8.5 , and -7.4 on the Positive and Negative Syndrome Scale were seen at endpoint for the 25- , 50- , and 75-mg risperidone groups , respectively ; all three change scores were significantly different from that seen with placebo ( + 2.6 ) . Improvements in positive and negative symptoms were also significantly greater in patients receiving risperidone . Long-acting risperidone was well tolerated . Adverse events related to extrapyramidal symptoms were spontaneously reported by 13 % of patients receiving placebo and 10 % of patients in the 25-mg risperidone group , with higher rates in the 50-mg and 75-mg groups . Severity of extrapyramidal symptoms was mild at baseline and throughout the trial in each treatment group . Mean weight changes were small in the 25- , 50- , and 75-mg risperidone groups ( 0.5 kg , 1.2 kg , and 1.9 kg , respectively ) . Injection site pain was rated as low by the patients , consistent with the investigators ' pain ratings . CONCLUSIONS Long-acting injectable risperidone was efficacious and well tolerated and provides both clinicians and patients with a new mode of treatment that can improve the outcome of long-term therapy The maintained antipsychotic efficacy of risperidone long-acting injectable ( RLAI ) was investigated in patients with schizophrenia or other psychoses who were transitioned directly from their previous antipsychotic medication . Patients symptomatically stable , but considered to require a treatment change , received 25 mg of RLAI ( increased to 37.5 or 50 mg , if necessary ) every 2 weeks for 6 months . Assessment s included Positive and Negative Syndrome Scale ( PANSS ) , Clinical Global Impression – Severity ( CGI-S ) , Global Assessment of Functioning ( GAF ) , SF-36 Health-Related Quality of Life Question naire and Extrapyramidal Symptoms Rating Scale ( ESRS ) . Of 1876 patients enrolled , 74 % completed the 6-month study . The most frequent reasons for treatment change were non-compliance ( 38 % ) , insufficient efficacy ( 33 % ) and side-effects ( 26 % ) . There was a significant reduction from baseline to endpoint in mean total PANSS score and in the scores on all PANSS subscales and symptom factors ( P<0.001 ) . CGI-S improved significantly , as did mean GAF score , all factors on the SF-36 and patient satisfaction with treatment . Scores on ESRS showed significant , sustained improvements throughout the study period . Direct initiation of RLAI was effective and well tolerated . RLAI provides an advancement in the treatment options available for a wide range of patients requiring long-term antipsychotic therapy A long-acting depot formulation of olanzapine that sustains plasma olanzapine concentrations for over a month after a single injection is currently under development . This multicenter , open-label study explored D2 receptor occupancy of a fixed dose of olanzapine pamoate ( OP ) depot given every 4 weeks . Patients ( nine male , five female ) with schizophrenia or schizoaffective disorder previously stabilized on oral olanzapine were switched to OP depot 300 mg by intramuscular injection every 4 weeks for 6 months . No visitwise within-group significant changes were found in Brief Psychiatric Rating Scale Total or Clinical Global Impressions-Severity of Illness scores , although seven patients received oral olanzapine supplementation during the first four injection cycles . To minimize impact on D2 occupancy , positron emission tomography ( PET ) scans were not completed during injection cycles that required supplemental oral olanzapine . Two patients reported transient injection site adverse events , which did not result in discontinuation . The most frequently reported treatment-emergent adverse events were insomnia , aggravated psychosis , and anxiety . Mean striatal D2 receptor occupancy , as measured by [11C]-raclopride PET , was 69 % on oral olanzapine ( 5–20 mg/day ) and 50 % ( trough ) on OP depot at steady state . Following an initial decline , occupancy returned to 84 % of baseline oral olanzapine occupancy after six injections . Over the study period , D2 receptor occupancy and plasma olanzapine concentrations were significantly correlated ( r=0.76 , P⩽0.001 ) . OP depot result ed in mean D2 receptor occupancy of approximately 60 % or higher at the end of the 6-month study period , a level consistent with antipsychotic efficacy and found during treatment with oral olanzapine . However , supplemental oral olanzapine or another dosing strategy may be necessary to maintain adequate therapeutic response during the first few injection cycles Recent meta-analytic work suggests atypical antipsychotics may be clinical ly superior to conventional antipsychotics , although many stable patients remain on conventional antipsychotic treatment . A long-acting atypical agent may benefit patients in realms of both advanced medication delivery and mechanism of action . In a multicentre , open-label study of 725 patients with schizophrenia or schizoaffective disorder , patients received 25–75 mg of long-acting risperidone every 2 weeks for up to 50 weeks , with performance of st and ard safety and efficacy assessment s. Data are presented on stable patients receiving oral conventional antipsychotics at study entry . In the 46 ( 6.3 % ) stable patients receiving oral conventional antipsychotics ( followed between 6 months and 1 year ; mean 468 days ) , mean ( SD ) Positive and Negative Syndrome Scale ( PANSS ) total score improved from 73.1±17.2 to 64.5±18.2 ( P=0.0006 ) . Clinical improvement of ≥20 % , ≥40 % or ≥60 % reduction in PANSS total score occurred in 49 % , 29 % and 10 % of stable patients , respectively . Extrapyramidal Symptom Rating Scale subjective ratings and objective physician ratings ( parkinsonism ) decreased significantly ( P<0.05 ) . The hypothesis that switching stable patients treated with oral conventional antipsychotics to long-acting risperidone may result in significant improvements in psychiatric and movement disorder symptomatology merits further investigation BACKGROUND The efficacy and safety of long-acting injectable risperidone have not been compared with those of an oral atypical antipsychotic . AIMS To compare long-acting risperidone and oral olanzapine in 377 patients with DSM-IV schizophrenia or schizoaffective disorder . METHOD Patients were r and omised to receive long-acting risperidone ( 25 mg or 50 mg every 14 days ) or olanzapine ( 5 - 20 mg/day ) . RESULTS In the 13-week phase , long-acting risperidone was at least as effective as ( not inferior to ) oral olanzapine . In the 12-month phase , significant improvements in the Positive and Negative Syndrome Scale ( PANSS ) total and factor scores from baseline to month 12 and end-point were seen in both groups of patients . Few patients discontinued treatment because of an adverse event . CONCLUSIONS Both treatments were efficacious and well tolerated BACKGROUND Elderly patients are often an underserved population in terms of optimizing treatment outcomes . Long-acting risperidone , the first long-acting injectable atypical antipsychotic , can improve outcomes through continuous medication delivery . OBJECTIVE To assess the efficacy and safety of long-acting injectable risperidone in elderly patients with psychotic disorders . METHODS This is a sub analysis of 57 patients aged > or = 65 years enrolled in an open-label study of long-acting risperidone that included 725 symptomatically stable patients with schizophrenia or schizoaffective disorder . Patients were assigned to receive 25 , 50 , or 75 mg of long-acting risperidone every 2 weeks for up to 50 weeks . RESULTS Fifty-seven elderly patients ( mean + /- SE age , 70.9 + /- 0.7 years ) were enrolled . Mean Positive and Negative Syndrome Scale ( PANSS ) total scores improved significantly throughout the study and at endpoint ( p < 0.001 ) . The PANSS factor scores ( positive symptoms , negative symptoms , disorganized thoughts , uncontrolled hostility/excitement , and anxiety/depression ) also significantly improved ( p < 0.01 ) . Clinical improvement ( > or = 20 % reduction in PANSS total scores ) was achieved by 49 % of these stable patients , and 55 % improved on the Clinical Global Impressions scale . Severity of movement disorders ( Extrapyramidal Symptom Rating Scale scores ) was reduced significantly . Adverse events reported in > 10 % of patients were insomnia ( 14 % ) , constipation ( 12 % ) , and bronchitis ( 12 % ) . CONCLUSIONS Long-acting risperidone was associated with significant symptom improvements in stable elderly patients with schizophrenia or schizoaffective disorder . Treatment was well tolerated OBJECTIVE Previous studies showed clinical benefit of risperidone long-acting injection in the treatment of schizophrenia . However , the equivalent switching dose from oral risperidone to risperidone long-acting injection was still in debate . This study , conducted among hospitalized patients , included a long-enough study period and optimal control of drug compliance to test the equivalent switching dose . METHOD Fifty symptomatic , stable hospitalized patients with DSM-IV schizophrenia were r and omly assigned to receive either daily oral risperidone or risperi-done long-acting injection every 2 weeks . Those originally receiving an oral risperidone dose of 4 mg/day or less received 25 mg of risperidone long-acting injection , those taking an oral dose of more than 4 mg/day but of 6 mg/day or less received 37.5 mg of risperidone long-acting injection , and those taking more than 6 mg/day received 50 mg of risperidone long-acting injection . Assessment s of clinical efficacy , side effects , metabolic safety , drug tolerance , and serum concentration of risperi-done metabolites were performed repeatedly . The study was conducted from March 2004 to May 2005 . RESULT Forty-five patients ( 90 % ) completed the study . There were no significant differences in Positive and Negative Syndrome Scale ( PANSS ) scores between the 2 groups , but the risperidone long-acting injection group showed reduced UKU Side Effect Rating Scale total scores ( p = .048 ) , Simpson-Angus Scale scores ( p = .028 ) , prolactin levels ( p = .046 ) , and serum concentrations of risperidone metabolites ( p = .028 ) . Among the risperidone long-acting injection group , patients who received either 25 mg q 2 weeks or 37.5 mg q 2 weeks of risperidone long-acting injection showed increased PANSS scores ( p = .058 ) , decreased serum metabolite concentrations ( p = .028 ) , and an increased tendency to relapse . CONCLUSIONS The results support good tolerability of risperidone long-acting injection , but it is suggested that the equivalent switching dose be adjusted as follows : those originally on an oral risperidone dose of 3 mg/day or less should receive 25 mg of risperidone long-acting injection , those taking an oral dose of more than 3 mg/day but of 5 mg/day or less should receive 37.5 mg , and those taking an oral dose of more than 5 mg/day should receive 50 mg of risperidone long-acting injection BACKGROUND We investigated the impact of treatment with long-acting , injectable risperidone versus placebo on health-related quality of life ( HRQoL ) in patients with schizophrenia . Results are discussed in the context of HRQoL in the general U.S. population . METHOD Patients with DSM-IV schizophrenia entered a r and omized , double-blind , placebo-controlled trial . After screening , previous antipsychotics were discontinued , and oral risperidone was titrated up to a dose of 4 mg/day over 1 week . Patients were then r and omly assigned to receive placebo [ N = 92 ] or long-acting risperidone ( 25 [ N = 93 ] , 50 [ N = 97 ] , or 75 mg [ N = 87 ] every 2 weeks ) for 12 weeks . HRQoL was measured using the Medical Outcomes Study Short-Form 36-item question naire ( SF-36 ) . RESULTS At week 12 , patients receiving long-acting risperidone had improved significantly ( p < .05 ) in 5 domains of the SF-36 ( bodily pain , general health , social functioning , role-emotional , and mental health ) compared with patients receiving placebo . The effect was greatest for the 25-mg group , with significant improvement versus placebo in 6 domains ( p < .05 ) . At baseline , all SF-36 domain scores except bodily pain were significantly lower ( p < .05 ) than normal values in all groups . With placebo , scores in all 8 domains remained below normal values after 12 weeks , while patients receiving long-acting risperidone showed improvement in HRQoL toward normal levels , with clinical ly meaningful improvements in all mental-health domains . In the 25-mg group , scores in 7 domains were not statistically different from normal values after 12 weeks . CONCLUSIONS Long-acting , injectable risperidone improved HRQoL toward normal levels . After 12 weeks , HRQoL of patients receiving 25 mg was not significantly different from normal Although efficacy trials have been conducted on risperidone long-acting injection ( RLAI ) , its most appropriate utilization in clinical practice remains unclear . This 6-month , follow-up study investigated prognostic indicators for early discontinuation of RLAI . Consecutive sampling was conducted for adult patients with a psychotic disorder commenced on RLAI , whose injection was dispensed by one of three South London psychiatric hospital pharmacies . Prescription data were collected prospect ively and clinical data retrospectively . Eightly-one out of 88 ( 92.0 % ) eligible patients were included , of whom 29 ( 35.8 % ) had treatment refractoriness and 30 ( 37.0 % ) discontinued within 6 months . Patients with a preceding oral antipsychotic were more likely to discontinue RLAI than those with a preceding depot ; treatment refractoriness weakly confounded this relationship [ summary adjusted odds ratio ( OR ) 2.68 , 95 % confidence interval ( CI ) 0.95–7.53 , P=0.061 ] . After adjusting for preceding antipsychotic type , patients with treatment refractoriness were no more likely to discontinue than those without ( summary adjusted OR 1.55 , 95 % CI 0.59–4.11 , P=0.376 ) . Sociodemographic factors and other clinical factors were non-predictive of discontinuation . For this first wave of patients commenced on RLAI , many had treatment refractoriness . RLAI discontinuation is high early on but subsequently tapers off . Preceding antipsychotic type ( depot versus oral ) is a stronger prognostic indicator than treatment refractoriness for RLAI discontinuation PURPOSE Although treatment advances have improved outcomes in schizophrenia , definitions of remission and recovery are still evolving . Recently proposed criteria for remission ( mild or less on multiple core-symptom ratings for at least 6 months ) have been applied to a 1-year study of long-acting risperidone injection . METHODS In a 50-week , open-label trial , stable patients with schizophrenia or schizoaffective disorder who received long-acting risperidone injection every 2 weeks were assessed using the Positive and Negative Syndrome Scale ( PANSS ) . Remission criteria for the PANSS were applied ; global illness severity ( Clinical Global Impressions ) and patient-rated health status ( 36-Item Short-form Health Survey ) were measured . RESULTS Groups were identified by initial remission status ( excluding the time component ) . Although considered clinical ly " stable , " 68.2 % ( 394/578 ) did not meet the symptom-severity component of remission criteria at baseline . Following long-acting , injectable risperidone treatment , 20.8 % ( 82 ) of nonremitted patients achieved symptom remission for at least 6 months , with significant decreases in mean PANSS total and cluster scores ( P < 0.0001 ) and significantly improved patient-rated health status ( P < 0.0001 ) . Percentages rated as not ill , very mild , or mild increased from 39 % to 88 % . Among 31.8 % ( 184/578 ) of patients meeting the symptom-severity component of remission criteria at baseline , 84.8 % ( 156 ) maintained these criteria at endpoint . CONCLUSIONS Among previously " stable , " nonremitted patients , many achieved symptom remission after long-acting , injectable risperidone treatment , with significant improvements in multiple symptom domains and patient-rated health status . These results warrant further study as these remission criteria may represent a meaningful clinical endpoint and an important step towards functional recovery Objective : This study aim ed to compare the efficacy of long-acting risperidone and zuclopenthixol in subjects with schizophrenia and substance abuse . Method : A total of 115 subjects with schizophrenia and substance use disorders were enrolled for an open , r and omized , controlled , 6-month follow-up study . Fifty-seven subjects were selected for treatment with long-acting injectable risperidone , while another 58 were treated with zuclopenthixol-depot . Results : Long-acting risperidone patients presented fewer positive urine tests ( 8.67 compared with 10.36 , P = 0.005 ) , showed improved scores on the Positive and Negative Syndrome Scale , and showed better compliance with the Substance Abuse Management program . The use of long-acting risperidone and less severe dependence explained the outcome at the end of the follow-up . Conclusions : Long-acting injectable risperidone was more effective than zuclopenthixol-depot in improving substance abuse and schizophrenia symptoms in subjects with dual diagnosis Using a long-acting antipsychotic to improve adherence early in the illness may reduce relapse rates and promote sustained remission , thereby improving the long-term outcome of schizophrenia . We assessed whether risperidone long-acting injection ( RLAI ) could be used safely and effectively in the treatment of recent-onset psychosis . Fifty patients aged 15 to 43 years with newly diagnosed schizophreniform disorder or schizophrenia were treated with RLAI 25 to 50 mg every 2 weeks for 2 years . Thirty-six patients ( 72 % ) completed the trial . Of 39 ( 78 % ) who showed a clinical response of 50 % , 4 relapsed . Thirty-two patients ( 64 % ) achieved remission . Mean maximum increase in Extrapyramidal Symptoms Rating Scale total score was 1.4 ( 95 % confidence interval , 0.61 - 2.10 ; n = 50 ) ; 10 patients required anticholinergic medication , and 1 subject developed persistent dyskinesia . Prolactin levels were elevated in 18 patients , 4 of whom reported possible prolactin-related adverse events . Mean increase in body mass index to last visit for all patients was 4.8 kg/m2 ( SD , 3.8 kg/m2 ) . The final RLAI dose was 25 mg for 54 % of patients , 37.5 mg for 30 % , and 50 mg for 16 % . This preliminary study suggests that RLAI was overall well tolerated and appears to be effective in recent-onset psychosis . Further investigation is warranted BACKGROUND The safety and efficacy of the first long-acting injectable atypical antipsychotic , risperidone , were assessed in stable patients with schizophrenia switched from oral antipsychotic medications . METHOD Data were collected between July 1 , 2001 , and October 25 , 2002 . The study population included patients from clinics , hospitals , and physicians ' offices . After a 4-week run-in period , symptomatically stable patients with schizophrenia ( DSM-IV ) who had been taking haloperidol ( N = 46 ) , quetiapine ( N = 45 ) , or olanzapine ( N = 50 ) received 25 mg of long-acting risperidone . The oral antipsychotics were continued for 3 weeks after the first injection of long-acting risperidone . Injections were administered every 2 weeks at 25 mg up to a maximum dose of 50 mg for 12 weeks in this multicenter , open-label study . RESULTS Long-acting risperidone was well tolerated . Of the 141 patients who participated in the study , the most frequently reported adverse events were insomnia ( 16 % ) , headache ( 15 % ) , psychosis ( 11 % ) , and agitation ( 11 % ) . The mean increase in body weight was 0.4 kg . No other clinical ly relevant laboratory abnormalities or significant electrocardiogram changes were observed during the 12-week treatment . Extrapyramidal Symptom Rating Scale total scores were reduced during treatment with long-acting risperidone . Improvements in symptoms of schizophrenia were observed with long-acting risperidone at week 4 and continued through the 12-week treatment with significant reductions in total Positive and Negative Syndrome Scale ( PANSS ) scores at week 8 ( -2.5 , p < .01 ) and week 12 ( -3.9 , p < .001 ) . At endpoint , 37 % ( 50/135 ) of these stable patients were rated as clinical ly improved ( > or = 20 % decrease in PANSS total scores ) . CONCLUSIONS Switching treatment from oral antipsychotics to long-acting risperidone without an intervening period of oral risperidone was safe and well tolerated . Long-acting risperidone also significantly reduced the severity of symptoms in these stable patients with schizophrenia We evaluated the efficacy and safety of the investigational long-acting injectable antipsychotic agent paliperidone palmitate ( PP ) in the treatment of schizophrenia . Patients were r and omized to receive gluteal injections of placebo or PP ( 50 or 100 mg eq. , fixed doses ) , without oral supplementation , on days 1 , 8 , and 36 ( 9-wk , double-blind phase ) in this phase 2b study . Patients ( n=197 , intent-to-treat analysis set ) were 62 % men , mean ( s.d . ) age 39 ( 10 ) yr , with a baseline mean ( s.d . ) Positive and Negative Syndrome Scale ( PANSS ) total score of 87.0 ( 12.5 ) . Mean ( s.d . ) PANSS total scores showed significant improvement at endpoint ( primary measure ) for both the PP 50 mg eq. [ -5.2 ( 21.5 ) ] and PP 100 mg eq. [ -7.8 ( 19.4 ) ] groups , vs. placebo [ 6.2 ( 18.3 ) ] ( p0.001 , each dose vs. placebo ) . This improvement was detected by day 8 and maintained to endpoint ( p0.011 ) for both doses . In the safety analysis set ( n=247 ) , fewer PP-treated patients ( 2 % ) discontinued for treatment-emergent adverse events vs. placebo-treated ( 10 % ) . Rates of treatment-emergent extrapyramidal syndrome-related adverse events were comparable between active treatment and placebo , with the exception of parkinsonism-related disorders ( 50 mg eq. 5 % , 100 mg eq. 8 % , placebo 1 % ) . Results of other safety measures suggest PP to be generally well-tolerated . Throughout the study , investigators rated injection-site pain as absent ( 56 - 71 % ) , mild ( 24 - 39 % ) , moderate ( 2 - 12 % ) , or severe ( 0 - 2 % ) . PP ( 50 and 100 mg eq. doses ) administered as a gluteal intramuscular injection was efficacious and generally tolerated in these patients with acute symptomatic schizophrenia Abstract Cognitive abnormalities represent an important therapeutic target in the treatment of schizophrenia . Working memory deficits are among the core abnormalities and affect social functioning . We used functional magnetic resonance imaging to examine cortical systems supporting working memory in patients with schizophrenia treated with risperidone long-acting injections ( RLAIs ) versus those on conventional depot medication ( CONV ) . Sixteen patients on RLAI , 16 patients on CONV matched for clinical symptoms and other illness variables , and 8 HCs performed an n-back task ( 1- , 2- , 3-back ) in the scanner . The level of performance decreased with increasing memory load , which was particularly evident in the CONV group . Patients on RLAI and controls demonstrated task-dependent decreases in activation in medial PFC , whereas the CONV group overactivated that region . The CONV group also showed underactivation of VLPFC compared with controls under conditions of increasing memory load , with the RLAI group showing an activation pattern not significantly different from either group . We conclude that RLAI may contribute to normalization of brain activation in regions involved in working memory functioning in people with chronic schizophrenia BACKGROUND Schizophrenia is associated with disproportionately high costs , mainly due to hospitalization rates . This study assessed healthcare re source use in patients with schizophrenia and schizoaffective disorder during treatment with long-acting risperidone . METHODS Patients ( n = 397 [ in patients , 24 % ; out patients , 76 % ] ) receiving stable doses of an antipsychotic for > or=4 weeks were eligible to enter this 1-year , open-label study . Following a 2-week run-in period ( oral risperidone 1 - 6 mg/day ) , patients received intramuscular long-acting risperidone ( 25 or 50 mg modal dose ) every 2 weeks . Healthcare re source use in the previous 12 weeks was assessed at baseline and 12-weekly intervals . RESULTS Patients needing hospitalization decreased significantly and continuously from 38 % during the 12 weeks before study entry to 12 % during the last 12 weeks . Mean hospitalization length during the study was 30.5 days ( out patients , 4.9 days ; in patients , 110 days ) . This included 28 patients ( 7 % ) who remained in hospital throughout the study . During treatment , 71 % of those hospitalized at baseline were discharged . Partial hospitalization decreased significantly from 7 % of patients during the 12 weeks before treatment to 3 % during the last 12 weeks . Outpatient consultations also decreased significantly from 70 % of patients to 30 % in the first 12 weeks of treatment and remained stable thereafter . Only 9 % of patients required an emergency room visit ; mostly for non-psychiatric conditions . CONCLUSION Healthcare re source use is significantly reduced in patients with stable schizophrenia or schizoaffective disorder receiving long-acting risperidone . It is highly likely that these reductions will decrease healthcare costs in patients receiving long-acting risperidone A double-blind study of long-acting injectable risperidone and oral risperidone tablets was conducted in 640 patients with schizophrenia . All patients received flexible doses of 1 - 6 mg of oral risperidone for 8 weeks . Doses were stable during weeks 5 - 8 . At the end of week 8 , symptomatically stable patients were r and omly assigned to receive long-acting risperidone ( active injections , dummy oral ) or continued oral risperidone ( dummy injections , active oral ) for 12 weeks . Significant improvements were demonstrated from baseline to endpoint in Positive and Negative Syndrome Scale ( PANSS ) total ( P<0.001 ) and factor scores ( P<0.05 ) in both groups . According to a noninferiority analysis , the two treatments showed comparable efficacy in total PANSS scores over the short-term . No unexpected adverse events were recorded . The findings indicate that symptomatically stable patients can be safely switched from oral risperidone to long-acting injectable risperidone without compromising efficacy BACKGROUND The treatment of schizoaffective disorder is often complicated by the variety of symptoms that contribute to its pathology . Data from a large study ( n=725 ) , which included schizoaffective patients to assess the effect of long-acting risperidone , are presented . METHOD A multicenter , open-label study enrolled non-acute , clinical ly stable patients with schizoaffective disorder ( n=110 ) . Patients on a stable dose of antipsychotic for at least 4 weeks at study entry were switched to long-acting risperidone every 2 weeks for 50 weeks . RESULTS Mean Positive and Negative Syndrome Scale ( PANSS ) total scores ( + /-S.E. ) improved significantly ( p<0.001 ) at each measured time point , including endpoint ( -9.0+/-1.6 ) , compared with baseline . Significant reductions were observed on mean PANSS cluster scores for both anxiety/depression ( -1.3+/-0.4 , p<0.001 ) and uncontrolled hostility/excitement ( -0.7+/-0.3 , p<0.05 ) . In addition , scores improved significantly for positive symptoms ( -2.2+/-0.5 , p<0.001 ) , negative symptoms ( -3.1+/-0.5 , p<0.001 ) , and disorganized thoughts ( -1.7+/-0.4 , p<0.001 ) . The overall subjective score of movement disorders was low at baseline ( 3.6+/-4.1 ) and had significantly decreased at endpoint ( 2.75 ; p<0.05 ) . Patients were previously treated with antipsychotics for 398+/-790 days before being switched to long-acting risperidone . LIMITATIONS Although this was a 50-week study , which included over 100 patients with schizoaffective disorder , limitations include the open-label design and that it was not design ed specifically to assess patients with this disorder . PANSS symptom domains previously defined by factor analytic methods were used for mood symptom measures . No specific mood symptom scales were administered in this study . CONCLUSION Patients with schizoaffective disorder , considered stable on their antipsychotic medication at study entry , experienced additional significant clinical improvements and minimal side effects with injections of long-acting risperidone over a 50-week study period BACKGROUND Conventional depot antipsychotics can provide constant pharmacologic treatment , eliminating partial compliance and reducing relapse risk . Atypical antipsychotics , have improved clinical profiles but require daily dosing , compromising their overall effectiveness . As oral risperidone provides safety and efficacy benefits over oral haloperidol , improvements may be realized by replacing conventional with atypical agents in long-acting therapy . This report examines 50-weeks of long-acting risperidone therapy in patients previously stabilized with conventional depot antipsychotics . METHODS A multi-center , open-label study enrolled 725 patients with schizophrenia or schizoaffective disorder , judged clinical ly stable and maintained on stable antipsychotic doses for > or = 4 weeks . Assignment by clinician judgment to receive 25 - 75 mg of long-acting risperidone every 2 weeks for 50 weeks followed , with performance of st and ard safety and efficacy assessment s. Data are presented on patients receiving conventional depot antipsychotic monotherapy at study entry . RESULTS In the 188 ( 25.9 % ) patients receiving conventional depot antipsychotic monotherapy at entry , mild-to-moderate mean ( + /-S.D. ) Positive and Negative Syndrome Scale (PANSS)-total scores improved significantly after receiving long-acting risperidone ( 64.2 + /- 18.9 to 58.2 + /- 20.3 ; P < 0.001 ) . Clinical improvement of > or = 20 % , 40 % , or 60 % reduction in PANSS-total score , occurred in 52 % , 34 % , and 16 % of patients , respectively . ESRS subjective ratings and objective physician ratings ( Parkinsonism ) decreased significantly ( P < 0.001 ) . CONCLUSION Stable patients with mild , residual symptomatology treated with conventional depot antipsychotics experienced significant improvement in psychiatric and movement disorder symptomatology following 1-year of treatment with long-acting risperidone Risperidone long-acting injection ( RLAI ) is the first depot preparation of the so-called atypical antipsychotics . Efficacy is well established but effectiveness and factors predicting favourable outcome have only tentatively been evaluated . Our aim was to evaluate naturalistic outcome in patients given RLAI in normal clinical practice and to uncover factors predicting favourable outcome . Prescribers provided details of all patients prescribed RLAI on starting treatment and fortnightly thereafter . Patients were followed up for 6 months or until RLAI was discontinued . Main outcome measures were continuation with RLAI at 6 months and improvement in Clinical Global Impression ( CGI ) score . These outcomes were compared with clinical and patient data . Of 250 patients starting RLAI , 118 ( 47.2 % ) were still receiving it at 6 months . Patients were more likely to continue treatment with RLAI to 6 months if older than 55 yr [ odds ratio ( OR ) 3.13 , 95 % CI 1.32 - 7.40 , p=0.006 ] and if receiving a dose of > 25 mg/2 wk RLAI ( OR 2.37 , 95 % CI 1.40 - 3.99 , p<0.001 ) . An improvement of one point on the CGI scale ( first vs. last assessment ) was more likely in those prescribed RLAI because of poor prior adherence ( OR 2.28 , 95 % CI 1.35 - 3.86 , p=0.002 ) and less likely in those who had previously been prescribed clozapine ( OR 0.29 , 95 % CI 0.14 - 0.61 , p=0.001 ) . Overall outcome of RLAI treatment is moderately good but better still when prescribed because of prior poor adherence and for more elderly patients . RLAI is less suitable for those who have previously received clozapine INTRODUCTION Treatment-emergent tardive dyskinesia ( TD ) can be a serious side effect of antipsychotic treatment . Atypical antipsychotics are associated with a lower risk for TD than are conventional agents . A long-acting atypical antipsychotic , with more stable blood levels and lower peak blood levels than an oral formulation , may provide differential benefit regarding side effects , including movement disorders . This analysis assessed TD by defined research criteria in patients receiving long-acting , injectable risperidone . METHODS Clinical ly stable subjects with schizophrenia or schizoaffective disorder participated in a 50-week , open-label trial of long-acting , injectable risperidone . TD was studied by defined research criteria ( Schooler , N.R. , Kane , J.M. , 1982 . Research diagnosis for tardive dyskinesia . Arch . Gen. Psychiatry . 39 , 486 - 487 ; Americal Psychiatric Association , 2000 . Diagnostic and Statistical Manual of Mental Disorders , fourth ed . American Psychiatric Association , Washington , DC ) . The severity of dyskinesia and other movement disorders were rated by the Extrapyramidal Symptom Rating Scale ( ESRS ) . RESULTS ESRS dyskinesia data were available for 662 patients . Five of 530 subjects without dyskinesia at baseline ( 0.94 % ) met the predefined criteria for emergent persistent TD during therapy . Based on either exposure to study medication or Kaplan-Meier analysis , the 1-year rate was 1.19 % . Among the 132 subjects with dyskinesia at baseline , the mean score on the ESRS physician 's exam for dyskinesia improved significantly at endpoint ( -2.77 ; P<0.0001 ) , regardless of anticholinergic drug use . ( P=0.243 for patients with versus without anticholinergic drug use . ) CONCLUSIONS In this open-label study , treatment with long-acting risperidone was associated with a low rate of emergent persistent TD . Significant improvement in existing dyskinesias was noted . The TD rate reported here is consistent with other reports of atypical antipsychotics and substantially lower than with conventional antipsychotics BACKGROUND The long-term safety and efficacy of long-acting injectable risperidone , the first long-acting second-generation antipsychotic , were evaluated in stable patients with schizophrenia . METHOD After a 2-week run-in period during which patients with DSM-IV schizophrenia received flexible doses of 1 to 6 mg of oral risperidone , patients received injections of 25 mg , 50 mg , or 75 mg of long-acting risperidone every 2 weeks for 12 months . Severity of extrapyramidal symptoms was assessed with the Extrapyramidal Symptom Rating Scale ( ESRS ) , and efficacy was assessed with the Positive and Negative Syndrome Scale ( PANSS ) . This study was conducted from March 29 , 1999 to July 19 , 2000 . RESULTS The subjects were 615 patients with schizophrenia who received at least 1 injection of long-acting risperidone . The 12-month trial was completed by 65 % of patients . Treatment was discontinued because of adverse events in 5 % of patients . Extrapyramidal symptoms as adverse events were reported by 25 % of the patients . Severity of extrapyramidal symptoms ( according to ESRS scores ) was low at baseline and decreased in each of the groups during the 12 months . The other most common adverse events were anxiety in 24 % , insomnia in 21 % , psychosis in 17 % , and depression in 14 % of the patients . Little pain was associated with the injections . Severity of symptoms of schizophrenia was improved in each group , with significant reductions in PANSS total scores ( p < .01 ) and positive ( p < .01 ) and negative ( p < .001 ) factor scores . CONCLUSION In terms of both safety and efficacy , symptomatically stable patients with schizophrenia benefit from being switched to long-acting injectable risperidone Modern atypical antipsychotics have advantages over older neuroleptics . We hypothesize that their utility may be further enhanced by sustained drug delivery without daily oral self-dosing . This report examines the effects of a year of treatment with long-acting risperidone for chronically psychotic patients previously stabilized with oral risperidone . This open trial of long-acting risperidone involved 336 patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder judged clinical ly stable on a consistent daily oral dose of risperidone for > or = 4 wk . Based on oral doses , subjects were assigned clinical ly to bi-weekly intramuscular injections of 25 - 75 mg of long-acting risperidone for up to 50 wk . Clinical assessment s at regular intervals included the Positive and Negative Syndrome Scale ( PANSS ) , Clinical Global Impressions ( CGI ) scale , adverse event reports , and the Extrapyramidal Symptom Rating Scale ( ESRS ) . PANSS total scores improved overall from a moderate baseline score of 64.5+/-17.7 to 58.8+/-19.9 at end-point ( p<0.001 ) , by > or = 20 % in 50 % of patients , with greatest improvement in negative symptoms . Prevalence of favourable CGI - Severity ratings increased by 2.4-fold ( p<0.0001 ) . Ratings of extrapyramidal symptoms also improved [ e.g. physician-rated parkinsonism scores decreased by 20 % ( p<0.0001 ) ] . Tissue reactions and other adverse effects of repeated intramuscular injections were rare and mild . Psychotic patients considered stable but symptomatic with oral risperidone treatment showed further improvements in symptom ratings and extrapyramidal dysfunction during a year of bi-weekly injections of long-acting risperidone Thirteen patients with schizophrenia received injections of 25 , 50 , or 75 mg of long-acting risperidone every 2 wk . Brain D2 receptor occupancy was assessed with [11C]raclopride 2 wk after the last ( fifth ) injection ( day 71 ) in seven subjects and 2 wk after the third injection ( day 44 ) in one subject . Stable plasma concentrations were reached after the third injection and steady-state concentrations of the active moiety ( risperidone + 9-hydroxyrisperidone ) after the fourth injection . Steady-state plasma concentrations were maintained for 4 - 5 wk after the last injection and then declined rapidly . After injections of 25 , 50 and 75 mg on day 44 or day 71 , D2 receptor occupancy ranged from 25 - 48 % , 59 - 83 % and 62 - 72 % respectively , while plasma active-moiety levels ranged from 4.4 - 8.8 , 15.0 - 31.1 and 22.5 - 26.3 ng/ml respectively . The results indicate that brain D2 receptor occupancy at steady state after injections of long-acting risperidone was in the range found in patients effectively treated with 2 - 6 mg of oral risperidone There is limited documentation on the pharmacokinetics of long-acting intramuscular risperidone in a naturalistic setting . The objective of this study was to investigate the concentrations of risperidone and its active metabolite 9-hydroxyrisperidone as well as the concentration/dose ( C/D ) ratios achieved after intramuscular depot administration in a routine therapeutic drug monitoring setting . Thirty sample s were collected from 10 female and 20 male patients receiving depot injections of risperidone . For 6 of the patients , the results could be compared with corresponding data available after previous oral administration of risperidone . In addition , data from a group of 278 patients using oral risperidone were retrieved . The median serum concentrations of risperidone plus 9-hydroxyrisperidone were 38 nmol/L 12 - 14 days after a intramuscular dose of 25 mg/14 days , 67 nmol/L after a dose of 37.5 mg/14 days , 99 nmol/L after a dose of 50 mg/14 days , and 148 nmol/L after a dose of 75 mg/14 days . The median C/D ratio for risperidone plus 9-hydroxy-risperidone was 22.2 (nmol/L)/(mg/d ) . In the group on oral medication , the median C/D ratio was 18.6 (nmol/L)/(mg/d ) . In the 6 patients previously using oral risperidone , switching to depot injections gave an average increase of 33 % ( range 12%-68 % ) in the C/D ratio . In conclusion , the authors ' data indicate that there are great interindividual differences in the extent to which the daily dose has to be reduced when switching from oral to intramuscular depot administration to achieve the same serum concentrations of risperidone plus 9-hydroxyrisperidone . Because the degree of dose adjustment required for the individual patient so far can not be predicted , guidance by therapeutic drug monitoring might be helpful OBJECTIVE To examine the efficacy and tolerability of a new injectable formulation of olanzapine , olanzapine long-acting injection ( LAI ) , relative to placebo for treatment of acutely ill patients with schizophrenia . METHOD Patients with DSM-IV or DSM-IV-TR schizophrenia in this 8-week , double-blind study were r and omly assigned to receive 210 mg/2 weeks , 300 mg/2 weeks , or 405 mg/4 weeks of olanzapine LAI or placebo/2 weeks . No oral antipsychotic supplementation was permitted . The primary efficacy measure was mean baseline-to-end point change in Positive and Negative Syndrome Scale ( PANSS ) total score . The study was conducted from June 2004 to April 2005 . RESULTS Mean baseline-to-end point decreases in PANSS total scores were significantly greater for all olanzapine LAI regimens relative to placebo ( all p values < .001 ) . The 300 mg/2 weeks and 405 mg/4 weeks olanzapine LAI groups separated from placebo on the PANSS total at 3 days after starting treatment , and all olanzapine LAI groups separated from placebo by 7 days . Rates of clinical improvement ( end point Clinical Global Impressions-Improvement scale score < or= 3 ) were significantly higher for all olanzapine LAI groups relative to placebo ( p < .001 ) . Incidences of sedation and increased appetite were significantly higher for 300 mg/2 weeks olanzapine LAI relative to placebo ( p < .05 ) . Mean weight gain ( 3.2 - 4.8 vs. 0.3 kg , p < .001 ) and incidence of weight gain > or= 7 % of baseline ( 23.6 - 35.4 % vs. 12.4 % , p < or= .046 ) were significantly greater for olanzapine LAI relative to placebo . Significant differences between all olanzapine LAI groups and placebo were observed regarding mean baseline-to-end point changes in fasting total cholesterol ( 5.5 - 10.4 vs. -7.0 mg/dL ; p < or= .015 ) and between the 210 mg/2 weeks and 405 mg/4 weeks groups ( 26.3 - 30.3 vs. -9.4 mg/dL ; p < or= .016 ) , but not the 300 mg/2 weeks group ( 17.6 mg/dL ; p = .055 ) , and placebo for fasting triglycerides . CONCLUSIONS In this 8-week study , olanzapine LAI administered at 2- or 4-week injection intervals was significantly more efficacious than placebo for the treatment of acutely ill patients with schizophrenia despite no use of supplemental oral antipsychotics . Consistent with changes previously observed with oral olanzapine , clinical ly significant weight gain and changes in some lipid parameters were observed in patients treated with olanzapine LAI |
13,272 | 27,203,274 | Conclusions : Our study revealed that current available tools are not sufficiently able to accurately and reliably assess SK to promote stroke prevention and management . | Background : Accurate assessment of stroke knowledge ( SK ) is fundamental to the successful underst and ing of , monitoring of , and intervening to improve the SK of patients and the public .
Purpose : The purpose of this study is to perform a systematic review of the existing SK tests and appraise their conceptual basis , feasibility , and psychometric properties . | BACKGROUND We describe the design and baseline data of an educational intervention targeting predominantly Mexican American middle school students and their parents in an effort to improve stroke awareness . Increasing awareness in this group may increase the number of patients eligible for acute stroke treatment by encouraging emergency medical services ( EMS ) activation . METHODS This is a prospect i ve , r and omized study in which six middle schools were r and omly assigned to receive a stroke education program or the st and ard health class . Primary outcome measures are the percentage of students and parents who recognize stroke symptoms and express the intent to activate EMS upon recognition of these findings . RESULTS A total of 547 students ( 271 control , 276 intervention ) and 484 parents ( 231 control , 253 intervention ) have been enrolled . Pretests were administered . The intervention has been successfully carried out in the parent and student cohorts over a three-year period . Posttests and persistence test results are pending . CONCLUSION Implementing a school-based stroke education initiative is feasible . Followup testing will demonstrate whether this educational initiative translates into a measurable and persistent improvement in stroke knowledge and behavioral intent to activate EMS upon recognition of stroke symptoms Background and Purpose — Reduction in the risk of stroke and increase in the speed of hospital presentation after the onset of stroke both depend on the level of knowledge of stroke in the general population . The aim of the present study was to assess baseline knowledge regarding stroke risk factors , symptoms , treatment , and information re sources . Methods — A community-based telephone interview survey was conducted in the Newcastle urban area in Australia . A total of 1278 potential participants between the ages of 18 to 80 were selected at r and om from an electronic telephone directory . A trained telephone interviewer conducted a telephone survey using the Computer-Assisted Telephone Interviewing ( CATI ) program . Results — A total of 822 participants completed the telephone interview . Six hundred three participants ( 73.4 % ) correctly identified the brain as the affected organ in stroke . The most common risk factors for stroke identified by respondents were smoking ( identified by 324 [ 39.4 % ] ) and stress ( identified by 277 [ 33.7 % ] ) . The most common warning sign of stroke described by respondents was “ blurred and double vision or loss of vision in an eye , ” listed by 198 ( 24.1 % ) . A total of 626 ( 76.2 % ) respondents correctly listed ≥1 established stroke risk factor , but only 409 ( 49.8 % ) respondents correctly listed ≥1 warning sign . Conclusions — The level of knowledge in the community of established stroke risk factors , warning signs , and treatment as indicated by this survey suggests that a community-based education program to increase public knowledge of stroke may contribute to reducing the risk of stroke and to increasing the speed of hospital presentation after the onset of stroke Background and Purpose — This study compared the psychometric properties of 3 clinical balance measures , the Berg Balance Scale ( BBS ) , the Balance subscale of the Fugl-Meyer test ( FM-B ) , and the Postural Assessment Scale for Stroke Patients ( PASS ) , in stroke patients with a broad range of neurological and functional impairment from the acute stage up to 180 days after onset . Methods — One hundred twenty-three stroke patients were followed up prospect ively with the 3 balance measures 14 , 30 , 90 , and 180 days after stroke onset ( DAS ) . Reliability ( interrater reliability and internal consistency ) and validity ( concurrent validity , convergent validity , and predictive validity ) of each measure were examined . A comparison of the responsiveness of each of the 3 measures was made on the basis of the entire group of patients and 3 separate groups classified by degree of neurological severity . Results — The FM-B and BBS showed a significant floor or ceiling effect at some DAS points , whereas the PASS did not show these effects . The BBS , FM-B , and PASS all had good reliability and validity for patients at different recovery stages after stroke . The results of effect size demonstrated fair to good responsiveness of all 3 measures within the first 90 DAS but , as expected , only a low level of responsiveness at 90 to 180 DAS . The PASS was more responsive to changes in severe stroke patients at the earliest period after stroke onset , 14 to 30 DAS . Conclusions — All 3 measures tested showed very acceptable levels of reliability , validity , and responsiveness for both clinicians and research ers . The PASS showed slightly better psychometric characteristics than the other 2 measures Background and Purpose — Previous overt stroke and sub clinical stroke are frequent in patients with stroke ; yet , their clinical significance and effects on stroke outcome are not clear . We studied the burden and outcome after acute ischemic stroke by prevalent ischemic brain disease in a national registry of hospitalized patients with acute stroke . Methods — Patients with ischemic stroke in the National Acute Stroke Israeli prospect i ve hospital-based registry ( February to March 2004 , March to April 2007 , and April to May 2010 ) with information on previous overt stroke and sub clinical stroke per computed tomography/MRI ( n=3757 ) were included . Of them , a sub sample ( n=787 ) was followed up at 3 months . Logistic regression models were computed for outcomes in patients with prior overt stroke or sub clinical stroke , compared with patients with first stroke , adjusting for age , sex , vascular risk factors , stroke severity , and clinical classification . Results — Two-thirds of patients had a prior overt stroke or sub clinical stroke . Death rates were similar for patients with and without prior stroke . Adjusted odds ratios ( OR ; 95 % confidence interval [ CI ] ) for disability were increased for patients with prior overt stroke ( OR , 1.31 ; 95 % CI , 1.03–1.66 ) and sub clinical stroke ( OR , 1.45 ; 95 % CI , 1.16–1.82 ) . Relative odds of Barthel Index ⩽60 for patients with prior overt stroke ( OR , 2.04 ; 95 % CI , 1.14–3.68 ) and with prior sub clinical stroke ( OR , 2.04 ; 95 % CI , 1.15–3.64 ) were twice higher than for patients with a first stroke . ORs for dependency were significantly increased for patients with prior overt stroke ( OR , 1.95 ; 95 % CI , 1.19–3.20 ) but not for those with sub clinical stroke ( OR , 1.36 ; 95 % CI , 0.84–2.19 ) . Conclusions — In our national cohort of patients with acute ischemic stroke , nearly two thirds had a prior overt stroke or sub clinical stroke . Risk of poor functional outcomes was increased for patients with prior stroke , both overt and sub clinical BACKGROUND The ideal method of providing stroke patients with information has not been established . OBJECTIVES To evaluate the effectiveness of providing stroke patients with computer-generated tailored written information . DESIGN R and omised controlled trial with blinded assessor . SETTING Acute stroke unit . PARTICIPANTS 138 stroke patients . METHODS Patients were r and omised to receive either computer-generated tailored written information about stroke or generic written information while in hospital . Three months following discharge , a blinded assessor evaluated the outcomes of knowledge about stroke , self-efficacy ( Self-Efficacy to Perform Self-Management Behaviours Scale ) , anxiety and depression ( Hospital Anxiety and Depression ( HAD ) Scale ) , perceived health status ( COOP charts ) , satisfaction with content and presentation of the written information received ( separate 10-point visual analogue scale for content and presentation ) , and desire for additional information . RESULTS Complete data were obtained for 133 ( 96.4 % ) patients . Patients in the intervention group were significantly more satisfied with the content ( difference on a 10-point visual analogue scale was 1 , 95 % confidence interval 0.4 to 1.7 , P = 0.003 ) and presentation ( difference on a 10-point visual analogue scale was 1.2 , 95 % confidence interval 0.6 to 1.9 , P < 0.001 ) . Significantly , fewer patients in the intervention group desired additional information about stroke at follow-up than patients in the control group ( 4.5 % versus 32.8 % ; P < 0.001 ) . Anxiety change scores improved slightly more in favour of the control group ( 1.4 difference on the HAD subscale , 95 % confidence interval 0.2 to 2.8 , P = 0.03 ) . No significant differences between the groups were observed for any of the other outcome measures . INTERPRETATION Providing stroke patients with computer-generated tailored written information improved satisfaction with the information that was received and was more effective in meeting patients ' informational needs than non-tailored information , but had no effect on knowledge about stroke , self-efficacy , depression , or perceived health status Objective : To determine levels of satisfaction with information and advice received about stroke disease and relevant issues by community-dwelling stroke survivors . Design : An interview question naire survey . Setting : A family health services authority area in northern Engl and . Subjects : Stroke survivors identified by a valid screening question naire from a stratified r and om sample of 2000 subjects aged 45 years and over . Main outcome measure : Proportion of subjects interviewed responding positively to the question ' Do you think you have received enough advice and information on ... ? ' eighteen topics considered relevant to stroke survivors . Results : The screening process identified 116 stroke survivors , of whom 76 agreed to be interviewed . The majority ( > 80 % ) of patients were satisfied with information and advice received on lifestyle and health promotion issues , incontinence and their current treatment . However , satisfaction was poor for the areas of stroke disease in general , its effects , available services , and legal and financial affairs ( range , 28 - 75 % satisfied ) . Conclusion : Deficits in the provision of adequate information and advice to stroke patients on relevant issues have been identified in this study of a representative sample of community-dwelling stroke survivors . These deficits need to be addressed by those providing care for stroke patients in order to improve patient satisfaction Background and Purpose — Increased knowledge of stroke risk factors in the general population may lead to improved prevention of stroke . The objective of the present study was to assess knowledge of stroke risk factors and to determine factors associated with knowledge . Methods — In a population -based survey , we sent a question naire to r and omly selected residents in Berlin who were ≥50 years of age enquiring about knowledge of stroke risk factors . Knowledge was assessed in an open-ended question . In addition , we enquired about the source of participants ' information . Sociodemographic factors , including age , sex , educational level , and nationality , were also assessed . Results — A total of 28 090 of 75 720 residents ( response rate , 37 % ) responded to the question naire . Of all respondents , 68 % were able to name ≥1 correct stroke risk factor , and 13 % named 4 correct risk factors . The majority of respondents named mass media as source of information ( 82 % ) , followed by family/friends ( 45 % ) and by general physicians ( 20 % ) . In multivariable analysis , increased knowledge of stroke risk factors was significantly associated with younger age , a higher educational level , not living alone , a German nationality , and having received any information about stroke during the last year . However , characteristics of respondents using the respective sources of information varied significantly . Conclusions — Mass media was most frequently named as a source of information about stroke risk factors . Source of information used varied according to population characteristics . Health education programs should take this into account and be adapted accordingly Background and Purpose — Quality of life ( QoL ) is important to stroke survivors yet is often recorded as a secondary measure in acute stroke r and omized controlled trials . We examined whether commonly used stroke outcome measures captured aspects of QoL. Methods — We examined primary outcomes by National Institutes of Health Stroke Scale ( NIHSS ) , Barthel Index ( BI ) and modified Rankin Scale ( mRS ) , and QoL by Stroke Impact Scale ( SIS ) and European Quality of Life Scale ( EQ-5D ) from the Virtual International Stroke Trials Archive ( VISTA ) . Using Spearman correlations and logistic regression , we described the relationships between QoL mRS , NIHSS , and BI at 3 months , stratified by respondent ( patient or proxy ) . Using & khgr;2 analyses , we examined the mismatch between good primary outcome ( mRS ⩽1 , NIHSS ⩽5 , or BI ≥95 ) but poor QoL , and poor primary outcome ( mRS ≥3 , NIHSS ≥20 , or BI ⩽60 ) but good QoL. Results — Patient-assessed QoL had a stronger association with mRS ( EQ-5D weighted score n=2987 , P<0.0001 , r=−0.7 , r2=0.53 ; SIS recovery n=2970 , P<0.0001 , r=−0.71 , r2=0.52 ) . Proxy responses had a stronger association with BI ( EQ-5D weighted score n=837 , P<0.0001 , r=0.78 , r2=0.63 ; SIS recovery n=867 , P<0.0001 , r=0.68 , r2=0.48 ) . mRS explained more of the variation in QoL ( EQ-5D weighted score=53 % , recovery by SIS v3.0=52 % ) than NIHSS or BI and result ed in fewer mismatches between good primary outcome and poor QoL ( P<0.0001 , EQ-5D weighted score=8.5 % ; SIS recovery=10 % ; SIS-16=4.4 % ) . Conclusions — The mRS seemed to align closely with stroke survivors ’ interests , capturing more information on QoL than either NIHSS or BI . This further supports its recommendation as a primary outcome measure in acute stroke r and omized controlled trials Abstract Background Training care givers reduces their burden and improves psychosocial outcomes in care givers and patients at one year . However , the cost effectiveness of this approach has not been investigated . Objective To evaluate the cost effectiveness of caregiver training by examining health and social care costs , informal care costs , and quality adjusted life years in care givers . Design A single , blind , r and omised controlled trial . Setting Stroke rehabilitation unit . Subjects 300 stroke patients and their care givers . Interventions Caregiver training in basic nursing and facilitation of personal care techniques compared with no caregiver training . Main outcome measures Health and social care costs , informal care costs , and quality adjusted life years in care givers over one year after stroke . Results Total health and social care costs over one year for patients whose care givers received training were significantly lower ( mean difference -£4043 ( $ 7249 ; € , 95 % confidence interval -£6544 to -£1595 ) . Inclusion of informal care costs , which were similar between the two groups , did not alter this conclusion . The cost difference was largely due to differences in length of hospital stay . The EQ-5D did not detect changes in quality adjusted life years in care givers . Conclusion Compared with no training , caregiver training during rehabilitation of patients reduced costs of care while improving overall quality of life in care givers at one year OBJECTIVE To measure stroke knowledge and prestroke personal health behaviors of stroke patients undergoing inpatient rehabilitation and their caregivers . DESIGN Prospect i ve cohort . SETTING Academic rehabilitation hospital . PARTICIPANTS A total of 130 stroke patients and 85 caregivers interviewed after ischemic stroke . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURE The Stroke Education Assessment measured stroke knowledge and prestroke personal health behaviors . RESULTS Large deficiencies in patient and caregiver stroke knowledge were found . Fifty-two percent of patients could not name any stroke risk factors , 52 % were unable to name a stroke warning sign , and 35 % were unable to identify appropriate actions to take in a stroke emergency . Older patients were less knowledgeable than younger patients . Caregivers were more knowledgeable than patients . Regarding prestroke personal health behaviors , 28 % of patients reported medication nonadherence , 26 % did not see their primary care physician in the preceding year , and less than 40 % of patients with diabetes or hypertension reported diets consistent with these diagnoses . CONCLUSIONS Stroke patients participating in inpatient rehabilitation and their caregivers have large gaps in stroke knowledge and have suboptimal personal health behaviors , thereby putting patients at high risk for recurrent stroke . Our finding highlights the need to develop stroke-education programs for rehabilitating patients that are effective in closing these gaps in knowledge and personal health behaviors Abstract Background Informal care givers support disabled stroke patients at home but receive little training for the caregiving role . Objective To evaluate the effectiveness of training care givers in reducing burden of stroke in patients and their care givers . Design A single , blind , r and omised controlled trial . Setting Stroke rehabilitation unit . Subjects300 stroke patients and their care givers . Interventions Training care givers in basic nursing and facilitation of personal care techniques . Main outcome measures Cost to health and social services , caregiving burden , patients ' and care givers ' functional status ( Barthel index , Frenchay activities index ) , psychological state ( hospital anxiety and depression score ) , quality of life ( EuroQol visual analogue scale ) and patients ' institutionalisation or mortality at one year . Results Patients were comparable for age ( median 76 years ; interquartile range 70 - 82 years ) , sex ( 53 % men ) , and severity of stroke ( median Barthel index 8 ; interquartile range 4 - 12 ) . The costs of care over one year for patients whose care givers had received training were significantly lower ( £ 10 133 v£13 794 ( $ 18 087 v$24 619 ; € 15 204 v€20 697 ) ; P = 0.001 ) . Trained care givers experienced less caregiving burden ( care giver burden score 32 v41 ; P = 0.0001 ) , anxiety ( anxiety score 3 v4 ; P = 0.0001 ) or depression ( depression score 2 v3 ; P = 0.0001 ) and had a higher quality of life ( EuroQol score 80 v70 ; P = 0.001 ) . Patients ' mortality , institutionalisation , and disability were not influenced by caregiver training . However , patients reported less anxiety ( 3 v4.5 ; P < 0.0001 ) and depression ( 3 v4 ; P < 0.0001 ) and better quality of life ( 65 v60 ; P = 0.009 ) in the caregiver training group . Conclusion Training care givers during patients ' rehabilitation reduced costs and caregiver burden while improving psychosocial outcomes in care givers and patients at one year Objectives : To assess the baseline knowledge regarding stroke risk factors , symptoms , treatment and information re sources in an Iranian urban population . Subjects and Methods : A community-based face-to-face interview survey was conducted in the Shiraz urban area in Iran . A total of 385 potential participants between the ages of 15 and 83 years were r and omly selected from people referred to Motahari Clinic , Shiraz University of Medical Sciences , Shiraz . All the participants answered the 63 questions about different aspects of stroke . SPSS software version 15 was used to analyze the data . Results : The 385 participants completed the face-to-face interview . The most common risk factors for stroke identified by respondents were hypertension ( 342 ; 88.8 % ) and smoking ( 338 ; 87.8 % ) . The most common warning signs of stroke were abdominal pain ( 370 ; 96.1 % ) and chest pain ( 338 ; 88.7 % ) . Conclusion : This study shows that the knowledge of and attitude towards stroke risk factors in the general population of Shiraz are adequate . By using the public media and school education , it is possible to promote the level of the population ’s knowledge of and attitude towards stroke BACKGROUND Patients with acute stroke often have a striking lack of knowledge of causes , warning signs , and risk factors . Lack of knowledge may lead to inappropriate secondary prevention behavior . We investigated the knowledge of patients with a TIA or minor stroke about specific aspects of their disease 3 months after the event . METHODS Patients with a TIA or minor stroke who participated in a r and omized controlled trial of the effect of health education by an individualized multimedia computer program ( IMCP ) were included . All patients received information about their disease from their treating neurologist and half of the patients received extra information through the IMCP . The patients ' knowledge was tested after 3 months by means of a question naire that contained items on pathogenesis , warning signs , vascular diseases , risk factors , lifestyle and treatment . The highest possible score was 71 points . RESULTS The 57 patients had a mean total score of 41.2 points ( SD 10.4 ) of the maximum 71 . Only 15 ( 26 % ) correctly identified the brain as the affected organ in stroke and TIA , and only 21 ( 37 % ) could give a correct description of a TIA or stroke . In contrast , 80 - 90 % of the patients identified hypertension and /or obesity as vascular risk factors . Knowledge of various treatment modalities of hypertension , hypercholesterolemia and obesity was moderate to high ( 40 - 91 % adequate responses ) . CONCLUSION The vast majority of patients with TIA or stroke lack specific knowledge about their disease , but they do have a reasonable knowledge of general vascular risk factors and treatment . This suggests that counseling by neurologists of patients with a TIA or stroke can be improved Objectives : To assess the impact of information packs on patients with stroke and their carers , and to pilot some of the methodology for a trial of a Family Support Organiser ( FSO ) . Subjects : Seventy-one patients admitted to Oxford hospitals with acute stroke during February – July 1995 , and 49 informal carers of these patients . Design : R and omized controlled trial . Intervention group received an information pack containing various Stroke Association publications one month after their stroke , or at discharge from hospital , whichever was sooner . Control group received nothing . Follow-up was by interview at the place of residence of the patients six months after their stroke . Measures : Outcome measures assessed knowledge about stroke ; satisfaction with information received ; patient behaviour in terms of access to community services and benefits ; and health status and quality of life . Results : Patients and carers in the intervention group tended to know more about stroke , but these differences were not significant once adjusted for age . Patients in the intervention group ( but not carers ) tended to be more satisfied with the information that they had received , but the differences were not significant . There were no differences with regard to any aspects of quality of life in patients in the intervention group , though carers in the intervention group were found to have significantly better mental health ( p = 0.04 ) . Conclusions : While the study was too small to generate firm conclusions , information leaflets may lead to improved knowledge about stroke several months after they have been distributed . This finding is worth following up with larger studies . The stroke knowledge question naire that was piloted in this trial seems to be able to detect differences between groups Abstract Purpose : To identify the effects of a brief educational intervention on stroke patients ’ recall and recognition of risk factors and performance of and stage of change for stroke risk-related behaviors . Methods : Sixty-six patients with stroke participated in a multisite r and omized controlled trial . The intervention group ( n = 35 ) received a brief education intervention ( tailored written stroke information , verbal reinforcement of information for 3 months after discharge , and provision of a telephone number ) . The control group ( n = 31 ) received usual care . Unprompted recall ( personal and general ) , prompted recognition of risk factors ( 0 - 13 ) , and performance of ( 0 - 10 ) and stage of change for up to 7 stroke risk-related behaviors were assessed before and 3 months after discharge . Results : No significant between-group differences were found . For all participants over time , there were significant improvements for personal ( mean difference [ MD ] , 0.3 ; 95 % CI , 0.004 - 0.69 ; P = .05 ) and general ( MD , 0.6 ; 95 % CI , 0.09 - 1.16 ; P = .02 ) risk factor recall ; performance of stroke risk-related behaviors ( MD , 0.8 ; 95 % CI , 0.28 - 1.26 ; P < .01 ) ; and progression from a nonaction to an action stage of change for 4 of 7 behaviors over time . There was a significant decline in total risk factor recognition scores ( MD , -0.8 ; 95 % CI , 0.39 - 1.13 ; P < .01 ) . Conclusion : Stroke patients ’ unprompted recall of risk factors and performance of risk-related behaviors improved over time ; readiness to change risk-related behaviors progressed for some behaviors . A brief educational intervention did not improve risk factor awareness or behavior change more than usual care Objective : To assess the knowledge of stroke risk factors and warning signs in a representative statewide sample of Michigan adults . Method : Respondents to the 1999 Michigan Behavioral Risk Factor Survey , a r and om-digit-dialed statewide survey of > 2,500 adults , were asked to report up to three risk factors and warning signs for stroke . Predictors of inadequate knowledge ( defined as not reporting any correct responses ) of stroke risk factors and warning signs were identified using multiple logistic regression . Results : Eighty percent reported at least one correct risk factor for stroke , and 28 % reported three . The most frequently mentioned risk factors were hypertension ( 32 % ) , smoking ( 29 % ) , and physical inactivity ( 26 % ) . Sixty-nine percent reported at least one correct warning sign of stroke , but only 14 % reported three . The most frequently mentioned warning signs were sudden weakness or numbness ( 46 % ) and sudden slurred speech , disorientation , or difficulty underst and ing ( 30 % ) . Predictors for inadequate knowledge of both stroke risk factors and warning signs were similar and included age , race , sex , education , hypertension , and smoking . Conclusions : Knowledge of stroke risk factors and warning signs was moderate at best . One in five respondents was not aware of any stroke risk factors , and almost one in three was not aware of any stroke warning signs . Stroke knowledge was poorest among groups that have the highest risk of stroke SIR— Interventions with an educational or counselling component have been reported to be effective in a variety of patient groups to encourage smoking cessation [ 1 ] , lower blood pressure ( BP ) [ 2 , 3 ] , achieve modest reductions in cholesterol [ 4 ] , and promote weight loss [ 5 ] . Evaluation of the impact of education on physical outcomes is lacking in stroke disease , despite evidence that inadequate provision of information may adversely affect compliance with secondary prevention and psychosocial outcomes [ 6 ] . We describe a single-blind r and omised controlled trial of health education and counselling for patients with stroke or transient ischaemic attack ( TIA ) , and its effects on risk factors , satisfaction , mood and perceived health status |
13,273 | 22,814,722 | Given the strength of the relationship between physical activity and breast cancer and the null findings of this review , it is unlikely that the effect of physical activity is mediated through an effect on breast density | Studies show a protective relationship between physical activity and breast cancer risk across the life course from menarche to postmenopausal years .
Mammographic breast density is a known and strong breast cancer risk factor .
Whether the association of physical activity with breast cancer risk is mediated through mammographic breast density is poorly understood .
This systematic review summarizes published studies that investigated the association between physical activity and mammographic breast density and discusses the method ological issues that need to be addressed . | BACKGROUND Mammographic breast density is a strong risk factor for breast cancer . Tamoxifen , which reduces the risk of breast cancer in women at high risk , also reduces mammographic breast density . However , it is not known if tamoxifen-induced reductions in breast density can be used to identify women who will benefit the most from prophylactic treatment with this drug . METHODS We conducted a nested case-control study within the first International Breast Cancer Intervention Study , a r and omized prevention trial of tamoxifen vs placebo . Mammographic breast density was assessed visually and expressed as a percentage of the total breast area in 5 % increments . Case subjects were 123 women diagnosed with breast cancer at or after their first follow-up mammogram , which took place 12 - 18 months after trial entry , and control subjects were 942 women without breast cancer . Multivariable logistic regression was used to adjust for other risk factors . All statistical tests were two-sided . RESULTS In the tamoxifen arm , 46 % of women had a 10 % or greater reduction in breast density at their 12- to 18-month mammogram . Compared with all women in the placebo group , women in the tamoxifen group who experienced a 10 % or greater reduction in breast density had 63 % reduction in breast cancer risk ( odds ratio = 0.37 , 95 % confidence interval = 0.20 to 0.69 , P = .002 ) , whereas those who took tamoxifen but experienced less than a 10 % reduction in breast density had no risk reduction ( odds ratio = 1.13 , 95 % confidence interval = 0.72 to 1.77 , P = .60 ) . In the placebo arm , there was no statistically significant difference in breast cancer risk between subjects who experienced less than a 10 % reduction in mammographic density and subjects who experienced a greater reduction . CONCLUSION The 12- to 18-month change in mammographic breast density is an excellent predictor of response to tamoxifen in the preventive setting CONTEXT There are few data directly comparing the effects of physical activity and body weight on cardiovascular biomarkers . OBJECTIVE To examine the association of physical activity and body mass index ( BMI , defined as weight in kilograms divided by the square of height in meters ) alone and in combination with cardiovascular biomarkers . DESIGN , SETTING , AND PARTICIPANTS Cross-sectional analysis of 27,158 apparently healthy US women ( mean age , 54.7 years ) at the time of enrollment ( 1992 - 1995 ) in the Women 's Health Study , a r and omized , double-blind , placebo-controlled trial of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer . MAIN OUTCOME MEASURES The association of physical activity and BMI with high-sensitivity C-reactive protein ( CRP ) , fibrinogen , soluble intracellular adhesion molecule 1 ( ICAM-1 ) , homocysteine , low- and high-density lipoprotein ( LDL and HDL ) cholesterol , total cholesterol , apolipoprotein A-1 and B100 , lipoprotein(a ) , and creatinine . RESULTS Lower levels of physical activity and higher levels of BMI were independently associated ( P for trend < .001 ) with adverse levels of nearly all lipid and inflammatory biomarkers . High BMI showed stronger associations with these biomarkers than physical inactivity . For example , using the reference group of physically active , normal weight women ( energy expenditure > or = 1000 kcal/week ; BMI , 18.5 - 24.9 ) and adjusting for age , race , smoking , blood pressure , diabetes , menopausal status , and hormone use , the odds ratios ( 95 % confidence intervals [ CIs ] ) for having CRP > 3 mg/L were : for inactive , normal weight women 1.26 ( 1.15 - 1.37 ) ; active , overweight 2.68 ( 2.41 - 2.98 ) ; inactive , overweight 3.11 ( 2.84 - 3.41 ) ; active , obese 8.25 ( 7.15 - 9.51 ) ; and inactive , obese 9.86 ( 8.84 - 10.99 ) . In similar analyses , the odds ratios ( 95 % CIs ) for having HDL cholesterol < 50 mg/dL were 1.20 ( 1.11 - 1.30 ) ; 2.25 ( 2.04 - 2.49 ) ; 2.62 ( 2.41 - 2.85 ) ; 4.21 ( 3.68 - 4.81 ) ; and 5.27 ( 4.77 - 5.84 ) , respectively , and for having apolipoprotein B100 > 120 mg/dL they were 1.21 ( 1.11 - 1.33 ) ; 1.86 ( 1.66 - 2.08 ) ; 2.06 ( 1.88 - 2.67 ) ; 2.35 ( 2.04 - 2.70 ) ; and 2.33 ( 2.09 - 2.59 ) . Fibrinogen , ICAM-1 , apolipoprotein A1 , total cholesterol , and LDL cholesterol showed similar associations . By contrast , homocysteine , lipoprotein ( a ) , and creatinine showed weak or nonsignificant associations . CONCLUSIONS High BMI was more strongly related to adverse cardiovascular biomarker levels than physical inactivity . However , within BMI categories , physical activity was generally associated with more favorable cardiovascular biomarker levels than inactivity Mammographic density is a strong risk factor for breast cancer ; however the mechanism that underlies this association is unclear . We hypothesized that measures of energy balance early in life and in adulthood may be associated with mammographic density . We conducted a cross-sectional analysis of 1,398 women in the Nurses ’ Health Study to examine associations between physical activity , childhood and current body fatness , weight gain from age 18 years to present and mammographic density . Percent mammographic density was measured from digitized mammograms by a computer-assisted method . Demographic and lifestyle data were obtained from prospect ively collected question naires . For all analyses , subjects were stratified into three groups : premenopausal women , postmenopausal women not currently taking hormones , and postmenopausal women currently taking hormones . Childhood body fatness was inversely associated with mammographic density . The correlations ranged from −0.15 to −0.19 in the three strata of women ( P ≤ 0.001 ) . The difference in mean percent mammographic density between the leanest and heaviest body types ranged from 6.2 to 9.9 % . Similarly , adult body fatness was inversely associated with percent mammographic density . The correlations ranged from −0.41 to −0.48 in the three strata of women ( P < 0.0001 ) . The difference in mean percent mammographic density between the leanest and heaviest body types ranged from 22.3 to 35.1 % . Weight gain from age 18 was also inversely associated with mammographic density . There was no association between recent physical activity and mammographic density . These findings indicate that childhood and adult body fatness and weight change from age 18 are inversely associated with mammographic density The ability to detect small tumors is impaired in dense mammograms . It has been suggested that the sensitivity of mammograms could be lower in mammograms obtained during the luteal phase of the menstrual cycle . We examined the change in mammographic density from the follicular to the luteal phase of the menstrual cycle in 11 women . Although the average increase in densities was quite small ( 1.2 % ; P = 0.08 ) , six women had clinical ly significant increases ( 1.4 - 7.8 % ) , suggesting that premenopausal women should undergo mammographic examinations in the follicular part of the menstrual cycle The authors examined sources of variance in self-reported physical activity in a cohort of healthy adults ( n = 580 ) from Worcester , Massachusetts ( the Seasonal Variation of Blood Cholesterol Study , 1994 - 1998 ) . Fifteen 24-hour physical activity recalls of total , occupational , and nonoccupational activity ( metabolic equivalent-hours/day ) were obtained over 12 months . R and om effects models were employed to estimate variance components for subject , season , day of the week , and residual error , from which the number of days of assessment required to achieve 80 % reliability was estimated . The largest proportional source of variance in total and nonoccupational activity was within-subject variance ( 50 - 60 % of the total ) . Differences between subjects accounted for 20 - 30 % of the overall variance in total activity , and seasonal and day-of-the-week effects accounted for 6 % and 15 % , respectively . For total activity , 7 - 10 days of assessment in men and 14 - 21 days of assessment in women were required to achieve 80 % reliability . For nonoccupational activity , 21 - 28 days of assessment were required . This study is among the first to have examined the sources of variance in daily physical activity levels in a large population of adults using 24-hour physical activity recall . These findings provide insight for underst and ing the strengths and limitations of short term and long term physical activity assessment s employed in epidemiologic studies Physical activity has been associated with a reduced risk of breast cancer . However , little is known about the association between recreational physical activity and mammographic density . We examined the association between recreational physical activity and mammographic density using mammograms from 375 white and African American women without breast cancer who served as controls in the Los Angeles component of the Women 's Contraceptive and Reproductive Experiences Study . We used data from 5 time periods of activity in the statistical analysis : from menarche to mammogram screening , the first 3 and 10 years after menarche , the most recent 10 years and the 3 years prior to mammogram screening . Lifetime history of recreational physical activity was obtained through interviews using a structured question naire . We used multiple linear regression to estimate least-squared mean values of absolute and percent mammographic density within categories of physical activity . Overall , we found no statistically significant evidence that physical activity reduced absolute or percent mammographic density . We observed a modest positive association between lifetime physical activity and percent mammographic density ( p for trend = 0.04 ) among younger women , and between recent physical activity and percent density among both younger ( < 50 years , p for trend = 0.09 ) and older ( > or = 50 years , p for trend = 0.06 ) women , but these associations diminished after additionally adjusting for body mass index ( BMI ) ( all p > or = 0.10 ) . However , among women younger than 50 years , we found some evidence for a protective effect of " strenuous " physical activity in the first 3 years after menarche , with a nonstatistically significant inverse association with both absolute ( p for trend = 0.07 ) and percent ( p for trend = 0.08 ) mammographic density after adjustment for BMI . Our results suggest that physical activity is not a strong predictor of mammographic density Background : We have examined the relationships between the measured properties of breast tissue and mammographic density and other risk factors for breast cancer , using breast tissue obtained at forensic autopsy and not selected for the presence of abnormalities . Methods : We used r and omly selected tissue blocks taken from breast tissue slices obtained by s.c . mastectomy at the time of forensic autopsy to measure histologic features using quantitative microscopy . The proportions of the biopsy occupied by cells ( estimated by nuclear area ) , gl and ular structures , and collagen were determined . These measurements were examined in relation to the percent density in the faxitron image of the tissue slice from which the biopsy was taken and other risk factors for breast cancer . Results : The percent mammographic density was associated with the proportion of the area of the biopsy occupied by nuclei , both epithelial and nonepithelial , and by collagen and the area of gl and ular structures . Several other risk factors for breast cancer , notably body weight , parity , and number of births , and menopausal status , that are associated with variations in mammographic density , were also associated with differences in one or more of these tissue features . Conclusion : All risk factors for breast cancer must ultimately exert their influence by an effect on the breast , and these findings suggest that , for some risk factors , this influence includes an effect on the number of cells and the quantity of collagen Background : The Alberta Physical Activity and Breast Cancer Prevention ( ALPHA ) Trial examined the influence of aerobic exercise on biological factors that are associated with breast cancer risk . Mammographic density , a secondary outcome , is reported here . Methods : The ALPHA Trial was a parallel group r and omized controlled trial conducted between May 2003 and July 2007 . Postmenopausal , sedentary women ages 50 to 74 years ( n = 320 ) were evenly r and omized to aerobic exercise ( 45 minutes , 5 days per week ) or control ( usual life-style ) for 1 year . Dense fibrogl and ular tissue and nondense fatty tissue were measured from mammograms at baseline and 1 year using computer-assisted thresholding software for area measurements and a new technique that relies on the calibration of mammography units with a tissue-equivalent phantom for volumetric measurements . Results : Nondense volume decreased in the exercise group relative to the control group ( difference between groups = −38.5 cm3 ; 95 % confidence interval , −61.6 to 15.4 ; P = 0.001 ) . Changes in total body fat accounted for this decrease . Changes in dense area and dense volume , measures that have previously been associated with breast cancer risk , were not significantly different between the groups ( P ≥ 0.26 ) . Conclusions : Achieving changes in mammographic measures may require more exercise or a study population with higher baseline levels of sex hormones or a wider range of mammographic density . The data from this study , however , suggest that the protective effect of exercise on breast cancer risk may operate through a mechanism other than mammographic density . Cancer Epidemiol Biomarkers Prev ; 19(4 ) ; 1112–21 . © 2010 AACR BACKGROUND Although mammographic breast density is associated with the risk of breast cancer and is influenced by hormone levels , the effects of tamoxifen on breast density in healthy women and whether tamoxifen-induced density changes are associated with breast cancer risk are unclear . We investigated mammographic breast density in healthy women with an increased risk of breast cancer at baseline and during 54 months of tamoxifen treatment . METHODS Mammograms were review ed from 818 breast cancer-free women ( 388 in the tamoxifen group and 430 in the placebo group ) at high risk for breast cancer , from the International Breast Cancer Intervention Study I , a trial of tamoxifen for breast cancer prevention . Breast density measurements , at baseline and during treatment , were obtained at 12- to 18-month intervals . Multivariable analysis was used to assess associations with breast density . All statistical tests were two-sided . RESULTS Breast density at baseline was similar in placebo ( 42.6 % , 95 % confidence interval [ CI ] = 39.6 % to 45.6 % ) and tamoxifen ( 41.9 % , 95 % CI = 38.8 % to 45.0 % ) groups . The main determinants of breast density at baseline were age , menopausal status , body mass index , and previous atypical hyperplasia . A greater density reduction in the tamoxifen group ( 7.9 % , 95 % CI = 6.9 % to 8.9 % ) than in the placebo group ( 3.5 % , 95 % CI = 2.7 % to 4.3 % ) was apparent within 18 months of treatment ( P<.001 ) ; the reduction in density continued until 54 months of treatment . After 54 months of tamoxifen treatment , breast density was 28.2 % ( decrease from baseline = 13.7 % , 95 % CI = 12.3 % to 15.1 % ; P<.001 ) in the tamoxifen group and 35.3 % ( decrease from baseline = 7.3 % , 95 % CI = 6.1 % to 8.4 % ; P<.001 ) in the placebo group . The tamoxifen-associated density reduction was apparent in all subgroups , but there was a statistically significant interaction with age . In women aged 45 years or younger at entry , the net reduction with tamoxifen was 13.4 % ( 95 % CI = 8.6 % to 18.1 % ) , whereas in women older than 55 years , it was 1.1 % ( 95 % CI = -3.0 % to 5.1 % ) . CONCLUSION Tamoxifen treatment was associated with reduction in breast density , most of which occurred during the first 18 months of treatment A protective effect of physical activity ( PA ) on breast cancer ( BC ) risk has been suggested . Few studies have examined the influence of PA on mammographic breast density ( MBD ) , a strong risk factor for BC . In a prospect i ve study in Florence , Italy , we identified 2,000 healthy women with a mammogram taken 5 years after enrollment . Individual mammograms were retrieved ( 83 % ) and MBD assessed according to Wolfe 's classification . Detailed information on PA at work and during leisure time , reproductive history , lifestyle and anthropometric measurements at enrollment were available for 1,666 women . Information on hormone replacement therapy ( HRT ) was also obtained at mammogram . Women with high-MBD ( P2 + DY Wolfe 's patterns ) were compared with women with low-MBD ( N1 + P1 ) by multivariate logistic models . Overall , high-MBD was inversely associated with increasing levels of leisure time PA ( p for trend = 0.04 ) and among peri-/postmenopausal women , also with increasing levels of recreational activities ( p for trend = 0.02 ) . An interaction between PA and HRT emerged , with a stronger inverse association of highest level of recreational activity with MBD among HRT nonusers ( p for interaction = 0.02 ) . A modifying effect by body mass index ( BMI ) was evident among 1,025 peri-/postmenopausal women who did not use HRT at the time of mammogram , with a stronger inverse association between recreational PA and MBD in the highest BMI tertile ( OR = 0.34 ; 95 % CI 0.20 - 0.57 ; p for interaction = 0.03 ) . This large study carried out in Mediterranean women suggests that leisure time PA may play a role in modulating MBD , particularly in overweight/obese peri-/postmenopausal women BACKGROUND Mammographic images from women with a high proportion of epithelial and stromal breast tissues are described as showing high-density parenchymal patterns . Most past studies that noted an increase in breast cancer risk associated with mammographic parenchymal patterns showing high density either 1 ) lacked information on other breast cancer risk factors , 2 ) were too small , or 3 ) included insufficient follow-up time to adequately resolve persisting doubts whether mammographic features are " independent " measures of breast cancer risk and not a detection artifact . PURPOSE The purpose of this study was twofold : 1 ) to evaluate the associations between mammographic features and other breast cancer risk factors and 2 ) to assess effects of mammographic features on breast cancer risk by time , age , and menopause status . METHODS To address these questions , we analyzed detailed information from a large , nested case-control study with 16 years of follow-up . This study used information from both screening and follow-up phases of the Breast Cancer Detection Demonstration Project , a nationwide program that offered annual breast cancer screening for more than 280,000 women from 1973 to 1980 . Mammographic features were assessed from the base-line screening mammographic examination for 1880 incident case subjects and 2152 control subjects . Control subjects were r and omly selected from women of the same age and race as each case subject . Control subjects attended the same screening center as the case subject and were free of breast cancer at the case subject 's date of diagnosis . Odds ratios ( ORs ) with 95 % confidence intervals ( CIs ) provided estimates of the relative risk of breast cancer . RESULTS Mammographic features were associated with known breast cancer risk factors . However , the high-density parenchymal pattern effects were independent of family history , age at first birth , alcohol consumption , and benign breast disease . The increase risk for women with Wolfe 's two high-density parenchymal patterns , P2 ( OR = 3.2 ; 95 % CI = 2.5 - 4.0 ) and Dy ( OR = 2.9 ; 95 % CI = 2.2 - 3.9 ) , was explained primarily by measured percent of the breast with dense mammographic appearance . Compared with women with no visible breast density , women who had a breast density of 75 % or greater had an almost fivefold increased risk of breast cancer ( 95 % CI = 3.6 - 7.1 ) . These effects persisted for 10 or more years and were noted for both premenopausal and postmenopausal women of all ages . CONCLUSIONS Of the breast cancer risk factors assessed in the participants , high-density mammographic parenchymal patterns , as measured by the proportion of breast area composed of epithelial and stromal tissue , had the greatest impact on breast cancer risk . Of the breast cancers in this study , 28 % were attributable to having 50 % or greater breast density Physical inactivity and high mammographic breast density have both been associated with increased breast cancer risk . However , the association between physical activity and mammographic breast density remains inconsistent . In the European Prospect i ve Investigation of Cancer (EPIC)-Norfolk population -based cohort study ( United Kingdom ) , the authors investigated the cross-sectional association between physical activity level at baseline during 1993 - 1997 and breast density among 1,394 postmenopausal , cancer-free women . Usual physical activity was assessed by a brief , vali date d question naire . Percentage breast density was determined visually from mammograms by three trained radiologists using the Boyd six-category scale . The association between physical activity level and breast density risk category was examined . No statistically significant association between physical activity and percentage breast density was observed in the unadjusted or adjusted regression models . A suggested increase in breast density for the most active women in the unadjusted regression analysis ( odds ratio = 1.13 , 95 % confidence interval : 0.71 , 1.80 ) was reversed after inclusion of body mass index and reproductive and lifestyle variables ( odds ratio = 0.78 , 95 % confidence interval : 0.45 , 1.34 ) . The lack of an association between physical activity and percentage breast density suggests that an association between physical activity and breast cancer risk is unlikely to be mediated through an effect on mammographic breast density BACKGROUND Mammographic density and circulating sex hormones are two well-confirmed predictors of breast cancer risk . Whether mammographic density reflects levels of endogenous sex hormones is unclear . We examined whether these predictors are independently associated with breast cancer risk in a prospect i ve study . METHODS We conducted a nested case-control study within the Nurses ' Health Study cohort of 253 case subjects with breast cancer and 520 control subjects . All participants were postmenopausal women who were not using postmenopausal hormones at the time of both blood collection and mammography . Plasma levels of estradiol , free estradiol , testosterone , and free testosterone were evaluated . Mammographic density was assessed by use of computer-assisted analysis of mammograms . Logistic regression models that were adjusted for matching variables and potential confounders were used to calculate relative risks ( RRs ) and 95 % confidence intervals ( CIs ) . All statistical tests were two-sided . RESULTS Levels of circulating sex steroids and mammographic density were both statistically significantly and independently associated with breast cancer risk . The relative risk of breast cancer associated with mammographic density ( RR for highest quartile compared with lowest quartile = 3.8 , 95 % CI = 2.2 to 6.6 ; P(trend)<.001 ) changed little when the analysis was adjusted for circulating estradiol ( RR = 3.9 , 95 % CI = 2.2 to 6.9 ; P(trend)<.001 ) or circulating testosterone ( RR = 4.1 , 95 % CI = 2.3 to 7.2 ; P(trend)<.001 ) . Circulating levels of estradiol ( RR = 2.4 , 95 % CI = 1.4 to 4.0 ) and of testosterone ( RR = 2.0 , 95 % CI = 1.2 to 3.1 ) were both associated with breast cancer risk , before and after adjustment for mammographic density . In a joint analysis of mammographic density and plasma testosterone , the risk of breast cancer was highest in the highest tertiles of both relative to the lowest tertiles of both ( RR = 6.0 , 95 % CI = 2.6 to 14.0 ) . A similar pattern was observed in the joint analysis of estradiol and mammographic density ( RR = 4.1 , 95 % CI = 1.7 to 9.8 ) . CONCLUSIONS Circulating sex steroid levels and mammographic density appear strongly and independently associated with the risk of breast cancer in postmenopausal women Objectives First , to compare the impact of nasally and orally dosed estradiol on breast density ; second , to investigate the utility of computer-based automated approaches to the assessment of breast density with reference to traditional methods . Methods Digitized images from two 2-year , r and omized , placebo-controlled trials formed the basis of the present post hoc analysis . Active treatments were 1 mg estradiol continuously combined with 0.125 mg trimegestone ( oral hormone replacement therapy , HRT ) or low-dose ( 150 or 300 µg estradiol ) nasal estradiol cyclically combined with 200 mg micronized progesterone ( nasal HRT ) . The effects on breast density were assessed by a radiologist , providing the BI-RADS ® score and the interactive threshold , and by a computer-based approach , providing the measure of stripiness and the HRT-effect specific measure of breast density . Results In the oral HRT trial , active treatment induced a significant increase in breast density , which was consistent in all methods used ( all p < 0.05 ) . In contrast , none of the methods detected significant changes in women receiving nasal HRT . The sensitivity of automated methods to discriminate HRT- from placebo-treated women was equal or better than the sensitivity of methods performed by the radiologist . Conclusions The markedly different pharmacokinetic profile of nasal estrogen seems to be associated with better breast safety . Automated computer-based analysis of digitized mammograms provides a sensitive measure of changes in breast density induced by hormones and could serve as a useful tool in future clinical trials Background : Evidence accumulates that physical inactivity is one of the few modifiable risk factors for breast cancer . The mechanism through which physical inactivity affects breast cancer risk is not clear . The study aim was to investigate the association between physical activity and breast density because mammographic density is strongly associated with breast cancer risk . Methods : We did a cross-sectional study in 620 women , of ages 49 to 68 years and participants of the Dutch Prospect -European Prospect i ve Investigation into Cancer and Nutrition cohort . A self-administered question naire was used to obtain information on duration and intensity of physical activity ( recreational , household , and occupational ) during the year preceding study recruitment . A total activity index ( inactive , moderately inactive , moderately active , and active ) was estimated by combining all activity types . Percent and absolute breast density were determined on screening mammograms using a computer-aided method . Multivariate linear regression was used to examine the association between physical activity and breast density . Results : Mean percent density was 35.3 % [ 95 % confidence interval ( 95 % CI ) , 31.8 - 38.8 ] for the inactive category compared with 36.1 % ( 95 % CI , 33.0 - 39.2 ) for the active category . Mean absolute density values for the inactive and active category were 45.8 cm2 ( 95 % CI , 40.9 - 50.7 ) and 42.6 cm2 ( 95 % CI , 38.3 - 47.0 ) , respectively . Subgroup analysis for postmenopausal women showed similar results , as did separate analyses for recreational and household activity . Conclusions : The result does not support a relation between current physical activity and mammographic density in postmenopausal women . ( Cancer Epidemiol Biomarkers Prev 2006;15(3):456–60 OBJECTIVES to evaluate the effects of different types of hormone replacement therapy ( HRT ) on mammographic density in postmenopausal women . METHODS In a prospect i ve 1-year study , 121 healthy postmenopausal women were allocated to one of the following five study groups : twenty-six women were treated with continuous transdermal 17beta-estradiol 50 mcg/die plus acetate nomegestrolo 5 mg/die sequentially added for 12 days per month ( Group A ) ; 25 women were treated with continuous transdermal 17beta-estradiol 50 mcg/die plus acetate nomegestrolo 2.5 mg/die added every day ( Group B ) ; 23 women were treated with continuous transdermal 17beta-estradiol 50 mcg/die ( Group C ) ; 24 women were treated with tibolone 2.5 mg/die ( Group D ) ; and 23 women not receiving any medication represented the control group ( Group E ) . At the time of recruitment and after 12 months a two-view mammography was performed to evaluate mammographic density according to a quantitative method : type 1 ( less than 25 % of mammary gl and covered by dense tissue ) , type 2 ( from 25 to 75 % of total gl and ular area covered by dense tissue ) , type 3 ( more than 75 % of mammary parenchyma covered by dense tissue ) . RESULTS After 12 months of HRT , seven out of 20 patients ( 35 % ) in group A , nine of 21 patients ( 42.85 % ) in group B , four out of 19 patients ( 21 % ) in group C and two of 20 patients ( 10 % ) in group D , showed an increase in mammographic density . No variation of density was observed at the second mammographic test in the control group . The mammographic density increase which occurred in groups A , B and C was statistically significant ( P<0.05 ) when compared with group E ; no statistically significant difference ( P=0.49 ) was found in mammographic density increase between group D and group E. When the different treatment types were compared each other , a statistically significant difference ( P=0.04 ) was found only between the mammographic density increase occurring in groups B and D. CONCLUSIONS HRT may cause an increase of mammographic density . The frequency of the density increase is related to the type of HRT and a replacement therapy including a progestin , especially in continuous combination with estrogen , leads to more evident mammographic changes . Tibolone does not significantly affect mammographic density OBJECTIVE To study the effect on mammographic breast density of two different continuous combined regimens for hormone therapy . DESIGN R and omized clinical study . SETTING University hospital . PATIENT(S ) Postmenopausal women without any previous history of breast disorder . INTERVENTION(S ) The women received either estradiol valerate/dienogest or estradiol/norethisterone acetate . Mammograms and venous blood sample s were obtained at baseline and after 6 months . MAIN OUTCOME MEASURE(S ) Change in mammographic breast density . Correlations with levels of hormones , growth factors , and binding proteins . RESULT ( S ) An increase in mammographic density was recorded in approximately 50 % of the women , and there were no differences between treatments . Increased density showed a positive correlation with estradiol , estrone , and sex hormone-binding globulin and showed a negative association to free T. Among hormonal factors , levels of free T were the most important for predicting increased density . CONCLUSION ( S ) Continuous combined hormone therapy with different progestogens has a marked impact on the breast OBJECTIVE The aim of this study was to evaluate the effects of different types of hormone replacement therapy ( HRT ) on mammographic density . MATERIAL S AND METHODS In a prospect i ve 1-year study , 103 postmenopausal women were r and omized to receive tibolone 2.5 mg/die , continuous conjugated equine estrogens 0.625 mg/die plus medroxyprogesterone acetate ( MPA ) 5mg/die or placebo . Mammograms were performed at baseline and after 12 months of treatment . Mammographic density was quantified according to the Wolfe classification . RESULTS After 12 months of HRT 16 of the 35 patients ( 45.1 % ) receiving continuous combined hormonal therapy showed an increase of breast density change in the Wolfe classification . After treatment with tibolone , an up grading in breast density , according to Wolfe 's classification , was found in 2 of the 43 patients ( 2.3 % ) . No changes were recorded in the 25 patients of the control group . The difference between the group treated with continuous combined hormonal therapy and the control group was highly significant ( p<0.001 ) . The difference in breast density between patients in treatment with tibolone and the control group was not statistically significant ( p=0.34 ) . DISCUSSION Continuous combination HRT may be more commonly associated with an increase of mammography density than tibolone treatment BACKGROUND The radiographic appearance of the female breast varies from woman to woman depending on the relative amounts of fat and connective and epithelial tissues present . Variations in the mammographic density of breast tissue are referred to as the parenchymal pattern of the breast . Fat is radiologically translucent or clear ( darker appearance ) , and both connective and epithelial tissues are radiologically dense ( lighter appearance ) . Previous studies have generally supported an association between parenchymal patterns and breast cancer risk ( greater risk with increasing densities ) , but there has been considerable heterogeneity in risk estimates reported . PURPOSE Our objective was to determine the level of breast cancer risk associated with varying mammographic densities by quantitatively classifying breast density with conventional radiological methods and novel computer-assisted methods . METHODS From the medical records of a cohort of 45,000 women assigned to mammography in the Canadian National Breast Cancer Screening Study ( NBSS ) , a multicenter , r and omized trial , mammograms from 354 case subjects and 354 control subjects were identified . Case subjects were selected from those women in whom histologically verified invasive breast cancer had developed 12 months or more after entering the trial . Control subjects were selected from those of similar age who , after a similar period of observation , had not developed breast cancer . The mammogram taken at the beginning of the NBSS was the image used for measurements . Mammograms were classified into six categories of density , either by radiologists or by computer-assisted measurements . All radiological classification and computer-assisted measurements were made using one craniocaudal view from the breast contralateral to the cancer site in case subjects and the corresponding breast of control subjects . All P values represent two-sided tests of statistical significance . RESULTS For all subjects , there was a 43 % increase in the relative risk ( RR ) between the lower and the next higher category of density , as determined by radiologists , and there was a 32 % increase as determined by the computer-assisted method . For all subjects , the RR in the most extensive category relative to the least was 6.05 ( 95 % confidence interval [ CI ] = 2.82 - 12.97 ) for radiologists and 4.04 ( 95 % CI = 2.12 - 7.69 ) for computer-assisted methods . Statistically significant increases in breast cancer risk associated with increasing mammographic density were found by both radiologists and computer-assisted methods for women in the age category 40 - 49 years ( P = .005 for radiologists and P = .003 for computer-assisted measurements ) and the age category 50 - 59 years ( P = .002 for radiologists and P = .001 for computer-assisted measurements ) . CONCLUSION These results show that increases in the level of breast tissue density as assessed by mammography are associated with increases in risk for breast cancer This study investigates relationships between familial and hormonal risk factors and breast density in women at high risk of developing breast cancer . The subjects are a subset of 102 women from the international breast cancer intervention study ( IBIS ) , for whom a series of repeated measurements of breast density were available . Details of familial and hormonal risk factors for breast cancer were collected at entry and multivariate ordered logistic regression used to identify risk factors for increased breast density . Lower body mass index and nulliparity were associated with high breast density , whereas smoking was associated with lower breast density . It is not yet known whether a reduction in breast density will lead to a corresponding reduction in breast cancer risk , so we propose that changes in breast density be investigated as a potential early indicator of efficacy in chemoprevention trials for breast cancer Objectives To compare the incidence of increased breast density and tenderness in postmenopausal women associated with transdermal ( Estalis/Combipatch ® , Novartis , Basel , Switzerl and ) and oral ( Kliogest ® , Schering AG , Berlin , Germany ) hormone replacement therapy ( HRT ) . Methods A total of 202 postmenopausal women were r and omized to transdermal or oral HRT . Mammograms obtained at study entry and after 1 year of treatment were assessed for percent breast density by means of the digital segmentation and thresholding technique . Breast tenderness was assessed at each study visit . Results The mean breast density by ANCOVA after adjusting for screening value at study end was significantly lower for women using Estalis ® ( 38.4 % , st and ard error 0.9 % ) compared with Kliogest ® ( 46.9 % , st and ard error 1.5 % ) ( p < 0.0001 ) . Significantly fewer women using transdermal HRT had an increase in mammographic breast density or breast tenderness compared to oral HRT . Of the women using transdermal HRT , 39.1 % had no change in breast density compared to 15.7 % for women using oral HRT . Only 4 % of women using transdermal HRT had a marked increase in density ( > 25 % ) compared to 15.7 % of women using oral HRT . Overall , 36.0 % of patients in the transdermal group reported breast tenderness at some point during the 1-year study , compared with 57.6 % in the oral HRT group ( p = 0.0002 ) . Conclusion Transdermal HRT use is associated with a significantly lower incidence of increased mammographic breast density and breast tenderness compared with oral HRT The extent of breast tissue density on mammograms is one of the strongest risk factors for breast cancer . The aim of this analysis was to evaluate whether tamoxifen can affect mammographic breast density . Subjects were participants in the National Surgical Adjuvant Breast Project Breast Cancer Prevention Trial ( BCPT ) , recruited and followed at the Breast Center of Saint-Sacrement Hospital in Quebec City , Canada . The Breast Cancer Prevention Trial is a double-blind trial in which women at high risk of breast cancer were r and omized to receive either 20 mg tamoxifen per day or placebo . Mammograms were taken before treatment began and yearly thereafter . For the purpose of this analysis , Wolfe 's parenchymal pattern and the percentage of the breast showing tissue densities were assessed by review of pre- and posttreatment mammograms without knowledge of treatment assignment . Among the 69 women included in this analysis , 36 received tamoxifen and 33 received placebo for an average of 3.3 and 3.5 years , respectively . Among women receiving tamoxifen , 16 of 36 ( 44.4 % ) changed to a parenchymal pattern of lower density compared with 5 of 33 ( 15.2 % ) women receiving placebo ( P = 0.010 ) . Moreover , in the tamoxifen-treated group , the difference in the percentage of the breast showing tissue densities between the pre- and posttreatment mammograms reached -9.4 % on average compared with a reduction of -3.6 % in the placebo group ( P = 0.010 ) . Our data show that tamoxifen can reduce high-risk mammographic features . Breast densities should be evaluated as possible early markers of the preventive effect of selective estrogen receptor modulators |
13,274 | 27,683,682 | There was no significant difference between the two groups in operation time , blood loss during operation , long-term all-complication rate and reoperation rate at the level of injury .
The ACDA group had significantly better neurological outcomes , as well as a significantly lower rate of adjacent segment diseases .
CONCLUSIONS Compared with ACDF , the ACDA procedure is associated with improved reoperation rate and reduction in neurological deficits amongst previously demonstrated benefits . | BACKGROUND Surgical approaches are usually required in cases of severe cervical disc disease .
The traditional method of anterior cervical disc fusion ( ACDF ) has been associated with reduced local mobility and increased occurrence of adjacent segment disease .
The newer method of anterior cervical disc arthroplasty ( ACDA ) relies upon artificial discs of various products .
Current literature is inconsistent in the comparative performance of these methods with regards to clinical , radiological and patient outcomes . | BACKGROUND CONTEXT Cervical total disc replacement ( TDR ) is intended to address radicular pain and preserve functional motion between two vertebral bodies in patients with symptomatic cervical disc disease ( SCDD ) . PURPOSE The purpose of this trial is to compare the safety and efficacy of cervical TDR , ProDisc-C ( Synthes Spine Company , L.P. , West Chester , PA ) , to anterior cervical discectomy and fusion ( ACDF ) surgery for the treatment of one-level SCDD between C3 and C7 . STUDY DESIGN / SETTING The study was conducted at 13 sites . A noninferiority design with a 1:1 r and omization was used . PATIENT SAMPLE Two hundred nine patients were r and omized and treated ( 106 ACDF ; 103 ProDisc-C ) . OUTCOME MEASURES Visual analog scale ( VAS ) pain and intensity ( neck and arm ) , VAS satisfaction , neck disability index ( NDI ) , neurological exam , device success , adverse event occurrence , and short form-36 ( SF-36 ) st and ardized question naires . METHODS A prospect i ve , r and omized , controlled clinical trial was performed . Patients were enrolled and treated in accordance with the US Food and Drug Administration ( FDA ) -approved protocol . Patients were assessed pre- and postoperatively at six weeks , 3 , 6 , 12 , 18 , and 24 months . RESULTS Demographics were similar between the two patient groups ( ProDisc-C : 42.1+/-8.4 years , 44.7 % males ; Fusion : 43.5 + /- 7.1 years , 46.2 % males ) . The most commonly treated level was C5-C6 ( ProDisc-C : 56.3 % ; Fusion=57.5 % ) . NDI and SF-36 scores were significantly less compared with presurgery scores at all follow-up visits for both the treatment groups ( p<.0001 ) . VAS neck pain intensity and frequency as well as VAS arm pain intensity and frequency were statistically lower at all follow-up timepoints compared with preoperative levels ( p<.0001 ) but were not different between treatments . Neurologic success ( improvement or maintenance ) was achieved at 24 months in 90.9 % of ProDisc-C and 88.0 % of Fusion patients ( p=.638 ) . Results show that at 24 months postoperatively , 84.4 % of ProDisc-C patients achieved a more than or equal to 4 degrees of motion or maintained motion relative to preoperative baseline at the operated level . There was a statistically significant difference in the number of secondary surgeries with 8.5 % of Fusion patients needing a re-operation , revision , or supplemental fixation within the 24 month postoperative period compared with 1.8 % of ProDisc-C patients ( p=.033 ) . At 24 months , there was a statistically significant difference in medication usage with 89.9 % of ProDisc-C patients not on strong narcotics or muscle relaxants , compared with 81.5 % of Fusion patients . CONCLUSIONS The results of this clinical trial demonstrate that ProDisc-C is a safe and effective surgical treatment for patients with disabling cervical radiculopathy because of single-level disease . By all primary and secondary measures evaluated , clinical outcomes after ProDisc-C implantation were either equivalent or superior to those same clinical outcomes after Fusion OBJECT The authors report the results of a prospect i ve r and omized multicenter study in which the results of cervical disc arthroplasty were compared with anterior cervical discectomy and fusion ( ACDF ) in patients treated for symptomatic single-level cervical degenerative disc disease ( DDD ) . METHODS Five hundred forty-one patients with single-level cervical DDD and radiculopathy were enrolled at 32 sites and r and omly assigned to one of two treatment groups : 276 patients in the investigational group underwent anterior cervical discectomy and decompression and arthroplasty with the PRESTIGE ST Cervical Disc System ( Medtronic Sofamor Danek ) ; 265 patients in the control group underwent decompressive ACDF . Eighty percent of the arthroplasty-treated patients ( 223 of 276 ) and 75 % of the control patients ( 198 of 265 ) completed clinical and radiographic follow-up examinations at routine intervals for 2 years after surgery . Analysis of all currently available postoperative 12- and 24-month data indicated a two-point greater improvement in the neck disability index score in the investigational group than the control group . The arthroplasty group also had a statistically significant higher rate of neurological success ( p = 0.005 ) as well as a lower rate of secondary revision surgeries ( p = 0.0277 ) and supplemental fixation ( p = 0.0031 ) . The mean improvement in the 36-Item Short Form Health Survey Physical Component Summary scores was greater in the investigational group at 12 and 24 months , as was relief of neck pain . The patients in the investigational group returned to work 16 days sooner than those in the control group , and the rate of adjacent-segment reoperation was significantly lower in the investigational group as well ( p = 0.0492 , log-rank test ) . The cervical disc implant maintained segmental sagittal angular motion averaging more than 7 degrees . In the investigational group , there were no cases of implant failure or migration . CONCLUSIONS The PRESTIGE ST Cervical Disc System maintained physiological segmental motion at 24 months after implantation and was associated with improved neurological success , improved clinical outcomes , and a reduced rate of secondary surgeries compared with ACDF Study Design Prospect i ve , r and omized , controlled . Level 1 evidence . Objective To report functional outcomes at 48 months follow-up on prospect ively r and omized patients to either the Bryan cervical disc prosthesis or anterior cervical discectomy and fusion ( ACDF ) at a single site . Summary of Background Data Surgical treatment of cervical disc pathology can involve discectomy and fusion ( ACDF ) , the gold st and ard technique . The safety and effectiveness of this procedure has been established and demonstrated in the literature , however , limitations have evolved and alternatives such as disc replacement are being investigated . Intervertebral disc replacement is design ed to preserve motion , both at affected and adjacent levels avoiding limitations of fusion such as adjacent level degeneration . New onset degenerative changes and possible recurring neurologic symptoms may be deferred or eliminated with cervical disc replacement . A recent multicenter trial with 24 months follow-up has shown the Bryan disc to compare favorably with ACDF . Continued follow-up is needed to further evaluate and compare functional outcomes in both these cohorts . Methods A total of 47 patients were enrolled at our site as part of an ongoing multicenter prospect ively r and omized study investigating ACDF versus Bryan cervical disc prosthesis . Functional outcomes are now reported at 48 months follow-up for our cohort of participants . Neck disability index score ( NDI ) , VAS neck and arm and SF-36 both physical and mental as well as complications and reoperations will be reported . Results Functional outcome data collected at routine follow-up for 48-months has favorably demonstrated improved functional outcomes for NDI , neck/arm pain VAS scores , and the SF-36 physical/mental health component scores for the Bryan arthroplasty and ACDF cohorts . The NDI scores for the Bryan arthroplasty preoperatively was 51 and at 48 months 10 . For ACDF preoperative NDI score was also 51 and at 48 months 16.7 . At 48 months NDI success , measured by ≥15 points NDI improvement demonstrated a 93.3 % success for Bryan arthroplasty and an 82.4 % success for ACDF . VAS neck pain scores for the Bryan arthroplasty preoperatively was 76.2 and at 48 months was 13.6 . VAS neck pain scores for ACDF preoperatively was 80.6 and at 48 months was 28.1 . Arm Pain scores were also measured and for the Bryan arthroplasty preoperatively measured 78.8 and at 48 months 10.8 . For ACDF arm pain scores preoperatively measured 77.1 and at 48 months 21.7 . These outcomes have not been associated with any degradation of outcome measures from 2 to 4 years . During the 48 months of follow-up at our institution we also report 6 secondary surgeries in our control group ( ACDF ) and only 1 in our investigational group ( Bryan ) . Of the 6 surgeries in the control group performed , 3 or 12 % to date were for adjacent level degenerative disease and 1 or 4 % for remote level degenerative disc disease . The remaining 2 surgeries were performed on the same patient for a pseudarthrosis . In the investigational group there was only 1 secondary surgery performed to date for adjacent level disease 5 % . Conclusions At 48 months , cervical arthroplasty with the Bryan cervical disc prosthesis continues to compare favorably to ACDF at our institution . There has been no degradation of functional outcomes from 24 to 48 months for NDI , VAS of neck and arm , and SF-36 . There has been a lower incidence of secondary surgeries for the Bryan arthroplasty cohort to date Study Design . Radiographic results of a multicenter , prospect i ve r and omized study comparing 1-level cervical total disc replacement ( TDR-C ) with anterior cervical discectomy and fusion ( ACDF ) . Objective . To evaluate the effect on device-level lordosis , cranial and caudal adjacent level lordosis , and overall cervical sagittal alignment ( C2–C6 ) after TDR-C or ACDF . Summary of Background Data . Cervical total disc replacement ( TDR-C ) has emerged as a promising alternative to ACDF in a select group of patients . The maintenance and /or improvement of sagittal balance is essential in preserving functionality after reconstructive spinal procedures . Recent studies have documented changes in spinal alignment after TDR-C , however , no studies have compared these changes to those noted in matched group of patients that have undergone ACDF . Methods . Radiographic data were obtained from the r and omized group of a multicenter , r and omized , prospect i ve , controlled study comparing TDR-C ( ProDisc-C , Synthes Spine , West Chester , PA ) with ACDF in the treatment of 1-level cervical disc disease . Complete radiographic data were available for 89 TDR-C patients ( average age : 42.2 years ) and 91 ACDF patients ( average age : 41.7 years ) . Cervical lordosis at the device level , cranial and caudal adjacent levels , and total cervical lordosis ( C2–C6 ) were independently measured before surgery and 2 years after surgery using custom image stabilization software ( Quantitative Motion Analysis , Medical Metrics , Inc , Houston , TX ) . Results . C5–C6 was the most common operative level ( TDR-C : 54 % ; ACDF : 55 % ) . At 2 years after surgery , the TDR-C group experienced statistically significant changes in lordosis of 3.0 ° ( P < 0.001 ) , 0.90 ° ( P = 0.006 ) , and −1.9 ° ( P < 0.001 ) at the operative , cranial , and caudal adj-acent levels , respectively . ACDF experienced changes in lordosis of 4.2 ° ( P < 0.001 ) , 1.0 ° ( P = 0.001 ) , and −1.5 ° ( P = 0.001 ) , respectively . The between-group differences were significant at the operative level ( P = 0.03 ) and the caudal adjacent level ( P = 0.05 ) . Total cervical lordosis increased in both TDR-C and ACDF by 3.1 ° and 3.8 ° , respectively ( P = 0.49 ) . Conclusion . In both TDR-C and ACDF , lordosis increased at the device-level , cranial adjacent level , and in total cervical lordosis , while lordosis decreased at the caudal adjacent level . Although ACDF facilitated a greater increase in device level lordosis ( + 1.25 ° ) and less loss of lordosis at the caudal adjacent level compared with TDR-C ( −0.39 ° ) , the clinical relevance of the small differences remain unknown Study Design . R and omized controlled study . Objective . To compare the rates of adverse events associated with disc arthroplasty versus those of anterior cervical discectomy and arthrodesis with allograft and plate . Summary of Background Data . Cervical disc arthroplasty as a substitute for fusion has been developed to maintain motion and , theoretically , prevent adjacent segment degeneration . Currently , cervical arthroplasty devices are undergoing clinical testing for safety and efficacy . The evaluation of safety is performed by critical analysis of all adverse occurrences following surgery to determine if the new device has a beneficial risk profile for the patient . Methods . Adverse events associated with Bryan Disc arthroplasty and arthrodesis were compared in a prospect i ve r and omized study . Four hundred sixty-three ( 463 ) patients having cervical radiculopathy and or myelopathy at a single level were treated at 31 sites . A total of 242 patients received the disc and 221 patients had anterior cervical discectomy and fusion . All patients were evaluated before surgery and at 1.5 , 3 , 6 , 12 , and 24 months after surgery . Adverse events were recorded concurrently and categorized by severity and as medically or surgically related . Results . No differences in overall medical events occurred between groups . Surgically related events occurred more frequently in the investigational group secondary to more complaints of postoperative dysphagia and late medical events occurred more frequently in the investigational patients . However , the more severe World Health Organization Grade 3 and 4 events occurred more frequently in the arthrodesis patients related to treatment of pseudarthrosis and persistent symptoms . Significantly , more cervical spine reoperations occurred in the fusion group . Only one spinal cord injury occurred and it was in the arthrodesis group and no patients had deep infection or death related to either procedure . Conclusion . Bryan cervical disc replacement and anterior cervical fusion are both safe procedures with a low incidence of significant adverse events related to the procedure . Statistically , more serious adverse events and reoperations occurred in the fusion group while a greater number of less serious surgically related events were seen in the investigational group Study Design . Post hoc analysis of data acquired in a prospect i ve , r and omized , controlled trial . Objective . To compare adjacent segment motion after anterior cervical discectomy and fusion ( ACDF ) versus cervical total disc arthroplasty ( TDA ) . Summary of Background Data . TDA has been design ed to be a motion-preserving device , thus theoretically normalizing adjacent segment kinematics . Clinical studies with short-term follow-up have yet to demonstrate a consistent significant difference in the incidence of adjacent segment disease . Methods . Two hundred nine patients at 13 sites were treated in a prospect i ve , r and omized , controlled trial of ACDF versus TDA for single-level symptomatic cervical degenerative disc disease ( SCDD ) . Flexion and extension radiographs were obtained at all follow-up visits . Changes in ROM were compared using the Wilcoxon signed-rank test and the Mann-Whitney U test . Predictors of postoperative ROM were determined by multivariate analysis using mixed effects linear regression . Results . Data for 199 patients were available with 24-month follow-up . The groups were similar with respect to baseline demographics . A significant increase in motion at the cranial and caudal adjacent segments after surgery was observed in the ACDF group only ( cranial : ACDF : + 1.4 ° ( 0.4 , 2.4 ) , P = 0.01 ; TDA : + 0.8 ° , ( −0.1 , + 1.7 ) , P = 0.166 ; caudal : ACDF : + 2.6 ° ( 1.3 , 3.9 ) , P < 0.0001 ; TDA : + 1.3 , ( −0.2 , + 2.8 ) , P = 0.359 ) . No significant difference in adjacent segment ROM was observed between ACDF and TDA . Only time was a significant predictor of postoperative ROM at both the cranial and caudal adjacent segments . Conclusion . Adjacent segment kinematics may be altered after ACDF and TDA . Multivariate analysis showed time to be a significant predictor of changes in adjacent segment ROM . No association between the treatment chosen ( ACDF vs. TDA ) and ROM was observed . Furthermore clinical follow-up is needed to determine whether possible differences in adjacent segment motion affect the prevalence of adjacent segment disease in the two groups OBJECT The purpose of this study was to evaluate the long-term results of cervical total disc replacement ( TDR ) and anterior cervical discectomy and fusion ( ACDF ) in the treatment of single-level cervical radiculopathy . METHODS The results of 2 separate prospect i ve , r and omized , US FDA Investigational Device Exemption pivotal trials ( Bryan Disc and Kineflex|C ) from a single investigational site were combined to evaluate outcomes at long-term follow-up . The primary clinical outcome measures included the Neck Disability Index ( NDI ) , visual analog scale ( VAS ) , and neurological examination . Patients were r and omized to receive cervical TDR in 2 separate prospect i ve , r and omized studies using the Bryan Disc or Kineflex|C cervical artificial disc compared with ACDF using structural allograft and an anterior plate . Patients were evaluated preoperatively ; at 6 weeks ; at 3 , 6 , and 12 months ; and then yearly for a minimum of 48 months . Plain radiographs were obtained at each study visit . RESULTS A total of 74 patients were enrolled and r and omly assigned to either the cervical TDR ( n = 41 ) or ACDF ( n = 33 ) group . A total of 63 patients ( 86 % ) completed a minimum of 4 years follow-up . Average follow-up was 6 years ( 72 months ) with a range from 48 to 108 months . In both the cervical TDR and ACDF groups , mean NDI scores improved significantly by 6 weeks after surgery and remained significantly improved throughout the minimum 48-month follow-up ( p < 0.001 ) . Similarly , the median VAS pain scores improved significantly by 6 weeks and remained significantly improved throughout the minimum 48-month follow-up ( p < 0.001 ) . There were no significant differences between groups in mean NDI or median VAS scores . The range of motion ( ROM ) in the cervical TDR group remained significantly greater than the preoperative mean , whereas the ROM in the ACDF group was significantly reduced from the preoperative mean . There was significantly greater ROM in the cervical TDR group compared with the ACDF group . There were 3 reoperations ( 7.3 % ) at index or adjacent levels in the cervical TDR group ; all were cervical laminoforaminotomies . There were 2 adjacent-level reoperations in the cervical TDR group ( 4.9 % ) . There was 1 reoperation ( 3.0 % ) in the ACDF group at an index or adjacent level ( a second ACDF at the adjacent level ) . There was no statistically significant difference in overall reoperation rate or adjacent-level reoperation rate between groups . CONCLUSIONS Both cervical TDR and ACDF groups showed excellent clinical outcomes that were maintained over long-term follow-up . Both groups showed low index-level and adjacent-level reoperation rates . Both cervical TDR and ACDF appear to be viable options for the treatment of single-level cervical radiculopathy Background Cervical total disk replacement ( TDR ) is intended to address pain and preserve motion between vertebral bodies in patients with symptomatic cervical disk disease . Two-year follow-up for the ProDisc-C ( Synthes USA Products , LLC , West Chester , Pennsylvania ) TDR clinical trial showed non-inferiority versus anterior cervical discectomy and fusion ( ACDF ) , showing superiority in many clinical outcomes . We present the 4-year interim follow-up results . Methods Patients were r and omized ( 1:1 ) to ProDisc-C ( PDC-R ) or ACDF . Patients were assessed preoperatively , and postoperatively at 6 weeks and 3 , 6 , 12 , 18 , 24 , 36 , and 48 months . After the r and omized portion , continued access ( CA ) patients also underwent ProDisc-C implantation , with follow-up visits up to 24 months . Evaluations included Neck Disability Index ( NDI ) , Visual Analog Scale ( VAS ) for pain/satisfaction , and radiographic and physical/neurologic examinations . Results R and omized patients ( 103 PDC-R and 106 ACDF ) and 136 CA patients were treated at 13 sites . VAS pain and NDI score improvements from baseline were significant for all patients ( P < .0001 ) but did not differ among groups . VAS satisfaction was higher at all time points for PDC-R versus ACDF patients ( P = .0499 at 48 months ) . The percentage of patients who responded yes to surgery again was 85.6 % at 24 months and 88.9 % at 48 months in the PDC-R group , 80.9 % at 24 months and 81.0 % at 48 months in the ACDF group , and 86.3 % at 24 months in the CA group . Five PDC-R patients ( 48 months ) and no CA patients ( 24 months ) had index-level bridging bone . By 48 months , approximately 4-fold more ACDF patients required secondary surgery ( 3 of 103 PDC-R patients [ 2.9 % ] vs 12 of 106 ACDF patients [ 11.3 % ] , P = .0292 ) . Of these , 6 ACDF patients ( 5.6 % ) required procedures at adjacent levels . Three CA patients required secondary procedures ( 24 months ) . Conclusions Our 4-year data support that ProDisc-C TDR and ACDF are viable surgical options for symptomatic cervical disk disease . Although ACDF patients may be at higher risk for additional surgical intervention , patients in both groups show good clinical results at longer-term follow-up Background Anterior cervical discectomy and fusion ( ACDF ) is the gold st and ard for treating symptomatic cervical disc degeneration . Cervical total disc replacements ( TDRs ) have emerged as an alternative for some patients . The purpose of this study was to evaluate the safety and effectiveness of a new TDR device compared with ACDF for treating single-level cervical disc degeneration . Methods This was a prospect i ve , r and omized , controlled , multicenter Food and Drug Administration ( FDA ) regulated Investigational Device Exemption ( IDE ) study . A total of 245 patients were treated ( 164 TDR : 81 ACDF ) . The primary outcome measure was overall success based on improvement in Neck Disability Index ( NDI ) , no subsequent surgical interventions , and no adverse events ( AEs ) classified as major complications . Secondary outcome measures included SF-12 , visual analog scale ( VAS ) assessing neck and arm pain , patient satisfaction , radiographic range of motion , and adjacent level degeneration . Patients were evaluated preoperatively and postoperatively at 6 weeks , 3 , 6 , 12 , 18 , and 24 months . The hypothesis was that the TDR success rate was non-inferior to ACDF at 24 months . Results Overall success rates were 73.6 % for TDR and 65.3 % for ACDF , confirming non-inferiority ( p < 0.0025 ) . TDR demonstrated earlier improvements with significant differences in NDI scores at 6 weeks and 3 months , and VAS neck pain and SF-12 PCS scores at 6 weeks ( p<0.05 ) . Operative level range of motion in the TDR group was maintained throughout follow-up . Radiographic evidence of inferior adjacent segment degeneration was significantly greater with ACDF at 12 and 24 months ( p < 0.05 ) . AE rates were similar . Conclusions Mobi-C TDR is a safe and effective treatment for single-level disc degeneration , producing outcomes similar to ACDF with less adjacent segment degeneration . Level of Evidence : Level I. Clinical relevance : This study adds to the literature supporting cervical TDR as a viable option to ACDF in appropriately selected patients with disc degeneration The aim of this r and omized controlled clinical trial was to evaluate over a 5-year period , the clinical outcome of shrinkage-free ZrSiO(4)-ceramic ( KaVo Everest HPC ) full coverage crowns on posterior teeth in comparison with conventional gold crowns that served as the control . This study reports results of a 5-year study protocol up to 24 months . Patients totalling 224 were r and omly divided into two treatment groups . Of these , 123 patients were restored with 123 Everest HPC crowns , fabricated by the Kavo Everest computer-aided manufacturing ( CAM ) procedure and 101 patients received 101 gold crowns , but two were excluded from analysis . All crowns were conventionally cemented with glass-ionomer cement . After an observation period of 6 , 12 and 24 months , the prospect i ve survival rates ( Kaplan-Meier ) for the KaVo Everest HPC crowns were 97.9 % , 95.1 % and 89.8 % and for the gold crowns 100 % , 94.8 % and 92.7 % , respectively . There were no significant differences between the two groups ( P = 0.2 ) . The 1-year failure rates were 4.9 % for the KaVo Everest HPC crowns and 5.2 % for the gold crowns . The 1-year cumulative risks for loss of vitality , secondary caries , fractures , loss of crown and extraction of abutment of the analyzed abutments ( 88 ) were 8.9 % , 0 % , 0 % , 1.1 % and 1.1 % , respectively , for the gold crowns and 2.8 % , 0 % , 4.7 % , 0 % and 0.9 % , respectively , for the ceramic crowns ( 107 analyzed abutments ) . No perfect marginal fit was shown by 49.5 % of the evaluated ceramic crowns and 26.1 % of the gold crowns . Only 1.9 % of the KaVo Everest HPC crowns had a marginal crevice . In conclusion , Everest HPC crowns with an adequate occlusal tooth reduction of > 1.5 mm are suitable for posterior restorations , but the marginal fit shows a potential for improvement The optimal surgical approach for cervical disk disease remains a matter of debate , especially for multilevel disease . The purpose of this study was to compare the results of 2 surgical strategies for cervical disk disease involving 3 levels : hybrid constructs , artificial disk replacement combined with midlevel anterior cervical diskectomy and fusion ( ACDF ) , and 3-level ACDF . The authors prospect ively compared patients who had cervical disk disease involving 3 levels that was treated with hybrid constructs or with 3-level ACDF . Patients were asked to use the Neck Disability Index ( NDI ) to grade their pain intensity preoperatively and at routine postoperative intervals of 1 , 3 , 6 , 12 , and 24 months . Dynamic flexion and extension lateral cervical radiographs were obtained while in the st and ing position preoperatively and at the postoperative intervals . The angular range of motion for C2-C7 and the adjacent segments was measured using the Cobb method . Twenty-four patients were treated , 12 with hybrid constructs and 12 with 3-level ACDF . Both groups had significant postoperative improvement in NDI scores and neck pain ( P<.05 ) . However , no significant difference was found between the groups ( P>.05 ) . The hybrid constructs group showed faster recovery of C2-C7 range of motion . Mean C2-C7 range of motion of the hybrid constructs group recovered to that of the preoperative value , but that of the 3-level ACDF group did not ( P<.05 ) . Range of motion of the superior and inferior adjacent segments showed significant differences between the 2 groups at 12 and 24 months postoperatively ( P<.05 ) . These findings suggest that the hybrid constructs is a safe and effective alternative for cervical disk disease involving 3 levels . The definite stabilization and maintained range of motion can be achieved right away , which can ensure a good preliminary clinical outcome Study Design . R and omized controlled trial . Objective . Analyze the clinical outcomes at 5 years comparing cervical total disc replacement ( TDR ) with ProDisc-C ( Synthes Spine USA Products ; LLC , West Chester , PA ) with anterior cervical discectomy and fusion ( ACDF ) . Summary of Background Data . Previous reports of 2- and 4-year results have shown that ProDisc-C , a TDR for surgical treatment of patients experiencing single-level symptomatic cervical disc disease between C3 and C7 , is safe and effective . Methods . Two hundred nine patients ( 103 ProDisc-C and 106 ACDF ) from 13 sites were r and omized and treated . Results including neck disability index , visual analog scale ( VAS ) neck and arm pain , Short Form-36 ( SF-36 ) , neurological examination , device success , adverse event occurrence , and VAS patient satisfaction were analyzed . Results . Demographics were similar between the 2 patient groups ( ProDisc-C : 42.1 ± 8.4 yr , 44.7 % males ; ACDF : 43.5 ± 7.1 yr , 46.2 % males ) . Rates of follow-up at 2 years were 98.1 % ProDisc-C and 94.8 % ACDF , and at 5 years 72.7 % ProDisc-C and 63.5 % ACDF . For all clinical outcomes for both groups , there was a statistically and clinical ly significant improvement at 2 and 5 years compared with baseline . At 5 years , ProDisc-C patients had statistically significantly less neck pain intensity and frequency . Both groups scored high VAS satisfaction scores at 5 years , with ProDisc-C 86.56 and ACDF 82.74 . There were no reports of device failures or implant migration with ProDisc-C. The ProDisc-C patients maintained motion at their index level . At 5 years , the ProDisc-C patients had a statistically significantly lower rate of reoperation compared with ACDF patients ( 2.9 % vs. 11.3 % ) . Conclusion . Five-year results show that TDR with ProDisc-C is a safe and effective treatment of single-level symptomatic cervical disc disease . Clinical outcomes were comparable with ACDF . ProDisc-C patients maintained motion at the index level and had significantly less neck pain intensity and frequency as well as a lower probability of secondary surgery In this prospect i ve study , our aim was to compare the functional results and radiographic outcomes of fusion and Bryan Cervical Disc replacement in the treatment of two-level cervical disc disease . A total of 65 patients with two-level cervical disc disease were r and omly assigned to two groups , those operated on with Bryan Cervical Disc replacement ( 31 ) and those operated on with anterior cervical fusion with an iliac crest autograft and plate ( 34 ) . Clinical evaluation was carried out using the visual analogue scale ( VAS ) , the Short Form 36 ( SF-36 ) and the neck disability index ( NDI ) during a two year follow-up . Radiological evaluation sought evidence of range of motion , stability and subsidence of the prosthesis . Substantial reduction in NDI scores occurred in both groups , with greater percent improvement in the Bryan group ( P = 0.023 ) . The arm pain VAS score improvement was substantial in both groups . Bryan artificial cervical disc replacement seems reliable and safe in the treatment of patients with two-level cervical disc disease . RésuméCette étude prospect i ve a pour but de comparer les résultats fonctionnels et radiographiques des patients ayant bénéficié soit d’une fusion , soit d’une athrodèse , soit d’une prothèse discale dans le traitement des lésions dégénératives des disques cervicaux portant sur deux niveaux . 65 patients présentant de telles lésions ont été r and omisés en deux groupes , ceux traités par la prothèse discale de Bryan ( 31 ) et ceux traités par ostéosynthèse antérieure avec autogreffe illiaque et plaque ( 34 ) . L’évaluation clinique a été réalisée en utilisant le score douleur VAS , ( échelle analogique ) , le score SF-36 , la raideur de la nuque index NDI , après deux ans de recul . L’évaluation radiologique permet de mettre en évidence les secteurs de mobilité de stabilité et la migration de la prothèse . Une diminution significative du score NDI est observée dans les deux groupes avec un pourcentage plus important d’amélioration dans le groupe des prothèses de type Bryan ( p = 0.023 ) . Le score douleur est nettement amélioré dans les deux groupes néanmoins il semble que la prothèse de type Bryan permet d’avoir des résultats beaucoup plus fiables et beaucoup plus sûrs dans le traitement de ces patients présentant des lésions discales dégénératives cervicales sur deux niveaux Study Design . Prospect i ve , r and omized trial . Objective . To assess the in vivo kinematics of the cervical spine after cervical fusion and arthroplasty . Summary of Background Data . Compared with spinal fusion , disc replacement may impede the development of adjacent segment disease . To achieve this goal , any arthroplasty device should achieve desired spinal alignment while maintaining physiologic spinal motion at both the operated and surrounding motion segments . Methods . As part of a multicenter , prospect i ve , r and omized Food and Drug Administration IDE clinical evaluation of the porous coated motion artificial cervical disc , patients underwent either a single-level total disc replacement ( TDR ; 272 patients ) or anterior cervical discectomy and fusion ( ACDF ; 182 patients ) for treatment of cervical radiculopathy or myelopathy . Neutral , flexion , and extension radiographs of the cervical spine obtained before surgery , and at 3 , 6 , and 12 months after surgery were assessed . Quantitative assessment s and comparisons of motion patterns were produced using vali date d computer-assisted methods . Kinematic parameters , including segmental rotation , translation , center of rotation ( COR ) , disc height , and disc angle were calculated . Results . Cervical TDR preserved angular motion at the operated level , although the range was reduced from 8.0 ° before surgery to 6.2 ° at 12 months after surgery ( P < 0.001 ) . Significantly after TDR , adjacent-level angular motion was unchanged . In patients treated with fusion , angular motion at the superior adjacent level increased from 9.6 ° before surgery to 11.0 ° ( P = 0.003 ) at 12 months , with a trend toward increased postoperative translation ( P = 0.07 ) . For the TDR group , the horizontal COR averaged 0.8 mm posterior to the disc center before surgery and 0.2 mm anterior to the center at 12 months after TDR ( P < 0.001 ) , and the vertical COR averaged 2.5 mm below the endplate before surgery and 4.0 mm below at 12 months ( P = 0.001 ) . COR at the adjacent levels was unaltered by fusion or TDR . Lordotic alignment and disc height at the index level increased after intervention in both groups . Conclusion . TDR with the porous coated motion implant is able to restore and maintain lordotic alignment and disc height and maintain angular motion while allowing for similar translation to that seen before surgery . In contrast , after ACDF , the superior adjacent level developed increased angular motion compared with preoperative range of motion . This study provides in vivo data regarding the functioning of TDR and ACDF and their impact on adjacent-level kinematics Study Design . A prospect i ve , r and omized , multicenter study of surgical treatment of cervical disc disease . Objective . To assess the safety and efficacy of cervical disc arthroplasty using a new arthroplasty device at 24-months follow-up . Summary of Background Data . Cervical disc arthroplasty preserves motion in the cervical spine . It is an alternative to fusion after neurologic decompression , whereas anterior decompression and fusion provides a rigorous comparative benchmark of success . Methods . We conducted a r and omized controlled multicenter clinical trial enrolling patients with cervical disc disease . Ultimately 242 received the investigational device ( Bryan Cervical Disc ) , and 221 patients underwent a single-level anterior cervical discectomy and decompression and fusion as a control group . Patients completed clinical and radiographic follow-up examinations at regular intervals for 2 years after surgery . Results . Analysis of 12- and 24-month postoperative data showed improvement in all clinical outcome measures for both groups ; however , 24 months after surgery , the investigational group patients treated with the artificial disc had a statistically greater improvement in the primary outcome variables : Neck disability index score ( P = 0.025 ) and overall success ( P = 0.010 ) . With regard to implant- or implant/surgical-procedure-associated serious adverse events , the investigational group had a rate of 1.7 % and the control group , 3.2 % . There was no statistical difference between the 2 groups with regard to the rate of secondary surgical procedures performed subsequentto the index procedure . Patients who received the artificial cervical disc returned to work nearly 2 weeks earlier than the fusion patients ( P = 0.015 ) . Conclusion . Two-year follow-up results indicate that cervical disc arthroplasty is a viable alternative to anterior cervical discectomy and fusion in patients with persistently symptomatic , single-level cervical disc disease Study Design Prospect i ve , r and omized , multicenter clinical trial . Objective Kinematic analysis of target level and adjacent motion segments after Bryan artificial cervical disc replacement versus anterior cervical fusion . Summary of Background Data Disc arthroplasty has been shown to provide short-term clinical results that are comparable or better than those attained with traditional anterior cervical discectomy and fusion . One purported benefit of arthroplasty is the ability to prevent or delay adjacent level operations . Methods All patients received either a single-level anterior cervical discectomy and fusion with an anterior cervical plate ( Atlantis anterior cervical plate , n=221 ) or a single-level artificial cervical disc replacement ( Bryan cervical disc prosthesis , n=242 ) at C3 to C7 . Flexion , extension , and neutral lateral radiographs were obtained preoperatively , and at regular intervals of 24 months . Cervical vertebral bodies were tracked to calculate the functional spinal unit motion parameters , including flexion/extension range of motion and translation . If visible , the functional spinal unit parameters were obtained at the operative level as well as the level above and below . Results Significantly more motion was retained in the disc replacement group than the plated group at the index level . The disc replacement group retained an average of 7.95 degrees at 24 months . The preoperative motion was 6.43 degrees and there was no evidence of degradation of motion over 24 months . In contrast , the average range of motion in the fusion group was 1.11 degrees at 3-month follow-up and gradually decreased to 0.87 degrees at 24 months . The preoperative motion was 8.39 degrees . The Bryan disc did not migrate . At 24-month follow-up , there was no case of subsidence of the Bryan disc . There was no evidence of bridging bone across any of the Bryan implant disc spaces . Conclusions The Bryan disc treatment , on average , maintained flexion/extension range of motion without degradation over 24 months . No ectopic bridging ossification was seen in any of the Bryan discs and no subsidence or displacement of the Bryan disc occurred This study compared the clinical and radiological outcomes of dynamic cervical implant ( DCI ; Scient'x , Villers-Bretonneux , France ) arthroplasty versus anterior cervical discectomy and fusion ( ACDF ) for the treatment of cervical degenerative disc disease . This prospect i ve cohort study enrolled patients with single-level cervical degenerative disc disease who underwent DCI arthroplasty or ACDF between September 2009 and June 2011 . Patients were followed up for more than 2years . Clinical evaluation included the Medical Outcomes Study 36-Item Short Form Health Survey ( SF-36 ) , Neck Disability Index ( NDI ) , Japan Orthopedic Association ( JOA ) score , and visual analog scale ( VAS ) scores for neck and arm pain . Radiological assessment s included segmental range of motion ( ROM ) , overall ROM ( C2-C7 ) , disc height ( DHI ) , and changes in adjacent disc spaces . The VAS , SF-36 , JOA , and NDI scores improved significantly after surgery in both the DCI and ACDF groups . The VAS , JOA , and SF-36 scores were not significantly different between the DCI and ACDF groups at the final follow-up . The segmental ROM at the treated level and overall ROM increased significantly after surgery in the DCI group , but the ROM in the adjacent cephalad and caudal segments did not change significantly . The mean DHI at the treated level was significantly restored after surgery in both groups . Five patients ( 12.8 % ) in the DCI group showed new signs of adjacent segment degeneration . These results indicate that DCI is an effective , reliable , and safe procedure for the treatment of cervical degenerative disc disease . However , there is no definitive evidence that DCI arthroplasty has better intermediate-term results than ACDF The purpose of this paper is to compare the new functional intervertebral cervical disc prosthesis replacement and the classical interbody fusion operation , including the clinical effect and maintenance of the stability and segmental motion of cervical vertebrae . Twenty-four patients with single C5 - 6 intervertebral disk hernias were specifically selected and divided r and omly into two groups : One group underwent artificial cervical disc replacement and the other group received interbody fusion . All patients were followed up and evaluated . The operation time for the single disc replacement was ( 130 ± 50 ) minutes and interbody fusion was ( 105 ± 53 ) minutes . Neurological or vascular complications were not observed during or after operation . There was no prosthesis subsidence or extrusion . The JOA score of the group with prosthesis replacement increased from an average of 8.6 to 15.8 . The JOA score of the group with interbody fusion increased from an average of 9 to 16.2 . The clinical effect and the ROM of the adjacent space of the two groups showed no statistical difference . The short follow-up time does not support the advantage of the cervical disc prosthesis . The clinical effect and the maintenance of the function of the motion of the intervertebral space are no better than the interbody fusion . At least 5 years of follow-up is needed to assess the long-term functionality of the prosthesis and the influence on adjacent levels . RésuméL’objectif de ce travail est de comparer les prothèses discales , cervicales à la classique arthrodèse intercorporéale , en analysant les aspects cliniques , la stabilité et la mobilité des vertèbres cervicales . 24 patients ayant présenté une hernie discale c5 c6 ont été sélectionnés et séparés en deux groupes r and omisés . Un groupe a bénéficié d’une prothèse discale et l’autre groupe d’une arthrodèse intercorporéale . Tous les patients ont été suivis et évalués . Résultats : le temps opératoire pour la prothèse discale a été de 50 à 130 minutes et le temps opératoire de l’arthrodèse de 53 à 105 minutes . Aucune complication neurologique ou vasculaire n’a été observée après les interventions . Le score JOA dans le groupe des prothèses a évolué de 8.6 à 15.8 et dans le groupe des arthrodèses de 9 à 16.2 . la symptopathologie clinique et la mobilité des espaces inter vertébraux adjacents à l’intervention chirurgicale ne montrent pas de différence statistique . En conclusion : ce suivi à court terme ne permet pas de mettre en évidence un avantage à la prothèse discale cervicale . Les résultats fonctionnels et la mobilité ne sont pas supérieurs à ceux d’une arthrodèse intercorporéale . Il faudra au moins cinq ans de suivi avant de mettre en évidence une éventuelle fonctionnalité à long terme des prothèses et leur influence bénéfique au niveau des espaces adjacents à l’intervention si tant est qu’il y en ait Anterior cervical discectomy and fusion ( ACDF ) may be considered to be the gold st and ard for treatment of symptomatic degenerative disc disease within the cervical spine . However , fusion of the segment may result in progressive degeneration of the adjacent segments . Therefore , dynamic stabilization procedures have been introduced . Among these , artificial disc replacement by disc prosthesis seems to be promising . However , to be so , segmental motion must be preserved . This , again , is very difficult to judge and has not yet been proven . The aim of the current study was to first analyse the segmental motion following artificial disc replacement using a disc prosthesis . A second aim was to compare both segmental motion as well as clinical result to the current gold st and ard ( ACDF ) . This is a prospect i ve controlled study . Twenty-five patients with cervical disc herniation were enrolled and assigned to either study group ( receiving a disc prosthesis ) or control group ( receiving ACDF , using a cage with bone graft and an anterior plate . ) Radiostereometric analysis was used to quantify intervertebral motion immediately as well as 3 , 6 , 12 and 24 weeks postoperatively . Further , clinical results were judged using visual analogue scale and neuro-examination . Cervical spine segmental motion decreased over time in the presence of disc prosthesis or ACDF . However , the loss of segmental motion is significantly higher in the ACDF group , when looked at 3 , 6 , 12 and 24 weeks after surgery . We observed significant pain reduction in neck and arm postoperatively , without significant difference between both groups ( P > 0.05 ) . Cervical spine disc prosthesis preserves cervical spine segmental motion within the first 6 months after surgery . The clinical results are the same when compared to the early results following ACDF OBJECT The purpose of this study was to evaluate the safety and effectiveness of 2-level total disc replacement ( TDR ) using a Mobi-C cervical artificial disc at 48 months ' follow-up . METHODS A prospect i ve r and omized , US FDA investigational device exemption pivotal trial of the Mobi-C cervical artificial disc was conducted at 24 centers in the U.S. Three hundred thirty patients with degenerative disc disease were r and omized and treated with cervical total disc replacement ( 225 patients ) or the control treatment , anterior cervical discectomy and fusion ( ACDF ) ( 105 patients ) . Patients were followed up at regular intervals for 4 years after surgery . RESULTS At 48 months , both groups demonstrated improvement in clinical outcome measures and a comparable safety profile . Data were available for 202 TDR patients and 89 ACDF patients in calculation of the primary endpoint . TDR patients had statistically significantly greater improvement than ACDF patients for the following outcome measures compared with baseline : Neck Disability Index scores , 12-Item Short Form Health Survey Physical Component Summary scores , patient satisfaction , and overall success . ACDF patients experienced higher subsequent surgery rates and displayed a higher rate of adjacent-segment degeneration as seen on radiographs . Overall , TDR patients maintained segmental range of motion through 48 months with no device failure . CONCLUSIONS Four-year results from this study continue to support TDR as a safe , effective , and statistically superior alternative to ACDF for the treatment of degenerative disc disease at 2 contiguous cervical levels . Clinical trial registration no. : NCT00389597 ( clinical trials.gov ) Study Design . Prospect i ve , multicenter , r and omized Food and Drug Administration approved investigational device exemption clinical trial . Objective . To evaluate the safety and effectiveness of the PCM Cervical Disc compared with anterior cervical discectomy and fusion ( ACDF ) in the treatment of patients with degenerative spondylosis and neurological symptoms at 1 level between C3–C4 and C7–T1 . Summary of Background Data . Cervical disc arthroplasty in the treatment of symptomatic cervical spondylosis has been studied in other series . The PCM Cervical Disc is a nonconstrained motion-sparing alternative to ACDF . Methods . Patients 18 to 65 years of age with single-level symptomatic cervical spondylosis with radiculopathy and /or myelopathy unresponsive to nonoperative treatment were enrolled , including patients with prior nonadjacent or adjacent single-level fusions . The per- protocol patient sample at 2 years included 342 patients ( 189 PCM , 153 ACDF ) . Longitudinal outcomes were comparatively evaluated . Results . At 2 years postoperatively , clinical measures —neck and arm pain visual analogue scale , Neck Disability Index ( NDI ) , SF-36 , and neurological status — were significantly improved from preoperative baselines in both groups . Mean NDI score at 2 years was significantly lower in PCM group ( P = 0.029 ) . There were no statistical differences between groups in rates of surgery-related serious adverse events ( 5.6 % PCM , 7.4 % ACDF ) or secondary surgical procedures ( 5.2 % PCM , 5.4 % ACDF ) . Patients with PCM reported lower dysphagia scores ( 8.8/100 vs. 12.1/100 ; P = 0.045 ) and higher patient satisfaction ( 82.8/100 vs. 81.4/100 ) . Overall success , a composite endpoint including minimum 20 % NDI improvement , no major complications , no neurological worsening , no secondary surgical procedures , and meeting radiographical criteria of motion for PCM and fusion for ACDF , was significantly greater in the PCM group ( 75.1 % vs. 64.9 % ; P = 0.020 ) . Conclusion . The treatment of symptomatic single-level cervical spondylosis with PCM achieves clinical outcomes that are at least equivalent to ACDF while maintaining motion . At 2 years , patients with PCM had lower NDI scores , statistically lower rate of prolonged dysphagia , greater patient satisfaction , and superior overall success . Level of Evidence : The object of this study is to compare radiographic outcomes of anterior cervical decompression and fusion ( ACDF ) versus cervical disc replacement using the Bryan Cervical Disc Prosthesis ( Medtronic Sofamor Danek , Memphis , TN ) in terms of range of motion ( ROM ) , Functional spinal unit ( FSU ) , overall sagittal alignment ( C2–C7 ) , anterior intervertebral height ( AIH ) , posterior intervertebral height ( PIH ) and radiographic changes at the implanted and adjacent levels . The study consisted of 105 patients . A total of 63 Bryan disc were placed in 51 patients . A single level procedure was performed in 39 patients and a two-level procedure in the other 12 . Fifty-four patients underwent ACDF , 26 single level cases and 28 double level cases . The Bryan group had a mean follow-up 19 months ( 12–38 ) . Mean follow-up for the ACDF group was 20 months ( 12–40 months ) . All patients were evaluated using static and dynamic cervical spine radiographs as well as MR imaging . All patients underwent anterior cervical discectomy followed by autogenous bone graft with plate ( or implantation of a cage ) or the Bryan artificial disc prosthesis . Clinical evaluation included the visual analogue scale ( VAS ) , and neck disability index ( NDI ) . Radiographic evaluation included static and dynamic flexion-extension radiographs using the computer software ( Infinitt PiviewSTAR 5051 ) program . ROM , disc space angle , intervertebral height were measured at the operative site and adjacent levels . FSU and overall sagittal alignment ( C2–C7 ) were also measured pre-operatively , postoperatively and at final follow-up . Radiological change was analyzed using χ2 test ( 95 % confidence interval ) . Other data were analyzed using the mixed model ( SAS enterprises guide 4.1 versions ) . There was clinical improvement within each group in terms of VAS and NDI scores from pre-op to final follow-up but not significantly between the two groups for both single ( VAS p = 0.8371 , NDI p = 0.2872 ) and double ( VAS p = 0.2938 , NDI p = 0.6753 ) level surgeries . Overall , ROM and intervertebral height was relatively well maintained during the follow-up in the Bryan group compared to ACDF . Regardless of the number of levels operated on , significant differences were noted for overall ROM of the cervical spine ( p < 0.0001 ) and all other levels except at the upper adjacent level for single level surgeries ( p = 0.2872 ) . Statistically significant ( p < 0.0001 and p = 0.0172 ) differences in the trend of intervertebral height measurements between the two groups were noted at all levels except for the AIH of single level surgeries at the upper ( p = 0.1264 ) and lower ( p = 0.7598 ) adjacent levels as well as PIH for double level surgeries at the upper ( p = 0.8363 ) adjacent level . Radiological change was 3.5 times more observed for the ACDF group . Clinical status of both groups , regardless of the number of levels , showed improvement . Although clinical outcomes between the two groups were not significantly different at final follow-up , radiographic parameters , namely ROM and intervertebral heights at the operated site , some adjacent levels as well as FSU and overall sagittal alignment of the cervical spine were relatively well maintained in Bryan group compared to ACDF group . We surmise that to a certain degree , the maintenance of these parameters could contribute to reduce development of adjacent level change . Noteworthy is that radiographic change was 3.5 times more observed for ACDF surgeries . A longer period of evaluation is needed , to see if all these radiographic changes will translate to symptomatic adjacent level disease OBJECT The authors assess the long-term safety and efficacy of cervical disc replacement with the Prestige Cervical Disc in a prospect i ve , r and omized , multicenter trial at 7 years of follow-up . METHODS At 31 investigational sites , 541 patients with single-level cervical disc disease with radiculopathy were r and omized to 1 of 2 treatment groups : 276 investigational group patients underwent anterior cervical discectomy and arthroplasty with the Prestige disc , and 265 control group patients underwent anterior cervical discectomy and fusion . Clinical outcomes included Neck Disability Index , the 36-Item Short-Form Health Survey , and neck and arm pain scores . Radiographs were assessed for angle of motion and fusion . Clinical and radiographic outcomes were evaluated preoperatively , intraoperatively , and at 1.5 , 3 , 6 , 12 , 24 , 36 , 60 , and 84 months . RESULTS Of the 541 patients treated , 395 patients ( 73 % ; 212 investigational and 183 control patients ) completed 7 years of clinical follow-up . Significant improvements achieved by 1.5 months in both groups were sustained at 7 years . In the investigational group , mean Neck Disability Index improvements from preoperative scores were 38.2 and 37.5 at 60 and 84 months , respectively . In the control group , the corresponding means were 33.8 and 31.9 . The differences between the investigational and control groups at the 60-month and 84-month periods were significant ( p = 0.014 and 0.002 , respectively ) . The overall rates of maintenance or improvement in neurological status in the investigational group were significantly higher : 92.2 % and 88.2 % at 60 months and 84 months , respectively , compared with 85.7 % and 79.7 % in the control group ( p = 0.017 and 0.011 , respectively ) . At 84 months , the percentage of working patients in the investigational group was 73.9 % , and in the control group , 73.1 % . Postoperatively , the implant effectively maintained average angular motion of 6.67 ° at 60 months and 6.75 ° at 84 months . Cumulative rates for surgery at the index level were lower ( p < 0.001 ) in the investigational group ( 11 [ 4.8 % ] of 276 ) when compared with the control group ( 29 [ 13.7 % ] of 265 ) ( based on life-table method ) , and there were statistical differences between the investigational and control groups with specific regard to the rate of subsequent revision and supplemental fixation surgical procedures . Rates for additional surgical procedures that involved adjacent levels were lower in the investigational group than in the control group ( 11 [ 4.6 % ] of 276 vs. 24 [ 11.9 % ] of 265 , respectively ) . CONCLUSIONS Cervical disc arthroplasty has the potential for preserving motion at the operated level while providing biomechanical stability and global neck mobility and may result in a reduction in adjacent-segment degeneration . The Prestige Cervical Disc maintains improved clinical outcomes and segmental motion after implantation at 7-year follow-up . Clinical trial registration no. NCT00642876 ( Clinical Trials.gov ) Study Design . Prospect i ve radiographic evaluation of patients that underwent cervical total disc replacement ( TDR-C ) or anterior cervical discectomy and fusion ( ACDF ) for one-level cervical disc disease . Objective . To evaluate the following : ( 1 ) total cervical range of motion ( ROM ) from C2 to C7 , and ( 2 ) the relative contribution to total cervical ROM from the operative level and each adjacent level after one-level TDR-C or ACDF . Summary of Background Data . The development of symptomatic adjacent segment disease after ACDF has served as the impetus for the development of motion-preserving alternatives , most notably cervical disc arthroplasty . While previous reports have evaluated device-level and total cervical motion , no study has comprehensively quantified the relative contribution made from each of the adjacent levels to total cervical ROM in TDR-C and ACDF . Methods . Radiographic review of 187 r and omized patients from a multicenter , prospect i ve , r and omized trial comparing TDR-C with ACDF for one-level cervical disc disease . There were 93 TDR-C and 94 ACDF patients included . ROM measurements were performed independently using quantitative motion analysis , a custom digitized image stabilization software program , to evaluate total cervical ROM and relative contribution to total ROM from each level from C2 to C7 preoperatively and at 24 months . Results . The most common operative level was C5/C6 ( 57 % ) followed by C6/C7 ( 34 % ) . At 2 years , the TDR-C group underwent a statistically greater improvement in total cervical ROM ( + 5.9 ° ) compared with ACDF ( –0.8 ° , P = 0.001 ) . In TDR-C , the relative contributions to total cervical ROM from the operative level and each caudal and cranial adjacent level were statistically equivalent from baseline to 24 months . In contrast , ACDF patients had significantly reduced contribution to total cervical ROM from the operative level ( by 15 % , P < 0.001 ) , and significantly elevated contribution from the caudal adjacent level ( by 5.9 % , P < 0.001 ) , first cranial adjacent level ( by 3.3 % , P < 0.001 ) , second cranial adjacent level ( by 5.3 % , P < 0.001 ) , and third cranial adjacent level ( by 3.0 % , P < 0.001 ) . Conclusion . Compensation for the loss of motion at the operative level in ACDF is seen throughout the unfused cervical spine . Cervical disc arthroplasty , however , increases total cervical ROM compared with ACDF and maintains a physiologic distribution of ROM throughout the cervical spine at 2 years , potentially lowering the risk for adjacent segment breakdown OBJECT Cervical total disc replacement ( CTDR ) represents a relatively novel procedure intended to address some of the shortcomings associated with anterior cervical discectomy and fusion ( ACDF ) by preserving motion at the treated level . This prospect i ve , r and omized , multicenter study evaluates the safety and efficacy of a new metal-on-metal CTDR implant ( Kineflex|C ) by comparing it with ACDF in the treatment of single-level spondylosis with radiculopathy . METHODS The study was a prospect i ve , r and omized US FDA Investigational Device Exemption ( IDE ) pivotal trial conducted at 21 centers across the US . The primary clinical outcome measures included the Neck Disability Index ( NDI ) , visual analog scale ( VAS ) scores , and a composite measure of clinical success . Patients were r and omized to CTDR using the Kineflex|C ( SpinalMotion , Inc. ) cervical artificial disc or ACDF using structural allograft and an anterior plate . RESULTS A total of 269 patients were enrolled and r and omly assigned to either CTDR ( 136 patients ) or to ACDF ( 133 patients ) . There were no significant differences between the CTDR and ACDF groups when comparing operative time , blood loss , length of hospital stay , or the reoperation rate at the index level . The overall success rate was significantly greater in the CTDR group ( 85 % ) compared with the ACDF group ( 71 % ) ( p = 0.05 ) . In both groups , the mean NDI scores improved significantly by 6 weeks after surgery and remained significantly improved throughout the 24-month follow-up ( p < 0.0001 ) . Similarly , the VAS pain scores improved significantly by 6 weeks and remained significantly improved through the 24-month follow-up ( p < 0.0001 ) . The range of motion ( ROM ) in the CTDR group decreased at 3 months but was significantly greater than the preoperative mean at 12- and 24-month follow-up . The ROM in the ACDF group was significantly reduced by 3 months and remained so throughout the follow-up . Adjacent-level degeneration was also evaluated in both groups from preoperatively to 2-year follow-up and was classified as none , mild , moderate , or severe . Preoperatively , there were no significant differences between groups when evaluating the different levels of adjacent-level degeneration . At the 2-year follow-up , there were significantly more patients in the ACDF group with severe adjacent-level radiographic changes ( p < 0.0001 ) . However , there were no significant differences between groups in adjacent-level reoperation rate ( 7.6 % for the Kineflex|C group and 6.1 % for the ACDF group ) . CONCLUSIONS Cervical total disc replacement allows for neural decompression and clinical results comparable to ACDF . Kineflex|C was associated with a significantly greater overall success rate than fusion while maintaining motion at the index level . Furthermore , there were significantly fewer Kineflex|C patients showing severe adjacent-level radiographic changes at the 2-year follow-up . These results from a prospect i ve , r and omized study support that Kineflex|C CTDR is a viable alternative to ACDF in select patients with cervical radiculopathy Study Design . Prospect i ve , r and omized , controlled , multicenter clinical trial . Objective . To compare outcomes of cervical disc arthroplasty with those of anterior cervical decompression and fusion ( ACDF ) in a Chinese population . Summary of Background Data . Cervical disc arthroplasty has been found to be superior to ACDF for maintaining range of motion ( ROM ) at the index spinal segment and possibly will avoid abnormal stress to adjacent segments . Methods . A total of 120 patients from 3 large hospitals in China were r and omly assigned to treatment with cervical disc arthroplasty ( n = 60 ) using the BRYAN prosthesis or ACDF ( n = 60 ) and were observed postoperatively for 24 months . Results . The 2 groups had similar preoperative demographics and baseline characteristics including ROM , neck disability index , and visual analogue scale for neck and arm pain . The total disc replacement ( TDR ) group had a significantly longer operation time than the ACDF group ( P < 0.001 ) . Outcome data obtained after 24 months revealed a significant difference between the groups in mean change from baseline in ROM at the index level ( P < 0.001 ) ; ROM was maintained in the TDR group but reduced in the ACDF group . There were no significant between-group differences in the baseline changes in neck disability index or visual analogue scale scores for pain . One patient in the TDR group and 4 patients in the ACDF group required reoperations . Conclusion . At 24 months after surgery , the cervical disc prosthesis yielded good clinical results while maintaining ROM at the index level . Cervical disc arthroplasty appears to be a viable alternative to ACDF |
13,275 | 27,098,973 | There was little evidence to show significant impact on LBM , and no trials looked at muscle strength .
Current evidence does not support the use of progesterone therapies for non-cancer cachexia .
There may however be a limited role for its use as an appetite stimulant in a palliative context on a case-by-case basis | BACKGROUND Cachexia describes a complex pathological syndrome of muscle wasting , anorexia and weight loss .
Progesterone therapies have been shown to improve appetite and promote weight gain in patients with cachexia ; however , research has focused heavily on patients with cancer , and its effectiveness in other diseases remains unclear .
AIMS This systematic review aim ed to present the evidence available for progesterone therapy as a treatment for non-cancer cachexia . | OBJECTIVE We examined the effects of megestrol acetate versus placebo and progressive resistance physical exercise on weight , lean muscle mass , quality of life , ability to exercise , proinflammatory cytokines , and anti-inflammatory cytokines , and their correlations with one another . DESIGN We organized a prospect i ve 20-week , r and omized , double-blind , placebo-controlled pilot trial of hemodialysis patients . SETTING This study took place at the Outpatient Unit of the Northport Veteran Affairs Medical Center . SUBJECTS We studied nine male hemodialysis patients who had two or more of the following : albumin level < 4.0 g/dL , total cholesterol < 150 mg/dL , protein catabolic rate < 0.8 g/kg/day , and predialysis serum urea nitrogen < 60 mg/dL. Their ages were 50 to 83 years . Two were diabetic , and seven were nondiabetic . INTERVENTIONS Interventions included megestrol acetate ( MA ) or placebo 800 mg oral daily for 20 weeks , along with weight resistance physical therapy with weights twice a week before dialysis . Patients were followed prospect ively for an additional 4 weeks . MAIN OUTCOME MEASUREMENTS Weight , body composition , activities of daily living , ability to exercise , and plasma cytokine levels were measured . RESULTS At 24 weeks , the MA group had a statistically significant weight gain ( 11.1-pound increase vs. 1.5-pound decrease for the placebo group , P = .018 ) , body fat gain ( 6.2-pound increase vs. a 0.4-pound decrease for the placebo group , P = .044 ) and fat-free mass gain ( 5-pound increase vs. a 1.2-pound decrease in the placebo group ) . The MA group also had a greater tendency toward increased appetite and sense of well-being . The MA group showed a greater improvement in ability to exercise ( mean change in rate of perceived exertion ( RPE ) , 4.7 ) vs. the placebo group ( mean change in RPE vs. 0.5 , P = .02 ) . Elevated cytokine levels were evident at baseline in both groups . In all patients , increases in weight , fat-free mass , sense of well-being , appetite , and ability to exercise were negatively correlated with tumor necrosis factor receptor subunit p75 ( P < .05 ) . There was a trend toward all of these parameters to be negatively correlated with tumor necrosis factor receptor subunit p55 , although only sense of well-being was statistically significant ( P < .05 ) . CONCLUSION In a pilot trial in dialysis patients , MA showed significant benefits in improving weight and ability to exercise . Cytokine changes were correlated with weight gains and increases in fat-free mass BACKGROUND Malnutrition-inflammation complex syndrome and anorexia , common conditions in maintenance dialysis patients , are strongly associated with higher mortality and hospitalization and lower quality of life ( QoL ) in this population . Megestrol acetate , 800 mg/day , has been shown to increase appetite and food intake and to mitigate inflammation in cachectic AIDS and cancer patients , leading to weight gain , but it is also associated with side effects at this dose . METHODS We evaluated the efficacy of the oral solution of megestrol acetate in half of its conventional dose in improving the nutritional state and inflammation in 10 hypoalbuminemic dialysis patients ( albumin < 3.7 g/dL ) . Six women and 4 men , ages 60.2 years , took 400 mg of megestrol acetate solution daily for 16 weeks . Anthropometry , dual energy x-ray absorptiometry , 24-hour diet recalls , and biochemical measurements of nutrition and inflammation , including serum C-reactive protein and leptin , were performed . RESULTS At the end of the 16 weeks of intervention , weight and body mass index increased by 9 % , body fat proportion by 31 % , and triceps skinfold by 40 % ( P < .01 ) . Serum albumin increased from 3.0 to 3.3 g/dL and continued to increase significantly to 3.6 g/dL after 3 months postintervention ( P = .03 ) . Serum leptin increased from 5.2 to 10.7 ng/mL ( P = .09 ) . Daily protein and energy intake increased progressively up to 27 % to 42 % by the end of the trial ( P < or = .01 ) . In 8 patients without acute infection , serum C-reactive protein declined from 1.24 to 0.78 mg/L ( P = .06 ) . QoL and appetite were reported to be improved . No major side effects were observed , and all 10 patients completed the 16 weeks of daily intake of megestrol acetate without interruption . CONCLUSIONS Megestrol acetate oral solution in half of its conventional dose is safe and improves the nutritional state , inflammation , and anorexia in maintenance dialysis patients . Larger-scale placebo-controlled r and omized studies are needed to confirm the beneficial effects of 400 mg/day of megestrol acetate in dialysis patients Weight loss is known to impact survival among patients infected with human immunodeficiency virus ( HIV ) even in the era of highly active antiretroviral therapy ( HAART ) . In a r and omized trial , we compared the effects of 2 months of treatment with either megestrol acetate ( 800 mg every day ) or ox and rolone ( 10 mg twice per day ) on body weight and composition in patients with weight loss of > or = 5 kg who were receiving HAART . The mean weight was 66 kg , and the mean body mass index was 21 . Mean weight gain in the megestrol acetate and the ox and rolone arms were 2.8 kg ( 4.6 % of the baseline value ) and 2.5 kg ( 3.9 % of the baseline value ) , respectively ( P=.80 ) . Lean body mass accounted for 39 % of weight gain in the megestrol acetate arm and 56 % in the ox and rolone arm ( P=.38 ) . Seven patients in the megestrol acetate arm and 5 patients in the ox and rolone arm reported minor adverse events ( P=.74 ) . In conclusion , megestrol acetate therapy and ox and rolone therapy have similar effects on body weight and composition and are safe and well-tolerated during HAART Aim : N-3 fatty acids , especially eicosapentaenoic acid ( EPA ) , may possess anticachectic properties . This trial compared a protein and energy dense supplement enriched with n-3 fatty acids and antioxidants ( experimental : E ) with an isocaloric isonitrogenous control supplement ( C ) for their effects on weight , lean body mass ( LBM ) , dietary intake , and quality of life in cachectic patients with advanced pancreatic cancer . Methods : A total of 200 patients ( 95 E ; 105 C ) were r and omised to consume two cans/day of the E or C supplement ( 480 ml , 620 kcal , 32 g protein ± 2.2 g EPA ) for eight weeks in a multicentre , r and omised , double blind trial . Results : At enrolment , patients ’ mean rate of weight loss was 3.3 kg/month . Intake of the supplements ( E or C ) was below the recommended dose ( 2 cans/day ) and averaged 1.4 cans/day . Over eight weeks , patients in both groups stopped losing weight ( Δ weight E : −0.25 kg/month versus C : −0.37 kg/month ; p = 0.74 ) and LBM ( Δ LBM E : + 0.27 kg/month versus C : + 0.12 kg/month ; p = 0.88 ) to an equal degree ( change from baseline E and C , p<0.001 ) . In view of evident non-compliance in both E and C groups , correlation analyses were undertaken to examine for potential dose-response relationships . E patients demonstrated significant correlations between their supplement intake and weight gain ( r = 0.50 , p<0.001 ) and increase in LBM ( r = 0.33 , p = 0.036 ) . Such correlations were not statistically significant in C patients . The relationship of supplement intake with change in LBM was significantly different between E and C patients ( p = 0.043 ) . Increased plasma EPA levels in the E group were associated with weight and LBM gain ( r = 0.50 , p<0.001 ; r = 0.51 , p = 0.001 ) . Weight gain was associated with improved quality of life ( p<0.01 ) only in the E group . Conclusion : Intention to treat group comparisons indicated that at the mean dose taken , enrichment with n-3 fatty acids did not provide a therapeutic advantage and that both supplements were equally effective in arresting weight loss . Post hoc dose-response analysis suggests that if taken in sufficient quantity , only the n-3 fatty acid enriched energy and protein dense supplement results in net gain of weight , lean tissue , and improved quality of life . Further trials are required to examine the potential role of n-3 enriched supplements in the treatment of cancer cachexia CONTEXT Reduced energy intake is a primary factor in HIV-associated wasting . Megestrol acetate ( MA ) stimulates appetite and weight gain . However , much of the weight gained is fat , possibly as a result of MA-induced hypogonadism . OBJECTIVE The objective of the study was to determine whether coadministration of testosterone with MA could enhance lean body mass ( LBM ) accrual and evaluate the effects of MA , alone or combined with testosterone , on sexual functioning and the hypothalamic-pituitary-adrenal axis . DESIGN This was a r and omized , double-blind , placebo-controlled , multicenter trial . SETTING Fourteen AIDS Clinical Trials Units in the United States participated in the study . SUBJECTS Seventy-nine HIV-positive men with 5 % or more weight loss or body mass index less than 20 kg/m2 took part in the study . INTERVENTION Subjects were r and omized to receive MA ( 800 mg daily ) plus testosterone enanthate ( 200 mg ; MA/TE ; n = 41 ) or placebo ( MA/PL ; n = 38 ) biweekly for 12 wk . MAIN OUTCOME MEASURES Weight , body composition ( bioelectric impedance analysis ) , adrenal and gonadal hormones , and sexual functioning ( question naire ) were measured . RESULTS Both groups experienced robust increases in weight ( median 5.3 and 7.3 kg in MA/TE and MA/PL , respectively ) , LBM ( 3.3 and 3.3 kg ) , and fat ( 3.0 and 3.8 kg ) . There were no significant differences between groups in the magnitude or composition of weight gain ( P = 0.44 , 0.90 , and 0.11 for weight , LBM , and fat , respectively ) . Trough testosterone concentrations decreased to a greater extent in MA/PL ( -12.3 vs. -6.1 nmol/liter in MA/TE ; P = 0.04 ) . Cortisol levels became nearly undetectable in subjects with plasma MA levels greater than 150 ng/ml . Sexual functioning was preserved with MA/TE but worsened in MA/PL . CONCLUSIONS MA produced robust weight gain . Coadministration of testosterone preserved sexual functioning but did not enhance LBM accrual BACKGROUND We examined changes in total body weight ( TBW ) and health-related quality of life ( HRQL ) during prolonged combination weight-gaining therapy and dietary advice in HIV . DESIGN This was a cohort study of patients initially r and omized to single agent therapy for 2 months , megestrol acetate ( 800 mg daily ) , or ox and rolone ( 10 mg twice daily ) , followed by both agents and dietary advice for 5 months . METHODS Two community health clinics and 1 urban infectious disease clinic were included , as were HIV-positive adult patients receiving highly active antiretroviral therapy with documented 5 % weight loss . TBW and HRQL were measured after 7 months ( 7 m ) . RESULTS Twenty-nine of 39 participants completed 7 m. The average sample age was 40 years , 75 % were male , and 52 % were of color at enrollment . Baseline mean TBW and body mass index ( BMI ) were 62.5 kg and 21 kg/m(2 ) , respectively . Net gains in TBW , lean body mass , and fat during the 7 m were 5.3 kg ( 8.5 % of baseline ) , 2.1 kg , and 3.1 kg , respectively ( p < .01 for each ) . BMI increased to 23.1 kg/m(2 ) ( p < .01 ) . Dietary intake increased by 467 kcal/day ( p = .03 ) . Physical health improved by 5.7 ( 100-point scale , p < .01 ) , and mental health was unchanged ( -4.2 , p = .11 ) . In multivariable models , female gender ( p < .01 ) , lower baseline HIV viral load ( p = .03 ) , and increasing age ( p < .01 ) were associated with TBW gain . Injection drug use ( p < .01 ) and higher baseline HIV viral load ( p < .01 ) were associated with reduction in physical health . CONCLUSIONS Prolonged combination therapy with megestrol acetate , ox and rolone , and dietary advice could reverse weight loss and low BMI associated with incomplete viral suppression and improve physical health AIMS Chronic heart failure is associated with maladaptive and prolonged neurohormonal and pro-inflammatory cytokine activation causing a metabolic shift favouring catabolism , vasodilator incapacity , and loss of skeletal muscle bulk and function . In men , and rogens are important determinants of anabolic function and physical strength and also possess anti-inflammatory and vasodilatory properties . METHODS AND RESULTS We conducted a r and omized , double-blind , placebo-controlled parallel trial of testosterone replacement therapy ( 5 mg And roderm ) at physiological doses in 76 men ( mean+/-SD , age 64+/-9.9 ) with heart failure ( ejection fraction 32.5+/-11 % ) over a maximum follow-up period of 12 months . The primary endpoint was functional capacity as assessed by the incremental shuttle walk test ( ISWT ) . At baseline , 18 ( 24 % ) had serum testosterone below the normal range and bioavailable testosterone correlated with distance walked on the initial ISWT ( r=0.3 , P=0.01 ) . Exercise capacity significantly improved with testosterone therapy compared with placebo over the full study period ( mean change + 25+/-15 m ) corresponding to a 15+/-11 % improvement from baseline ( P=0.006 ANOVA ) . Symptoms improved by at least one functional class on testosterone in 13 ( 35 % ) vs. 3 ( 8 % ) on placebo ( P=0.01 ) . No significant changes were found in h and grip strength , skeletal muscle bulk by cross-sectional computed tomography , or in tumour necrosis factor levels . Testosterone therapy was safe with no excess of adverse events although the patch preparation was not well tolerated by the study patients . CONCLUSION Testosterone replacement therapy improves functional capacity and symptoms in men with moderately severe heart failure Cachexia is a common problem in persons infected with the human immunodeficiency virus ( HIV ) . Megestrol acetate , an agent used for the treatment of metastatic breast cancer , is associated with appetite stimulation and weight gain . To determine whether this drug might benefit HIV-positive patients , 22 such subjects ( 14 previously reported ) were treated with oral megestrol acetate , beginning at a dose of 80 mg four times daily . All patients had lost at least 10 % of their preillness weight prior to treatment ; the median loss was 11.4 kg ( range , 5.5 to 26.8 ) . Preliminary data from patients observed during therapy from 2 to 72 weeks showed that 21 of the 22 patients gained weight ; the average weight gain was 7.3 kg ( range , -4.1 to 17.3 ) . Three patients failed to gain weight on 320 mg per day of megestrol acetate ; both appetite stimulation and weight gain were achieved with 460 mg per day in one and 640 mg per day in another . One patient continued to lose weight despite 480 mg per day megestrol acetate . The median time to peak weight during megestrol acetate treatment was 14 weeks . Seven patients returned to within 1 kg of their normal body weight . In three of the 22 patients treated , megestrol acetate and zidovudine were started simultaneously . For these three patients , weight gain was potentially due to the recognized weight gain associated with the initiation of zidovudine . For the remaining 18 patients , however , appetite stimulation and weight gain were a result of megestrol acetate . All patients tolerated the drug well . One patient developed a deep vein thrombosis . No patient developed peripheral edema or drug-related impotence . The appetite improvement and weight gain seen in this initial series are encouraging . The true effectiveness of megestrol acetate for HIV-related cachexia and the effects of treatment on quality of life are currently being assessed in a national prospect i ve , r and omized , double-blind , placebo-controlled trial BACKGROUND Weight loss among older patients is a severe problem , associated with an increased incidence of infections , decubiti , and death . Megestrol acetate ( MA ) causes weight gain in cachectic cancer and AIDS patients , but its effects in older cachectic patients are unknown . OBJECTIVE To compare the effects of MA oral suspension ( O.S. ) , 800 mg/day , versus placebo on weight in geriatric nursing home patients with weight loss or low body weight . DESIGN Twelve-week , r and omized , double-blind , placebo-controlled trial with a 13-week follow-up period . SETTING Veterans Administration Medical Center ( VMAC ) nursing home . PATIENTS Nursing home patients with weight loss of > or = 5 % of usual body weight over the past 3 months , or body weight 20 % below their ideal body weight . INTERVENTIONS Patients were r and omly assigned to receive placebo or MA 800 mg/day for 12 weeks and were then followed for 13 weeks off treatment . MEASUREMENTS Primary outcome was measured by weight and appetite change . Secondary outcome measures included sense of well-being , enjoyment of life , change in depression scale , laboratory nutrition parameters , energy intake counts , body composition , and adverse events . RESULTS At 12 weeks there were no significant differences in weight gain between treatment groups , whereas MA-treated patients reported significantly greater improvement in appetite , enjoyment of life , and well-being . Body composition was not statistically different between the two groups . At Week 25 ( 3 months after treatment ) , 61.9 % of MA-treated patients had gained > or = 1.82 kg ( 4 lbs ) compared to 21.7 % of placebo patients . CONCLUSIONS In geriatric patients with weight loss or low body weight MA improves appetite and well-being after 12 weeks of treatment . During the 3 months of MA treatment , there was no statistically significant weight gain ( > or = 4 lbs ) . Three months after treatment , weight gain ( > or = 4 lbs ) was significantly increased in MA-treated patients PURPOSE To determine whether dronabinol administered alone or with megestrol acetate was more , less , or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia . PATIENTS AND METHODS Four hundred sixty-nine assessable advanced cancer patients were r and omized to ( 1 ) oral megestrol acetate 800 mg/d liquid suspension plus placebo , ( 2 ) oral dronabinol 2.5 mg twice a day plus placebo , or ( 3 ) both agents . Eligible patients acknowledged that loss of appetite or weight was a problem and reported the loss of 5 pounds or more during 2 months and /or a daily intake of less than 20 calories/kg of body weight . RESULTS Groups were comparable at baseline in age , sex , tumor type , weight loss , and performance status . A greater percentage of megestrol acetate-treated patients reported appetite improvement and weight gain compared with dronabinol-treated patients : 75 % versus 49 % ( P = .0001 ) for appetite and 11 % versus 3 % ( P = .02 ) for > or = 10 % baseline weight gain . Combination treatment result ed in no significant differences in appetite or weight compared with megestrol acetate alone . The Functional Assessment of Anorexia/Cachexia Therapy question naire , which emphasizes anorexia-related questions , demonstrated an improvement in quality of life ( QOL ) among megestrol acetate-treated and combination-treated patients . The single-item Uniscale , a global QOL instrument , found comparable scores . Toxicity was also comparable , with the exception of an increased incidence of impotence among men who received megestrol acetate . CONCLUSION In the doses and schedules we studied , megestrol acetate provided superior anorexia palliation among advanced cancer patients compared with dronabinol alone . Combination therapy did not appear to confer additional benefit UNLABELLED Dietary intervention studies in COPD patients often are short-term inpatient studies where a certain amount of extra energy is guaranteed . The aim of this study was to evaluate the effect of an 1 year individual multifaceted dietary intervention during multidisciplinary rehabilitation . Eighty-seven patients with severe COPD , not dem and ing oxygen therapy were included , 24 of them served as controls . A dietary history interview was performed at baseline and at study end . Dietary advice given were based on results from the dietary history and socio-economic status . The intervention group was divided into three parts ; NW : normal weight ( dietary advice given aim ing to weight maintenance ) , OW : overweight ( weight-reducing advice ) and UW : underweight ( dietary advise based on an energy- and protein-rich diet ) . RESULTS UW-group : Eighty-one per cent of the patients gained weight or kept a stable weight . OW-group : Fifty-seven per cent lost more than 2 kg NW-group : Seventy-six per cent kept a stable weight or gained weight . Increased dietary intake from baseline was seen for energy protein , carbohydrates and certain micronutrients ( P < 0.05 ) in the UW group . Six minutes walking distance increased by approximately 20 m in both NW ( P < 0.05 ) and UW patients . To conclude , slight , but uniform , indications of positive effects of dietary intervention during multidisciplinary rehabilitation was seen . Dietary intervention in underweight COPD patients might be a prerequisite for physical training We have examined the effect of a medroxyprogesterone therapy in HIV-infected patients under appropriate nutrition for anabolism . The experiments were performed on 12 men ( mean age 40 y ) , HIV seropositive but free of any clinical ly active opportunistic infection for at least one month . The patients underwent a 2-week baseline diet period ( 1.2 g protein x kg(-1 ) body weight ( BW ) x d(-1 ) ) and then a 5-week experimental period with again the baseline diet in conjunction with supplements including Tonexis HP ( 0.7 g protein x kg(-1 ) BW ) x d(-1 ) ) , L-threonine ( 0.018 g x kg(-1 ) BW x d(-1 ) ) and L-methionine ( 0.013 g x kg(-1 ) BW x d(-1 ) ) . Indeed HIV-infected patients showed deficiencies in these amino acids . They were r and omly divided into groups I and II under double-blinded condition . Group II was given medroxyprogesterone acetate ( 0.4 g x d(-1 ) ) during the last 3 weeks whereas group I received a placebo . All the patients significantly increased their body weight ( P < 0.05 ) during the experimental periods . Those under medroxyprogesterone tended to show a higher but not significant weight gain ( + 3.1 + /- 1.0 kg in group II and + 1.9 + /- 0.3 kg in group I ) . Blood free amino acids were used as rough indicators of amino acid utilization and were analyzed prior and during acute 150 min intravenous infusion of a complete glucose-amino acid mixture . This test was done before and at the end of the experimental periods . Basal essential blood free amino acids were similar in the two groups and did not change during the experimental period . Most essential amino acids increased following glucose-amino acid infusions . The incremental increase was of less magnitude after the experimental period than before when medroxyprogesterone was present ( P < 0.05 for valine , leucine , lysine , threonine and methionine ) . This was not the case in the absence of the hormone . We concluded that medroxyprogesterone might improve the efficacy of an oral protein-rich nutritional support in HIV-infected patients Introduction : Megestrol acetate ( MA ) is a progestational agent used for palliation of breast and endometrial cancer . The drug promotes weight gain via appetite stimulation . This property has led to widespread use in patients with wasting illnesses . Increasing numbers of reports suggest glucocorticoid activity . Objective : Unrecognized adrenal suppression may result from MA use . This is the first study to examine the prevalence of adrenal suppression in hospitalized patients treated with MA . Subjects and design : This is a cross-sectional study of hospitalized patients receiving MA compared to control subjects . Morning cortisol levels , endocrine signs and symptoms , and duration of MA therapy were evaluated in 28 hospitalized medical patients treated with MA , and 21 control patients admitted to the same hospital service during the study period . Results : Median cortisol levels were significantly lower in patients using MA vs controls ( 160 vs 386 nmol/l , p=0.003 ) . Forty-three percent of subjects on MA demonstrated morning cortisol levels below the normal range ( 138 - 690 nmol/l ) , compared with 10 % of controls ( p=0.013 ) . Ninety-three percent of subjects taking MA had morning cortisol levels below the level that excludes adrenal insufficiency in hospitalized patients ( 497 nmol/l ) vs 71 % of controls ( p=0.06 ) . Conclusions : MA use is associated with significant adrenal suppression in acutely ill individuals . This should alert physicians to the possibility of adrenal insufficiency and the need to assess for signs or symptoms of adrenal insufficiency , and m and ates a low threshold for testing adrenal function in hospitalized patients taking MA BACKGROUND Megestrol acetate ( MA ) is a progestin widely used to treat weight loss and cachexia in patients suffering from AIDS or cancer . Although MA is also frequently prescribed for similarly malnourished elderly individuals , the efficacy and morbidity of MA treatment in this patient population remain unclear . OBJECTIVE The goal of this study was to examine the effects of MA therapy on weight and overall mortality in elderly nursing home residents . METHODS This was a case-control cohort study of 17,328 nursing home residents admitted to Beverly Healthcare nursing home between January 1 , 2000 , and December 31 , 2003 , who had lost either 5 % of total body weight within 3 months or 10 % of total body weight within 6 months . Residents within this weight loss group who received MA therapy -- within 30 days of their weight loss documentation -- were matched ( 1:2 ) with non-MA-treated residents with respect to age , sex , race , weight , and first notation of weight loss . Residents were further matched by propensity score for activities of daily living , cognitive functioning , number of medications taken during the 7 days before data entry , clinical condition ( unstable , acute episode of a recurrent problem , end-stage disease ) , cancer diagnosis , and human immunodeficiency virus diagnosis . RESULTS A total of 709 patients ( mean [SD]age , 84.1 [9.7]years ; 70.9 % female ) who received MA therapy were matched with 1418 non-MA-treated patients ( mean [ SD ] age , 84.2 [ 9.0 ] years ; 70.9 % female ) . Of the 709 MA patients , 281 ( 39.6 % ) were alive and in the nursing home at last follow-up , 149 ( 21.0 % ) were alive and discharged to another facility or to home , and 279 ( 39.4 % ) died in the nursing home . For the controls , 651 ( 45.9 % ) were alive and in the nursing home , 308 ( 21.7 % ) were discharged to another facility or to home , and 459 ( 32.4 % ) died in the nursing home . The median survival of MA-treated residents ( 23.9 months ; 95 % CI , 20.2 - 27.5 ) was significantly less than untreated residents ( 31.2 months ; 95 % CI , 27.8 - 35.9 ) ( P < 0.001 ) . Median weight and median of weight differences were unchanged after 6 months of treatment with MA compared with matched controls . CONCLUSIONS MA treatment of elderly nursing home residents with significant weight loss was associated with a significant increase in all-cause mortality without a significant increase in weight . R and omized , prospect i ve studies of the use of MA in elderly nursing home residents are necessary to more fully evaluate morbidity and mortality associated with this therapy Weight loss occurs in almost all patients with human immunodeficiency virus ( HIV ) infection , and its causes are multifactorial . One of the most common causes is anorexia , and there are presently two drugs available for these patients : megestrol acetate ( Megace ; Bristol-Myers Oncology Division , Princeton , NJ ) and dronabinol ( Marinol ; Roxane Labs , Columbus , OH ) . A r and omized , double-blind , placebo-controlled , multicenter study using megestrol acetate is review ed here.1 The purpose of this study was to compare the effects of different doses of the drug on weight gain and other parameters in acquired immunodeficiency syndrome ( AIDS ) patients who presented with weight loss . In an outpatient setting , 270 patients were evaluated for safety of the drug . Only 195 patients could be used for evaluation of both safety and efficacy . The megestrol acetate was administered at 100 , 400 , or 800 mg daily for 12 weeks . Patients had lost either 20 % or their premorbid weight or were ≤90 % of their ideal body weight . No one was Two appetite stimulants , megestrol acetate and cyproheptadine were administered in a r and omized trial to 14 patients who had no evidence of opportunistic infection or malabsorption but were wasted ( had lost more than 5 kg body weight ) as a result of human immunodeficiency virus ( HIV ) infection . Energy intakes were calculated from a 7 day weighed dietary record . Mean energy intakes per kilogramme body weight were similar in both treatment groups ( greater than 34 kcal/kg ) and were higher than that in well British males . Energy intakes increased by just over 500 kcal during both treatments , but fell to pretreatment levels after therapy . Patients in both treatment groups gained a moderate amount of weight . Megestrol acetate was associated with impotence in 4 patients . Insufficient calorie intake alone is not a common cause of wasting associated with HIV and the role of appetite stimulants is likely to be limited This r and omized , open-labeled , multicenter study was design ed to assess safety and pharmacokinetics of dronabinol ( Marinol ) tablets and megestrol acetate ( Megace ) micronized tablets , alone and in combination , for treatment of HIV wasting syndrome . Weight and quality of life data were also collected . Fifty-two patients ( mean CD4 + count , 59 cells/microliter ) were r and omized to one of four treatment arms : dronabinol 2.5 mg twice/day ( D ) ; megestrol acetate 750 mg/day ( M750 ) ; megestrol acetate 750 mg/day+dronabinol 2.5 mg twice/day ( M750+D ) ; or megestrol acetate 250 mg/day+dronabinol 2.5 mg twice/day ( M250+D ) . After therapy initiation , 47 patients returned for at least one visit , and 39 completed the planned 12 weeks of study visits . Occurrence of adverse events , drug discontinuation , new AIDS-defining conditions , or CD4 + T lymphocyte changes were not statistically significantly different among arms . Serious adverse events assessed as related to dronabinol included CNS events ( e.g. , confusion , anxiety , emotional lability , euphoria , hallucinations ) and those assessed as related to megestrol acetate included dyspnea , liver enzyme changes , and hyperglycemia . The mean weight change + /- SE over 12 weeks was as follows : D , -2.0 + /- 1.3 kg ; M750 , + 6.5 + /- 1.1 kg ; M750+D , + 6.0 + /- 1.0 kg ; and M250+D , -0.3 + /- 1.0 kg ( difference among treatment arms , p = 0.0001 ) . Pharmacokinetic parameters measured after 2 weeks of therapy for M750 were Cmax = 985 ng/ml and AUC = 22,487 ng x hr/ml , and for dronabinol and its active metabolite ( HO-THC ) , respectively , were Cmax = 2.01 ; 4.61 ng/ml and AUC = 5.3 ; 23.7 ng x hr/ml . For megestrol acetate , but not dronabinol , there was a positive correlation at week 2 between both Cmax and AUC with each of the following : ( 1 ) weight change , ( 2 ) breakfast visual analog scale for hunger ( VASH ) score , and ( 3 ) dinner VASH score This r and omized , prospect i ve study compared three treatments , n and rolone decanoate ( ND ) , megestrol acetate ( MA ) or dietary counselling , for managing human immunodeficiency syndrome ( HIV ) associated weight loss . It was centred on a Tertiary referral hospital , Sydney , Australia . Fifteen patients were r and omized to receive ND ( 100 mg/fortnight ) , or MA ( 400 mg/day ) or dietary counselling for 12 weeks . Those patients r and omized to dietary counselling were further r and omized to receive n and rolone or megestrol after completing the dietary counselling arm . Weight , fat free mass ( FFM ) , percentage body fat mass ( FM ) , dietary intake and appetite were assessed before commencing and at the completion of each treatment arm . Weight increased significantly in all treatment arms ( dietary counselling 1.13 kg + /- 0.36 , n and rolone 4.01 kg + /- 1.68 , megestrol 10.20 kg + /- 4.51 , p < 0.05 paired t-test ) . FFM increased significantly in patients receiving ND ( 3.54 + /- 1.98 kg , p=0.001 ) and those receiving MA ( 2.76 + /- 0.55 kg , p=0.002 ) , whereas the change in those receiving dietary counselling alone was not significant . Percentage body fat mass increased significantly only in those receiving MA ( 7.77 + /- 4.85 % , p=0.049 ) . The change in weight and percentage body fat mass was significantly greater in those receiving MA than the other two treatment arms . The increase in FFM was significantly greater in both the n and rolone and megestrol arms than the dietary counselling arm . It was concluded that ND and MA both result ed in an increase in FFM greater than dietary counselling alone . Megestrol produced a significantly greater increase in weight , percentage fat mass , intake and appetite than did the other two treatment arms , suggesting it may be the preferred agent , particularly in a palliative care setting in which weight , appetite and intake increase are desirable without regard to the composition of the body . The long-term use of these agents in people with HIV should be review ed in the context of improved survival on highly active antiretroviral therapy regimens |
13,276 | 26,689,087 | Results show that perseverative cognition affects cardiovascular , autonomic , and endocrine nervous system activity , suggesting a pathogenic pathway to long-term disease outcomes and clarifying the still unexplained relationship between chronic stress and health vulnerability | Rumination about the past and worries about the future ( perseverative cognition ) are extremely common , although pervasive and distressing , dysfunctional cognitive processes .
Perseverative cognition is not only implicated in psychological health , contributing to mood worsening and psychopathology but , due to its ability to elicit prolonged physiological activity , is also considered to play a role in somatic health .
Although there is emerging evidence that such negative and persistent thoughts have consequences on the body , this association has not yet been quantified .
The aim of this study was to meta-analyze available studies on the physiological concomitants of perseverative cognition in healthy subjects . | Background : Although mindfulness meditation interventions have recently shown benefits for reducing stress in various population s , little is known about their relative efficacy compared with relaxation interventions . Purpose : This r and omized controlled trial examines the effects of a 1-month mindfulness meditation versus somatic relaxation training as compared to a control group in 83 students ( M age=25 ; 16 men and 67 women ) reporting distress . Method : Psychological distress , positive states of mind , distractive and ruminative thoughts and behaviors , and spiritual experience were measured , while controlling for social desirability . Results : Hierarchical linear modeling reveals that both meditation and relaxation groups experienced significant decreases in distress as well as increases in positive mood states over time , compared with the control group ( p<.05 in all cases ) . There were no significant differences between meditation and relaxation on distress and positive mood states over time . Effect sizes for distress were large for both meditation and relaxation ( Cohen ’s d=1.36 and .91 , respectively ) , whereas the meditation group showed a larger effect size for positive states of mind than relaxation ( Cohen ’s d=.71 and .25 , respectively ) . The meditation group also demonstrated significant pre-post decreases in both distractive and ruminative thoughts/behaviors compared with the control group ( p<.04 in all cases ; Cohen ’s d=.57 for rumination and .25 for distraction for the meditation group ) , with mediation models suggesting that mindfulness meditation ’s effects on reducing distress were partially mediated by reducing rumination . No significant effects were found for spiritual experience . Conclusions : The data suggest that compared with a no-treatment control , brief training in mindfulness meditation or somatic relaxation reduces distress and improves positive mood states . However , mindfulness meditation may be specific in its ability to reduce distractive and ruminative thoughts and behaviors , and this ability may provide a unique mechanism by which mindfulness meditation reduces distress Depressive rumination - a central characteristic of Major Depressive Disorder ( MDD ) - is a maladaptive emotion regulation strategy that prolongs sad mood and depressive episodes . Considerable research demonstrates the emotional and behavioral consequences of depressive rumination , yet few studies investigate its effect on neuroendocrine functioning . The current study examined the effect of an emotion regulation manipulation on the trajectory of cortisol concentrations among individuals with MDD and healthy controls ( CTL ) . Sadness was induced via forced failure . Participants then were r and omly assigned to a depressive rumination or distraction emotion regulation induction . MDDs in the rumination condition exhibited less cortisol decline compared to MDDs in the distraction condition and compared to CTLs in either condition . Findings suggest that depressive rumination alters the trajectory of cortisol secretion in MDD and may prolong cortisol production . Results thereby provide important insights into the interaction of biological and psychological factors through which distress contributes to MDD This study examined an experiential avoidance conceptualization of depressive rumination in 3 ways : 1 ) associations among question naire measures of rumination , experiential avoidance , and fear of emotions ; 2 ) performance on a dichotic listening task that highlights preferences for non-depressive material ; and 3 ) psychophysiological reactivity in an avoidance paradigm modeled after the one used by Borkovec , Lyonfields , Wiser , and Deihl ( 1993 ) in their examination of worry . One hundred and thirty-eight undergraduates completed question naire measures and participated in a clinical interview to diagnose current and past episodes of depression . Of those , 100 were r and omly assigned to a rumination or relaxation induction condition and participated in a dichotic listening task , rumination/relaxation induction , and depression induction . Question naire measures confirmed a relationship between rumination status and avoidance ; however , no significant effects were found in the dichotic listening task . Psychophysiological measures indicated no difference in physiological response to a depression induction among high ruminators ( HR ) . However , low ruminators ( LR ) in the relaxation condition exhibited a larger IBI response than LR in the rumination condition . Overall , these results provide partial support for an avoidance conceptualization of depressive rumination . Implication s of these findings are discussed CONTEXT The terrorist attacks of 9/11 ( September 11 , 2001 ) present an unusual opportunity to examine prospect ively the physical health impact of extreme stress in a national sample . OBJECTIVE To examine the degree to which acute stress reactions to the 9/11 terrorist attacks predict cardiovascular outcomes in a national probability sample over the subsequent 3 years . DESIGN , SETTING , AND PARTICIPANTS A national probability sample of 2729 adults ( 78.1 % participation rate ) , 95.0 % of whom had completed a health survey before 9/11 ( final health sample , 2592 ) , completed a Web-based assessment of acute stress responses approximately 9 to 14 days after the terrorist attacks . Follow-up health surveys reassessed physician-diagnosed cardiovascular ailments 1 ( n = 1923 , 84.3 % participation rate ) , 2 ( n = 1576 , 74.2 % participation rate ) , and 3 ( n = 1950 , 78.9 % participation rate ) years following the attacks . MAIN OUTCOME MEASURES Reports of physician-diagnosed cardiovascular ailments over the 3 years following the attacks . RESULTS Acute stress responses to the 9/11 attacks were associated with a 53 % increased incidence of cardiovascular ailments over the 3 subsequent years , even after adjusting for pre-9/11 cardiovascular and mental health status , degree of exposure to the attacks , cardiovascular risk factors ( ie , smoking , body mass index , and number of endocrine ailments ) , total number of physical health ailments , somatization , and demographics . Individuals reporting high levels of acute stress immediately following the attacks reported an increased incidence of physician-diagnosed hypertension ( rate ratios , 2.15 at 1 year and 1.75 at 2 years ) and heart problems ( rate ratios , 2.98 at 1 year and 3.12 at 2 years ) over 2 years . Among individuals reporting ongoing worry about terrorism post-9/11 , high 9/11-related acute stress symptoms predicted increased risk of physician-diagnosed heart problems 2 to 3 years following the attacks ( rate ratios , 4.67 at 2 years and 3.22 at 3 years ) . CONCLUSION Using health data collected before 9/11 as a baseline , acute stress response to the terrorist attacks predicted increased reports of physician-diagnosed cardiovascular ailments over 3 years following the attacks BACKGROUND Worry is an important component of anxiety , which recent work suggests is related to increased incidence of coronary heart disease ( CHD ) . Chronic worry has also been associated with decreased heart rate variability . We hypothesized that high levels of worry may increase CHD risk . METHOD AND RESULTS We examined prospect ively the relationship of worry with CHD incidence in the Normative Aging Study , an ongoing cohort of older men . In 1975 , 1759 men free of diagnosed CHD completed a Worries Scale , indicating the extent to which they worried about each of five worry domains : social conditions , health , financial , self-definition , and aging . During 20 years of follow-up , 323 cases of incident CHD occurred : 113 cases of nonfatal myocardial infa rct ion ( MI ) ; 86 cases of fatal CHD ; and 124 cases of angina pectoris . Worry about social conditions was the domain most strongly associated with incident CHD . Compared with men reporting the lowest levels of social conditions worry , men reporting the highest levels had multivariate adjusted relative risks of 2.41 ( 95 % CI , 1.40 to 4.13 ) for nonfatal MI and 1.48 ( 95 % CI , 0.99 to 2.20 ) for total CHD ( nonfatal MI and fatal CHD ) . A dose-response relation was found between level of worry and both nonfatal MI ( P for trend , .002 ) and total CHD ( P for trend , .04 ) . CONCLUSIONS These results suggest that high levels of worry in specific domains may increase the risk of CHD in older men Objective : Cardiovascular recovery of prestress baseline blood pressure has been implicated as a possible additional determinant of sustained blood pressure elevation . We hypothesize that angry ruminations may slow the recovery process . Method : A within-subjects design was used in which resting baseline blood pressure and heart rate measurements were assessed on 60 subjects , who then took part in two anger-recall tasks . After each task , subjects sat quietly and alone during a 12-minute recovery period r and omized to with or without distractions . During baseline , task , and recovery , blood pressure was continuously monitored ; during recovery , subjects reported their thoughts at five fixed intervals . Results : Fewer angry thoughts were reported in the distraction condition ( 17 % ) compared with no distraction ( 31 % ; p = .002 ) ; an interaction showed that this effect was largely the result of the two intervals immediately after the anger-recall task . Trait rumination interacted with distraction condition such that high ruminators in the no-distraction condition evidence d the poorest blood pressure recovery , assessed as area under the curve ( p = .044 [ systolic blood pressure ] and p = .046 [ diastolic pressure ] ) . Conclusions : People who have a tendency to ruminate about past anger-provoking events may be at greater risk for target organ damage as a result of sustained blood pressure elevations ; the effect is exacerbated when distractions are not available to interrupt the ruminative process . ANOVA = analysis of variance ; AUC = area under the curve ; BP = blood pressure ; HTN = hypertension ; CHD = coronary heart disease ; CVR = cardiovascular reactivity ; CVD = cardiovascular disease ; HR = heart rate ; DAB-VR = Destructive Anger Behavior-Verbal Rumination ; DBP = diastolic BP ; HPA = hypothalamic-pituitary-adrenal ; SBP = systolic BP In this study we examined the prospect i ve relationships between perseverative thoughts , internalizing negative emotions , and somatic complaints in children aged 9 - 13 , and evaluated whether a perseverative thoughts intervention had a beneficial effect on these experiences . Children ( N=227 ) from 7 primary schools in Leiden , the Netherl and s , recorded their perseverative thoughts during one week , 138 of whom were instructed to postpone these thoughts to a special 30min period in the early evening . Children who had received the postponement instructions showed a reduction in the frequency of perseverative thoughts , and girls also in the duration of them . Girl 's perseverative thoughts were positively associated with the number of somatic complaints and with negative emotions . The postponement intervention also seemed to reduce somatic complaints in the seventh grade children . These findings confirm the previously found prospect i ve relationship between perseverative thoughts and children 's well-being and provide initial validation for the use of the postponement intervention to reduce perseverative thoughts in this age group , particularly for girls Recent models of generalized anxiety disorder ( GAD ) have exp and ed on Borkovec 's avoidance theory by delineating emotion regulation deficits associated with the excessive worry characteristic of this disorder ( see Behar , DiMarco , Hekler , Mohlman , & Staples , 2009 ) . However , it has been difficult to determine whether emotion regulation is simply a useful heuristic for the avoidant properties of worry or an important extension to conceptualizations of GAD . Some of this difficulty may arise from a focus on purported maladaptive regulation strategies , which may be confounded with symptomatic distress components of the disorder ( such as worry ) . We examined the implementation of adaptive regulation strategies by participants with and without a diagnosis of GAD while watching emotion-eliciting film clips . In a between-subjects design , participants were r and omly assigned to accept , reappraise , or were not given specific regulation instructions . Implementation of adaptive regulation strategies produced differential effects in the physiological ( but not subjective ) domain across diagnostic groups . Whereas participants with GAD demonstrated lower cardiac flexibility when implementing adaptive regulation strategies than when not given specific instructions on how to regulate , healthy controls showed the opposite pattern , suggesting they benefited from the use of adaptive regulation strategies . We discuss the implication s of these findings for the delineation of emotion regulation deficits in psychopathology Comorbidity among affective disorders is high . Rumination has been found to mediate cross-sectional and prospect i ve relations between anxiety and depressive symptoms in adolescents and adults . We examined whether rumination and worry , both forms of repetitive negative thinking , also explain the associations between affective disorders . This was studied using a prospect i ve cohort study . In a mixed sample of 2981 adults ( persons with a prior history of or a current affective disorder and healthy individuals ) we assessed DSM-IV affective disorders ( CIDI ) , rumination ( LEIDS-R ) and worry ( PSWQ ) . All measures were repeated 2 years and 4 years later . Using structural equation models , we found that baseline rumination and worry partly mediated the association of baseline fear disorders ( social anxiety disorder , panic disorder , agoraphobia ) with distress disorders ( dysthymia , major depressive disorder , generalized anxiety disorder ) . Moreover , baseline fear disorders predicted changes in distress disorders and changes in worry and rumination mediated these associations . The association between baseline distress disorders and changes in fear disorders was mediated by changes in rumination but not by changes in worry . From these results it can be concluded that repetitive negative thinking is an important transdiagnostic factor . Rumination and worry are partly responsible for the cross-sectional and prospect i ve co-occurrence of affective disorders and may be suitable targets for treatment Trauma-related rumination has been shown to predict the maintenance of posttraumatic stress disorder ( PTSD ) . However , it is still unclear how rumination can be distinguished from functional forms of thinking about traumatic events . The current study used an analogue design to experimentally test the hypothesis that the abstract ness of thinking is responsible for the dysfunctional effects of trauma-related rumination . Eighty-three healthy university students first watched a distressing video and were then r and omly assigned to abstract ruminative thinking , concrete thinking or distraction . Abstract thinking was found to lead to a significantly longer maintenance of negative mood and arousal than both concrete thinking and distraction . These results are in line with earlier findings in the context of excessive worry and depressive rumination and support the view that abstract ness is a critical factor for the dysfunctional effects of trauma-related rumination . However , results regarding intrusive memories were not supportive of the hypotheses . Unexpectedly , the distraction group showed the highest number of intrusions , whereas the abstract and concrete conditions did not significantly differ . Implication s for theoretical models of trauma-related rumination and possible clinical implication s are discussed BACKGROUND Inflammation and vagally mediated heart rate variability ( vmHRV ) have been implicated in a number of conditions including diabetes and cardiovascular disease . Consistent with the inflammatory reflex termed the ' cholinergic anti-inflammatory pathway ' , numerous cross-sectional studies have demonstrated negative associations between vmHRV and inflammatory markers such as C-reactive protein ( CRP ) . The only prospect i ve study , however , showed the opposite : higher CRP at baseline predicted higher high-frequency heart rate variability ( HF-HRV ) at follow-up . Thus , additional studies are needed to examine the prospect i ve association between vmHRV and CRP . METHODS Healthy employees participated in a voluntary on-site health assessment . Blood sample s and ambulatory heart rate recordings were obtained , and night-time HF-HRV was calculated . Useable heart rate data were available in 2007 for 106 nonsmoking employees ( 9 % women ; age 44.4 ± 8 years ) , all of whom returned for an identical follow-up health assessment in 2011 . Bootstrapped ( 500 replications ) bivariate ( r ) and partial Pearson 's correlations ( ppc ) adjusting for sex , age and body mass index at baseline ( 2007 ) were calculated . RESULTS Zero-order correlations indicated that higher HF-HRV was associated with lower levels of CRP at both time-points ( 2007 : r = -0.19 , P < 0.05 ; 2011 : r = -0.34 , P < 0.001 ) . After adjustment , HF-HRV remained a significant predictor of CRP ( ppc = -0.20 , P < 0.05 ) . CONCLUSION In this study , we have provided in vivo support for the cholinergic anti-inflammatory pathway in humans . Cardiac vagal modulation at baseline predicts level of CRP 4 years later . Our findings have important implication s for the role of vmHRV as a risk factor for cardiovascular disease morbidity and mortality . Interventions targeted at vmHRV might be useful in the prevention of diseases associated with elevated systemic inflammation |
13,277 | 25,949,881 | Since Th17 cells are a sub population of IL-17 + cells and had a different correlation with prognosis than total IL-17 , we substantiate that a distinction should be made between Th17 and other IL-17 + cells | Both IL-17 and Th17 cells have been ascribed tumor promoting as well as tumor suppressing functions . | Background and Aims An immune imbalance in the cytokine profile exerts a profound influence on the progression of hepatitis B virus ( HBV ) infections and hepatocellular carcinoma ( HCC ) . The present study evaluated the immune status of T helper ( Th ) 17 and Th1 cells in patients with HBV-related and non-HBV-related HCC . Methods We r and omly enrolled 150 patients with HCC . Blood sample s and tissue sample s were obtained . The distributions and phenotypic features of Th17 and Th1 cells were determined by flow cytometry and /or immunohistochemistry . Results Compared to corresponding non-tumor regions , the levels of Th17 and Th1 cells were significantly increased in tumors of patients with HCC ( P<0.001 ) . The intratumoral densities of IL-17-producing cells and IFN-γ-producing cells were associated with overall survival ( OS , P = 0.001 ) and disease-free survival ( DFS , P = 0.001 ) of patients with HCC . The ratio of Th17 to Th1 in HBV-related HCC was higher than in non-HBV-related HCC . A multivariate Cox analysis revealed that the Th17 to Th1 ratio was an independent prognostic factor for OS ( HR = 2.651 , P = 0.007 ) and DFS ( HR = 2.456 , P = 0.002 ) . Conclusions HBV infections can lead to an imbalance in immune status in patients with HCC . An elevated Th17 to Th1 ratio may promote tumor progression . The Th17 to Th1 ratio could serve as a potential prognostic marker for scoring the severity of HCC Purpose The role of interleukin-17 ( IL-17 ) in the tumor microenvironment is controversial . We analyzed the in situ tumor expression of IL-17 in colorectal cancer ( CRC ) , adenoma and non-tumor tissue to explore the possible correlation of IL-17 expression to clinicopathological characteristics , tumor-infiltrating neutrophils ( TINs ) and survival in CRC . Methods We review ed the records of 78 consecutive patients diagnosed with CRC . Archival tissues were used . Thirty-six patients with colorectal adenoma were also included . From the 78 CRC patients , we r and omly chose 40 cases and collected non-tumor tissue at 10 cm from the edge of the resected tumor . Immunohistochemistry was performed using anti-IL-17 and anti-CD15 ( targeting neutrophils ) antibody , respectively . Real-time PCR was used to detect IL-17 mRNA in different tissues . Associations between IL-17 expression , clinicopathological parameters and prognosis were evaluated . Results The level of IL-17 mRNA was higher in CRC than in adenoma and non-tumor tissue ( P < 0.05 ) . Positive IL-17 protein expression was observed more frequently in CRC as compared to colorectal adenoma and non-tumor tissue , respectively ( P < 0.01 ) . IL-17 expression correlated to well differentiation and early stage CRC . The number of CD15 + neutrophils significantly increased in CRC and positively correlated to the expression of IL-17 ( P < 0.05 ) . Both Kaplan – Meier analysis and multivariate Cox regression analysis indicated that patients with positive IL-17 expression showed better overall survival . Conclusions The association between IL-17 expression and the clinicopathological parameters , as well as the clinical outcome suggests a significant role of IL-17 in CRC . IL-17 is a marker of favorable prognosis Purpose : To determine safety and feasibility of adjuvant ipilimumab following resection of high-risk melanoma and to identify surrogate markers for benefit . Experimental Design : In this phase II trial , 75 patients with resected stage IIIc/IV melanoma received the CTLA-4 antibody ipilimumab every 6 to 8 weeks for 1 year . Eligible patients received further maintenance treatments . The first 25 patients received 3 mg/kg of ipilimumab , and an additional 50 patients received 10 mg/kg . HLA-A*0201 + patients received multipeptide immunizations in combination with ipilimumab . Leukapheresis was performed prior to and 6 months after initiation of treatment . Results : Median overall and relapse-free survivals were not reached after a median follow-up of 29.5 months . Significant immune-related adverse events were observed in 28 of 75 patients and were positively associated with longer relapse-free survival . Antigen-specific T cell responses to vaccine were variable , and vaccine combination was not associated with additional benefit . No effects on T regulatory cells were observed . Higher changes in Th-17 inducible frequency were a surrogate marker of freedom from relapse ( P = 0.047 ) , and higher baseline C-reactive protein ( CRP ) levels were associated with freedom from relapse ( P = 0.035 ) . Conclusions : Adjuvant ipilimumab following resection of melanoma at high risk for relapse appeared to be associated with improved outcome compared to historical reports . Significant immune-related adverse events were generally reversible and appeared to be associated with improved relapse-free survival . Although vaccination failed to induce a consistent in vitro measurable response , a higher change in Th-17 inducible cells and higher baseline CRP levels were positively associated with freedom from relapse . Clin Cancer Res ; 17(4 ) ; 896–906 . © 2010 AACR Transarterial chemoembolization ( TACE ) has therapeutic effects in patients with unresectable hepatocellular carcinoma ( HCC ) , but its impact on the cellular immune response during disease progression is largely unknown . Here we conducted a prospect i ve study to evaluate the effect of TACE on immune status and to identify prognostic immune markers governing treatment success . In this study , 51 stage III HCC patients , 28 stage I HCC patients ( TNM classification ) and 20 healthy donors were enrolled . Flow cytometry and cytometric bead array were used to evaluate the circulating immune cell subsets , including CD4 + T cells ( Th1 , Th17 and Treg cells ) , CD8 + T cells , NK cells , and NKT cells , and plasma cytokines before TACE and 30 days after TACE . Interestingly , among those immune parameters , the frequency of circulating Th17 cells was higher in stage III HCC patients than in stage I HCC patients ( P = 0.015 ) and healthy donors ( P<0.001 ) . Moreover , an increased frequency of circulating Th17 cells was observed 30 days after TACE ( Th17D30 ) compared with the baseline level ( P = 0.036 ) . Kaplan-Meier analysis demonstrated that Th17D30 was positively associated with overall survival ( OS ; P = 0.007 ) and time to progression ( TTP ; P = 0.009 ) . Multivariate Cox analysis revealed that Th17D30 was an independent prognostic factor for OS ( HR = 0.317 , P = 0.032 ) and TTP ( HR = 0.304 , P = 0.010 ) . These results provide a potential prognostic marker for stage III HCC patients undergoing TACE and may be useful for identifying patients who can benefit from adjuvant immunotherapies Host immunity may have important role in the prognosis of hepatocellular carcinoma ( HCC ) . The aim of this study was to evaluate the correlation between circulating immune regulators and clinical outcome in patients with HCC . Sixty-three HCC patients were prospect ively enrolled . Serum levels of interleukin-10 ( IL-10 ) , transforming growth factor-beta ( TGF-β ) , interferon-gamma ( IFN-γ ) and interferon gamma-inducible protein 10 ( IP-10 ) were measured , as well as the prevalence of regulatory T cells ( Treg ) , NK(+ ) T cells , invariant natural killer T cells ( iNKT ) , programmed cell death-1 (PD-1)(+ ) CD8(+ ) T cells , T helper 17 cells ( Th17 ) , CD69(+ ) and CD45RO(+ ) T cells in peripheral blood mononuclear cells ( P BMC ) . Correlation between these immune regulators and clinical outcome were analyzed . A low serum IFN-γ level ( < 50 pg/mL ) was significantly associated tumor stage ( BCLC stage B : 61.25 % vs. stage A : 25 % , p = 0.010 ) and tumor size ( > 5 cm : 53.8 % vs. < 5 cm : 25 % , p = 0.047 ) . Recurrence-free survival was evaluated in 48 patients receiving curative treatment of HCC . By multivariate analysis , BCLC stage [ hazard ratio ( HR ) = 32.180 , p < 0.001 ] , tumor size ( HR = 15.373 , p = 0.005 ) , AST ( HR = 3.796 , p = 0.011 ) and IFN-γ ( HR = 0.354 , p = 0.018 ) levels were independent factors associated with recurrence-free survival . In conclusion , serum IFN-γ level correlates with tumor stage and tumor size in HCC patients . Patients with lower baseline IFN-γ levels have a higher risk of tumor recurrence after curative treatment . IFN-γ may reflect host anti-tumor immunity and may be a potential marker of HCC recurrence after curative treatment BACKGROUND / AIMS To characterize IL-17-producing cells , a newly defined T helper cell subset with potent pro-inflammatory properties , in hepatocellular carcinoma ( HCC ) and to determine their prognostic values . METHODS One hundred and seventy-eight HCC patients were enrolled r and omly . Distribution and phenotypic features of IL-17-producing cells were determined by flow cytometry and /or immunohistochemistry . RESULTS Compared with corresponding non-tumor regions , the levels of Th17 cells were significantly increased in tumors of HCC patients ( P<0.001 ) . Most intratumoral Th17 cells exhibited an effector memory phenotype with increased expression of CCR4 and CCR6 . Intratumoral IL-17-producing cell density was associated with overall survival ( OS , P=0.001 ) and disease-free survival ( DFS , P=0.001 ) in HCC patients . Multivariate Cox analysis revealed that intratumoral IL-17-producing cell density was an independent prognostic factor for OS ( HR=2.351 , P=0.009 ) and DFS ( HR=2.256 , P=0.002 ) . Moreover , the levels of intratumoral Th17 cells were positively correlated with microvessel density in tumors ( r=0.616 , P=0.001 ) . CONCLUSION Accumulation of intratumoral IL-17-producing cells may promote tumor progression through fostering angiogenesis , and intratumoral IL-17-producing cell could serve as a potential prognostic marker and a novel therapeutic target for HCC |
13,278 | 16,956,802 | Although weight-bearing exercise appears to enhance bone mineral accrual in children , particularly during early puberty ; it remains unclear as to what constitutes the optimal exercise programme .
In addition , the measurement of bone quality parameters and volumetric BMD would provide a greater insight into the mechanisms implicated in the adaptation of bone to exercise | INTRODUCTION Osteoporosis is a serious skeletal disease and as there is currently no cure , there is a large emphasis on its prevention , including the optimisation of peak bone mass .
There is increasing evidence that regular weight-bearing exercise is an effective strategy for enhancing bone status during growth .
This systematic review evaluates r and omised and non-r and omised controlled trials to date , on the effects of exercise on bone mineral accrual in children and adolescents . | BACKGROUND Osteoporosis may be prevented or delayed by maximizing peak bone mass through diet modification and physical activity during adolescence . OBJECTIVE We studied whether increases in calcium intake and physical activity effectively increase the bone mineral status of adolescent girls aged 16 - 18 y. DESIGN We conducted a 15.5-mo study of calcium supplementation ( 1000 mg Ca/d as carbonate ) in 144 adolescent girls aged 17.3 + /- 0.3 y ( + /- SD ) . The subjects were r and omly allocated to an exercise ( three 45-min exercise-to-music classes/wk during term time ) or nonexercise group . Dual-energy X-ray absorptiometry of the whole body , spine , forearm , and hip was performed before and after intervention . RESULTS The mean ( + /- SD ) percentage of subjects compliant with supplement taking was 70 + /- 27 % and with exercise class attendance was 36 + /- 25 % . Baseline calcium intake was 938 + /- 411 mg/d . Calcium supplementation significantly increased size-adjusted bone mineral content . The effect was stronger in subjects with good compliance ( percentage difference + /- SE ) : whole body , 0.8 + /- 0.3 % ( P < or = 0.01 ) ; lumbar spine , 1.9 + /- 0.5 % ( P < or = 0.001 ) ; ultradistal radius , 1.3 + /- 0.6 % ( P < or = 0.05 ) ; total hip , 2.7 + /- 0.6 % ( P < or = 0.001 ) ; femoral neck , 2.2 + /- 0.7 % ( P < or = 0.001 ) ; trochanter , 4.8 + /- 0.9 % ( P < or = 0.001 ) . Attendance at > 50 % of the exercise sessions was significant at the total hip ( 1.4 + /- 0.7 % ; P < or = 0.05 ) and trochanter ( 2.6 + /- 1.2 % ; P < or = 0.05 ) . CONCLUSIONS Calcium supplementation and exercise enhanced bone mineral status in adolescent girls . Whether this is a lasting benefit , leading to the optimization of peak bone mass and a reduction in fracture risk , needs to be determined Exercise during growth has a positive influence on bone mineral accrual , yet little is known about how bone geometry and strength adapt to loading during growth . Our primary objective was to compare changes in proximal femur bone geometry and strength between 31 prepubertal ( Tanner Stage 1 ) boys who participated in a school-based , high-impact circuit intervention ( 12 min , three times a week ) for 20 months and 33 maturity-matched controls . Our secondary objective was to compare changes in total body ( TB ) , proximal femur ( PF ) , and lumbar spine ( LS ) bone mineral content ( BMC ) and bone area ( BA ) in these groups . We assessed geometric variables and bone strength at the narrow neck ( NN ) , intertrochanteric ( TR ) region , and femoral shaft regions by applying the Hip Structure Analysis program to proximal femur dual energy X-ray absorptiometry scans ( DXA , Hologic QDR 4500 ) . Further , we assessed total body , lumbar spine , and proximal femur BMC and BA by DXA and derived total body lean mass and fat mass from total body scans . Intervention ( 10.2 + /- 0.5 years ) and control boys ( 10.1 + /- 0.5 years ) had similar baseline height ( 140.8 vs. 141.3 cm ) and weight ( 36.9 vs. 35.4 kg ) , and average 20-month physical activity scores ( Physical Activity Question naire for Children , PAQ-C ) and calcium intakes ( 861 vs. 852 mg/day , food frequency question naire ) . Twenty-month height and weight changes were not significantly different between groups ; lean mass changed more ( P < 0.05 ) in intervention boys ( 22.8 % ) than control boys ( 18.6 % ) . At the NN region , intervention boys had greater bone expansion on both the periosteal ( + 2.6 % , P = 0.1 ) and endosteal ( + 2.7 % , P = 0.2 ) surfaces , result ing in significantly greater changes in section modulus ( bone bending strength ) ( + 7.5 % , P = 0.02 , ANCOVA , adjusting for height change , final Tanner Stage , and baseline bone values ) . Changes at the intertrochanteric and femoral shaft regions were not significantly different between groups . Femoral neck ( FN ) BMC changes were significantly greater in intervention boys ( + 4.3 % , P < 0.01 ) ; changes in BA and BMC for other regions were not significantly different between groups . In summary , a school-based , high-impact exercise intervention implemented three times a week for 12 min is an effective strategy for site-specific gains in bone strength at the narrow neck region of the proximal femur Cross-sectional studies of elite athletes suggest that growth is an opportune time for exercise to increase areal bone mineral density ( BMD ) . However , as the exercise undertaken by athletes is beyond the reach of most individuals , these studies provide little basis for making recommendations regarding the role of exercise in musculoskeletal health in the community . To determine whether moderate exercise increases bone mass , size , areal , and volumetric BMD , two socioeconomically equivalent schools were r and omly allocated to be the source of an exercise group or controls . Twenty boys ( mean age 10.4 years , range 8.4 - 11.8 ) allocated to 8 months of 30-minute sessions of weight-bearing physical education lessons three times weekly were compared with 20 controls matched for age , st and ing and sitting height , weight , and baseline areal BMD . Areal BMD , measured using dual-energy X-ray absorptiometry , increased in both groups at all sites , except at the head and arms . The increase in areal BMD in the exercise group was twice that in controls ; lumbar spine ( 0.61 + /- 0.11 vs. 0.26 + /- 0.09%/month ) , legs ( 0.76 + /- 0.07 vs. 0.34 + /- 0.08%/month ) , and total body ( 0.32 + /- 0.04 vs. 0.17 + /- 0.06%/month ) ( all p < 0.05 ) . In the exercise group , femoral midshaft cortical thickness increased by 0.97 + /- 0 . 32%/month due to a 0.93 + /- 0.33%/month decrease in endocortical ( medullary ) diameter ( both p < 0.05 ) . There was no periosteal expansion so that volumetric BMD increased by 1.14 + /- 0.33%/month , ( p < 0.05 ) . Cortical thickness and volumetric BMD did not change in controls . Femoral midshaft section modulus increased by 2.34 + /- 2 . 35 cm3 in the exercise group , and 3.04 + /- 1.14 cm3 in controls ( p < 0.05 ) . The growing skeleton is sensitive to exercise . Moderate and readily accessible weight-bearing exercise undertaken before puberty may increase femoral volumetric BMD by increasing cortical thickness . Although endocortical apposition may be a less effective means of increasing bone strength than periosteal apposition , both mechanisms will result in higher cortical thickness that is likely to offset bone fragility conferred by menopause-related and age-related endocortical bone resorption Abstract : The maximum amount of bone a person can obtain during the first two decades of life is an important determinant of bone mass in later life , and an increase in peak bone mass has been associated with decreased risk for osteoporotic fractures . It is known that growth of bone and thus development of peak bone mass are strongly controlled by genetic factors , but information on the role of environmental factors , such as exercise and nutrition , ( e.g. , exercise ) on growing bone is limited . We tested a hypothesis that in growing girls the benefit of mechanical loading on bone mineral mass and bone strength is better before rather than after the menarche . Sixty-four girls ( 25 premenarcheal , 39 postmenarcheal ) carried out a supervised 9-month step-aerobic program ( two sessions per week ) , each session complemented with additional jumps . Sixty-two girls ( 33 premenarcheal , 29 postmenarcheal ) served as controls . Bone mineral content ( BMC ) at the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometry ( DXA ) . In addition , the cortical density ( CoD , mg/cm3 ) and cortical cross-sectional area ( CoA , mm2 ) and the density-weighted polar section modulus ( BSI , mm3 ) of the tibial midshaft were determined by peripheral quantitative tomography ( pQCT ) . In the premenarcheal girls , BMC increased statistically significantly more in the trainees than controls at the lumbar spine ( p= 0.012 ) ( 8.6 % vs 5.3 % ) and femoral neck ( p= 0.014 ) ( 9.3 % vs 5.3 % ) . In the tibial midshaft , the intergroup differences ( CoD , CoA and BSI ) were not significant . The postmenarcheal girls showed no significant post-training intergroup differences in any of the bone parameters ( BMC increased in the lumbar spine 6.0 % vs 4.9 % ; femoral neck 3.4 % vs 3.2 % ; and trochanter 2.6 % vs 3.5 % ) . Although a large proportion of bone mineral increase in the growing girls of this study was attributable to growth itself , this 9-month exercise intervention showed that a clear and large additional bone gain could be obtained in exercising premenarcheal girls , but not in exercising postmenarcheal girls . In other words , exercise seemed more beneficial for additional bone mineral acquisition before menarche ( i.e. , during the growth spurt ) rather than after it Physical activity during childhood is advocated as one strategy for enhancing peak bone mass ( bone mineral content [ BMC ] ) as a means to reduce osteoporosis-related fractures . Thus , we investigated the effects of high-intensity jumping on hip and lumbar spine bone mass in children . Eighty-nine prepubescent children between the ages of 5.9 and 9.8 years were r and omized into a jumping ( n = 25 boys and n = 20 girls ) or control group ( n = 26 boys and n = 18 girls ) . Both groups participated in the 7-month exercise intervention during the school day three times per week . The jumping group performed 100 , two-footed jumps off 61-cm boxes each session , while the control group performed nonimpact stretching exercises . BMC ( g ) , bone area ( BA ; cm2 ) , and bone mineral density ( BMD ; g/cm2 ) of the left proximal femoral neck and lumbar spine ( L1-L4 ) were assessed by dual-energy X-ray absorptiometry ( DXA ; Hologic QDR/4500-A ) . Peak ground reaction forces were calculated across 100 , two-footed jumps from a 61-cm box . In addition , anthropometric characteristics ( height , weight , and body fat ) , physical activity , and dietary calcium intake were assessed . At baseline there were no differences between groups for anthropometric characteristics , dietary calcium intake , or bone variables . After 7 months , jumpers and controls had similar increases in height , weight , and body fat . Using repeated measures analysis of covariance ( ANCOVA ; covariates , initial age and bone values , and changes in height and weight ) for BMC , the primary outcome variable , jumpers had significantly greater 7-month changes at the femoral neck and lumbar spine than controls ( 4.5 % and 3.1 % , respectively ) . In repeated measures ANCOVA of secondary outcomes ( BMD and BA ) , BMD at the lumbar spine was significantly greater in jumpers than in controls ( 2.0 % ) and approached statistical significance at the femoral neck ( 1.4 % ; p = 0.085 ) . For BA , jumpers had significantly greater increases at the femoral neck area than controls ( 2.9 % ) but were not different at the spine . Our data indicate that jumping at ground reaction forces of eight times body weight is a safe , effective , and simple method of improving bone mass at the hip and spine in children . This program could be easily incorporated into physical education classes OBJECTIVE To evaluate the effects of an elementary school-based physical education exercise intervention program on bone mineral accrual in prepubertal and early pubertal girls . STUDY DESIGN A total of 14 schools were r and omly assigned to control ( C ) and intervention ( I ) groups . Girls in the I group completed a 10-minute , 3 times per week circuit of varied jumping activities over 7 months . We measured total body , lumbar spine , proximal femur , femoral neck , and trochanteric bone mineral content and areal bone mineral density and estimated femoral neck volumetric bone mineral density at baseline and final measurement in 87 girls in the I group and 90 girls in the C group . Girls were between 8.7 and 11.7 years at baseline . Tanner stage 1 girls were considered prepubertal ; Tanner stages 2 and 3 girls were considered early pubertal . We used analysis of covariance ( adjusting for baseline bone values , change in size , age , and maturity ) to compare 7-month change in bone mineral content , areal bone mineral density , and volumetric bone mineral density between C and I groups within prepubertal and early pubertal girls . RESULTS There was no difference in 7-month change in bone parameters between prepubertal I and C groups . Early pubertal girls in the I group gained 1.5 % to 3.1 % more bone at the femoral neck and lumbar spine than early pubertal girls in the C group ( P < .05 ) ; gain at other sites did not differ . CONCLUSIONS In girls , early puberty may be a particularly opportune time during growth for simple exercise interventions to have a positive effect on bone health Background : Mechanical loading during childhood plays a critical role in normal growth and development of the skeleton . Ground reaction forces ( GRFs ) may provide a surrogate measure for the strain experienced by bone on l and ing and at take off . However , there appear to be no paediatric studies that assess GRFs across a variety of loading activities . Objectives : To measure biomechanical variables in commonly performed childhood activities used in an elementary physical education intervention study which augmented bone health in boys and girls . Methods : Maximal GFR , maximal rates of force , and time to maximum force were measured for 12 different jumping activities on a force platform . The jumps measured were drop jumps from 10 , 30 , and 50 cm , all followed by a plyometric jump , submaximal and maximal jumping jacks , alternating feet jump , counter movement jumps , and side to side jumps over 10 and 20 cm foam barriers . The subjects were 70 children ( 36 boys and 34 girls ) , 8.3–11.7 years old . Results : Subjects ranged in height from 128.4 to 172.6 cm and had a mass of 25.0–57.0 kg . Mean ( SD ) for vertical jump was 24.2 ( 5.5 ) cm and 135.2 ( 16.6 ) cm for st and ing long jump . The children engaged in loaded physical activity 5.7 ( 5.3 ) hours a week , on average . The highest mean maximal GRFs , normalised for body weight ( BW ) , were generated from the plyometric portion of the drop jumps and the counter movement jump ( about 5 times BW ) compared with 3.5 times BW for jumping jacks . Similarly , the highest rates of change in force were 514 times BW/s for the drop jump from 10 cm and 493 times BW/s for the counter movement jump . Conclusions : Simple jumps requiring minimal equipment produce GRFs of 3.5–5 times BW and rates of force of around 500 times BW/s . As children appear to attenuate higher impact forces when jumping from increased heights , it can not be assumed that merely increasing the height of the jump will necessarily “ progress ” the exercise intervention The aim of this study was to determine whether high-impact exercises have an osteogenic effect in 21 prepubertal female monozygotic twins aged 8.7 ( SD 0.7 ) years . Bone mineral density ( aBMD ) , bone mineral content ( BMC ) , bone area , and body composition were derived from DXA . Skeletal maturity was assessed by the Tanner-Whitehouse technique . Anthropometric dimensions ( 28 dimensions ) were measured and also used to derive adiposity and muscularity indices , and information about physical activity was obtained by question naire . These measurements were taken before and after the exercise period . The exercise program consisted of high-impact exercises . During 9 months , one girl of each twin pair performed the exercises 3 times a week under supervision of a teacher while their sisters served as control group . At baseline there were no differences between the groups . After 9 months , exercisers ( Ex ) and controls ( Con ) had similar increases in height and weight . Significant lower adiposity was observed in the exercise group vs the control group . None of the bone indices differed significantly between the two groups . When the analyses were done for a subgroup of twin pairs ( n=12 ) who did not participate in high-impact sports during their leisure time , significant differences were obtained for aBMD and BMC of the proximal femur in favor of the exercise group . These results indicate that for prepubertal girls who are not involved in sport activities or who are only involved in low-impact sport activities this exercise program has an osteogenic effect on the proximal femur , but for girls who are already involved in high-impact sports this protocol does not have any additional effect on the bone status OBJECTIVE To examine the effects of 15 months of resistance training on bone mineral density ( BMD ) in female adolescents ( aged 14 to 17 years ) . STUDY DESIGN Participants were r and omly assigned to either a training ( n = 46 ) or control group ( n = 21 ) . BMD and body composition were measured by using dual-energy x-ray absorptiometry . Strength was assessed by means of one-repetition maximums for the leg press and bench press . The exercise group trained 30 to 45 minutes a day , 3 days per week , using 15 different resistance exercises . Control participants remained sedentary ( < 2 hours of exercise per week ) . RESULTS Leg strength increased significantly ( 40 % ) in the exercise group , but there were no changes in the control group . Femoral neck BMD increased significantly in the training group ( 1.035 to 1.073 g/cm(2 ) , P < .01 ) but not in the control group ( 1.034 to 1.048 g/cm(2 ) ) . No significant changes were seen in either group in lumbar spine BMD ( 1.113 to 1.142 g/cm(2 ) and 1.158 to 1.190 g/cm(2 ) , respectively ) or total body BMD ( 1.103 to 1.134 g/cm(2 ) and 1.111 to 1.129 g/cm(2 ) , respectively ) . CONCLUSION Resistance training is a potential method for increasing bone density in adolescents , although such a program would be best done as part of the school curriculum High calcium intake combined with physical activity during childhood have been shown to improve bone mass accrual and bone mineral density . Our aim was to study the combined effect of calcium and exercise on bone gain in children . Two milk-powder products containing either 800 mg of calcium phosphate ( calcium ) or not ( placebo ) were r and omly allocated to 113 healthy premenarchal girls on a daily basis for 1 year . The group was composed of 63 exercise ( 7.2 + /- 4 hours of exercise/week ) and 50 sedentary ( 1.2 + /- 0.8 hours of exercise/week ) children . The final experiment had 4 groups : exercise/calcium ( n = 12 ) , exercise/placebo ( n = 42 ) , sedentary/calcium ( n = 10 ) , and sedentary/placebo ( n = 21 ) . Bone mineral density ( BMD ) at 6 skeletal sites and body composition were determined by DXA . Bone age was calculated and the daily spontaneous calcium intake was assessed by a frequency question naire . All the tests were performed at baseline and 1 year by the same observer . BMD gains were significantly greater in the exercise/calcium group than in other groups at the total body ( increase of 6.3 % , p < 0.05 ) , lumbar spine ( 11 % , p < 0.05 ) , femoral neck ( 8.2 % , p < 0.02 ) , and Ward 's triangle ( 9.3 % , p < 0.01 ) . There was no difference between the other groups . These data suggest that calcium supplementation increases the effect of physical exercise on bone mineral acquisition in the period preceding puberty , and that calcium supplementation without physical activity does not improve the BMD acquisition during this period . Physical exercise that stimulates bone accretion needs a high calcium intake to be completely effective Objectives : To examine the effects of a simple and inexpensive physical activity intervention on change in bone mass and structure in school aged children . Methods : Fifty one children ( n = 23 boys and 28 girls ; mean age 10.1 years ) participated in “ Bounce at the Bell ” which consisted of 10 counter-movement jumps 3 × per day ( total ∼3 min/day ) . Controls were 71 matched children who followed usual school practice . We assessed dietary calcium , physical activity , physical performance , and anthropometry in September and after 8 months of intervention ( June ) . We measured bone mineral content ( BMC ) and bone area at the lumbar spine , total body , and proximal femur . Proximal femur scans were also analysed for bone geometry and structural strength using the hip structural analysis program . Lean and fat mass ( g ) were also calculated . Results : Groups were similar at baseline and did not differ in weight , height , total body , lumbar spine , proximal femur , or femoral neck BMC . Control children had a greater increase in adjusted total body BMC ( 1.4 % ) . Intervention children gained significantly more BMC at the total proximal femur ( 2 % ) and the intertrochanteric region ( 27 % ) . Change in bone structural parameters did not differ between groups . Conclusions : This novel , easily implemented exercise program , took only a few minutes each day and enhanced bone mass at the weight bearing proximal femur in early pubertal children . A large , r and omised study of boys and girls should be undertaken powered to test the effectiveness of Bounce at the Bell in children at different stages of maturity , and in boys and girls independently Mechanical loading of the living skeleton influences bone formation , mass , and strength . The primary purpose of the present study was to examine the influence of different loading schedules ( days/week ) on the bone response to external loading using an in vivo rat tibia four-point bending model . Three studies were conducted to ( 1 ) characterize the loaded region , ( 2 ) examine the variation of the response within the loaded region , and ( 3 ) test the response to different loading schedules . In all studies adult female retired breeder Sprague-Dawley rats were used ( 6 months , 285 g ) . First , the location of the loaded region during four-point bending was determined by radiogrammetry of 7 rats . Second , 5 rats were externally loaded for 8 of 10 days at 31 N , 36 cycles , and 2 Hz ( 1349 + /- 244 mu epsilon ) . The extent of labeled ( forming ) periosteal and endocortical surface in the loaded region was compared both among four serial sections from the same tibia and between the loaded and the contralateral tibiae . Finally , 50 rats were r and omized into five groups : two nonloaded , control and sham , and three loaded , alternate day , Monday , Wednesday , and Friday , and daily . The rats were externally loaded for 3 weeks at 35 N , 36 cycles , and 2 Hz ( 1533 + /- 308 mu epsilon ) . The tibia and fibula were studied for labeled surfaces and mineral apposition rate . For adult female rats with tibial length 39 mm , the loaded region was located 3.5 - 14 ( + /- 0.7 ) mm proximal to the tibia-fibula junction ( TFJ ) . ( ABSTRACT TRUNCATED AT 250 WORDS We have prospect ively studied forearm trabecular and cortical bone mineral density gain ( ΔBMD ) in relation to nutrient intake , weight‐bearing physical activity ( WPA ) and daylight exposure ( DE ) in 470 healthy boys and girls aged 8.2‐16.5 years at the baseline . BMD was assessed using single photon absorptiometry ( SPA ) . Cortical ΔBMD peaked at the age of 14.0 ± 0.3 and 16.0 ± 0.3 ( SD ) years in girls and boys , respectively . Girls had achieved adult premenopausal values of trabecular BMD by the age of 15 years and cortical BMD values by the age of 16.5 years . WPA , BMD , body height , height gain , weight , weight gain , dietary polyunsaturated fat and sodium were correlated with ΔBMD . WPA , predicting cortical as well as trabecular ΔBMD , had the greatest effect on trabecular ΔBMD in the presence of a high calcium intake in children below 11 years of age . In conclusion , our results indicate that physical activity and calcium intake should be encouraged at a prepubertal age in order to increase bone density Combining exercise with calcium supplementation may produce additive or multiplicative effects at loaded sites ; thus , we conducted a single blind , prospect i ve , r and omized controlled study in pre- and early-pubertal girls to test the following hypotheses . ( 1 ) At the loaded sites , exercise and calcium will produce greater benefits than exercise or calcium alone . ( 2 ) At non-loaded sites , exercise will have no benefit , whereas calcium with or without exercise will increase bone mass over that in exercise alone or no intervention . Sixty-six girls aged 8.8 + /- 0.1 years were r and omly assigned to one of four study groups : moderate-impact exercise with or without calcium or low-impact exercise with or without calcium . All participants exercised for 20 minutes , three times a week and received Ca-fortified ( 434 + /- 19 mg/day ) or non-fortified foods for 8.5 months . Analysis of covariance ( ANCOVA ) was used to determine interaction and main effects for exercise and calcium on bone mass after adjusting for baseline bone mineral content and growth in limb lengths . An exercise-calcium interaction was detected at the femur ( 7.1 % , p < 0.05 ) . In contrast , there was no exercise-calcium interaction detected at the tibia-fibula ; however , there was a main effect of exercise : bone mineral content increased 3 % more in the exercise than non-exercise groups ( p < 0.05 ) . Bone mineral content increased 2 - 4 % more in the calcium-supplemented groups than the non-supplemented groups at the humerus ( 12.0 % vs. 9.8 % , respectively , p < 0.09 ) and radius-ulna ( 12.6 % vs. 8.6 % , respectively , p < 0.01 ) . In conclusion , greater gains in bone mass at loaded sites may be achieved when short bouts of moderate exercise are combined with increased dietary calcium , the former conferring region-specific effects and the latter producing generalized effects OBJECTIVE To establish rates of skeletal mineralization in children and adolescents , and to identify factors that influence these rates . DESIGN Three-year observational study . SETTING University hospital . SUBJECTS Ninety white children , aged 6 to 14 years . MEASUREMENTS Bone mineral density of the radius , spine , and hip was measured at baseline and 3 years later . Physical activity was assessed by question naires at 6-month intervals and dietary calcium intake by diet diary 1 day per month for 36 months . Sexual maturation ( Tanner stage ) was determined by an endocrinologist at 6-month intervals , as necessary to classify children as prepubertal , peripubertal , or postpubertal . RESULTS Skeletal mineralization accelerated markedly at puberty in the spine ( 0.077 vs 0.027 gm/cm2 per year , peripubertal vs prepubertal ) and greater trochanter ( 0.050 vs 0.027 gm/cm2 per year ) , less markedly in the femoral neck ( 0.047 vs 0.030 gm/cm2 per year ) , and only slightly in the radius . Nearly one third ( 15 gm ) of the total skeletal mineral in the lumbar spine of adult women ( approximately 52 gm ) was accumulated in the 3 years around the onset of puberty . Increases in height and weight were the strongest correlates of skeletal mineralization : weight changes were more strongly correlated with trabecular bone sites and changes in height with cortical bone sites . Increases in calf muscle area were strongly associated with mineralization , particularly in peripubertal children , and physical activity was associated with more rapid mineralization in prepubertal children . CONCLUSIONS Puberty has varying effects on skeletal mineralization depending on skeletal site ; trabecular bone is apparently more sensitive to changing hormone concentrations . Physical activity and normal growth are also positively associated with skeletal mineralization , also depending on skeletal site and sexual maturation BACKGROUND Of the few exercise intervention studies focusing on pediatric population s , none have confined the intervention to the scheduled physical education curriculum . OBJECTIVE To examine the effect of an 8-month school-based jumping program on the change in areal bone mineral density ( aBMD ) , in grams per square centimeter , of healthy third- and fourth- grade children . STUDY DESIGN Ten elementary schools were r and omized to exercise ( n = 63 ) and control groups ( n = 81 ) . Exercise groups did 10 tuck jumps 3 times weekly and incorporated jumping , hopping , and skipping into twice weekly physical education classes . Control groups did regular physical education classes . At baseline and after 8 months of intervention , we measured aBMD and lean and fat mass by dual-energy x-ray absorptiometry ( Hologic QDR-4500 ) . Calcium intake , physical activity , and maturity were estimated by question naire . RESULTS The exercise group showed significantly greater change in femoral trochanteric aBMD ( 4.4 % vs 3.2 % ; P < .05 ) . There were no group differences at other sites . Results were similar after controlling for covariates ( baseline aBMD change in height , change in lean , calcium , physical activity , sex , and ethnicity ) in hierarchical regression . CONCLUSIONS An easily implemented school-based jumping intervention augments aBMD at the trochanteric region in the prepubertal and early pubertal skeleton We compared 7-month changes in bone structural properties in pre- and early-pubertal girls r and omized to exercise intervention ( 10-minute , 3 times per week , jumping program ) or control groups . Girls were classified as prepubertal ( PRE ; Tanner breast stage 1 ; n = 43 for intervention [ I ] and n = 25 for control [ C ] ) or early-pubertal ( EARLY ; Tanner stages 2 and 3 ; n = 43 for I and n = 63 for C ) . Mean + /- SD age was 10.0 + /- 0.6 and 10.5 + /- 0.6 for the PRE and EARLY groups , respectively . Proximal femur scans were analyzed using a hip structural analysis ( HSA ) program to assess bone mineral density ( BMD ) , subperiosteal width , and cross-sectional area and to estimate cortical thickness , endosteal diameter , and section modulus at the femoral neck ( FN ) , intertrochanter ( IT ) , and femoral shaft ( FS ) regions . There were no differences between intervention and control groups for baseline height , weight , calcium intake , or physical activity or for change over 7 months ( p > 0.05 ) . We used analysis of covariance ( ANCOVA ) to examine group differences in changes of bone structure , adjusting for baseline weight , height change , Tanner breast stage , and physical activity . There were no differences in change for bone structure in the PRE girls . The more mature girls ( EARLY ) in the intervention group showed significantly greater gains in FN ( + 2.6 % , p = 0.03 ) and IT ( + 1.7 % , p = 0.02 ) BMD . Underpinning these changes were increased bone cross-sectional area and reduced endosteal expansion . Changes in subperiosteal dimensions did not differ . Structural changes improved section modulus ( bending strength ) at the FN ( + 4.0 % , p = 0.04 ) , but not at the IT region . There were no differences at the primarily cortical FS . These data provide insight into geometric changes that underpin exercise-associated gain in bone strength in early-pubertal girls |
13,279 | 30,304,033 | Therefore , we aim ed at examining comparative intervention studies that assessed the effects of age , sex , maturation , and resistance or plyometric training descriptors ( e.g. , training intensity , volume etc . )
Sex has no major impact on resistance training related outcomes ( e.g. , maximal strength , 10 repetition maximum ) .
In terms of plyometric training , around-PHV boys appear to respond with larger performance improvements ( e.g. , jump height , jump distance ) compared with girls .
Different types of resistance training ( e.g. , body weight , free weights ) are effective in improving measures of muscle strength ( e.g. , maximum voluntary contraction ) in untrained children and adolescents .
Effects of plyometric training in untrained youth primarily follow the principle of training specificity . | INTRODUCTION To date , several meta-analyses clearly demonstrated that resistance and plyometric training are effective to improve physical fitness in children and adolescents .
However , a method ological limitation of meta-analyses is that they synthesize results from different studies and hence ignore important differences across studies ( i.e. , mixing apples and oranges ) .
on measures of physical fitness while holding other variables constant .
on components of physical fitness ( i.e. , muscle strength and power ) . | Background . Previous research has shown that children can increase their muscular strength and muscular endurance as a result of regular participation in a progressive resistance training program . However , the most effective exercise prescription regarding the number of repetitions remains question able . Objective . To compare the effects of a low repetition – heavy load resistance training program and a high repetition – moderate load resistance training program on the development of muscular strength and muscular endurance in children . Design . Prospect i ve , controlled trial . Setting . Community-based youth fitness center . Subjects . Eleven girls and 32 boys between the ages of 5.2 and 11.8 years . Intervention . In twice-weekly sessions of resistance training for 8 weeks , children performed 1 set of 6 to 8 repetitions with a heavy load ( n = 15 ) or 1 set of 13 to 15 repetitions with a moderate load ( n = 16 ) on child-size exercise machines . Children in the control group ( n = 12 ) did not resistance train . One repetition maximum ( RM ) strength and muscular endurance ( repetitions performed posttraining with the pretraining 1-RM load ) were determined on the leg extension and chest press exercises . Results . One RM leg extension strength significantly increased in both exercise groups compared with that in the control subjects . Increases of 31.0 % and 40.9 % , respectively , for the low repetition – heavy load and high repetition – moderate load groups were observed . Leg extension muscular endurance significantly increased in both exercise groups compared with that in the control subjects , although gains result ing from high repetition – moderate load training ( 13.1 ± 6.2 repetitions ) were significantly greater than those result ing from low repetition – heavy load training ( 8.7 ± 2.9 repetitions ) . On the chest press exercise , only the high repetition – moderate load exercise group made gains in 1-RM strength ( 16.3 % ) and muscular endurance ( 5.2 ± 3.6 repetitions ) that were significantly greater than gains in the control subjects . Conclusion . These findings support the concept that muscular strength and muscular endurance can be improved during the childhood years and favor the prescription of higher repetition – moderate load resistance training programs during the initial adaptation period The purpose of the present study was to examine the influence of direct supervision on muscular strength , power , and running speed during 12 weeks of resistance training in young rugby league players . Two matched groups of young ( 16.7 ± 1.1 years [ mean ± SD ] ) , talented rugby league players completed the same periodized resistance-training program in either a supervised ( SUP ) ( N = 21 ) or an unsupervised ( UNSUP ) ( N = 21 ) environment . Measures of 3 repetition maximum ( 3RM ) bench press , 3RM squat , maximal chin-ups , vertical jump , 10– and 20-m sprints , and body mass were completed pretest ( week 0 ) , midtest ( week 6 ) , and posttest ( week 12 ) training program . Results show that 12 weeks of periodized resistance training result ed in an increased body mass , 3RM bench press , 3RM squat , maximum number of chin-ups , vertical jump height , and 10– and 20-m sprint performance in both groups ( p < 0.05 ) . The SUP group completed significantly more training sessions , which were significantly correlated to strength increases for 3RM bench press and squat ( p < 0.05 ) . Furthermore , the SUP group significantly increased 3RM squat strength ( at 6 and 12 weeks ) and 3RM bench press strength ( 12 weeks ) when compared to the UNSUP group ( p < 0.05 ) . Finally , the percent increase in the 3RM bench press , 3RM squat , and chin-upmax was also significantly greater in the SUP group than in the UNSUP group ( p < 0.05 ) . These findings show that the direct supervision of resistance training in young athletes results in greater training adherence and increased strength gains than does unsupervised training BACKGROUND : In developed societies levels of daily physical activity ( PA ) among school-age children are decreasing . This implies risk factors for cardiovascular and metabolic diseases . Specific strategies to improve levels of PA are needed . In prepubertal boys there is evidence that strength training increases spontaneous PA outside of training . METHODS : A total of 102 schoolchildren ( age 10–14 years ) in Switzerl and were r and omly assigned to physical education classes or to participate twice weekly at a guided strength training program for 19 weeks . Spontaneous PA energy expenditure ( PAEE ; 3axial accelerometry for 7 days ) , leg and arm strength , and body composition ( dual energy radiograph absorptiometry ) were measured at baseline , after 19 weeks of training intervention , and after 3 months of washout . RESULTS : There were no significant differences between the groups at baseline . In the intervention group , PAEE increased by 10 % from baseline to end of training in boys ( P = .02 ) , but not in girls . Leg and arm strength were increased owing to training intervention in both boys and girls . All other variables were unchanged . Baseline PAEE was significantly negatively correlated with changes of PAEE . CONCLUSIONS : Targeted strength training significantly increases daily spontaneous PA behavior in boys . The less active children showed the greatest increase in spontaneous PAEE . Girls showed a similar increase in strength , but not in spontaneous PAEE . This may be explained by their earlier pubertal development . Strength training may be a promising strategy in schools to counteract decreasing levels of PA The aim of this study was to determine the effectiveness of two different resistance training programs on lower limb explosive and reactive strength in young female athletes . Fifty seven rhythmic gymnasts were r and omly assigned to unspecific resistance training with dumbbells ( 12 repetition maximum squats ) ( n = 19 ; age = 12.0 + /- 1.8 years ) or to specific resistance training with weighted belts ( 6 % of body mass ; n = 18 ; age = 11.9 + /- 1.0 years ) . Squat jump test , counter movement jump test , hopping test , flexibility of the hip , and anthropometric measures were assessed before and after six weeks training . The main result was that both unspecific resistance training and specific resistance training protocol s positively affected the jumping performance , with an increase of the lower limb explosive strength of 6 - 7 % , with no side effects . Counter movement jump flight time increased significantly ( p < 0.01 ) while hopping test ground contact time significantly decreased ( p < 0.01 ) . No significant differences were detected among groups for flexibility , body mass , calf and thigh circumferences . Therefore , six weeks of resistance training that integrates different elements of rhythmic gymnastics training enhance jumping ability in young female athletes Abstract Ramírez-Campillo , R , Gallardo , F , Henriquez-Olguín , C , Meylan , CMP , Martínez , C , Álvarez , C , Caniuqueo , A , Cadore , EL , and Izquierdo , M. Effect of vertical , horizontal , and combined plyometric training on explosive , balance , and endurance performance of young soccer players . J Strength Cond Res 29(7 ) : 1784–1795 , 2015—The aim of this study was to compare the effects of 6 weeks of vertical , horizontal , or combined vertical and horizontal plyometric training on muscle explosive , endurance , and balance performance . Forty young soccer players aged between 10 and 14 years were r and omly divided into control ( CG ; n = 10 ) , vertical plyometric group ( VG ; n = 10 ) , horizontal plyometric group ( HG ; n = 10 ) , and combined vertical and horizontal plyometric group ( VHG ; n = 10 ) . Players performance in the vertical and horizontal countermovement jump with arms , 5 multiple bounds test ( MB5 ) , 20-cm drop jump reactive strength index ( RSI20 ) , maximal kicking velocity ( MKV ) , sprint , change of direction speed ( CODS ) , Yo-Yo intermittent recovery level 1 test ( Yo-Yo IR1 ) , and balance was measured . No significant or meaningful changes in the CG , apart from small change in the Yo-Yo IR1 , were observed while all training programs result ed in meaningful changes in explosive , endurance , and balance performance . However , only VHG showed a statistically significant ( p ⩽ 0.05 ) increase in all performance test and most meaningful training effect difference with the CG across tests . Although no significant differences in performance changes were observed between experimental groups , the VHG program was more effective compared with VG ( i.e. , jumps , MKV , sprint , CODS , and balance performance ) and HG ( i.e. , sprint , CODS , and balance performance ) to small effect . The study demonstrated that vertical , horizontal , and combined vertical and horizontal jumps induced meaningful improvement in explosive actions , balance , and intermittent endurance capacity . However , combining vertical and horizontal drills seems more advantageous to induce greater performance improvements The purpose of this study was to investigate whether 6 weeks of static hamstring stretching effects range of motion ( ROM ) , sprint , and vertical jump performances in athletes . Twenty-one healthy division III women 's track and field athletes participated in the study . Subjects were tested for bilateral knee ROM ; 55-m sprint time ; and vertical jump height before , at 3 weeks , and after the 6-week flexibility program . Subjects were r and omly assigned to treatment and control groups and warmed up with a 10-minute jog on a track before a hamstring stretching protocol . The stretching protocol consisted of four repetitions held for 45 seconds , 4 days per week . Four variables ( left and right leg ROM , 55-m sprint time , vertical jump ) were analyzed using a repeated- measures analysis of variance design . No significant differences ( P ≤ 0.05 ) were found with any of the four variables between the stretching and control groups . Six weeks of a static hamstring stretching protocol did not improve knee ROM or sprint and vertical jump performances in women track and field athletes . The use of static stretching should be restricted to post practice or competition because of the detrimental effects reported throughout the literature . Based on the current investigation , it does not seem that chronic static stretching has a positive or negative impact on athletic performance . Thus , the efficacy of utilizing this practice is question able and requires further investigation The aim of this study was to investigate whether variation in estrogen levels during the menstrual cycle influences susceptibility to exercise-induced muscle damage after stretch-shortening cycle exercise . Physically active women ( n = 18 ; age = 20.2 ± 1.7 yr ) participated in this research . The subjects performed one session of 100 maximal drop jumps on day 1 or 2 of the follicular phase and another identical session on day 1 or 2 of the ovulatory phase ; the order of the sessions was r and omized . Quadriceps femoris muscle peak torque evoked by electrical stimulation and maximal voluntary contraction , muscle pain , and CK activity were measured before and at various times up to 72 h after exercise . It was found that the high estrogen level during the ovulatory phase might be related to an earlier return to baseline muscle strength after strenuous stretch-shortening cycle exercise in that phase compared with the follicular phase . The estrogen effect appears to be highly specific to the damaged site because the differences in most EIMD markers ( CK , soreness , and low-frequency fatigue ) between the two menstrual cycle phases were small Abstract Escamilla , RF , Ionno , M , deMahy , MS , Fleisig , GS , Wilk , KE , Yamashiro , K , Mikla , T , Paulos , L , and And rews , JR . Comparison of three baseball-specific 6-week training programs on throwing velocity in high school baseball players . J Strength Cond Res 26(7 ) : 1767–1781 , 2012 . Throwing velocity is an important baseball performance variable for baseball pitchers , because greater throwing velocity results in less time for hitters to make a decision to swing . Throwing velocity is also an important baseball performance variable for position players , because greater throwing velocity results in decreased time for a runner to advance to the next base . This study compared the effects of 3 baseball-specific 6-week training programs on maximum throwing velocity . Sixty-eight high school baseball players 14–17 years of age were r and omly and equally divided into 3 training groups and a nontraining control group . The 3 training groups were the Throwers Ten ( TT ) , Keiser Pneumatic ( KP ) , and Plyometric ( PLY ) . Each training group trained 3 d·wk−1 for 6 weeks , which comprised approximately 5–10 minutes for warm-up , 45 minutes of resistance training , and 5–10 for cool-down . Throwing velocity was assessed before ( pretest ) and just after ( posttest ) the 6-week training program for all the subjects . A 2-factor repeated measures analysis of variance with post hoc paired t-tests was used to assess throwing velocity differences ( p < 0.05 ) . Compared with pretest throwing velocity values , posttest throwing velocity values were significantly greater in the TT group ( 1.7 % increase ) , the KP group ( 1.2 % increase ) , and the PLY group ( 2.0 % increase ) but not significantly different in the control group . These results demonstrate that all 3 training programs were effective in increasing throwing velocity in high school baseball players , but the results of this study did not demonstrate that 1 resistance training program was more effective than another resistance training program in increasing throwing velocity Abstract Radnor , JM , Lloyd , RS , and Oliver , JL . Individual response to different forms of resistance training in school-aged boys . J Strength Cond Res 31(3 ) : 787–797 , 2017—The aim of this study was to examine individual responses to different forms of resistance training on measures of jumping and sprinting performance in school-aged boys . Eighty boys were categorized into 2 maturity groups ( pre- or post – peak height velocity [ PHV ] ) and r and omly assigned to a plyometric training , resistance training , combined training , or control group . Intervention groups participated in training twice weekly for 6 weeks , with measures of acceleration , maximal running velocity , squat jump height , and reactive strength index ( RSI ) collected preintervention and postintervention . In the pre-PHV cohort , plyometric training and combined training result ed in significantly more positive responders than the other 2 groups in both sprint variables ( st and ardized residual values > 1.96 ) . In the post-PHV cohort , significantly more positive responders for acceleration and squat jump height result ed from traditional strength training and combined training groups , compared with other groups . Conversely , plyometric training and combined training result ed in a significantly greater number of positive responders than the other 2 groups for maximal velocity and RSI . Control participants rarely demonstrated meaningful changes in performance over the 6-week period . Irrespective of maturation , it would seem that combined training provides the greatest opportunity for most individuals to make short-term improvements in jump and sprint performance . Taking maturation into account , our data show that a plyometric training stimulus is important for individuals in the pre-PHV stage of development , whether as a st and -alone method or in combination with traditional strength training , when attempting to improve jumping and sprinting ability . However , individuals in the post-PHV stage require a more specific training stimulus depending on the performance variable that is being targeted for improvement This study compared high- ( HL ) and low-load ( LL ) resistance training ( RT ) on strength , absolute endurance , volume-load , and their relationships in untrained adolescents . Thirty-three untrained adolescents of both sexes ( males , n = 17 ; females , n = 16 ; 14 ± 1 years ) were r and omly assigned into either ( i ) HL ( n = 17 ) : performing 3 sets of 4 - 6 repetitions to momentary concentric failure ; or ( ii ) LL ( n = 16 ) : performing 2 sets of 12 - 15 repetitions to momentary concentric failure . RT was performed for 2 × /week for 9 weeks . Change in maximum strength ( 1 repetition maximum ) and absolute muscular endurance for barbell bench press was assessed . Weekly volume-load was calculated as sets ( n ) × repetitions ( n ) × load ( kg ) . Ninety-five percent confidence intervals ( CIs ) revealed that both groups significantly increased in strength and absolute endurance with large effect sizes ( d = 1.51 - 1.66 ) . There were no between-group differences for change in strength or absolute endurance . Ninety-five percent CIs revealed that both groups significantly increased in weekly volume-load with large effect sizes ( HL = 1.66 , LL = 1.02 ) . There were no between-group differences for change in volume-load though average weekly volume-load was significantly greater for LL ( p < 0.001 ) . Significant Pearson 's correlations were found for the HL group between average weekly volume-load and both strength ( r = 0.650 , p = 0.005 ) and absolute endurance ( r = 0.552 , p = 0.022 ) increases . Strength and absolute endurance increases do not differ between HL and LL conditions in adolescents when performed to momentary concentric failure . Under HL conditions greater weekly volume-load is associated with greater strength and absolute endurance increases The purpose of this study was to assess the lifting performance of boys ( N = 12 ; age 11.3 + /- 0.8 yr ) , teens ( N = 13 ; age 13.6 + /- 0.6 yr ) , and men ( N = 17 ; age 21.4 + /- 2.1 yr ) to various rest interval ( RI ) lengths on the bench press exercise . Each subject performed 3 sets with a 10 repetition maximum load and a 1 , 2 , and 3 min RI between sets . Significant differences in lifting performance between age groups were observed within each RI for selected sets with boys and teens performing significantly more total repetitions than adults following protocol s with 1 min ( 27.9 + /- 3.1 , 26.9 + /- 3.9 , and 18.2 + /- 4.1 , respectively ) , 2 min ( 29.6 + /- 1.0 , 27.8 + /- 3.5 , and 21.4 + /- .1 , respectively ) and 3 min ( 30.0 + /- 0.0 , 28.8 + /- 2.4 , and 23.9 + /- 5.3 , respectively ) RIs . Significant differences in average velocity and average power between age groups were also observed . These findings indicate that boys and teens are better able to maintain muscle performance during intermittent moderate-intensity resistance exercise as compared with men Objective : To identify the contribution of anthropometric variables to predict the maturational stage in young males . Methods : Cross-sectional study that enrolled 190 male subjects aged between eight and 18 years , r and omly selected from public and private schools in Natal , Northeast Brazil . Thirtytwo anthropometric variables were measured following the recommendations of the International Society for the Advancement of Kineanthropometry ( ISAK ) . The assessment of sexual maturation was based on the observation of two experienced experts , who identified the pubertal development according to Tanner guidelines ( 1962 ) . Results : The anthropometric variables showed a significant increase of their values during the advancement of pubertal development ( p<0.05 ) . The following variables showed the best value for prediction of maturational groups : sitting height , femoral biepicondylar diameter , forearm girth , triceps skinfold , tibiale laterale and acromiale-radiale bonelenghts . These variables were able to estimate the pubertal stages in 76.3 % of the sujects . Conclusion : The anthropometric characteristics showed significant differences between the moments of maturational stages , being found , representatively , seven variables that best predict the stages of sexual maturation The purpose of this study was to examine the effect of 3 volumes of heavy resistance , average relative training intensity ( expressed as a percentage of 1 repetition maximum that represented the absolute kilograms lifted divided by the number of repetitions performed ) programs on maximal strength ( 1RM ) in Snatch ( Sn ) , Clean & Jerk ( C&J ) , and Squat ( Sq ) . Twenty-nine experienced ( .3 years ) , trained junior weight-lifters were r and omly assigned into 1 of 3 groups : low-intensity group ( LIG ; n = 12 ) , moderate-intensity group ( MIG ; n = 9 ) , and high-intensity group ( HIG ; n = 8) . All subjects trained for 10 weeks , 4–5 days a week , in a periodized routine using the same exercises and training volume ( expressed as total number of repetitions performed at intensities equal to or greater than 60 % of 1RM ) , but different programmed total repetitions at intensities of .90–100 % of 1RM for the entire 10-week period : LIG ( 46 repetitions ) , MIG ( 93 repetitions ) , and HIG ( 184 repetitions ) . During the training period , MIG and LIG showed a significant increase ( p < 0.01–0.05 ) for C & J ( 10.5 % and 3 % for MIG and LIG , respectively ) and Sq ( 9.5 % and 5.3 % for MIG and LIG , respectively ) , whereas in HIG the increase took place only in Sq ( 6.9 % , p < 0.05 ) . A calculation of effect sizes revealed greater strength gains in the MIG than in HIG or LIG . There were no significant differences between LIG and HIG training volume-induced strength gains . All the subjects in HIG were unable to fully accomplish the repetitions programmed at relative intensities greater than 90 % of 1RM . The present results indicate that short-term resistance training using moderate volumes of high relative intensity tended to produce higher enhancements in weightlifting performance compared with low and high volumes of high relative training intensities of equal total volume in experienced , trained young weightlifters . Therefore , for the present population of weightlifters , it may be beneficial to use the MIG training protocol to improve the weightlifting program at least in a short-term ( 10 weeks ) cycle of training CONTEXT Several groups have undertaken studies to evaluate the physiologic effects of whole-body vibration ( WBV ) . However , the value of WBV in a training program remains unknown . OBJECTIVE To investigate whether a WBV program results in a better strength and postural control performance than an equivalent exercise program performed without vibration . DESIGN R and omized , controlled trial . SETTING Laboratory . PATIENTS OR OTHER PARTICIPANTS Thirty-three Belgian competitive skiers ( ages = 9 - 15 years ) . INTERVENTION(S ) Subjects were assigned to either the WBV group or the equivalent resistance ( ER ) group for 6 weeks of training at 3 times per week . MAIN OUTCOME MEASURE(S ) Isokinetic plantar and dorsiflexion peak torque , isokinetic knee flexion and extension peak torque , explosive strength ( high box test ) , and postural control were assessed before and after the training period . RESULTS Both training programs significantly improved isokinetic ankle and knee muscle strength and explosive strength . Moreover , the increases in explosive strength and in plantar-flexor strength at low speed were significantly higher in the WBV group than in the ER group after 6 weeks . However , neither WBV training nor ER training seemed to have an effect on postural control . CONCLUSIONS A strength training program that includes WBV appears to have additive effects in young skiers compared with an equivalent program that does not include WBV . Therefore , our findings support the hypothesis that WBV training may be a beneficial supplementary training technique in strength programs for young athletes Abstract Objective To investigate the effect of a structured warm-up programme design ed to reduce the incidence of knee and ankle injuries in young people participating in sports . Design Cluster r and omised controlled trial with clubs as the unit of r and omisation . Setting 120 team h and ball clubs from central and eastern Norway ( 61 clubs in the intervention group , 59 in the control group ) followed for one league season ( eight months ) . Participants 1837 players aged 15 - 17 years ; 958 players ( 808 female and 150 male ) in the intervention group ; 879 players ( 778 female and 101 male ) in the control group . Intervention A structured warm-up programme to improve running , cutting , and l and ing technique as well as neuromuscular control , balance , and strength . Main outcome measure The rate of acute injuries to the knee or ankle . Results During the season , 129 acute knee or ankle injuries occurred , 81 injuries in the control group ( 0.9 ( SE 0.09 ) injuries per 1000 player hours ; 0.3 ( SE 0.17 ) in training v 5.3 ( SE 0.06 ) during matches ) and 48 injuries in the intervention group ( 0.5 ( SE 0.11 ) injuries per 1000 player hours ; 0.2 ( SE 0.18 ) in training v 2.5 ( SE 0.06 ) during matches ) . Fewer injured players were in the intervention group than in the control group ( 46 ( 4.8 % ) v ( 76 ( 8.6 % ) ; relative risk intervention group v control group 0.53 , 95 % confidence interval 0.35 to 0.81 ) . Conclusion A structured programme of warm-up exercises can prevent knee and ankle injuries in young people playing sports . Preventive training should therefore be introduced as an integral part of youth sports programmes The purpose of the current study was to evaluate the transferability of 2 different resistance training protocol s on service velocity and its precision consistency in junior tennis players . Thirty-six male athletes ( 15.03 ± 1.64 years ) were r and omly assigned to a machine-based resistance-training group ( RG , n = 12 ) , a plyometric training group ( PG , n = 12 ) , and a control group ( CG , n = 12 ) . For a period of 8 weeks , both intervention groups resistance trained 2 days per week in addition to their regular tennis training , whereas the CG had no extra training . Mean service velocity over 20 maximum-velocity serves increased significantly more in PG ( 3.78 % ; p < .05 ) when compared with CG , whereas no such changes could be found in the RG ( 1.18 % ; p > .05 ) . Service precision did not change from pre- to posttest in all three groups ( p > .05 ) . Only the plyometric training program tested , improved mean service velocity over 20 maximum-velocity serves in junior tennis players but did not affect service precision Thomas , K , French , D , and Hayes , PR . The effect of two plyometric training techniques on muscular power and agility in youth soccer players . J Strength Cond Res 23(1 ) : 332 - 335 , 2009-The aim of this study was to compare the effects of two plyometric training techniques on power and agility in youth soccer players . Twelve males from a semiprofessional football club 's academy ( age = 17.3 ± 0.4 years , stature = 177.9 ± 5.1 cm , mass = 68.7 ± 5.6 kg ) were r and omly assigned to 6 weeks of depth jump ( DJ ) or countermovement jump ( CMJ ) training twice weekly . Participants in the DJ group performed drop jumps with instructions to minimize ground-contact time while maximizing height . Participants in the CMJ group performed jumps from a st and ing start position with instructions to gain maximum jump height . Posttraining , both groups experienced improvements in vertical jump height ( p < 0.05 ) and agility time ( p < 0.05 ) and no change in sprint performance ( p > 0.05 ) . There were no differences between the treatment groups ( p > 0.05 ) . The study concludes that both DJ and CMJ plyometrics are worthwhile training activities for improving power and agility in youth soccer players This study aim ed at examining the effects of plyometric training on stable ( SPT ) vs. unstable ( UPT ) surfaces on physical fitness in prepuberal soccer players . Male athletes were r and omly assigned to SPT ( n=18 ; age=12.7±0.2 years ) or UPT ( n=16 ; age=12.2±0.5 years ) . Both groups conducted 3 regular soccer training sessions per week combined with either 2 SPT or UPT sessions . Assessment of jumping ability ( countermovement jump [ CMJ ] , and st and ing long jump [ SLJ ] ) , speed ( 10-m , 20-m , 30-m sprint ) , agility ( Illinois agility test [ IAT ] ) , and balance ( stable [ SSBT ] , unstable [ USBT ] stork balance test ; stable [ SYBT ] , unstable [ UYBT ] Y balance test ) was conducted pre- and post-training . An ANCOVA model was used to test for between-group differences ( SPT vs. UPT ) at post-test using baseline values as covariates . No significant differences were found for CMJ height ( p>0.05 , d=0.54 ) , SLJ ( p>0.05 ; d=0.81 ) , 10-m , 20-m , and 30-m sprint performances ( p>0.05 , d=0.00 - 0.24 ) , IAT ( p>0.05 , d=0.48 ) , and dynamic balance ( SYBT and UYBT , both p>0.05 , d=0.39 , 0.08 , respectively ) . Statistically significant between-group differences were detected for the USBT ( p<0.01 , d=1.86 ) and the SSBT ( p<0.01 , d=1.75 ) in favor of UPT . Following 8 weeks of SPT or UPT in prepuberal athletes , similar performance levels were observed in both groups for measures of jumping ability , speed , dynamic balance , and agility . However , if the goal is to additionally enhance static balance , UPT has an advantage over SPT To investigate the effects of two different strength-training programs with the same workload ( impulse ) on throwing velocity in water polo , 30 water polo players ( M age = 17.1 yr . , SD = 4.9 ; M mass = 71.2 kg , SD = 14.7 ; M height = 1.75 m , SD = 0.09 m ) were r and omly divided in two groups based upon throwing performance with water polo ball . The medicine-ball training group performed 3 × 6 reps with a 3-kg medicine ball , while the combination training group completed 1 × 9 repetitions with the 3-kg medicine ball , followed by 3 × 14 repetitions with a water polo ball . Both groups trained eight weeks twice per week in addition to their regular water polo training . Throwing velocity was measured with a Doppler radar gun before and after the training period . Testing included throws with a water polo ball on l and and in water , as well as with 1-kg and 3-kg medicine balls on l and . Statistically significant increases were found in mean peak throwing velocity with the water polo , 1-kg , and 3-kg medicine balls after training . No differences between the groups were found , except in throwing velocity with water polo on l and , with a statistically significantly larger increase for the combination training group ( + 7.6 % ) than the medicine-ball training group ( + 3.4 % ) . These findings indicate that after training with the same workload ( impulse ) , increases in throwing velocity in water polo are similar and suggesting workload may be a critical variable for training results Abstract Campillo , RR , And rade , DC , and Izquierdo , M. Effects of plyometric training volume and training surface on explosive strength . J Strength Cond Res 27(10 ) : 2714–2722 , 2013—The purpose of this study is to examine the effects of different volume and training surfaces during a short-term plyometric training program on neuromuscular performance . Twenty-nine subjects were r and omly assigned to 4 groups : control group ( CG , n = 5 ) , moderate volume group ( MVG , n = 9 , 780 jumps ) , moderate volume hard surface group ( MVGHS , n = 8 , 780 jumps ) , and high volume group ( HVG , n = 7 , 1,560 jumps ) . A series of tests were performed by the subjects before and after 7 weeks of plyometric training . These tests were measurement of maximum strength ( 5 maximum repetitions [ 5RMs ] ) , drop jumps ( DJs ) of varying heights ( 20 , 40 , and 60 cm ) , squat and countermovement jumps ( SJ and CMJ , respectively ) , timed 20-m sprint , agility , body weight , and height . The results of the present study suggest that high training volume leads to a significant increase in explosive performance that requires fast stretch-shortening cycle ( SSC ) actions ( such as DJ and sprint ) in comparison to what is observed after a moderate training volume regimen . Second , when plyometric training is performed on a hard training surface ( high-impact reaction force ) , a moderate training volume induces optimal stimulus to increase explosive performance requiring fast SSC actions ( e.g. , DJ ) , maximal dynamic strength enhancement , and higher training efficiency . Thus , a finding of interest in the study was that after 7 weeks of plyometric training , performance enhancement in maximal strength and in actions requiring fast SSC ( such as DJ and sprint ) were dependent on the volume of training and the surface on which it was performed . This must be taken into account when using plyometric training on different surfaces Abstract Chaouachi , A , Hammami , R , Kaabi , S , Chamari , K , Drinkwater , EJ , and Behm , DG . Olympic weightlifting and plyometric training with children provides similar or greater performance improvements than traditional resistance training . J Strength Cond Res 28(6 ) : 1483–1496 , 2014—A number of organizations recommend that advanced resistance training ( RT ) techniques can be implemented with children . The objective of this study was to evaluate the effectiveness of Olympic-style weightlifting ( OWL ) , plyometrics , and traditional RT programs with children . Sixty-three children ( 10–12 years ) were r and omly allocated to a 12-week control OWL , plyometric , or traditional RT program . Pre- and post-training tests included body mass index ( BMI ) , sum of skinfolds , countermovement jump ( CMJ ) , horizontal jump , balance , 5- and 20-m sprint times , isokinetic force and power at 60 and 300 ° ·s−1 . Magnitude-based inferences were used to analyze the likelihood of an effect having a st and ardized ( Cohen 's ) effect size exceeding 0.20 . All interventions were generally superior to the control group . Olympic weightlifting was > 80 % likely to provide substantially better improvements than plyometric training for CMJ , horizontal jump , and 5- and 20-m sprint times , whereas > 75 % likely to substantially exceed traditional RT for balance and isokinetic power at 300 ° ·s−1 . Plyometric training was > 78 % likely to elicit substantially better training adaptations than traditional RT for balance , isokinetic force at 60 and 300 ° ·s−1 , isokinetic power at 300 ° ·s−1 , and 5- and 20-m sprints . Traditional RT only exceeded plyometric training for BMI and isokinetic power at 60 ° ·s−1 . Hence , OWL and plyometrics can provide similar or greater performance adaptations for children . It is recommended that any of the 3 training modalities can be implemented under professional supervision with proper training progressions to enhance training adaptations in children Background : High-intensity progressive resistance training ( PRT ) improves adiposity and metabolic risk in adults , but has not been investigated in children within a r and omized controlled trial ( RCT ) . Objective : We hypothesized that high-intensity PRT ( 8 weeks , twice a week ) would decrease central adiposity in children , as assessed via waist circumference . Methods Design / Setting / Participants : Concealed r and omization stratified by age and gender was used to allocate rural New Zeal and school students to the wait-list control or PRT group . Intervention : Participants were prescribed two sets ( eight repetitions per set ) of 11 exercises targeting all the major muscle groups at high intensity . Primary Outcome : Waist circumference ; secondary outcomes included whole body fat , muscular fitness ( one repetition maximum ) , cardiorespiratory fitness ( peak oxygen consumption during a treadmill test ) , lipids , insulin sensitivity and fasting glucose . Results : Of the 78 children ( 32 girls and 46 boys ; mean age 12.2(1.3 ) years ) , 51 % were either overweight ( 33 % ) or obese ( 18 % ) . High-intensity PRT significantly improved waist circumference ( mean change PRT −0.8 ( 2.2 ) cm vs + 0.5 ( 1.7 ) cm control ; F=7.59 , P=0.008 ) , fat mass ( mean change PRT + 0.2 ( 1.4 ) kg vs + 1.0 ( 1.2 ) kg control ; F=6.00 , P=0.017 ) , percent body fat ( mean change PRT –0.3 (1.8)% vs + 1.2 (2.1)% control ; F=9.04 , P=0.004 ) , body mass index ( mean change PRT −0.01 ( 0.8 ) kg m−2 vs + 0.4 ( 0.7 ) kg m−2 control ; F=6.02 , P=0.017 ) , upper body strength ( mean change PRT+11.6(6.1 ) kg vs + 2.9(3.7 ) kg control ; F=48.6 , P<0.001 ) and lower body strength ( mean change PRT + 42.9(26.6 ) kg vs + 28.5(26.6 ) kg control ; F=4.72 , P=0.034 ) compared to the control group . Waist circumference decreased the most in those with the greatest baseline relative strength ( r=−0.257 , P=0.036 ) , and greatest relative ( r=−0.400 , P=0.001 ) and absolute ( r=0.340 , P=0.006 ) strength gains during the intervention . Conclusion : Isolated high-intensity PRT significantly improves central and whole body adiposity in association with muscle strength in normal-weight and overweight children . The clinical relevance and sustainability of these changes in adiposity should be addressed in future long-term studies Abstract Ramírez-Campillo , R , Meylan , CMP , Álvarez-Lepín , C , Henriquez-Olguín , C , Martinez , C , And rade , DC , Castro-Sepúlveda , M , Burgos , C , Baez , EI , and Izquierdo , M. The effects of interday rest on adaptation to 6 weeks of plyometric training in young soccer players . J Strength Cond Res 29(4 ) : 972–979 , 2015—The purpose of this study was to determine the effects of short-term plyometric training interposed with 24 or 48 hours of rest between training sessions on explosive and endurance adaptations in young soccer players . A total of 166 players , between 10 and 17 years of age , were r and omly divided into 3 groups : a control group ( CG ; n = 55 ) and 2 plyometric training groups with 24 hours ( PT24 ; n = 54 ) and 48 hours ( PT48 ; n = 57 ) of rest between training sessions . Before and after intervention , players were measured in squat jump , countermovement jump , 20 ( RSI20 ) cm drop jump reactive strength index , broad long jump , 20-m sprint time , 10 × 5-m agility time , 20-m multistage shuttle run test , and sit- and -reach test . The plyometric training program was applied during 6 weeks , 2 sessions per week , with a load from 140 to 260 jumps per session , replacing some soccer-specific drills . After intervention , the CG did not show significant performance changes . PT24 and PT48 groups showed a small-to-moderate significant improvement in all performance tests ( p < 0.001 ) , with no differences between treatments . Although it has been recommended that plyometric drills should not be conducted on consecutive days , the study shows that plyometric training applied twice weekly on consecutive or nonconsecutive days results in similar explosive and endurance adaptations in young male soccer players The purpose of this study was to examine the effect of 3 different plyometric training frequencies ( e.g. , 1 day per week , 2 days per week , 4 days per week ) associated with 3 different plyometric training volumes on maximal strength , vertical jump performance , and sprinting ability . Forty-two students were r and omly assigned to 1 of 4 groups : control ( n = 10 , 7 sessions of drop jump ( DJ ) training , 1 day per week , 420 DJs ) , 14 sessions of DJ training ( n = 12 , 2 days per week , 840 DJs ) , and 28 sessions of DJ training ( n = 9 , 4 days per week , 1680 DJs ) . The training protocol s included DJ from 3 different heights 20 , 40 , and 60 cm . Maximal strength ( 1 repetition maximum [ 1RM ] and maximal isometric strength ) , vertical height in countermovement jumps and DJs , and 20-m sprint time tests were carried out before and after 7 weeks of plyometric training . No significant differences were observed among the groups in pre-training in any of the variables tested . No significant changes were observed in the control group in any of the variables tested at any point . Short-term plyometric training using moderate training frequency and volume of jumps ( 2 days per week , 840 jumps ) produces similar enhancements in jumping performance , but greater training efficiency ( ∼12 % and 0.014 % per jump ) compared with high jumping ( 4 days per week , 1680 jumps ) training frequency ( ∼18 % and 0.011 % per jump ) . In addition , similar enhancements in 20-m-sprint time , jumping contact times and maximal strength were observed in both a moderate and low number of training sessions per week compared with high training frequencies , despite the fact that the average number of jumps accomplished in 7S ( 420 jumps ) and 14S ( 840 jumps ) was 25 and 50 % of that performed in 28S ( 1680 jumps ) . These observations may have considerable practical relevance for the optimal design of plyometric training programs for athletes , given that a moderate volume is more efficient than a higher plyometric training volume BACKGROUND Although the plyometric training has proved its efficiency , it remains generally unknown whether a limited amount of plyometric training could improve movements in subjects who already demonstrate high level of performance . METHODS Three different training regimens were performed in order to study effects of plyometric training on elite junior basketball players . While control group ( CG ) participated only in the regular midseason training activity , another two groups performed a limited amount of plyometric training employing drop jumps from the height of either 50 cm ( EG-50 ) or 100 cm ( EG-100 ) . The height of the maximal vertical jump ( CMJ ) , as well as the maximal voluntary force ( F ) and the rate of force development ( RFD ) of hip and knee extensors were tested prior to and after the training . RESULTS An increase in CMJ ( 4.8 and 5.6 cm in EG-50 and EG-100 , respectively ) , as well as in F of hip extensors and RFD of knee extensors was observed in both experimental groups , while no significant changes were recorded in CG . When the pretest scores were used as a covariate , both experimental groups demonstrated higher increase in CMJ and RFD of knee extensors then CG . However , no differences were observed between EG-50 and EG-100 . The multiple correlation between four isometric parameters and CMJ revealed R2=0.29 . CONCLUSIONS A limited amount of plyometric training could improve jumping performance in elite junior basketball players and this improvement could be partly related with an increase in F of hip extensors and RFD of knee extensors . However , neither of the two initial heights of the applied drop jumps proved to be more effective OBJECTIVES To determine changes in maximal strength between two different resistance training progression models , linear ( LP ) and daily undulating ( DUP ) , over a 12-week resistance training programme in sub-elite adolescent rugby union players . DESIGN The study used a quasi-experimental study design . Following baseline assessment s , participants from Squad 1 were r and omised to either LP or DUP ; participants from Squad 2 formed a non-r and omised comparison group ( CON ) . METHODS Participants were 26 sub-elite adolescent rugby union players who were assessed at baseline and after 12 weeks . Outcomes included 5 repetition maximum ( RM ) box squat and bench press , height , body weight , skeletal muscle mass , percentage body fat and maturation status . RESULTS Participants in both the LP and DUP groups significantly increased their squat and bench press strength from baseline to 12 weeks . There were no significant differences between groups for squat and bench press increases after 12 weeks ( p>0.05 ) . No significant increases in squat or bench press strength were observed after 12 weeks in the CON group . Increases in lower body strength were large in the LP group ( ES : 1.64 ) and very large in the DUP group ( ES : 2.33 ) . Upper body strength changes were small in both groups ( LP , ES : 0.57 ; DUP , ES : 0.31 ) . CONCLUSIONS Twelve weeks of LP or DUP resistance training are both effective at increasing maximal lower and upper body strength in adolescent rugby athletes . Additionally , twice weekly frequency of resistance training in adolescent rugby athletes with greater than 6-months resistance training experience is sufficient to elicit substantial increases in maximal strength Abstract van den Tillaar , R and Marques , MC . Effect of different training workload on overhead throwing performance with different weighted balls . J Strength Cond Res 27(5 ) : 1196–1201 , 2013—The purpose of this study was to investigate the effect of a single and a double training workload with 3-kg medicine ball on the throwing speed in 2-h and ed overhead throwing movement . Second , what the effect of training with 3-kg medicine balls had on throwing speed with other ball weights . Forty high school students ( age 15.9 ± 1.0 year , mass 60.9 ± 9 kg , height 1.68 ± 0.08 m ) , divided into 3 speed-matched groups , participated in the study . The first group was a control group and did not train any throwing program regimen , whereas the other 2 groups trained overhead throwing with a single ( 3 series of 6 throws with a 3-kg medicine ball ) or double training workload ( 6 series of 6 throws with a 3-kg medicine ball ) for 6 weeks . Throwing speed with 0.35- , 0.45- , 1- , and 3-kg medicine balls was tested before and after a training period of 6 weeks with 2 sessions per week . A significant ( p ⩽ 0.05 ) increase in throwing speed was found after the 6-week training period with the 0.35- ( 5.1 % ) , 1- ( 3.5 % ) , and 3-kg medicine balls ( 5.2 % ) for both training groups , but not with the 0.45-kg ball ( 0.6 % ) . This increase was mainly caused by the increase of the double workload group . This indicates that training workload is of importance in these subjects for enhancement of ball throwing performance and in design ing training programs . Furthermore , that throwing with high enough training volume of throws with a 3-kg medicine ball also can increase ball speed with lighter balls Abstract Tibana , RA , Prestes , J , da Cunha Nascimento , D , Martins , OV , de Santana , FS , and Balsamo , S. Higher muscle performance in adolescents compared with adults after a resistance training session with different rest intervals . J Strength Cond Res 26(4 ) : 1027–1032 , 2012—The aim of the present study was to compare the effect of 3 different rest intervals between sets on the total training volume , number of repetitions , ratings of perceived exertion ( RPE ) , and resistance to fatigue in adolescents and adults during a resistance training session in the isoinertial chest press exercise . Fifteen male adolescents ( 15.2 ± 1.2 years ; 20.7 ± 2.0 kg·m−2 ; Tanner −4 ; 61.5 ± 8.9 , 10 repetition maximum [ RM ] ) and 15 adults ( 22.2 ± 2.7 years ; 23.3 ± 2.0 kg·m−2 ; Tanner −5 ; 84.3 ± 13.5 , 10RM ) without previous experience with resistance training participated in the study . After 10RM test-retest on 3 different occasions , participants were r and omly assigned to a resistance training protocol with 30- , 60- , and 120-second rest interval between sets . The protocol consisted of 3 sets with 10RM . In all studied variables , with exception to total training volume and RPE , adolescents presented superior results as compared with adults ( p < 0.001 ) . On the other h and , both adults and adolescents exhibited a higher resistance to fatigue , total training volume , and number of repetitions with a longer rest interval ( 120 > 60 > 30 seconds ) ( p < 0.01 ) . Thus , these results indicate that adolescents present a higher recovery capacity between sets in a resistance training session than adults and a longer rest interval results in a higher number of repetitions completed , total training volume , and resistance to fatigue The purpose of this study was to compare the effects of 1 and 2 days per week of strength training on upper body strength , lower body strength , and motor performance ability in children . Twenty-one girls and 34 boys between the ages of 7.1 and 12.3 years volunteered to participate in this study . Participants strength trained either once per week ( n = 22 ) or twice per week ( n = 20 ) for 8 weeks at a community-based youth fitness center . Each training session consisted of a single set of 10 - 15 repetitions on 12 exercises using child-size weight machines . Thirteen children who did not strength train served as age-matched controls . One repetition maximum ( 1RM ) strength on the chest press and leg press , h and grip strength , long jump , vertical jump , and flexibility were assessed at baseline and posttraining . Only participants who strength trained twice per week made significantly greater gains in 1RM chest press strength , compared to the control group ( 11.5 and 4.4 % respectively , p < .05 ) . Participants who trained once and twice per week made gains in 1RM leg press strength ( 14.2 and 24.7 % , respectively ) that were significantly greater than control group gains ( 2.4 % ) . On average , participants who strength trained once per week achieved 67 % of the 1RM strength gains . No significant differences between groups were observed on other outcome measures . These findings support the concept that muscular strength can be improved during the childhood years and favor a training frequency of twice per week for children participating in an introductory strength training program In brief : Fifty-three male high school students aged 13 to 18 participated in a leg strength study to determine whether variable resistance ( isotonic ) or accommodative resistance ( isokinetic ) training was superior in developing leg muscle strength , endurance , and performance . Subjects were r and omly assigned to three experimental groups : one that trained on isotonic equipment , one on modified isokinetic equipment , and a control group . The results suggest that training equipment can be used to increase strength , muscular endurance , and performance . However , there appears to be no clear superiority of one type of equipment over another when using the same training method This study examined the effect of 12 weeks of medicine ball training on high school baseball players . Forty-nine baseball players ( age 15.4 ± 1.2 years ) were r and omly assigned using a stratified sampling technique to 1 of 2 groups . Group 1 ( n = 24 ) and group 2 ( n = 25 ) performed the same full-body resistance exercises according to a stepwise periodized model and took 100 bat swings a day , 3 days per week , with their normal game bat for 12 weeks . Group 2 performed additional rotational and full-body medicine ball exercises 3 days per week for 12 weeks . Pre- and post-testing consisted of a 3 repetition maximum ( RM ) dominant and nondominant torso rotational strength and sequential hip-torso-arm rotational strength ( medicine ball hitter 's throw ) . A 3RM parallel squat and bench press were measured at 0 and after 4 , 8 , and 12 weeks of training . Although both groups made statistically significant increases ( p > 0.05 ) in dominant ( 10.5 vs. 17.1 % ) and nondominant ( 10.2 vs. 18.3 % ) torso rotational strength and the medicine ball hitter 's throw ( 3.0 vs. 10.6 % ) , group 2 showed significantly greater increases in all 3 variables than group 1 . Furthermore , both groups made significant increases in predicted 1RM parallel squat and bench press after 4 , 8 , and 12 weeks of training ; however , there were no differences between groups . These data indicate that performing a 12-week medicine ball training program in addition to a stepwise periodized resistance training program with bat swings provided greater sport-specific training improvements in torso rotational and sequential hip-torso-arm rotational strength for high school baseball players Abstract Klusemann , MJ , Pyne , DB , Fay , T , and Drinkwater , EJ . Online Video – Based Resistance Training Improves the Physical Capacity of Junior Basketball Athletes . J Strength Cond Res 26(10 ) : 2677–2684 , 2012—Junior basketball athletes require a well- design ed resistance training program to improve their physical development . Lack of expert supervision and resistance training in junior development pathways may be overcome by implementing an online video – based program . The aim of this study was to compare the magnitude of improvement ( change ) in physical performance and strength and functional movement patterns of junior basketball athletes using either a fully supervised or an online video – based resistance training program . Thirty-eight junior basketball athletes ( males , n = 17 ; age , 14 ± 1 year ; height , 1.79 ± 0.10 m ; mass , 67 ± 12 kg ; females , n = 21 ; age , 15 ± 1 year ; height , 1.70 ± 0.07 m ; mass , 62 ± 8 kg ) were r and omly assigned into a supervised resistance training group ( SG , n = 13 ) , video training group ( VG , n = 13 ) or control group ( CG , n = 12 ) and participated in a 6-week controlled experimental trial . Pre- and posttesting included measures of physical performance ( 20-m sprint , step-in vertical jump , agility , sit and reach , line drill , and Yo-Yo intermittent recovery level 1 ) , strength ( 15 s push-up and pull-up ) , and functional movement screening ( FMS ) . Both SG and VG achieved 3–5 % ± 2–4 % ( mean ± 90 % confidence limits ) greater improvements in several physical performance measures ( vertical jump height , 20-m sprint time , and Yo-Yo endurance performance ) and a 28 ± 21 % greater improvement in push-up strength compared with the CG . The SG attained substantially larger gains in FMS scores over both the VG ( 12 ± 10 % ) and CG ( 13 ± 8 % ) . Video-based training appears to be a viable option to improve physical performance and strength in junior basketball athletes . Qualified supervision is recommended to improve functional movement patterns in junior athletes The purpose of this study was to compare symptoms of exercise-induced muscle damage after an initial and repeated bout of plyometric exercise in men and boys . Ten boys ( 9 - 10 yr ) and 10 men ( 20 - 29 yr ) completed two bouts of eight sets of 10 plyometric jumps , 2 wk apart . Perceived soreness ( 0 - 10 , visual analog scale ) , isometric strength of the quadriceps at six knee flexion angles , and countermovement jump and squat jump height were assessed before and at 30 min , 24 h , 48 h , and 72 h after each bout . All variables followed the expected patterns of change in men , with soreness peaking at 24 - 48 h ( 5.8 + /- 1.7 ) and decrements in muscle function peaking at 30 min after the first bout ( 73 - 85 % of baseline scores ) . Symptoms remained for 72 h after the first bout in men . In boys , symptoms were much less severe and peaked at 30 min ( visual analog scale = 2.1 + /- 1.8 , functional decrements 87 - 92 % of baseline ) and , with the exception of soreness , returned to baseline after 24 h. After the second bout of plyometric exercise , the level of soreness and decrements in countermovement jump , squat jump , and isometric strength were lower , although the effect was stronger in men , in all cases . The results of this study suggest that although children may experience symptoms of muscle damage after intensive plyometric exercise , they are much less severe . A prior bout of plyometric exercise also appears to provide children with some protection from soreness after a subsequent bout of plyometric exercise . Explanations for milder symptoms of exercise-induced muscle damage in children include greater flexibility leading to less overextension of sarcomeres during eccentric exercise , fewer fast-twitch muscle fibers , and greater and perhaps more varied habitual physical activity patterns Abstract Moraes , E , Fleck , SJ , Dias , MR , and Simão , R. Effects on strength , power , and flexibility in adolescents of nonperiodized vs. daily nonlinear periodized weight training . J Strength Cond Res 27(12 ) : 3310–3321 , 2013—The aim of this study was to compare 2 models of resistance training ( RT ) programs , nonperiodized ( NP ) training and daily nonlinear periodized ( DNLP ) training , on strength , power , and flexibility in untrained adolescents . Thirty-eight untrained male adolescents were r and omly assigned to 1 of 3 groups : a control group , NP RT program , and DNLP program . The subjects were tested pretraining and after 4 , 8 , and 12 weeks for 1 repetition maximum ( 1RM ) resistances in the bench press and 45 ° leg press , sit and reach test , countermovement vertical jump ( CMVJ ) , and st and ing long jump ( SLJ ) . Both training groups performed the same sequence of exercises 3 times a week for a total of 36 sessions . The NP RT consisted of 3 sets of 10–12RM throughout the training period . The DNLP training consisted of 3 sets using different training intensities for each of the 3 training sessions per week . The total volume of the training programs was not significantly different . Both the NP and DNLP groups exhibited a significant increase in the 1RM for the bench press and 45 ° leg press posttraining compared with that pretraining , but there were no significant differences between groups ( p ⩽ 0.05 ) . The DNLP group ’s 1RM changes showed greater percentage improvements and effect sizes . Training intensity for the bench press and 45 ° leg press did not significantly change during the training . In the CMVJ and SLJ tests , NP and DNLP training showed no significant change . The DNLP group showed a significant increase in the sit and reach test after 8 and 12 weeks of training compared with pretraining ; this did not occur with NP training . In summary , in untrained adolescents during a 12-week training period , a DNLP program can be used to elicit similar and possible superior maximal strength and flexibility gains compared with an NP multiset training model PURPOSE To examine the effects of a novel isoinertial eccentric-overload and vibration training ( EVT ) paradigm on change-of-direction ( COD ) speed and multiple performance tests applicable to soccer . METHODS Twenty-four young male players were assigned to an EVT ( n = 12 ) or conventional combined ( CONV , n = 12 ) group , once weekly for 11 wk . EVT consisted of 2 sets of 6 - 10 repetitions in 5 specific and 3 complementary exercises . CONV used comparable volume ( 2 sets of 6 - 10 reps in 3 sequences of 3 exercises ) of conventional combined weight , plyometric , and linear speed exercises . Pre- and postintervention tests included 25-m sprint with 4 × 45 ° COD every 5th m ( V-cut test ) , 10- and 30-m sprints , repeat-sprint ability , countermovement jump , and hopping ( RJ5 ) . RESULTS Group comparison showed very likely to likely better performance for EVT in the COD ( effect size [ ES ] = 1.42 ) , 30-m ( ES = 0.98 ) , 10-m ( ES = 1.17 ) , and average power ( ES = 0.69 ) and jump height ( ES = 0.69 ) during RJ5 . There was a large ( r = -.55 ) relationship between the increase in average hopping power and the reduced V-cut time . CONCLUSIONS As EVT , not CONV , improved not only COD ability but also linear speed and reactive jumping , this " proof-of-principle " study suggests that this novel exercise paradigm performed once weekly could serve as a viable adjunct to improve performance tasks specific to soccer OBJECTIVES Previous studies examining the reliability of self-reported Tanner stages have given conflicting results . We report on the reliability of self-reported Tanner stages in lean healthy children . METHODS Self-reported Tanner staging of 240 children ( 130 girls , 110 boys ) were compared to the ratings of a pediatric endocrinologist who was unaware of the children 's self- assessment s. The correlation between the two approaches was analyzed using kappa statistics . RESULTS 40 % ( kappa coeffcient = 0.49 , p < 0.001 ) and 23 % ( kappa coefficient = 0.68 , p < 0.001 ) of the girls rated their breast and pubic Tanner stage incorrectly , respectively ; 39 % of the boys ( kappa coefficient = 0.49 , p < 0.001 ) rated their pubic stage incorrectly . The age of the children who self-rated correctly and incorrectly was not different ; no independent predictors for correct Tanner staging self- assessment were found . CONCLUSIONS The results of this analysis suggest that self-rated Tanner pubertal staging is not influenced by age and is not a reliable method of assessing Tanner stage The purpose of this study was to examine the effects of 3 resistance training volumes on maximal strength in the snatch ( Sn ) , clean & jerk ( C&J ) , and squat ( Sq ) exercises during a 10-week training period . Fifty-one experienced ( .3 years ) , trained junior lifters were r and omly assigned to one of 3 groups : a low-volume group ( LVG , n = 16 ) , a moderate-volume group ( MVG , n = 17 ) , and a high-volume group ( HVG , n = 18 ) . All subjects trained 4–5 days a week with a periodized routine using the same exercises and relative intensities but a different total number of sets and repetitions at each relative load : LVG ( 1,923 repetitions ) , MVG ( 2,481 repetitions ) , and HVG ( 3,030 repetitions ) . The training was periodized from moderate intensity ( 60–80 % of 1 repetition maximum [ 1RM ] ) and high number of repetitions per set ( 2–6 ) to high intensity ( 90–100 % of 1RM ) and low number of repetitions per set ( 1–3 ) . During the training period , the MVG showed a significant increase for the Sn , C&J , and Sq exercises ( 6.1 , 3.7 , and 4.2 % , respectively , p < 0.01 ) , whereas in the LVG and HVG , the increase took place only with the C&J exercise ( 3.7 and 3 % , respectively , p < 0.05 ) and the Sq exercise ( 4.6 % , p < 0.05 , and 4.8 % , p < 0.01 , respectively ) . The increase in the Sn exercise for the MVG was significantly higher than in the LVG ( p = 0.015 ) . Calculation of effect sizes showed higher strength gains in the MVG than in the HVG or LVG . There were no significant differences between the LVG and HVG training volume-induced strength gains . The present results indicate that junior experienced lifters can optimize performance by exercising with only 85 % or less of the maximal volume that they can tolerate . These observations may have important practical relevance for the optimal design of strength training programs for resistance-trained athletes , since we have shown that performing at a moderate volume is more effective and efficient than performing at a higher volume Jumping is an important performance component of many sporting activities . A number of training modalities have been used to enhance jumping performance including plyometrics . The positive effects of plyometric training on jumping performance are a function of the stretch-shortening cycle phenomenon . However , there has been little research on the effects of the surface on jumping performance . This study examined the effects of performing 2 different plyometric exercises , depth jump ( DJ ) and counter movement jump ( CMJ ) , on noncompliant ( ground ) and compliant ( mini-trampoline ) surfaces . Male participants ( N = 20 ; age = 21.8 ± 3.8 years ; height = 184.6 ± 7.6 cm ; mass = 83.6 ± 8.2 kg ) r and omly performed 10 CMJ and 10 DJ on compliant and noncompliant surfaces . Kinematic data were determined via 2-dimensional high-speed video . There were significant ( p < 0.05 ) differences in DJ and CMJ joint and segment range of movement for ankle , knee , hip and trunk , indicating less crouch when the participants performed plyometric exercises on the compliant surface The aim of the study was to compare the effects of plyometric training using 30 , 60 , or 120 s of rest between sets on explosive adaptations in young soccer players . Four groups of athletes ( age 10.4 ± 2.3 y ; soccer experience 3.3 ± 1.5 y ) were r and omly formed : control ( CG ; n = 15 ) , plyometric training with 30 s ( G30 ; n = 13 ) , 60 s ( G60 ; n = 14 ) , and 120 s ( G120 ; n = 12 ) of rest between training sets . Before and after intervention players were measured in jump ability , 20-m sprint time , change of direction speed ( CODS ) , and kicking performance . The training program was applied during 7 weeks , 2 sessions per week , for a total of 840 jumps . After intervention the G30 , G60 and G120 groups showed a significant ( p = 0.0001 - 0.04 ) and small to moderate effect size ( ES ) improvement in the countermovement jump ( ES = 0.49 ; 0.58 ; 0.55 ) , 20 cm drop jump reactive strength index ( ES = 0.81 ; 0.89 ; 0.86 ) , CODS ( ES = -1.03 ; -0.87 ; -1.04 ) , and kicking performance ( ES = 0.39 ; 0.49 ; 0.43 ) , with no differences between treatments . The study shows that 30 , 60 , and 120 s of rest between sets ensure similar significant and small to moderate ES improvement in jump , CODS , and kicking performance during high-intensity short-term explosive training in young male soccer players . Key pointsReplacing some soccer drills by low volume high-intensity plyometric training would be beneficial in jumping , change of direction speed , and kicking ability in young soccer players . A rest period of 30 , 60 or 120 seconds between low-volume high-intensity plyometric sets would induce significant and similar explosive adaptations during a short-term training period in young soccer players . Data from this research can be helpful for soccer trainers in choosing efficient drills and characteristics of between sets recovery programs to enhance performances in young male soccer players This study examined the effects of 4 different resistance training protocol s on upper-body strength and local muscle endurance development in children . Untrained boys and girls ( mean ± SD age , 8.1 ± 1.6 years ) trained twice per week for 8 weeks using child-sized weight machines and medicine balls weighing 1–2.5 kg . In addition to general conditioning exercises , subjects in each exercise group performed 1 set of the following exercise protocol s for upperbody conditioning : 6–8 repetitions with a heavy load on the chest press exercise ( HL , n = 15 ) ; 13–15 repetitions with a moderate load on the chest press exercise ( ML , n = 16 ) ; 6–8 repetitions with a heavy load on the chest press exercise immediately followed by 6–8 medicine ball chest passes ( CX , n = 12 ) ; or 13–15 medicine ball chest passes ( MB , n = 11 ) . Twelve children served as nontraining controls ( CT ) . After training , only the ML and CX groups demonstrated significant ( p < 0.05 ) improvements in 1RM chest press strength ( 16.8 % and 16.3 % , respectively ) as compared with the CT group . Local muscle endurance , as determined by the number of repetitions performed posttraining on the chest press exercise with the pretraining 1RM load , significantly increased in the ML group ( 5.9 ± 3.2 repetitions ) and CX group ( 5.2 ± 3.6 repetitions ) as compared with the CT group . In terms of enhancing the upper-body strength and local muscle endurance of untrained children , these findings favor the prescription of higher-repetition training protocol s during the nitial adaptation period PURPOSE The purpose of this intervention study was to investigate if a low-dose of plyometric training ( PT ) could improve sprint and jump performance in groups of different maturity status . METHOD Male youth field hockey players were divided into Pre-PHV ( from -1 to -1.9 from PHV ; Experimental : n = 9 ; Control = 12 ) and Mid-PHV ( 0 to + 0.9 from PHV ; Experimental : n = 8 ; Control = 9 ) groups . Participants in the experimental groups completed 60 foot contacts , twice-weekly for 6 weeks . RESULTS PT exerted a positive effect ( effect size : 0.4 [ -0.4 - 1.2 ] ) on 10 m sprint time in the experimental Mid-PHV group but this was less pronounced in the Pre-PHV group ( 0.1 [ -0.6 - 0.9 ] ) . Sprint time over 30 m ( Mid-PHV : 0.1 [ -0.8 - 0.9 ] ; Pre-PHV : 0.1 [ -0.7 - 0.9 ] ) and CMJ ( Mid-PHV : 0.1 [ -0.8 - 0.9 ] ; Pre-PHV : 0.0 [ -0.7 - 0.8 ] ) was maintained across both experimental groups . Conversely , the control groups showed decreased performance in most tests at follow up . Between-group analysis showed positive effect sizes across all performance tests in the Mid-PHV group , contrasting with all negative effect sizes in the Pre-PHV group . CONCLUSION These results indicate that more mature hockey players may benefit to a greater extent than less mature hockey players from a low-dose PT stimulus . Sixty foot contacts , twice per week , seems effective in improving short sprint performance in Mid-PHV hockey players Abstract Lloyd , RS , Radnor , JM , De Ste Croix , MBA , Cronin , JB , and Oliver , JL . Changes in sprint and jump performances after traditional , plyometric , and combined resistance training in male youth pre- and post-peak height velocity . J Strength Cond Res 30(5 ) : 1239–1247 , 2016—The purpose of this study was to compare the effectiveness of 6-week training interventions using different modes of resistance ( traditional strength , plyometric , and combined training ) on sprinting and jumping performances in boys before and after peak height velocity ( PHV ) . Eighty school-aged boys were categorized into 2 maturity groups ( pre- or post-PHV ) and then r and omly assigned to ( a ) plyometric training , ( b ) traditional strength training , ( c ) combined training , or ( d ) a control group . Experimental groups participated in twice-weekly training programs for 6 weeks . Acceleration , maximal running velocity , squat jump height , and reactive strength index data were collected pre- and postintervention . All training groups made significant gains in measures of sprinting and jumping irrespective of the mode of resistance training and maturity . Plyometric training elicited the greatest gains across all performance variables in pre-PHV children , whereas combined training was the most effective in eliciting change in all performance variables for the post-PHV cohort . Statistical analysis indicated that plyometric training produced greater changes in squat jump and acceleration performances in the pre-PHV group compared with the post-PHV cohort . All other training responses between pre- and post-PHV cohorts were not significant and not clinical ly meaningful . The study indicates that plyometric training might be more effective in eliciting short-term gains in jumping and sprinting in boys who are pre-PHV , whereas those who are post-PHV may benefit from the additive stimulus of combined training Abstract Moran , J , S and ercock , GRH , Ramírez-Campillo , R , Wooller , J-J , Logothetis , S , Schoenmakers , PPJM , and Parry , DA . Maturation-related differences in adaptations to resistance training in young male swimmers . J Strength Cond Res 32(1 ) : 139–149 , 2018—This study examined the effects of resistance training on muscular strength and jump performances in young male swimmers . It was hypothesized that adaptations would be of a lower magnitude in less mature ( prepeak height velocity [ PHV ] ) than in more mature ( post-PHV ) subjects . Fourteen pre-PHV ( −1.8 ± 1.0 years ) and 8 post-PHV ( 1.6 ± 0.5 years ) swimmers undertook a 30 minutes , twice-weekly resistance training program for 8 weeks . They were compared with matched control groups ( pre-PHV : −2.0 ± 1.1 , n = 15 ; post-PHV : 1.2 ± 1.0 , n = 7 ) . The effects on lower-body isometric strength ( LBS ) , measured with midthigh pull , and vertical jump ( VJ ) height in the post-PHV group were large ( effect size : 1.3 [ 0.4 to 2.2 ] ) and small ( 0.4 [ −0.4 to 1.2 ] ) , respectively . Effects on LBS and VJ height in the pre-PHV group were moderate ( 0.8 [ 0.1 to 1.4 ] ) and trivial ( 0.2 [ −0.5 to 0.8 ] ) , respectively . Estimates in the post-PHV control group ( LBS : 0.7 [ −0.2 to 1.6 ] ; VJ : 0.2 [ −0.7 to 1.0 ] ) and the pre-PHV control group ( LBS : 0.1 [ −0.5 to 0.7 ] ; VJ : −0.3 [ −0.9 to 0.3 ] ) may indicate the extent to which maturation could contribute to the performance changes seen in the respective training groups . Lower-body isometric strength and VJ are trainable , but to different magnitudes , in pre- and post-PHV swimmers . After appropriate foundational training to establish technical competency , twice-weekly resistance training sessions of 30 minutes duration , comprising 3 sets of 4 exercises can be effective in pre- and post-PHV youth Abstract Chaouachi , A , Othman , AB , Hammami , R , Drinkwater , EJ , and Behm , DG . The combination of plyometric and balance training improves sprint and shuttle run performances more often than plyometric-only training with children . J Strength Cond Res 28(2 ) : 401–412 , 2014—Because balance is not fully developed in children and studies have shown functional improvements with balance only training studies , a combination of plyometric and balance activities might enhance static balance , dynamic balance , and power . The objective of this study was to compare the effectiveness of plyometric only ( PLYO ) with balance and plyometric ( COMBINED ) training on balance and power measures in children . Before and after an 8-week training period , testing assessed lower-body strength ( 1 repetition maximum leg press ) , power ( horizontal and vertical jumps , triple hop for distance , reactive strength , and leg stiffness ) , running speed ( 10-m and 30-m sprint ) , static and dynamic balance ( St and ing Stork Test and Star Excursion Balance Test ) , and agility ( shuttle run ) . Subjects were r and omly divided into 2 training groups ( PLYO [ n = 14 ] and COMBINED [ n = 14 ] ) and a control group ( n = 12 ) . Results based on magnitude-based inferences and precision of estimation indicated that the COMBINED training group was considered likely to be superior to the PLYO group in leg stiffness ( d = 0.69 , 91 % likely ) , 10-m sprint ( d = 0.57 , 84 % likely ) , and shuttle run ( d = 0.52 , 80 % likely ) . The difference between the groups was unclear in 8 of the 11 dependent variables . COMBINED training enhanced activities such as 10-m sprints and shuttle runs to a greater degree . COMBINED training could be an important consideration for reducing the high velocity impacts of PLYO training . This reduction in stretch-shortening cycle stress on neuromuscular system with the replacement of balance and l and ing exercises might help to alleviate the overtraining effects of excessive repetitive high load activities |
13,280 | 30,776,418 | Results Our pooled meta‐analyses showed that nonsedating second‐generation H1‐antihistamines ( nsAHs ) are effective in the treatment of ColdU and that updosing of nsAHs significantly reduced CTTs relative to their own st and ard doses and placebos .
Omalizumab result ed in a marked reduction of CTTs in H1‐antihistamine – resistant patients .
Of 118 adverse events in 8 studies , st and ard‐dose nsAHs , updosed nsAHs , and omalizumab produced lower numbers of adverse events than first‐generation antihistamines .
Conclusions Our study showed that greater dosages of nsAHs were more effective than st and ard dosages in controlling ColdU symptoms .
Increasing the dosages was not significantly associated with higher adverse event rates .
Omalizumab at 150 and 300 mg every 4 weeks was shown to be effective for patients with ColdU refractory to antihistamines | Background Several treatment options for cold urticaria ( ColdU ) have been studied and reported , but systematic review s and meta‐analyses are limited .
Objectives We sought to meta‐analyze and review the efficacy and safety of ColdU treatments . | BACKGROUND Treatment of primary acquired cold urticaria ( CU ) is quite difficult because of variable clinical effectiveness and side effects of classic antihistamines . OBJECTIVE The objective of the study was to assess the efficacy and safety of mizolastine , an antihistaminic with antiallergic properties , versus placebo in primary acquired CU . METHODS This study was a phase II , multicenter , r and omized , double-blind , crossover , placebo-controlled study of mizolastine ( 10 mg , once daily ) versus placebo in 28 patients with primary acquired CU . Efficacy was measured by the cold-stimulation time test , the wheal response , and pruritus intensity after an ice-cube test . RESULTS Mizolastine delayed the cold-induced wheal reaction , reduced wheal response at 3 and 10 minutes , and reduced pruritus intensity . Statistically significant differences were observed versus placebo for the cold-stimulation time test , wheal response at 3 and 10 minutes , and pruritus intensity ( P = .006,.015,.009 , and .005 , respectively ) . No clinical ly relevant adverse events were reported . CONCLUSIONS Mizolastine ( 10 mg , once daily ) was shown to be superior to placebo for both delaying and reducing the cold-induced wheal reaction without significant adverse events . Results suggest that mizolastine may be effective in the treatment of CU BACKGROUND Patients with acquired cold urticaria ( ACU ) show itchy wheals during cold exposure . This disturbing condition involves histamine and platelet-activating factor in its pathogenesis . Rupatadine is a dual antagonist of both histamine and platelet-activating factor . OBJECTIVE To assess rupatadine efficacy in preventing reactions to cold challenge in patients with ACU . METHODS A crossover , r and omized , double-blind , placebo-controlled study in which 21 patients with ACU received rupatadine , 20 mg/d , or placebo for 1 week each is presented . The main outcome was the critical stimulation time threshold ( CSTT ) determined by ice cube challenge . Secondary outcomes included CSTT and the critical temperature threshold assessed by a cold provocation device ( TempTest 3.0 ) , as well as scores for wheal reactions , pruritus , burning sensations , and subjective complaints after cold challenge . RESULTS After rupatadine treatment , 11 ( 52 % ) of 21 patients exhibited a complete response ( ie , no urticaria lesions after ice cube provocation ) . A significant improvement in CSTT compared with placebo was observed after ice cube and TempTest 3.0 challenge ( P = .03 and P = .004 , respectively ) . A significant reduction of critical temperature threshold ( P < .001 ) and reduced scores for cold provocation-induced wheal reactions ( P = .01 ) , pruritus ( P = .005 ) , burning sensation ( P = .03 ) , and subjective complaints ( P = .03 ) after rupatadine treatment were also found . Mild fatigue ( n = 4 ) , somnolence ( n = 1 ) , and moderate headache ( n = 1 ) were reported during active treatment . CONCLUSION Rupatadine , 20 mg/d , shows high efficacy and is well tolerated in the treatment of ACU symptoms The efficacy of the new nonsedating antihistamines loratadine and cetirizine was compared in a r and omized , single-blind , crossover , controlled study with that of the classical antihistamines cyproheptadine and ketotifen in seven patients with primary acquired cold urticaria ( ACU ) . The patients received each of the four drugs for 14 consecutive days with a 7-day interval between drugs . We evaluated clinical symptomatology , adverse effects , minimum time of cold contact stimulation required to induce an immediate coalescent wheal ( CSTT ) , and inhibition of histamine-induced wheal response . Both loratadine and cetirizine showed suppression of symptoms with infrequent adverse effects . Important side-effects were observed in patients receiving cyproheptadine . Improvement in CSTT was statistically significant for all drugs compared with baseline values , without differences among them . The histamine-induced skin test was significantly inhibited by all antihistamines . Wheal reductions were 34.6 % for loratadine and 50.9 % for cetirizine . This study suggests that both loratadine and cetirizine may be effective in the treatment of primary ACU A double-blind , crossover trial with a new triprolidine derivative , acrivastine ( BW 825C ; 8 mg 3 times daily ) , cyproheptadine ( 4 mg 3 times daily ) and placebo was carried out in 18 patients suffering from idiopathic cold urticaria . Acrivastine and cyproheptadine significantly ( p less than 0.01 ) reduced weal areas following ice cube challenge when compared to placebo . Acrivastine was found to be significantly more effective ( p less than 0.01 ) than cyproheptadine in reducing weal areas . Furthermore , cyproheptadine caused significantly more drowsiness than acrivastine ( p = 0.021 ) or placebo ( p = 0.013 ) , which did not differ from each other . This study shows that acrivastine is an effective agent in the treatment of cold urticaria and suggests that acrivastine in the dose used lacks adverse effects , such as drowsiness , traditionally associated with antihistamine therapy Eleven patients with primary acquired cold-induced urticaria were treated with ketotifen ( 1 mg b.i.d . ) or placebo in a double-blind , crossover design trial . After seven days of ketotifen treatment , reaction times to a cold stimulus were significantly delayed in ten of the 11 subjects . No effect was seen after placebo treatment . It is concluded that ketotifen may have a place in the treatment of primary acquired cold urticaria The study was performed in 6 Thai children with primary acquired cold urticaria . They all suffered from generalized urticaria and two of them also had angioedema . All of them had normal erythrocyte sedimentation rate , complement 3 and negative VDRL , TPHA , hepatitis B screen and cold agglutinin titer . Cryoglobulin was checked in 3 cases and showed negative results A double-blind cross-over study to compare the effectiveness of cyproheptadine and ketotifen demonstrated that the efficacy of cyproheptadine and ketotifen on clinical symptoms and ice cube test was not significantly different ( p > 0.05 ) . Both of them showed good results in the treatment of cold urticaria with mild side effects . During the follow up , 5 cases showed complete recovery while the other one developed one or two exacerbations per year upon cold exposure . However , the symptoms were mild and subsided on administration of one or two doses of H1 antihistamine . Our data demonstrated that ketotifen was as effective as cyproheptadine in the treatment of cold urticaria in Thai children BACKGROUND Proof-of-concept studies with omalizumab in patients with chronic idiopathic urticaria ( CIU ) have shown significant decreases in mean urticaria activity scores ( UASs ) . OBJECTIVE We sought to evaluate the efficacy and safety of omalizumab in patients with CIU who remain symptomatic despite concomitant H(1)-antihistamine therapy . METHODS This phase II , prospect i ve , double-blind , placebo-controlled , dose-ranging study investigated omalizumab in patients aged 12 to 75 years in the United States and 18 to 75 years in Germany with a UAS over 7 days ( UAS7 ) of 12 or greater despite antihistamine therapy . Patients were r and omized 1:1:1:1 to receive a single subcutaneous dose of 75 , 300 , or 600 mg of omalizumab or placebo added to a stable dose of H(1)-antihistamine . The primary efficacy outcome was change from baseline to week 4 in UAS7 . Patients were followed for an additional 12 weeks to monitor safety . RESULTS Ninety patients from the United States or Germany were enrolled . Both the 300-mg omalizumab group ( -19.9 vs -6.9 , P < .001 ) and the 600-mg omalizumab group ( -14.6 vs -6.9 , P = .047 ) showed greater improvement versus the placebo group in UAS7 . No meaningful difference was observed for the 75-mg omalizumab group . Similar results were seen for key secondary end points of weekly hive and itch scores . Onset of effect occurred after 1 to 2 weeks . Omalizumab was well tolerated , and the incidence of adverse events was similar across treatment groups . CONCLUSION This study demonstrated that a fixed dose of 300 or 600 mg of omalizumab provides rapid and effective treatment of CIU in patients who are symptomatic despite treatment with H(1)-antihistamines Eight subjects with primary -acquired cold urticaria were treated with chlorpheniramine maleate , cyproheptadine hydrochloride , and placebo in a double-blind clinical trial . During three separate seven-day treatment periods , each patient took 4 mg of either active drug or lactose placebo three times a day . Objective measurements were made at the beginning and end of each treatment period by establishing the minimum time ( MT ) of cold stimulus application required to provoke urtication . In addition , the spontaneous appearance of cold urticaria lesions was recorded during each treatment period . The MT required for induction of urtication with a cold stimulus was significantly greater for eight patients receiving cyproheptadine as compared to chlorpheniramine or placebo ( P less than .01 ) . The study demonstrated that cyproheptadine had a significant suppressive action on experimental cold-induced urticaria , while placebo and chlorpheniramine proved ineffective Chronic cold urticaria ( ColdU ) is a rare disease characterized by mast cell-mediated wheals and angioedema following cold exposure . Second-generation H1-antihistamines , such as rupatadine , are the recommended first-line therapy . As of yet , the effects of rupatadine up-dosing on development of ColdU symptom have only been partially characterized . Two-centre , r and omized , double-blind , 3-way crossover , placebo-controlled study in patients with a confirmed ColdU was design ed to assess the effects of up-dosing of rupatadine . A total of 23 patients were r and omized to receive placebo , rupatadine 20 mg/day , and rupatadine 40 mg/day for 1 week . The primary outcome was change in critical temperature thresholds and critical stimulation time thresholds after treatment . Secondary endpoints included assessment of safety and tolerability of rupatadine . Both 20 and 40 mg rupatadine were highly effective in reducing critical temperature thresholds ( p < 0.001 ) and critical stimulation time thresholds ( p < 0.001 ) . In conclusion , rupatadine 20 and 40 mg significantly reduced the development of chronic cold urticaria symptom without an increase in adverse effects BACKGROUND Increased dosing of nonsedating antihistamines is recommended by the current European Academy of Allergology and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum guidelines on patients with acquired cold urticaria ( ACU ) who do not respond satisfactorily to the st and ard dose . Prospect i ve data supporting this recommendation are scant . OBJECTIVE We sought to assess the effects of 5 and 20 mg of desloratadine and placebo on cold-induced urticarial reactions in patients with ACU . METHODS In this prospect i ve , r and omized , double-blind , 3-way crossover trial , patients with ACU ( n = 30 ) received placebo , 5 mg of desloratadine , and 20 mg of desloratadine every day each for 7 days separated by 14-day washout periods . At the end of each treatment , patients underwent cold provocation with the TempTest 2.0/2.1 system , and urticarial reactions were assessed by using digital 3-dimensional time-lapse photography and thermography ; the critical temperature threshold ( CTT ) and critical stimulation time threshold ( CSTT ) were measured . Adverse events ( AEs ) reported during the study were assessed . RESULTS Compared with placebo , 7 days of desloratadine at 5 and 20 mg/d significantly reduced the volume of cold-induced wheals and areas of hyperthermic skin and improved CTT and CSTT results . Desloratadine at 20 mg/d significantly reduced cold-induced wheal volume and CTT and CSTT values versus desloratadine at 5 mg/d . Desloratadine was well tolerated , with no increased rate of somnolence or other AEs with 20 mg of desloratadine . CONCLUSIONS Desloratadine at st and ard and high doses significantly improved objective signs of ACU provoked by cold exposure . Desloratadine at 4 times the st and ard dose significantly reduced ACU lesion severity versus 5 mg of desloratadine without an increase in AEs . This study supports current guidelines that increased desloratadine dosing might benefit patients with urticaria who do not respond to st and ard doses Background : Omalizumab , a recombinant anti‐IgE antibody , effectively treats chronic spontaneous urticaria . Evidence is lacking in patients with chronic inducible urticarias ( CIndUs ) , which are frequently H1‐antihistamine resistant . Objective : From the current published literature , we aim ed to determine the strength of evidence for omalizumab efficacy and safety in the treatment of CIndUs . Methods : We performed a PubMed search to identify evidence on omalizumab use in the following 9 CIndU subtypes : symptomatic dermographism , cold urticaria , delayed‐pressure urticaria , solar urticaria , heat urticaria , vibratory angioedema , cholinergic urticaria , contact urticaria , and aquagenic urticaria . Results : Forty‐three trials , case studies , case reports , and analyses were identified . Our review indicates that omalizumab has substantial benefits in patients with various CIndUs . The evidence is strongest for symptomatic dermographism , cold urticaria , and solar urticaria . Little/no evidence was available on vibratory angioedema and aquagenic and contact urticaria . Our review supports rapid onset of action demonstrated through early symptom control in most cases , sometimes within 24 hours . Many patients gained complete/partial symptom relief and substantially improved quality of life . Adverse events were generally low , with omalizumab being well tolerated by most patients , including children . Conclusions : A strong body of evidence supports the use of omalizumab in the treatment of patients with therapy‐refractory CIndU. More data from r and omized controlled studies are warranted BACKGROUND Many patients with chronic idiopathic urticaria ( also called chronic spontaneous urticaria ) do not have a response to therapy with H-antihistamines , even at high doses . In phase 2 trials , omalizumab , an anti-IgE monoclonal antibody [ corrected ] that targets IgE and affects mast-cell and basophil function , has shown efficacy in such patients . METHODS In this phase 3 , multicenter , r and omized , double-blind study , we evaluated the efficacy and safety of omalizumab in patients with moderate-to-severe chronic idiopathic urticaria who remained symptomatic despite H-antihistamine therapy ( licensed doses ) . We r and omly assigned 323 patients to receive three subcutaneous injections , spaced 4 weeks apart , of omalizumab at doses of 75 mg , 150 mg , or 300 mg or placebo , followed by a 16-week observation period . The primary efficacy outcome was the change from baseline in a weekly itch-severity score ( ranging from 0 to 21 , with higher scores indicating more severe itching ) . RESULTS The baseline weekly itch-severity score was approximately 14 in all four study groups . At week 12 , the mean ( ±SD ) change from baseline in the weekly itch-severity score was -5.1±5.6 in the placebo group , -5.9±6.5 in the 75-mg group ( P=0.46 ) , -8.1±6.4 in the 150-mg group ( P=0.001 ) , and -9.8±6.0 in the 300-mg group ( P<0.001 ) . Most prespecified secondary outcomes at week 12 showed similar dose-dependent effects . The frequency of adverse events was similar across groups . The frequency of serious adverse events was low , although the rate was higher in the 300-mg group ( 6 % ) than in the placebo group ( 3 % ) or in either the 75-mg or 150-mg group ( 1 % for each ) . CONCLUSIONS Omalizumab diminished clinical symptoms and signs of chronic idiopathic urticaria in patients who had remained symptomatic despite the use of approved doses of H-antihistamines . ( Funded by Genentech and Novartis Pharma ; Clinical Trials.gov number , NCT01292473 . ) |
13,281 | 31,361,320 | No association was observed with stroke incidence and heart failure .
This systematic review and meta- analysis revealed a beneficial role of nut consumption in reducing the incidence of , and mortality from , different CVD outcomes | CONTEXT Previous meta-analyses evaluating the association between nut consumption and the risk of cardiovascular disease ( CVD ) had substantial method ological limitations and lacked recently published large prospect i ve studies ; hence , making an up date d meta- analysis highly desirable . | Background Atrial Fibrillation is highly prevalent in clinical practice affecting approximately 2.3 million people in USA and 4.5 million people in European Union . The aim of the study was to examine the association between nut consumption and incident atrial fibrillation . Methods Prospect i ve cohort of 21,054 male participants of Physicians ' Health Study I. Nut consumption was estimated using food frequency question naire and incident atrial fibrillation was ascertained through yearly follow-up question naires . Cox regression was used to estimate relative risks of atrial fibrillation . Results The average age was 54.6 ± 9.5 years ( 40.7 - 87.1 ) . During a mean follow up of 20 years ( median 24 years ) , 3,317 cases of atrial fibrillation occurred . The crude incidence rate was 7.6 , 7.4 , 8.2 , 7.9 , and 6.8 cases/1000 person-years for people reporting nut consumption of rarely/never , 1 - 3/month , 1/per week , 2 - 6/week , and ≥ 7/week , respectively . Multivariable adjusted hazard ratios ( 95 % CI ) for incident atrial fibrillation were 1.00 ( ref ) , 1.00 ( 0.90 - 1.11 ) , 1.09 ( 0.97 - 1.21 ) , 1.07 ( 0.95 - 1.21 ) , and 0.91 ( 0.70 - 1.17 ) for nut consumption from the lowest to the highest category of nut consumption ( p for trend 0.26 ) . No statistically significant association between nut consumption and atrial fibrillation was found when stratified by body mass index ( BMI < 25 vs ≥ 25 kg/m2 ) or age ( < 65 vs. ≥ 65 years ) . Conclusions Our data did not show an association between nut consumption and incident atrial fibrillation among US male physicians BACKGROUND Heart failure is highly prevalent among older adults and is associated with high cost and societal burden . Although previous studies have reported beneficial effects of dietary factors on heart failure predictors , no previous study has examined whether frequent consumption of nuts is associated with a lower risk of heart failure in a large prospect i ve cohort . OBJECTIVE We examined the association between nut consumption and incident heart failure to determine whether such a relation is modified by overweight or obesity . DESIGN This was a prospect i ve cohort study of 20,976 participants from the Physicians ' Health Study I. Nut consumption was assessed with a simple abbreviated food question naire , and self-reported heart failure was ascertained by follow-up question naires . We used Cox regression to estimate relative risks of heart failure . RESULTS After an average follow-up of 19.6 y , 1,093 new cases of heart failure occurred . Nut consumption was not associated with the risk of developing heart failure in this cohort : multivariable adjusted hazard ratios were 1.0 ( reference ) , 0.98 ( 95 % CI : 0.83 , 1.15 ) , 1.06 ( 95 % CI : 0.89 , 1.27 ) , and 1.01 ( 95 % CI : 0.84 , 1.22 ) for nut consumption of < 1 , 1 , and > or = 2 servings/wk , respectively ( P for linear trend : 0.64 ) . The lack of a meaningful relation between nut intake and incident heart failure was seen in both lean and overweight or obese participants ( P for interaction : 0.96 ) . CONCLUSION Our data do not provide evidence for an association between nut consumption and incident heart failure in US male physicians . However , our data can not rule out possible benefits of nut consumption on subtypes of heart failure not prevalent in this cohort Background A number of prospect i ve studies have observed inverse associations between nut consumption and chronic diseases . However , these studies have predominantly been conducted in Western countries , where nut consumption tends to be more common among individuals with healthier lifestyles . It is important to examine the association in other parts of the world , and particularly among population s with different patterns of disease , socioeconomic status , lifestyles and disease risk factors . Our objective was to examine the association between nut consumption and mortality in a population whose nut consumption does not track with a healthy lifestyle . Methods We examined the association between nut consumption and all-cause and cause-specific mortality in the 50 045 participants of the Golestan Cohort Study . Participants were aged 40 and older at baseline in 2004 , and have been actively followed since that time . Dietary data were collected using a vali date d semi-quantitative food frequency question naire that was administered at baseline . Results During 349 677 person-years of follow-up , 3981 cohort participants died , including 1732 women and 2249 men . Nut consumption was associated inversely with all-cause mortality . The pooled multivariate adjusted hazard ratios for death among participants who ate nuts , as compared with those who did not , were 0.89 [ 95 % confidence interval ( CI ) , 0.82 - 0.95 ] for the consumption of less than one serving of nuts per week , 0.75 ( 95 % CI , 0.67 - 0.85 ) for one to less than three servings per week and 0.71 ( 95 % CI , 0.58 - 0.86 ) for three or more servings per week ( P < 0.001 for trend ) . Among specific causes , significant inverse associations were observed between nut consumption and deaths due to cardiovascular disease , all cancers and gastrointestinal cancers . Conclusions This study provides evidence for an inverse association between nut consumption and mortality in a developing country , where nut consumption does not track with a healthy lifestyle . Further work is needed to establish the underlying mechanisms responsible for this association Background Nut consumption has been found to be inversely associated with cardiovascular disease mortality , but the association between nut consumption and incidence of specific cardiovascular diseases is unclear . We examined the association between nut consumption and incidence of seven cardiovascular diseases . Methods This prospect i ve study included 61 364 Swedish adults who had completed a Food Frequency Question naire and were followed up for 17 years through linkage with the Swedish National Patient and Death Registers . Results Nut consumption was inversely associated with risk of myocardial infa rct ion , heart failure , atrial fibrillation and abdominal aortic aneurysm in the age-adjusted and sex-adjusted analysis . However , adjustment for multiple risk factors attenuated these associations and only a linear , dose – response , association with atrial fibrillation ( ptrend=0.004 ) and a non-linear association ( pnon-linearity=0.003 ) with heart failure remained . Compared with no consumption of nuts , the multivariable HRs ( 95 % CI ) of atrial fibrillation across categories of nut consumption were 0.97 ( 0.93 to 1.02 ) for 1–3 times/month , 0.88 ( 0.79 to 0.99 ) for 1–2 times/week and 0.82 ( 0.68 to 0.99 ) for ≥3 times/week . For heart failure , the corresponding HRs ( 95 % CI ) were 0.87 ( 0.80 to 0.94 ) , 0.80 ( 0.67 to 0.97 ) and 0.98 ( 0.76 to 1.27 ) . Nut consumption was not associated with risk of aortic valve stenosis , ischaemic stroke or intracerebral haemorrhage . Conclusions These findings suggest that nut consumption or factors associated with this nutritional behaviour may play a role in reducing the risk of atrial fibrillation and possibly heart failure . Trial registration number NCT01127711 and NCT01127698 ; Results BACKGROUND Prospect i ve studies evaluating associations between food intake and risk of heart failure ( HF ) in diverse population s are needed . OBJECTIVES Relationships between incident HF ( death or hospitalization ) and intake of seven food categories ( whole grains , fruits/vegetables , fish , nuts , high-fat dairy , eggs , red meat ) were investigated in an observational cohort of 14,153 African-American and white adults , age 45 to 64 years , sample d from four US communities . METHODS Between baseline ( 1987 - 1989 ) and Exam 3 ( 1993 - 1995 ) , dietary intake was based on responses to a 66-item food frequency question naire administered at baseline ; thereafter , intake was based on averaged baseline and Exam 3 responses . Hazard ratios ( HR [ 95 % CI ] ) for HF were calculated per 1-daily serving difference in food group intake . RESULTS During a mean of 13 years , 1,140 HF hospitalizations were identified . After multivariable adjustment ( energy intake , demographics , lifestyle factors , prevalent cardiovascular disease , diabetes , hypertension ) , HF risk was lower with greater whole-grain intake ( 0.93 [ 0.87 , 0.99 ] ) , but HF risk was higher with greater intake of eggs ( 1.23 [ 1.08 , 1.41 ] ) and high-fat dairy ( 1.08 [ 1.01 , 1.16 ] ) . These associations remained significant independent of intakes of the five other food categories , which were not associated with HF . CONCLUSIONS In this large , population -based sample of African-American and white adults , whole-grain intake was associated with lower HF risk , whereas intake of eggs and high-fat dairy were associated with greater HF risk after adjustment for several confounders Background / Objectives : There is still a need for scientific evidence about which foods characterize a healthy diet in terms of primary prevention of major chronic diseases . Therefore , we aim ed to give a comprehensive overview on health-related foods , based on 8 years of follow-up of the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Potsdam study .Subjects/ Methods : We used data from 23 531 participants of the EPIC-Potsdam study to analyse the associations between 45 single food groups and risk of major chronic diseases , namely , cardiovascular diseases ( CVD ) , type 2 diabetes and cancer using multivariable-adjusted Cox regression . Habitual dietary intake was assessed at baseline using food-frequency question naires . Incident chronic diseases were determined by self-administered follow-up question naires and medically verified , based on inquiry to treating physicians , cancer registries or through death certificates . Results : During follow-up , 363 incident CVD , 837 type 2 diabetes and 844 cancer cases were identified . Higher intakes of whole-grain bread , raw vegetables , coffee and cakes and cookies were found to be significantly associated with a lower risk of chronic diseases . Conversely , higher intakes of low-fat dairy , butter , red meat and sauce were associated with higher risks of chronic diseases . Conclusion : Overall , a healthy diet was characterized by a high consumption of whole-grain bread , raw vegetables and a low consumption of red meat and possibly butter , which is generally in line with previous findings . The paradoxical findings concerning the potential health benefit of coffee as well as cakes and cookies are interesting and should be investigated further Background Prospect i ve data examining the relationship between dietary protein intake and incident coronary heart disease ( CHD ) are inconclusive . Most evidence is derived from homogenous population s such as health professionals . Large community-based analyses in more diverse sample s are lacking . Methods We studied the association of protein type and major dietary protein sources and risk for incident CHD in 12,066 middle-aged adults ( aged 45–64 at baseline , 1987–1989 ) from four U.S. communities enrolled in the Atherosclerosis Risk in Communities ( ARIC ) Study who were free of diabetes mellitus and cardiovascular disease at baseline . Dietary protein intake was assessed at baseline and after 6 years of follow-up by food frequency question naire . Our primary outcome was adjudicated coronary heart disease events or deaths with following up through December 31 , 2010 . Cox proportional hazard models with multivariable adjustment were used for statistical analyses . Results During a median follow-up of 22 years , there were 1,147 CHD events . In multivariable analyses total , animal and vegetable protein were not associated with an increased risk for CHD before or after adjustment . In food group analyses of major dietary protein sources , protein intake from red and processed meat , dairy products , fish , nuts , eggs , and legumes were not significantly associated with CHD risk . The hazard ratios [ with 95 % confidence intervals ] for risk of CHD across quintiles of protein from poultry were 1.00 [ ref ] , 0.83 [ 0.70–0.99 ] , 0.93 [ 0.75–1.15 ] , 0.88 [ 0.73–1.06 ] , 0.79 [ 0.64–0.98 ] , P for trend = 0.16 ) . Replacement analyses evaluating the association of substituting one source of dietary protein for another or of decreasing protein intake at the expense of carbohydrates or total fats did not show any statistically significant association with CHD risk . Conclusion Based on a large community cohort we found no overall relationship between protein type and major dietary protein sources and risk for CHD Background and Purpose — Few dietary protein sources have been studied prospect ively in relation to stroke . We examined the relation between foods that are major protein sources and risk of stroke . Methods — We prospect ively followed 84 010 women aged 30 to 55 years at baseline and 43 150 men aged 40 to 75 years at baseline without diagnosed cancer , diabetes , or cardiovascular disease . Diet was assessed repeatedly by a st and ardized and vali date d question naire . We examined the association between protein sources and incidence of stroke using a proportional hazard model adjusted for stroke risk factors . Results — During 26 and 22 years of follow-up in women and men , respectively , we documented 2633 and 1397 strokes , respectively . In multivariable analyses , higher intake of red meat was associated with an elevated risk of stroke , whereas a higher intake of poultry was associated with a lower risk . In models estimating the effects of exchanging different protein sources , compared with 1 serving/day of red meat , 1 serving/day of poultry was associated with a 27 % ( 95 % CI , 12%–39 % ) lower risk of stroke , nuts with a 17 % ( 95 % CI . 4%–27 % ) lower risk , fish with a 17 % ( 95 % CI , 0%–30 % ) lower risk , low-fat dairy with an 11 % ( 95 % CI , 5%–17 % ) lower risk , and whole-fat dairy with a 10 % ( 95 % CI , 4%–16 % ) lower risk . We did not see significant associations with exchanging legumes or eggs for red meat . Conclusions — These data suggest that stroke risk may be reduced by replacing red meat with other dietary sources of protein In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias BACKGROUND Although dietary factors are suspected to be important determinants of coronary heart disease ( CHD ) risk , the direct evidence is relatively sparse . METHODS The Adventist Health Study is a prospect i ve cohort investigation of 31,208 non-Hispanic white California Seventh-Day Adventists . Extensive dietary information was obtained at baseline , along with the values of traditional coronary risk factors . These were related to risk of definite fatal CHD or definite nonfatal myocardial infa rct ion . RESULTS Subjects who consumed nuts frequently ( more than four times per week ) experienced substantially fewer definite fatal CHD events ( relative risk , 0.52 ; 95 % confidence interval [ CI ] , 0.36 to 0.76 ) and definite nonfatal myocardial infa rct ions ( relative risk , 0.49 ; 95 % CI , 0.28 to 0.85 ) , when compared with those who consumed nuts less than once per week . These findings persisted on covariate adjustment and were seen in almost all of 16 different subgroups of the population . Subjects who usually consumed whole wheat bread also experienced lower rates of definite nonfatal myocardial infa rct ion ( relative risk , 0.56 ; 95 % CI , 0.35 to 0.89 ) and definite fatal CHD ( relative risk , 0.89 ; 95 % CI , 0.60 to 1.33 ) when compared with those who usually ate white bread . Men who ate beef at least three times each week had a higher risk of definite fatal CHD ( relative risk , 2.31 ; 95 % CI , 1.11 to 4.78 ) , but this effect was not seen in women or for the nonfatal myocardial infa rct ion end point . CONCLUSION Our data strongly suggest that the frequent consumption of nuts may protect against risk of CHD events . The favorable fatty acid profile of many nuts is one possible explanation for such an effect Although previous studies have shown that dietary consumption of certain food groups is associated with a lower risk of cancer , heart disease and stroke mortality in western population s , limited prospect i ve data are available from China . We prospect ively examined the association between dietary intake of different food groups at baseline and risk of total , cancer , heart disease and stroke mortality outcomes in the Linxian Nutrition Intervention Trials(NIT ) cohort . In 1984–1991 , 2445 subjects aged 40–69 years from the Linxian NIT cohort completed a food frequency question naire . Deaths from esophageal and gastric cancer , heart disease and stroke were identified through up to 26 years of follow-up . We used Cox proportional hazard models to calculate hazard ratios and 95 % confidence intervals for associations between intake of groups of food items and these mortality endpoints . We concluded that higher intake of certain food groups was associated with lower risk of gastric cancer , heart disease and stroke mortality in a prospect i ve cohort in rural China . Our findings provide additional evidence that increasing intake of grains , vegetables , beans , fruits and nuts may help reduce mortality from these diseases Background Prospect i ve studies in non-Mediterranean population s have consistently related increasing nut consumption to lower coronary heart disease mortality . A small protective effect on all-cause and cancer mortality has also been suggested . To examine the association between frequency of nut consumption and mortality in individuals at high cardiovascular risk from Spain , a Mediterranean country with a relatively high average nut intake per person . Methods We evaluated 7,216 men and women aged 55 to 80 years r and omized to 1 of 3 interventions ( Mediterranean diets supplemented with nuts or olive oil and control diet ) in the PREDIMED ( ‘ PREvención con DIeta MEDiterránea ’ ) study . Nut consumption was assessed at baseline and mortality was ascertained by medical records and linkage to the National Death Index . Multivariable-adjusted Cox regression and multivariable analyses with generalized estimating equation models were used to assess the association between yearly repeated measurements of nut consumption and mortality . Results During a median follow-up of 4.8 years , 323 total deaths , 81 cardiovascular deaths and 130 cancer deaths occurred . Nut consumption was associated with a significantly reduced risk of all-cause mortality ( P for trend < 0.05 , all ) . Compared to non-consumers , subjects consuming nuts > 3 servings/week ( 32 % of the cohort ) had a 39 % lower mortality risk ( hazard ratio ( HR ) 0.61 ; 95 % CI 0.45 to 0.83 ) . A similar protective effect against cardiovascular and cancer mortality was observed . Participants allocated to the Mediterranean diet with nuts group who consumed nuts > 3 servings/week at baseline had the lowest total mortality risk ( HR 0.37 ; 95 % CI 0.22 to 0.66 ) . Conclusions Increased frequency of nut consumption was associated with a significantly reduced risk of mortality in a Mediterranean population at high cardiovascular risk . Please see related commentary : http://www.biomed central .com/1741 - 7015/11/165.Trial registration Clinical trials.gov . International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 35739639 . Registration date : 5 October 2005 Nut intake has been associated with reduced inflammatory status and lower risk of CVD and mortality . The aim of this study was to examine the relationship between nut consumption and mortality and the role of inflammation . We conducted a population -based prospect i ve investigation on 19 386 subjects enrolled in the Moli-sani study . Food intake was recorded by the Italian version of the European Project Investigation into Cancer and Nutrition FFQ . C-reactive protein , leucocyte and platelet counts and the neutrophil : lymphocyte ratio were used as biomarkers of low- grade inflammation . Hazard ratios ( HR ) were calculated using multivariable Cox proportional hazard models . During a median follow-up of 4·3 years , 334 all-cause deaths occurred . As compared with subjects who never ate nuts , rare intake ( ≤2 times/month ) was inversely associated with mortality ( multivariable HR=0·68 ; 95 % CI 0·54 , 0·87 ) . At intake ≥8 times/month , a greater protection was observed ( HR=0·53 ; 0·32 , 0·90 ) . Nut intake ( v. no intake ) conveyed a higher protection to individuals poorly adhering to the Mediterranean diet ( MD ) . A significant reduction in cancer deaths ( HR=0·64 ; 95 % CI 0·44 , 0·94 ) was also observed , whereas the impact on CVD deaths was limited to an inverse , but not significant , trend . Biomarkers of low- grade inflammation were reduced in nut consumers but did not account for the association with mortality . In conclusion , nut intake was associated with reduced cancer and total mortality . The protection was stronger in individuals with lower adherence to MD , whereas it was similar in high-risk groups ( diabetics , obese , smokers or those with the metabolic syndrome ) , as compared with low-risk subjects . Inflammation did not explain the observed relationship Epidemiologic studies have found that dietary patterns characterized by high intakes of certain minerals and fiber are associated with low blood pressure . Dietary Approaches to Stop Hypertension ( DASH ) is a multicenter , r and omized , controlled-feeding trial design ed to test the effects on blood pressure of two such dietary patterns consumed for 8 weeks . The two experimental diets will be compared with each other and with a control dietary pattern that is relatively low in potassium , magnesium , calcium , and fiber , and has a fat and protein profile mirroring current consumption . The first experimental diet , arguably termed " ideal , " is high in fruits , vegetables , whole cereal products , low-fat dairy products , fish , chicken , and lean meats design ed to be low in saturated fat and cholesterol ; moderately high in protein ; and high in minerals and fiber . The second experimental diet tests the effect of fruits and vegetables alone . Its potassium , magnesium , and dietary fiber content will be at the same high levels as the ideal dietary pattern , while its fat , protein , and calcium content will resemble that of the control dietary pattern . The study population will consist of 456 healthy men and women , aged 22 years or older , with systolic blood pressure less than 160 mm Hg and diastolic blood pressure 80 to 95 mm Hg . African-American and other minority groups will comprise 67 % of the population . Participants will eat one of the three dietary patterns . The DASH trial has unique features . First , dietary patterns rather than single nutrients are being tested . Second , all food for the experimental diets is provided to the participants using a st and ardized multicenter protocol . Because the dietary patterns are constructed with commonly consumed food items , the results , if positive , may be conveniently implemented in dietary recommendations to the general public BACKGROUND Dietary nut intake has been associated with a reduced risk of coronary heart disease mortality ; however , the mechanism is unclear . Since components of nuts may have antiarrhythmic properties , part of the benefit may be due to a reduction in sudden cardiac death . METHODS We prospect ively assessed whether increasing frequency of nut consumption , as ascertained by an abbreviated food frequency question naire at 12 months of follow-up , was associated with a lower risk of sudden cardiac death and other coronary heart disease end points among 21 454 male participants enrolled in the US Physicians ' Health Study . Participants were followed up for an average of 17 years . RESULTS Dietary nut intake was associated with a significantly reduced risk of sudden cardiac death after controlling for known cardiac risk factors and other dietary habits ( P for trend,.01 ) . Compared with men who rarely or never consumed nuts , those who consumed nuts 2 or more times per week had reduced risks of sudden cardiac death ( relative risk , 0.53 ; 95 % confidence interval , 0.30 - 0.92 ) and total coronary heart disease death ( relative risk , 0.70 ; 95 % confidence interval , 0.50 - 0.98 ) . In contrast , nut intake was not associated with significantly reduced risks of nonsudden coronary heart disease death or nonfatal myocardial infa rct ion . CONCLUSION These prospect i ve data in US male physicians suggest that the inverse association between nut consumption and total coronary heart disease death is primarily due to a reduction in the risk of sudden cardiac death BACKGROUND & AIMS While nut consumption has been shown to lower the risk of hypertension and coronary disease , it is not known whether nut consumption is associated with the risk of stroke . We sought to examine whether nut consumption is associated with total and subtypes of stroke . METHODS Prospect i ve cohort of 21,078 participants from the Physicians ' Health Study ( 1982 - 2008 ) who were free of stroke at baseline . Nut consumption was assessed using a simple 19-item food question naire and stroke cases were confirmed after review ing medical records . We used Cox 's proportional hazards regression to estimate relative risks of total , ischemic , and hemorrhagic stroke according to consumption of any nuts . RESULTS During a mean follow up of 21.1 years , 1424 incident cases of stroke occurred ( 219 hemorrhagic , 1189 ischemic , and 16 of undetermined cause ) . There was no statistically significant association between nut consumption and total or ischemic stroke . In contrast , there was a suggestive non-linear relation between nut intake and hemorrhagic stroke : compared to subjects who did not consume nuts , multivariable-adjusted hazard ratios ( 95 % CI ) for hemorrhagic stroke for subjects consuming nuts < 1 , 1 , 2 - 4 , 5 - 6 , and ≥7 times/week were 1.13 ( 0.78 - 1.62 ) , 1.05 ( 0.70 - 1.58 ) , 0.49 ( 0.27 - 0.89 ) , 1.50 ( 0.79 - 2.84 ) , and 1.84 ( 0.95 - 3.57 ) , respectively ( p for quadratic trend 0.12 ) . CONCLUSIONS Our data showed no association between nuts and ischemic stroke and suggested a J-shaped relation between nut consumption and hemorrhagic stroke . Replication of our findings in the general population is warranted BACKGROUND The associations between specific types of nuts , specifically peanuts and walnuts , and cardiovascular disease remain unclear . OBJECTIVES The authors sought to analyze the associations between the intake of total and specific types of nuts and cardiovascular disease , coronary heart disease , and stroke risk . METHODS The authors included 76,364 women from the Nurses ' Health Study ( 1980 to 2012 ) , 92,946 women from the Nurses ' Health Study II ( 1991 to 2013 ) , and 41,526 men from the Health Professionals Follow-Up Study ( 1986 to 2012 ) who were free of cancer , heart disease , and stroke at baseline . Nut consumption was assessed using food frequency question naires at baseline and was up date d every 4 years . RESULTS During 5,063,439 person-years of follow-up , the authors documented 14,136 incident cardiovascular disease cases , including 8,390 coronary heart disease cases and 5,910 stroke cases . Total nut consumption was inversely associated with total cardiovascular disease and coronary heart disease after adjustment for cardiovascular risk factors . The pooled multivariable hazard ratios for cardiovascular disease and coronary heart disease among participants who consumed 1 serving of nuts ( 28 g ) 5 or more times per week , compared with the reference category ( never or almost never ) , were 0.86 ( 95 % confidence interval : 0.79 to 0.93 ; p for trend = 0.0002 ) and 0.80 ( 95 % confidence interval : 0.72 to 0.89 ; p for trend < 0.001 ) , respectively . Consumption of peanuts and tree nuts ( 2 or more times/week ) and walnuts ( 1 or more times/week ) was associated with a 13 % to 19 % lower risk of total cardiovascular disease and 15 % to 23 % lower risk of coronary heart disease . CONCLUSIONS In 3 large prospect i ve cohort studies , higher consumption of total and specific types of nuts was inversely associated with total cardiovascular disease and coronary heart disease BACKGROUND Previous studies have suggested that nut consumption is associated with beneficial cardiovascular outcomes . However , limited data are available on the association between nut intake and all-cause mortality . OBJECTIVE Our aim was to test the hypothesis that nut consumption is inversely associated with the risk of all-cause mortality . DESIGN In this prospect i ve cohort study in 20,742 male physicians , we assessed nut intake between 1999 and 2002 via a food-frequency question naire and ascertained deaths through an endpoint committee . We used Cox regression to estimate multivariable-adjusted HRs for death according to nut consumption . In secondary analyses , we evaluated associations of nut consumption with cause-specific mortality . RESULTS During a mean follow-up of 9.6 y , there were 2732 deaths . The mean ( ±SD ) age at baseline was 66.6 ± 9.3 y. Median nut consumption was 1 serving/wk . Multivariable-adjusted HRs ( 95 % CIs ) were 1.0 ( reference ) , 0.92 ( 0.83 , 1.01 ) , 0.85 ( 0.76 , 0.96 ) , 0.86 ( 0.75 , 0.98 ) , and 0.74 ( 0.63 , 0.87 ) for nut consumption of never or < 1 serving/mo , 1 - 3 servings/mo , 1 serving/wk , 2 - 4 servings/wk , and ≥5 servings/wk , respectively ( P-linear trend < 0.0001 ) , after adjustment for age , body mass index , alcohol use , smoking , exercise , prevalent diabetes and hypertension , and intakes of energy , saturated fat , fruit and vegetables , and red meat . In a secondary analysis , results were consistent for cardiovascular disease mortality but only suggestive and non-statistically significant for coronary artery disease and cancer mortality . CONCLUSION Our data are consistent with an inverse association between nut consumption and the risk of all-cause and cardiovascular disease mortality in US male physicians In the GRADE approach , r and omized trials are classified as high quality evidence and observational studies as low quality evidence but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted Background / Objectives : Nuts have beneficial effects on coronary heart disease and many cardiovascular risk factors . However , their effect on stroke is less established , and no studies on the topic are available in Northern and Central European population s. Therefore , we aim ed at investigating the association between nut consumption and the risk of stroke in a German population .Subjects/ Methods : We used data from a prospect i ve cohort of 26 285 participants of the European Prospect i ve Investigation into the Cancer and Nutrition Potsdam Study . During a median follow-up time of 8.3 years ( interquartile range : 7.5–9.2 ) , 288 incident cases of stroke occurred . Nut consumption ( st and ard portion size of 50 g ) was assessed at baseline with a semiquantitative food-frequency question naire . Results : The median nut intake was 0.82 g per day , interquartile range : 0.41–4.11 . In the multivariable model , an increased risk of stroke was observed among participants who never consumed nuts ( hazard ratio ( HR ) : 1.56 , 95 % confidence interval : 1.17–2.08 ) , compared with those consuming < ½ portion/week . However , there was no evidence of a dose – response relationship between nut consumption and stroke . Compared with those who consumed < ½ portion/week , the multivariable HR for total stroke was 1.06 ( 0.75–1.52 ) among those who consumed ½ to 1 portion/week and 1.37 ( 0.92–2.05 ) for those who consumed > 1 portion/week . Similar nonsignificant associations were observed in stratified analysis for gender , or for fatal and nonfatal stroke . Conclusions : We could not observe an association between nut consumption and the risk of developing stroke ( fatal/nonfatal ) in a population with low habitual nut consumption BACKGROUND AND AIMS The published literature shows that nut consumption has a favorable impact on health . We aim ed to assess the association between nut consumption and risk of 15-year total mortality , and mortality from cardiovascular disease ( CVD ) ( including ischemic heart disease , IHD , and stroke ) , and cancer . METHODS AND RESULTS Prospect i ve analyses involved 2893 participants aged ≥49 years at baseline . Dietary data were collected by using a semi-quantitative food-frequency question naire , and nut intakes were calculated . Deaths and cause of death were confirmed by data linkage with the Australian National Death Index . Over 15 years , 1044 participants had died , of these 430 had died from stroke and another 430 had died from IHD . Participants in the second tertile of nut consumption versus those in the first tertile of intake had reduced risk of total mortality : multivariable-adjusted HR 0.76 ( 95 % CI 0.65 - 0.89 ) . Participants in the second tertile compared to those in the first tertile had 24 % and 23 % reduced risk of 15-year CVD and IHD mortality , respectively . Associations were more marked in women compared to men . Women in the second versus first tertile of nut consumption had 27 % , 39 % , 34 % and 49 % reduced risk of death from all causes ( n = 489 ) , CVD ( n = 258 ) , IHD ( n = 188 ) and stroke mortality ( n = 101 ) , respectively . CONCLUSIONS Nut consumption was independently associated with a decreased risk of overall and vascular-disease mortality , particularly in women Rationale : The evidence regarding the potential health benefits of nut consumption among individuals with type 2 diabetes mellitus is limited . Objective : To examine intake of total and specific types of nuts , including tree nuts and peanuts , in relation to subsequent risk of cardiovascular disease ( CVD ) , including coronary heart disease and stroke , and all-cause and cause-specific mortality among individuals with diabetes mellitus . Methods and Results : This prospect i ve analysis included 16 217 men and women with diabetes mellitus at baseline or diagnosed during follow-up ( Nurses ’ Health Study : 1980–2014 , Health Professionals Follow-Up Study : 1986–2014 ) . Nut consumption was assessed using a vali date d food frequency question naire and up date d every 2 to 4 years . During 223 682 and 254 923 person-years of follow-up , there were 3336 incident CVD cases and 5682 deaths , respectively . Higher total nut consumption was associated with a lower risk of CVD incidence and mortality . The multivariate-adjusted hazard ratios ( 95 % CIs ) for participants who consumed 5 or more servings of total nuts per week ( 1 serving=28 g ) , compared with those who consumed < 1 serving per month , were 0.83 ( 0.71–0.98 ; P trend=0.01 ) for total CVD incidence , 0.80 ( 0.67–0.96 ; P trend=0.005 ) for coronary heart disease incidence , 0.66 ( 0.52–0.84 ; P trend < 0.001 ) for CVD mortality , and 0.69 ( 0.61–0.77 ; P trend < 0.001 ) for all-cause mortality . Total nut consumption was not significantly associated with risk of stroke incidence or cancer mortality . For specific types of nuts , higher tree nut consumption was associated with lower risk of total CVD , coronary heart disease incidence , and mortality because of CVD , cancer , and all causes , whereas peanut consumption was associated with lower all-cause mortality only ( all P trend < 0.001 ) . In addition , compared with participants who did not change the consumption of total nuts from pre- to post-diabetes mellitus diagnosis , participants who increased consumption of total nuts after diabetes mellitus diagnosis had an 11 % lower risk of CVD , a 15 % lower coronary heart disease risk , a 25 % lower CVD mortality , and a 27 % lower all-cause mortality . The associations persisted in subgroup analyses stratified by sex/cohort , body mass index at diabetes mellitus diagnosis , smoking status , diabetes mellitus duration , nut consumption before diabetes mellitus diagnosis , or diet quality . Conclusions : Higher consumption of nuts , especially tree nuts , is associated with lower CVD incidence and mortality among participants with diabetes mellitus . These data provide novel evidence that supports the recommendation of incorporating nuts into healthy dietary patterns for the prevention of CVD complications and premature deaths among individuals with diabetes mellitus |
13,282 | 31,664,267 | CONCLUSION Within the limits of this systematic review , it can be concluded that the survival rates of implants and overdentures and patient satisfaction with a maxillary overdenture supported by four implants were not influenced by the overdenture design , and no statistical difference was detected between the splinted and unsplinted groups | PURPOSE To investigate the influence of splinted vs unsplinted design s for a maxillary overdenture supported by four implants in terms of the outcome measures implant survival , overdenture longevity , and patient satisfaction . | Abstract Objective To compare a four‐ and six‐implant maxillary overdenture after an observation period of 5 years . Material and methods Fifty subjects with functional problems concerning their maxillary denture , who had ample bone volume in the anterior region to place four or six implants , were included and r and omly assigned to either group . Implant and overdenture survival , clinical performance , marginal bone loss and patient satisfaction were assessed . Results Forty‐six patients completed the 5‐year follow‐up . One implant failed in the six implants group ( 99.2 % survival ) and none in the four implants group ( 100 % survival ) . No overdentures had to be replaced during the observation period and the number of complications was limited . Clinical function was good , with no difference in clinical parameters between the groups . Mean marginal bone resorption was 0.50 ± 0.37 and 0.52 ± 0.43 mm in the four and six implant group respectively . Conclusion In patients with functional complaints of their maxillary denture , bar‐supported overdentures on four implants in the anterior maxillary region were not inferior to overdentures supported by six implants after 5 years of function . Implant survival and patient satisfaction were high , clinical parameters favourable , bone loss and complications to the denture were minor in both groups ( Clinical trial registration number : NTR2969 ) OBJECTIVE Comparing treatment outcome of four and six bar-connected implants in the anterior maxillary region to support an overdenture during a 1-year follow-up period . MATERIAL AND METHODS Fifty edentulous patients with lack of retention and stability of the upper denture , but with sufficient bone volume to place implants in the anterior maxillary region , were selected . R and omization assigned patients to either four or six implants . Implant survival , overdenture survival , clinical scores , radiographic bone height changes , and patients ' satisfaction were assessed . RESULTS Forty-nine patients ( one drop out ) completed the 1-year follow-up . After 1 year , implant survival was 100 % in the four implants group and 99.3 % in the six implants group ( one implant lost ) . Overdenture survival was 100 % in both groups . Mean clinical scores were low and did not differ between groups ( independent Student 's t-test ) . Mean marginal bone resorption was 0.24 ± 0.32 mm in the four implants group and 0.25 ± 0.29 mm in the six implants group . Patients ' satisfaction had improved in both groups ( paired Student 's t-test ) . CONCLUSION Bar-supported overdentures on four implants in the anterior maxillary region are not inferior to overdentures supported by six bar-connected implants . Implant survival was high , peri-implant conditions were healthy and patients ' satisfaction had increased significantly in both groups PURPOSE To analyze maintenance service of fixed maxillary prostheses and overdentures based on conventional gold bars or titanium bars and frameworks fabricated with computer-aided design /computer-assisted manufacture ( CAD/CAM ) technology . MATERIAL S AND METHODS Forty-one patients participated ; 16 received an implant overdenture with a gold bar ( gold OD ) , 12 received a CAD/CAM-fabricated implant OD with a titanium bar ( Ti OD ) , and 13 received a CAD/CAM implant-supported fixed prosthesis ( IFP ) . The bars and frameworks were screw-retained at the implant level . Maintenance service performed during the first 2 years was recorded and compared between the three groups . After this 2-year period , the Oral Health Impact Profile ( OHIP ) was administered . RESULTS For ODs ( gold , Ti ) most service consisted of activation of the matrices . Fractures of matrices and bar extensions occurred only in the gold OD group , and 65 % of these patients exhibited hyperplasia of the peri-implant mucosa . The maintenance rates were 1.24 ( gold OD ) , 1.36 ( Ti OD ) , and 0.98 ( IFP ) . These differences were not statistically significant . Retightening of occlusal screws was not necessary in any group . The probability that a complication occurred in the first year was high ( 60 % to 70 % ) and statistically not different between the three groups . The probability that a second complication occurred was significantly lower for the IFP group versus the gold OD group . The mean OHIP values were 1.7 ( IFP ) , 6.7 ( gold OD ) , and 7.3 ( Ti OD ) ; ratings in the IFP group were significantly better . CONCLUSIONS Maintenance service was typical for implant prostheses in the edentulous maxilla . Direct screw retention at the implant level without abutments had a favorable effect in all groups . A trend toward a reduction in problems was observed with the CAD/CAM superstructures . The OHIP confirmed high satisfaction , but quality of life appeared to be slightly higher with fixed prostheses In this prospect i ve multicenter study , non-submerged ITI implants were followed in order to evaluate their long-term prognosis in fully edentulous jaws . A total of 1286 implants were inserted in 233 consecutive patients and , after a healing period of three to six months , the successfully integrated implants were restored with 163 overdentures and 95 fixed full-arch bridges . This prospect i ve study not only calculated the 10-year cumulative survival and success rates for the 1286 implants by life table analysis , but also evaluated the actual survival and success rates for 498 implants after at least five years of functional loading . In addition , cumulative success rates were calculated for implant subgroups according to implant length and location . Additional analyses were performed to evaluate the estimated and actual survival and success rates of the implants in relation to various prosthetic rehabilitation techniques . The 10-year cumulative survival and success rates were 95.9 % and 92.7 % , respectively . The actual 5-year survival and success rates of the first 498 implants that were inserted were 97.7 % and 95.0 % , respectively . The analysis of implant subgroups showed slightly more favourable cumulative success rates for 12 mm long implants ( 93 % ) , in comparison to 10 mm and 8 mm long implants ( 91.6 % and 89.6 % , respectively ) . The cumulative success rate for m and ibular implants ( approximately 94 % ) was also more favourable than that for maxillary implants ( approximately 91 % ) . Patients who were loaded with both maxillary and m and ibular prostheses maintained success rates well above 90 % ; while only implants that were inserted to support maxillary overdentures that were retained by Dolder bars showed a success rate below 90 % OBJECTIVE To compare the treatment outcome of 4 vs. 6 bar-connected implants in the posterior region of the maxilla to support an overdenture during a 1-year follow-up period . MATERIAL S AND METHODS Sixty-six edentulous patients with an insufficient amount of bone volume in the maxilla to place implants were asked to participate in this study . R and omization assigned patients to either 4 or 6 implants . In all patients , a maxillary sinus floor elevation procedure with bone from the iliac crest was performed , and after a 3-month healing period , 4 or 6 dental implants were inserted in the maxillary posterior region in a one-stage procedure . After 3 months of osseointegration , a bar-supported overdenture was constructed . Implant survival , overdenture survival , clinical scores , peri-implant bone height changes and patients ' satisfaction were assessed . Study analysis was performed according a non-inferiority design . RESULTS All patients completed the one-year follow-up . After a functional period of 1-year , implant survival was 100 % in the 4 implants group and 99.5 % in the 6 implants group . Overdenture survival was 100 % in both groups . Mean clinical scores were very low and did not significantly differ between groups . Mean marginal bone resorption was 0.35 ± 0.31 mm and 0.46 ± 0.34 mm in the 4 and 6 implants group , respectively . Patients ' satisfaction improved significantly in both groups , but did not differ between groups . CONCLUSION A bar-supported overdenture on 4 implants in the posterior maxillary region is not inferior to an overdenture supported by 6 bar-connected dental implants PURPOSE To evaluate patient-related outcomes in restoring the edentulous maxilla with an implant overdenture . MATERIAL S AND METHODS A comprehensive systematic review of the literature was conducted . Publications reporting patient-based outcomes with concomitant data on implant and /or prosthetic success were selected using predetermined inclusion criteria that were agreed upon by the two review ers . RESULTS Twenty-three publications related to 20 study cohorts were identified to meet the inclusion criteria for maxillary implant overdentures : two r and omized controlled trials ( RCTs ) , 13 prospect i ve case series including two crossover trials , and five retrospective studies . CONCLUSION An implant overdenture offers a stabilized removable solution for the edentulous maxilla , which provides increased patient satisfaction and quality of life improvement . A palateless design supported by four to six implants with a wide anteroposterior span has been successfully applied in some investigations . A higher failure rate was experienced with machined implants , particularly with short implants ( length < 10 mm ) . Although both splinted and solitary anchorage systems are advocated , maintenance is higher for solitary attachments and inflammation is increased beneath the bars . Long-term maintenance care is essential for all design s. Well- design ed RCTs with larger sample cohorts with longer follow-up periods are required to amplify patient- and clinician-based outcomes Although maxillary implant overdentures are used in oral rehabilitation , different design s have not been compared previously in clinical trials . This crossover trial was design ed to measure differences in patient satisfaction with maxillary long-bar implant overdentures with and without palatal coverage opposed by a fixed m and ibular implant-supported prosthesis . Data were also gathered on new conventional dentures and on maxillary conventional dentures opposed by m and ibular fixed prostheses . Sixteen participants were selected from a population wearing conventional dentures . Fifteen received new upper and lower dentures ( 1 drop-out ) . Four implants were placed in the maxilla and m and ible ( 2 drop-outs ) . A m and ibular fixed prosthesis was inserted in 13 participants , who were then divided into 2 groups . One group ( n = 7 ) received long-bar overdentures with palate , then long-bar overdentures without palate . The other group ( n = 6 ) received the same treatments in the reverse order . Mastication tests and psychometric evaluations using Visual Analog Scales and Categorical Scales were performed throughout the study . General satisfaction was very high with both maxillary implant-supported prostheses , as were ratings of almost all psychosocial and functional variables . There were no significant differences between treatments , suggesting that patients are equally satisfied with long-bar overdentures with and without palate when these are opposed by m and ibular fixed prostheses . However , the ratings given to the maxillary implant prostheses were not significantly higher than for new conventional maxillary prostheses . This suggests that maxillary implant prostheses should not be considered as a general treatment of choice in patients with good bony support for maxillary conventional prostheses PURPOSE To evaluate telescopic crown ( TC ) , bar , and locator attachments used in removable four implant-supported overdentures for patients with edentulous maxillae . MATERIAL S AND METHODS A total of 30 maxillary edentulous patients were enrolled in a 3-year prospect i ve study . Ten patients ( group A ) were treated with overdentures supported by TCs , 10 patients ( group B ) with overdentures supported by bar attachments , and 10 patients ( group C ) with overdentures supported by locator attachments . A total of 120 implants were used to restore oral function . During the 3-year follow-up period , implant survival and success rates , biologic and mechanical complications , prosthodontic maintenance efforts , and patient satisfaction were evaluated . RESULTS All 30 patients were available for the 3-year follow-up and exhibited 100 % implant survival and success rates . Peri-implant marginal bone resorption was not statistically significant for the three groups . There were lower plaque , bleeding , gingiva , and calculus indices in group C compared with groups A and B. The number of prosthodontic maintenance visits revealed eight complications in the TC group , seven complications in the bar group , and four complications in the locator group . However , there were no differences in the clinical effects of the overdentures in the three groups . CONCLUSION Within the limits of this prospect i ve study , it was concluded that the locator system produced superior clinical results compared with the TC and bar attachments in terms of peri-implant hygiene parameters , the frequency of prosthodontic maintenance measures , cost , and ease of denture preparation . However , longer-term prospect i ve studies are required to confirm these results |
13,283 | 27,040,448 | There were no data on the effects on drug/alcohol use for individual therapy .
Evidence showed that individual trauma-focused psychological therapy delivered alongside SUD therapy did better than TAU/minimal intervention in reducing PTSD severity post-treatment and at long-term follow-up , but only reduced SUD at long-term follow-up .
There was evidence that fewer participants receiving trauma-focused therapy completed treatment .
There was very little evidence to support use of non-trauma-focused individual- or group-based integrated therapies . | BACKGROUND Post-traumatic stress disorder ( PTSD ) is a debilitating mental health disorder that may develop after exposure to traumatic events .
Substance use disorder ( SUD ) is a behavioural disorder in which the use of one or more substances is associated with heightened levels of distress , clinical ly significant impairment of functioning , or both .
PTSD and SUD frequently occur together .
The comorbidity is widely recognised as being difficult to treat and is associated with poorer treatment completion and poorer outcomes than for either condition alone .
Several psychological therapies have been developed to treat the comorbidity , however there is no consensus about which therapies are most effective .
OBJECTIVES To determine the efficacy of psychological therapies aim ed at treating traumatic stress symptoms , substance misuse symptoms , or both in people with comorbid PTSD and SUD in comparison with control conditions ( usual care , waiting-list conditions , and no treatment ) and other psychological therapies . | This article describes a second treatment- outcome study of cognitive trauma therapy for battered women with posttraumatic stress disorder ( PTSD ; CTT-BW ) . CTT-BW includes trauma history exploration : PTSD education ; stress management ; exposure to abuse and abuser reminders ; self-monitoring of negative self-talk ; cognitive therapy for guilt ; and modules on self-advocacy , assertiveness , and how to identify perpetrators . One hundred twenty-five ethnically diverse women were r and omly assigned to immediate or delayed CTT-BW . PTSD remitted in 87 % of women who completed CTT-BW , with large reductions in depression and guilt and substantial increases in self-esteem . White and ethnic minority women benefited equally from CTT-BW . Similar treatment outcomes were obtained by male and female therapists and by therapists with different levels of education and training . Gains were maintained at 3- and 6-month follow-ups OBJECTIVE Veterans who served in Operation Enduring Freedom ( OEF ) and Operation Iraqi Freedom ( OIF ) commonly experience alcohol misuse and symptoms of posttraumatic stress disorder ( PTSD ) following their return from deployment to a war zone . We conducted a r and omized clinical trial to evaluate the efficacy of a newly developed , 8-module , self-management web intervention ( VetChange ) based on motivational and cognitive-behavioral principles to reduce alcohol consumption , alcohol-related problems , and PTSD symptoms in returning combat veterans . METHOD Six hundred participants , recruited through targeted Facebook ads , were r and omized to either an Initial Intervention Group ( IIG ; n = 404 ) or a Delayed Intervention Group ( DIG ; n = 196 ) that waited 8 weeks for access to VetChange . Primary outcome measures were Drinks per Drinking Day , Average Weekly Drinks , Percent Heavy Drinking Days , and PTSD symptoms . Intent-to-treat analyses compared changes in outcome measures over time between IIG and DIG as well as within-group changes . RESULTS IIG participants demonstrated greater reductions in drinking ( p < .001 for each measure ) and PTSD symptoms ( p = .009 ) between baseline and end-of-intervention than did DIG participants between baseline and the end of the waiting period . DIG participants showed similar improvements to those in IIG following participation in VetChange . Alcohol problems were also reduced within each group between baseline and 3-month follow-up . CONCLUSIONS Results indicate that VetChange is effective in reducing drinking and PTSD symptoms in OIF/OEF veterans . Further studies of VetChange are needed to assess web-based recruitment and retention methods and to determine VetChange 's effectiveness in demographic and clinical sub- population s of returning veterans AIMS To examine the impact of post-traumatic stress disorder ( PTSD ) on 2-year treatment outcomes for heroin dependence . DESIGN Prospect i ve longitudinal study . PARTICIPANTS Data were obtained from a predominantly treatment seeking sample of 615 dependent heroin users who were followed-up at 3 , 12 and 24 months ( follow-up rates : 89 % , 81 % and 76 % , respectively ) . MEASUREMENTS Outcomes examined include treatment retention and exposure , substance use , general physical and mental health and employment . FINDINGS Despite improvements in substance use , PTSD was associated with continued physical ( beta - 1.69 , SE 0.61 , P < 0.01 ) and mental disability ( beta - 2.07 , SE 0.66 , P < 0.01 ) , and reduced occupational functioning ( OR 0.67 , 95 % CI : 0.48 - 0.93 ) throughout the 2-year follow-up . CONCLUSIONS Although conventional treatment services are successful in producing improvements in substance use and associated disability , the disability associated with PTSD remains . An intervention targeting both heroin dependence and PTSD may help to improve the outcomes of those with PTSD The prevalence of alcohol use disorder ( e.g. , alcohol dependence ; AD ) among individuals with posttraumatic stress disorder ( PTSD ) is quite high , with estimates of 52 % for men and 30 % for women ( Kessler , Sonnega , Bromet , Hughes , & Nelson , 1995 ) . There are several interviews and self-report measures of PTSD with good published psychometric properties , and they are routinely used with comorbid AD and PTSD . However , none of these instruments was vali date d with this population . The current study fills this gap by examining the psychometric properties of the PTSD Symptom Scale-Interview ( PSS-I ) and the self-report PTSD Diagnostic Scale ( PDS ) in individuals diagnosed with current PTSD and AD . Both scales comprised of 17 items provide diagnostic and symptom severity information according to DSM-IV-TR criteria . Participants were 167 individuals who were diagnosed with AD and chronic PTSD and were enrolled in a r and omized controlled treatment study . Results revealed excellent internal consistency of both the PSS-I and the PDS , good test-retest reliability over a 1-month period , and good convergent validity with the SCID . The specificity of the PSS-I diagnosis of PTSD was better than the PDS diagnosis , the latter exhibiting a greater percentage of false positives . In sum , the results showed that the PSS-I and PDS performed well in this population and can be used with confidence to assess PTSD diagnosis and symptom severity BACKGROUND Although women with substance use disorders ( SUDs ) have high rates of trauma and posttraumatic stress , many addiction programs do not offer trauma-specific treatments . One promising intervention is Pennebaker 's expressive writing , which involves daily , 20-minute writing sessions to facilitate disclosure of stressful experiences . METHODS Women ( N = 149 ) in residential treatment completed a r and omized clinical trial comparing expressive writing with control writing . Repeated- measures analysis of variance was used to document change in psychological and physical distress from baseline to 2-week and 1-month follow-ups . Analyses also examined immediate levels of negative affect following expressive writing . RESULTS Expressive writing participants showed greater reductions in posttraumatic symptom severity , depression , and anxiety scores , when compared with control writing participants at the 2-week follow-up . No group differences were found at the 1-month follow-up . Safety data were encouraging : although expressive writing participants showed increased negative affect immediately after each writing session , there were no differences in pre-writing negative affect scores between conditions the following day . By the final writing session , participants were able to write about traumatic/stressful events without having a spike in negative affect . CONCLUSIONS Results suggest that expressive writing may be a brief , safe , low-cost , adjunct to SUD treatment that warrants further study as a strategy for addressing posttraumatic distress in substance-abusing women Addressing affect dysregulation may provide a complementary alternative or adjunctive approach to the empirically supported trauma memory processing models of cognitive behavior therapy ( CBT ) for posttraumatic stress disorder ( PTSD ) . A CBT design ed to enhance affect regulation without trauma memory processing -- trauma affect regulation : guide for education and therapy (TARGET)--was compared to present centered therapy ( PCT ) and wait-list ( WL ) conditions in a r and omized clinical trial with 146 primarily low-income and ethnoracial minority mothers with PTSD . TARGET achieved statistically and clinical ly significant improvement on PTSD and affect regulation measures compared to WL , with more consistent and sustained ( over a 6-month follow-up period ) evidence of improvement than PCT . Drop-out rates ( ~25 % ) were comparable in TARGET and PCT , similar to those previously reported for trauma memory processing CBTs . Symptom worsening was rare ( 2 - 8 % ) and transient . Affect regulation-based CBT without trauma memory processing warrants further research as a potentially efficacious therapy for victimization-related PTSD IMPORTANCE Alcohol dependence comorbid with posttraumatic stress disorder ( PTSD ) has been found to be resistant to treatment . In addition , there is a concern that prolonged exposure therapy for PTSD may exacerbate alcohol use . OBJECTIVE To compare the efficacy of an evidence -based treatment for alcohol dependence ( naltrexone ) plus an evidence -based treatment for PTSD ( prolonged exposure therapy ) , their combination , and supportive counseling . DESIGN , SETTING , AND PARTICIPANTS A single-blind , r and omized clinical trial of 165 participants with PTSD and alcohol dependence conducted at the University of Pennsylvania and the Philadelphia Veterans Administration . Participant enrollment began on February 8 , 2001 , and ended on June 25 , 2009 . Data collection was completed on August 12 , 2010 . INTERVENTIONS Participants were r and omly assigned to ( 1 ) prolonged exposure therapy plus naltrexone ( 100 mg/d ) , ( 2 ) prolonged exposure therapy plus pill placebo , ( 3 ) supportive counseling plus naltrexone ( 100 mg/d ) , or ( 4 ) supportive counseling plus pill placebo . Prolonged exposure therapy was composed of 12 weekly 90-minute sessions followed by 6 biweekly sessions . All participants received supportive counseling . MAIN OUTCOMES AND MEASURES The Timeline Follow-Back Interview and the PTSD Symptom Severity Interview were used to assess the percentage of days drinking alcohol and PTSD severity , respectively , and the Penn Alcohol Craving Scale was used to assess alcohol craving . Independent evaluations occurred prior to treatment ( week 0 ) , at posttreatment ( week 24 ) , and at 6 months after treatment discontinuation ( week 52 ) . RESULTS Participants in all 4 treatment groups had large reductions in the percentage of days drinking ( mean change , -63.9 % [ 95 % CI , -73.6 % to -54.2 % ] for prolonged exposure therapy plus naltrexone ; -63.9 % [ 95 % CI , -73.9 % to -53.8 % ] for prolonged exposure therapy plus placebo ; -69.9 % [ 95 % CI , -78.7 % to -61.2 % ] for supportive counseling plus naltrexone ; and -61.0 % [ 95 % CI , -68.9 % to -53.0 % ] for supportive counseling plus placebo ) . However , those who received naltrexone had lower percentages of days drinking than those who received placebo ( mean difference , 7.93 % ; P = .008 ) . There was also a reduction in PTSD symptoms in all 4 groups , but the main effect of prolonged exposure therapy was not statistically significant . Six months after the end of treatment , participants in all 4 groups had increases in percentage of days drinking . However , those in the prolonged exposure therapy plus naltrexone group had the smallest increases . CONCLUSIONS AND RELEVANCE In this study of patients with alcohol dependence and PTSD , naltrexone treatment result ed in a decrease in the percentage of days drinking . Prolonged exposure therapy was not associated with an exacerbation of alcohol use disorder . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00006489 A cognitive-behavioral therapy ( CBT ) program for posttraumatic stress disorder ( PTSD ) was developed to address its high prevalence in persons with severe mental illness receiving treatment at community mental health centers . CBT was compared with treatment as usual ( TAU ) in a r and omized controlled trial with 108 clients with PTSD and either major mood disorder ( 85 % ) or schizophrenia or schizoaffective disorder ( 15 % ) , of whom 25 % also had borderline personality disorder . Eighty-one percent of clients assigned to CBT participated in the program . Intent-to-treat analyses showed that CBT clients improved significantly more than did clients in TAU at blinded posttreatment and 3- and 6-month follow-up assessment s in PTSD symptoms , other symptoms , perceived health , negative trauma-related beliefs , knowledge about PTSD , and case manager working alliance . The effects of CBT on PTSD were strongest in clients with severe PTSD . Homework completion in CBT predicted greater reductions in symptoms . Changes in trauma-related beliefs in CBT mediated improvements in PTSD . The findings suggest that clients with severe mental illness and PTSD can benefit from CBT , despite severe symptoms , suicidal thinking , psychosis , and vulnerability to hospitalizations Women in drug treatment struggle with co-occurring problems , including trauma and post-traumatic stress disorder ( PTSD ) , which can heighten HIV risk . This study examines the impact of two group therapy interventions on reduction of unprotected sexual occasions ( USO ) among women with substance use disorders ( SUD ) and PTSD . Participants were 346 women recruited from and receiving treatment at six community-based drug treatment programs participating in NIDA ’s Clinical Trials Network . Participants were r and omized to receive 12-sessions of either seeking safety ( SS ) , a cognitive behavioral intervention for women with PTSD and SUD , or women ’s health education ( WHE ) , an attention control psychoeducational group . Participants receiving SS who were at higher sexual risk ( i.e. , at least 12 USO per month ) significantly reduced the number of USO over 12-month follow up compared to WHE . High risk women with co-occurring PTSD and addiction may benefit from treatment addressing coping skills and trauma to reduce HIV risk This r and omized controlled pilot study compared a cognitive-behavioral therapy ( Seeking Safety ; SS ) plus treatment-as-usual ( TAU ) to TAU-alone in 49 incarcerated women with substance use disorder ( SUD ) and posttraumatic stress disorder ( PTSD ; full or subthreshold ) . Seeking Safety consisted of a voluntary group treatment during incarceration and individual treatment after prison release . TAU was required in the prison and comprised 180 to 240 hours of individual and group treatment over 6 to 8 weeks . Assessment s occurred at intake , 12 weeks after intake , and 3 and 6 months after release from prison . There were no significant differences between conditions on all key domains ( PTSD , SUD , psychopathology , and legal problems ) ; but both conditions showed significant improvements from intake to later time points on all of these outcomes across time . Secondary analyses at follow-up found trends for SS participants improving on clinician-rated PTSD symptoms and TAU participants worsening on self-reported PTSD symptoms . Also , SS demonstrated continued improvement on psychopathology at 3 and 6 months , whereas TAU did not . However , alcohol use improved more for TAU during follow-up . Satisfaction with SS was high , and a greater number of SS sessions was associated with greater improvement on PTSD and drug use . Six months after release from prison , 53 % of the women in both conditions reported a remission in PTSD . Study limitations include lack of assessment of SS outcomes at end of group treatment ; lack of blind assessment ; omission of the SS case management component ; and possible contamination between the two conditions . The complex needs of this population are discussed OBJECTIVE The current study marks the first r and omized controlled trial to test the benefit of combining Seeking Safety ( SS ) , a present-focused cognitive-behavioral therapy for co-occurring posttraumatic stress disorder ( PTSD ) and alcohol use disorder ( AUD ) , with sertraline , a front-line medication for PTSD shown to also impact drinking outcomes . METHOD Sixty-nine participants ( 81 % female ; 59 % African American ) with primarily childhood sexual ( 46 % ) and physical ( 39 % ) trauma exposure , and drug dependence in addition to AUD were r and omized to receive a partial-dose ( 12 sessions ) of SS with either sertraline ( n = 32 ; M = 7 sessions ) or placebo ( n = 37 ; M = 6 sessions ) . Assessment s conducted at baseline , end-of-treatment , 6- and 12-months posttreatment measured PTSD and AUD symptom severity . RESULTS Both groups demonstrated significant improvement in PTSD symptoms . The SS plus sertraline group exhibited a significantly greater reduction in PTSD symptoms than the SS plus placebo group at end-of-treatment ( M difference = -16.15 , p = .04 , d = 0.83 ) , which was sustained at 6- and 12-month follow-up ( M difference = -13.81 , p = .04 , d = 0.71 , and M difference = -12.72 , p = .05 , d = 0.65 , respectively ) . Both SS groups improved significantly on AUD severity at all posttreatment time points with no significant differences between SS plus sertraline and SS plus placebo . CONCLUSION Results support the combining of a cognitive-behavioral therapy and sertraline for PTSD/AUD . Clinical ly significant reductions in both PTSD and AUD severity were achieved and sustained through 12-months follow-up , Moreover , greater mean improvement in PTSD symptoms was observed across all follow-up assessment s in the SS plus sertraline group . ( PsycINFO Data base BACKGROUND Individuals with comorbid substance use and posttraumatic stress disorder may differentially benefit from integrated trauma-focused interventions based on specific presenting characteristics such as substance use type and PTSD severity . The current study is a secondary analysis of a NIDA Clinical Trials Network study exploring the effectiveness of two interventions for women with comorbid PTSD and substance use disorders . METHOD Generalized estimating equations were used to examine the association of baseline alcohol misuse with PTSD outcome measures over time for all r and omized participants . RESULTS Women entering treatment with baseline alcohol misuse had higher Post Traumatic Stress Disorder Symptom Scale ( PSS-SR ) total scores ( t=2.43 , p<.05 ) , cluster C ( avoidance/numbing ) scores ( t=2.63 , p<.01 ) , and cluster D ( hyper-arousal ) scores ( t=2.31 , p<.05 ) . For women with alcohol misuse , after treatment week 1 , PSS-SR scores were significantly lower in the Seeking Safety intervention during treatment ( chi(2)(1)=4.00 , p<.05 ) and follow-up ( chi(2)(1)=4.87 , p<.05 ) compared to those in the health education intervention . Alcohol misusers in the Seeking Safety group who had higher baseline hyper-arousal severity improved more quickly than those with lower baseline hyper-arousal severity during treatment ( chi(2)(1)=4.06 , p<.05 ) . CONCLUSIONS These findings suggest that the type of substance abuse at treatment entry may inform treatment selection , predict treatment response among those with co-occurring PTSD and substance use disorders , and indicate a more severe clinical picture This r and omized , controlled trial evaluated a manualized psychotherapy , Seeking Safety ( SS ) , for posttraumatic stress disorder ( PTSD ) and substance use disorder ( SUD ) in adolescent females . To our knowledge , no prior study has evaluated any psychotherapy design ed for this population . SS was compared to treatment as usual ( TAU ) for 33 out patients , at intake , end-of-treatment , and 3 months follow-up . SS evidence d significantly better outcomes than TAU in a variety of domains at posttreatment , including substance use and associated problems , some trauma-related symptoms , cognitions related to SUD and PTSD , and several areas of pathology not targeted in the treatment ( e.g. , anorexia , somatization ) . Effect sizes were generally in the moderate to high range . Some gains were sustained at follow-up . SS appears a promising treatment for this population , but needs further study and perhaps additional clinical modification Background : The stimulant methylpheni date ( MPH ) has been a mainstay of treatment for attention-deficit/hyperactivity disorder ( ADHD ) for many years . Owing to the short half-life and the issues associated with multiple daily dosing of immediate-release MPH formulations , a new generation of long-acting MPH formulations has emerged . Direct head-to-head studies of these long-acting MPH formulations are important to facilitate an evaluation of their comparative pharmacokinetics and efficacy ; however , to date , relatively few head-to-head studies have been performed . The objective of this systematic review was to compare the evidence available from head-to-head studies of long-acting MPH formulations and provide information that can guide treatment selection . Methods : A systematic literature search was conducted in MEDLINE and PsycINFO in March 2012 using the MeSH terms : attention deficit disorder with hyperactivity/drug therapy ; methylpheni date /therapeutic use and All Fields : Concerta ; Ritalin LA ; OROS and ADHD ; Medikinet ; Equasym XL and ADHD ; long-acting methylpheni date ; Diffucaps and ADHD ; SODAS and methylpheni date . No filters were applied and no language , publication date or publication status limitations were imposed . Articles were selected if the title indicated a comparison of two or more long-acting MPH preparations in human subjects of any age ; non- systematic review articles and unpublished data were not included . Results : Of 15,295 references returned in the literature search and screened by title , 34 articles were identified for inclusion : nine articles from pharmacokinetic studies ( nine studies ) ; nine articles from laboratory school studies ( six studies ) ; two articles from r and omized controlled trials ( two studies ) ; three articles from switching studies ( two studies ) and three articles from one observational study . Conclusions : Emerging head-to-head studies provide important data on the comparative efficacy of the formulations available . At a group level , efficacy across the day generally follows the pharmacokinetic profile of the MPH formulation . No formulation is clearly superior to another ; careful consideration of patient needs and subtle differences between formulations is required to optimize treatment . For patients achieving suboptimal symptom control , switching long-acting MPH formulations may be beneficial . When switching formulations , it is usually appropriate to titrate the immediate-release component of the formulation ; a limitation of current studies is a focus on total daily dose rather than equivalent immediate-release components . Further studies are necessary to provide guidance in clinical practice , particularly in the treatment of adults and pre-school children and the impact of comorbidities and symptom severity on treatment response BACKGROUND Posttraumatic stress disorder ( PTSD ) and substance use disorders ( SUD ) frequently co-occur . Previous research demonstrates the utility of goals in attaining improved SUD outcomes , however , no previous studies have examined goal choices in the context of integrated treatment for comorbid PTSD and SUD . OBJECTIVES The present study investigated correlates of treatment entry goals to either reduce or abstain from substance use . METHODS Participants ( N = 60 ) were treatment-seeking veterans with current PTSD and SUD . Participants completed self-report and clinician-rated measures of substance use , PTSD , and affective symptoms as part of a larger r and omized controlled trial . RESULTS Half ( 30/60 ) of participants endorsed a treatment entry goal to reduce substance use ( reducers ) . Compared to participants who endorsed a treatment entry goal of abstinence ( abstainers ) , reducers were significantly younger , more likely to be employed , more likely to have served in recent military conflicts ( Operations Enduring/Iraqi Freedom ) , and endorsed significantly fewer symptoms of alcohol dependence . CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE The findings demonstrate clinical ly relevant differences based on treatment entry goals , suggesting that individuals are often able to choose conceivably appropriate treatment goals based , most notably , on the severity of their SUD . Collaboratively engaging patients in establishing treatment goals that are consistent with their beliefs and desires in conjunction with empirical findings is particularly relevant in the context of treatment for SUD and PTSD where many patients are ambivalent about treatment and attrition is common This study examined the efficacy of a condensed version of the Seeking Safety intervention in the reduction of trauma-related symptoms and improved drug abstinence rates among women in residential chemical dependence treatment . One hundred and four women were r and omly assigned to treatment including a condensed ( six session ) Seeking Safety intervention or the st and ard chemical dependence intervention . The Seeking Safety participants reported lower sexual-abuse-related trauma symptoms at 30 days posttreatment as compared to participants who received only st and ard treatment . However , the condensed Seeking Safety intervention was not more advantageous in reducing overall trauma symptoms or relapse 30 days after treatment ended OBJECTIVE The authors ' goal was to compare the efficacy of a manualized cognitive behavior therapy that addresses both posttraumatic stress disorder ( PTSD ) and substance abuse ( seeking safety ) with a manualized cognitive behavior therapy that addresses only substance abuse ( relapse prevention ) and with st and ard community care for the treatment of comorbid posttraumatic stress disorder ( PTSD ) and substance use disorder . METHOD One hundred seven women from an urban , low-income population who had comorbid PTSD and substance use disorder were r and omly assigned to receive the two kinds of cognitive behavior therapy or received st and ard community treatment . Participants were recruited from both community and clinical population s and evaluated with structured clinical instruments . Forty-one women received seeking safety therapy , 34 received relapse prevention therapy , and 32 received st and ard community care . RESULTS At the end of 3 months of treatment , participants in both cognitive behavior therapy conditions had significant reductions in substance use , PTSD , and psychiatric symptoms , but community care participants worsened over time . Both groups receiving cognitive behavior therapy sustained greater improvement in substance use and PTSD symptoms at 6-month and 9-month follow-ups than subjects in the community care group . CONCLUSIONS Seeking safety and relapse prevention are efficacious short-term treatments for low-income urban women with PTSD , substance use disorder , and other psychiatric symptoms With a sample ( N = 43 ) of participants meeting current diagnostic criteria for both alcohol dependence and posttraumatic stress disorder ( PTSD ) , the authors tested the hypothesis that alcohol craving elicited by a trauma cue might be attenuated if trauma-elicited negative emotion were reduced following trauma-focused imaginal exposure . In a laboratory-based experiment , participants were r and omly assigned to either trauma-focused imaginal exposure or imagery-based relaxation . A cue reactivity paradigm was used to assess alcohol craving prior to , and after completion of , the 6 clinical sessions . Attrition was high but did not differ between experimental conditions . For study completers , PTSD symptoms decreased in the exposure condition but not in the relaxation condition . Alcohol craving and distress elicited by trauma images decreased in the exposure condition but did not change in the relaxation condition . Results support the hypothesis that negative emotion is a mechanism of alcohol craving Background This r and omized controlled trial ( RCT ) investigated the effectiveness of a combined treatment for co-morbid Posttraumatic Stress Disorder ( PTSD ) and severe Substance Use Disorder ( SUD ) . Methods Structured Writing Therapy for PTSD ( SWT ) , an evidence -based traumafocused intervention , was added on to Treatment As Usual ( TAU ) , consisting of an intensive cognitive behavioral inpatient or day group treatment for SUD . The outcomes of the combined treatment ( TAU + SWT ) were compared to TAU alone in a sample of 34 patients . Results Results showed a general reduction of SUD symptoms for both TAU + SWT and TAU . Treatment superiority of TAU + SWT was neither confirmed by interaction effects ( time x condition ) for SUD or PTSD symptoms , nor by a group difference for SUD diagnostic status at post-treatment . However , planned contrasts revealed that improvements for PTSD severity over time were only significant within the TAU + SWT group . In addition , within the TAU + SWT group the remission of PTSD diagnoses after treatment was significant , which was not the case for TAU . Finally , at post-treatment a trend was noticed for between group differences for the number of PTSD diagnoses favoring TAU + SWT above TAU . Conclusions In sum , the current study provides preliminary evidence that adding a trauma-focused treatment on to st and ard SUD treatment may be beneficial Background Traumatic experiences and , more specifically , posttraumatic stress disorder ( PTSD ) are highly prevalent among substance use disorder ( SUD ) patients . This comorbidity is associated with worse treatment outcomes in substance use treatment programs and more crisis interventions . International guidelines advise an integrated approach to the treatment of trauma related problems and SUD . Seeking Safety is an integrated treatment program that was developed in the United States . The aim of the current study is to test the efficacy of this program in the Netherl and s in an outpatient SUD population . Methods / Design A r and omized controlled trial ( RCT ) will be used to test the efficacy of Seeking Safety compared to Cognitive Behavioral Therapy ( CBT ) in a population of SUD out patients . Each treatment will consist of 12 group sessions . The primary outcome measure will be substance use severity . Secondary outcome measures are PTSD and trauma symptoms , coping skills , functioning , and cognitions . Question naires will be administered at the start of treatment , at the end of treatment ( three months after the start of treatment ) and at follow-up ( six months after the start of treatment ) . Discussion This study protocol presents a RCT in which the efficacy of an integrated treatment for comorbid PTSD and SUD , Seeking Safety , is evaluated in a SUD outpatient population compared to CBT . It is expected that the intervention group will show significantly more improvement in substance use severity compared to the control group at end-of-treatment and at follow-up . Furthermore , a lower drop-out rate is expected for the intervention group . If the intervention proves to be effective , it can be implemented . A cost-effectiveness analysis will be conducted to evaluate the two treatments . Trial registration The protocol for this study is registered with the Netherl and s Trial Register with number NTR3084 and approved by the local medical ethical committee ( METC\11270.haa ) BACKGROUND Alcohol misuse occurs at high rates among U.S. Military Veterans presenting to primary care and is linked to numerous negative social and health consequences . The Veterans Health Administration has recently implemented brief alcohol interventions ( BAI ) in VA primary care setting s. An emerging literature suggests that BAIs that target alcohol consumption may also have secondary health benefits such as reducing symptoms of depression and anxiety in civilian sample s. The present study sought to examine whether secondary health benefits of BAIs observed in civilians generalize to a sample of alcohol misusing Veterans presenting to primary care . METHODS Veterans ( N=167 ) screening positive for alcohol misuse during a routine primary care visit were r and omized to receive treatment-as-usual ( TAU ) or TAU plus a web-delivered BAI . Assessment of overall mental health functioning , posttraumatic stress disorder , and depression occurred at baseline , three- and six-month post-treatment . RESULTS Veterans receiving both BAI protocol s demonstrated significant improvements in mental health functioning , depressive symptoms , and use of approach coping from baseline to six-month follow-up . No differential treatment effects on these outcomes were observed . LIMITATIONS Findings are limited by the lack of a no-treatment control group , and the potential impact of regression to the mean and assessment effects on outcomes . CONCLUSIONS Our findings replicate prior studies suggesting that a single-dose BAI may have some secondary mental health benefits for Veterans presenting to primary care with alcohol misuse Laboratory studies have shown that exposure to trauma memories increases both craving and salivation responses to alcohol cues among individual with co-occurring posttraumatic stress disorder ( PTSD ) and alcohol dependence ( AD ) . The purpose of the present study was to examine 1 ) whether this cue reactivity is dampened following exposure-based treatment for PTSD and 2 ) how changes in reactivity to trauma cues correspond to changes in alcohol cue-reactivity . Adults with current PTSD and AD ( N = 120 ) were r and omly assigned to 9 - 12 sessions of either Trauma-focused Exposure Therapy ( EXP ) for PTSD or Health & Lifestyles ( HLS , a non-trauma focused comparison treatment ) , concurrent with 6-week residential AD treatment-as-usual . Participants completed trauma and alcohol cue-reactivity laboratory sessions before and after treatment . Compared to HLS , individuals receiving EXP showed significantly greater reductions in negative affect elicited by trauma cues following treatment . Both treatments demonstrated similar , moderate to large reductions in craving and salivary reactivity over time . Interestingly , latent change in trauma cue-elicited distress over the course of treatment predicted latent change in both trauma cue-elicited alcohol craving and salivation . Overall , findings highlight the utility of integrating trauma-focused therapies like EXP into substance use treatment in the interests of reducing PTSD symptoms and distress associated with trauma cues A substantial number of women who enter substance abuse treatment have a history of trauma and meet criteria for posttraumatic stress disorder ( PTSD ) . Fear regarding the extent to which PTSD treatment can evoke negative consequences remains a research question . This study explored adverse events related to the implementation of an integrated treatment for women with trauma and substance use disorder ( Seeking Safety ) compared with a nontrauma-focused intervention ( Women 's Health Education ) . Three hundred fifty-three women enrolled in community substance abuse treatment were r and omized to 1 of the 2 study groups and monitored weekly for adverse events . There were no differences between the two intervention groups in the number of women reporting study -related adverse events ( 28 [ 9.6 % ] for the Seeking Safety group and 21[7.2 % ] for the Women 's Health Education group ) . Implementing PTSD treatment in substance abuse treatment programs appears to be safe , with minimal impact on intervention-related adverse psychiatric and substance abuse symptoms . More research is needed on the efficacy of such interventions to improve outcomes of PTSD and substance use CONTEXT There is concern that exposure therapy , an evidence -based cognitive-behavioral treatment for posttraumatic stress disorder ( PTSD ) , may be inappropriate because of risk of relapse for patients with co-occurring substance dependence . OBJECTIVE To determine whether an integrated treatment for PTSD and substance dependence , Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure ( COPE ) , can achieve greater reductions in PTSD and substance dependence symptom severity compared with usual treatment for substance dependence . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial enrolling 103 participants who met DSM-IV-TR criteria for both PTSD and substance dependence . Participants were recruited from 2007 - 2009 in Sydney , Australia ; outcomes were assessed at 9 months postbaseline , with interim measures collected at 6 weeks and 3 months postbaseline . INTERVENTIONS Participants were r and omized to receive COPE plus usual treatment ( n = 55 ) or usual treatment alone ( control ) ( n = 48 ) . COPE consists of 13 individual 90-minute sessions ( ie , 19.5 hours ) with a clinical psychologist . MAIN OUTCOME MEASURES Change in PTSD symptom severity as measured by the Clinician-Administered PTSD Scale ( CAPS ; scale range , 0 - 240 ) and change in severity of substance dependence as measured by the number of dependence criteria met according to the Composite International Diagnostic Interview version 3.0 ( CIDI ; range , 0 - 7 ) , from baseline to 9-month follow-up . A change of 15 points on the CAPS scale and 1 dependence criterion on the CIDI were considered clinical ly significant . RESULTS From baseline to 9-month follow-up , significant reductions in PTSD symptom severity were found for both the treatment group ( mean difference , -38.24 [ 95 % CI , -47.93 to -28.54 ] ) and the control group ( mean difference , -22.14 [ 95 % CI , -30.33 to -13.95 ] ) ; however , the treatment group demonstrated a significantly greater reduction in PTSD symptom severity ( mean difference , -16.09 [ 95 % CI , -29.00 to -3.19 ] ) . No significant between-group difference was found in relation to improvement in severity of substance dependence ( 0.43 vs 0.52 ; incidence rate ratio , 0.85 [ 95 % CI , 0.60 to 1.21 ) , nor were there any significant between-group differences in relation to changes in substance use , depression , or anxiety . CONCLUSION Among patients with PTSD and substance dependence , the combined use of COPE plus usual treatment , compared with usual treatment alone , result ed in improvement in PTSD symptom severity without an increase in severity of substance dependence . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N12908171 OBJECTIVE The purpose of this study was to test the efficacy of 2 brief interventions for alcohol misuse in a sample of combat veterans of the wars in Iraq and Afghanistan . METHOD Participants were 68 combat veterans ( 91.2 % male ; 64.7 % White , 27.9 % Black ) with a mean age of 32.31 years ( SD = 8.84 ) who screened positive for hazardous drinking in a Veterans Affairs Medical Center primary care clinic using the Alcohol Use Disorders Identification Test ( Babor , Higgins-Biddle , Saunders , & Monteiro , 2001 ) . More than half of the sample ( 57.4 % ) met criteria for posttraumatic stress disorder ( PTSD ; based on the Clinician-Administered PTSD Scale ; Blake et al. , 1995 ) . Eligible veterans who elected to participate completed a baseline assessment and were r and omized to receive 1 of 2 interventions ( personalized feedback delivered with or without a motivational interviewing counseling session ) . Both interventions included information on hazardous drinking , PTSD symptoms , depression , and coping . Follow-up assessment s were conducted at 6 weeks and 6 months post-intervention . RESULTS Both conditions result ed in statistically significant reductions in quantity and frequency of alcohol use as well as frequency of binge drinking and alcohol-related consequences . Within-group effect sizes ( ds ) were in the small to medium range ( .21-.55 ) for quantity and frequency of alcohol use . There were no statistically significant Condition × Time interactions , suggesting that both interventions were similarly effective . PTSD and non-PTSD veterans responded equally well to both interventions , but veterans with PTSD assigned to feedback plus motivational interviewing reported greater reductions in weekly drinking at the 6-week follow-up . CONCLUSIONS These findings suggest that brief interventions for alcohol misuse may be effective for reducing drinking , even in an Operation Enduring Freedom/Operation Iraqi Freedom veteran population with a high degree of PTSD The authors compared the effectiveness of the Seeking Safety group , cognitive-behavioral treatment for substance use disorder and posttraumatic stress disorder ( PTSD ) , to an active comparison health education group ( Women 's Health Education [ WHE ] ) within the National Institute on Drug Abuse 's Clinical Trials Network . The authors r and omized 353 women to receive 12 sessions of Seeking Safety ( M = 6.2 sessions ) or WHE ( M = 6.0 sessions ) with follow-up assessment 1 week and 3 , 6 , and 12 months posttreatment . Primary outcomes were the Clinician Administered PTSD Scale ( CAPS ) , the PTSD Symptom Scale-Self Report ( PSS-SR ) , and a substance use inventory ( self-reported abstinence and percentage of days of use over 7 days ) . Intention-to-treat analysis showed large , clinical ly significant reductions in CAPS and PSS-SR symptoms ( d = 1.94 and 1.12 , respectively ) but no reliable difference between conditions . Substance use outcomes were not significantly different over time between the two treatments and at follow-up showed no significant change from baseline . Study results do not favor Seeking Safety over WHE as an adjunct to substance use disorder treatment for women with PTSD and reflect considerable opportunity to improve clinical outcomes in community-based treatments for these co-occurring conditions Abstract Objective : This study investigated the effects of st and ard eye movement desensitization and reprocessing ( EMDR ) protocol in chronically dependent patients . We propose that reprocessing traumatic memories with EMDR would lead to measurable changes of addiction symptoms . Method : Twelve patients with alcohol and /or drug dependency were r and omly assigned to one of two treatment conditions : treatment as usual ( TAU ) or TAU plus eight sessions of EMDR ( TAU+EMDR ) . Measures of PTSD symptoms , addiction symptoms , depression , anxiety , self-esteem , and alexithymia were included in this study . Results : The TAU+EMDR group showed a significant reduction in PTSD symptoms but not in addiction symptoms . EMDR treatment was also associated with a significant decrease in depressive symptoms , while patients receiving TAU showed no improvement in this area . The TAU+EMDR group also showed significant changes in self-esteem and alexithymia post-treatment . Conclusions : This study suggests that PTSD symptoms can be successfully treated with st and ard EMDR protocol in substance abuse patients BACKGROUND AND AIMS Post-traumatic stress disorder ( PTSD ) is common among people with substance use disorders , and the comorbidity is associated with negative outcomes . We report on a r and omized controlled trial comparing the effect of integrated cognitive-behavioral therapy ( ICBT ) plus st and ard care , individual addiction counseling plus st and ard care and st and ard care alone on substance use and PTSD symptoms . DESIGN Three-group , multi-site r and omized controlled trial . SETTING Seven addiction treatment programs in Vermont and New Hampshire , USA . PARTICIPANTS /CASES Recruitment took place between December 2010 and January 2013 . In this single-blind study , 221 participants were r and omized to one of three conditions : ICBT plus st and ard care ( SC ) ( n = 73 ) , individual addiction counseling ( IAC ) plus SC ( n = 75 ) or SC only ( n = 73 ) . One hundred and seventy-two patients were assessed at 6-month follow-up ( 58 ICBT ; 61 IAC ; 53 SC ) . Intervention and comparators : ICBT is a manual-guided therapy focused on PTSD and substance use symptom reduction with three main components : patient education , mindful relaxation and flexible thinking . IAC is a manual-guided therapy focused exclusively on substance use and recovery with modules organized in a stage-based approach : treatment initiation , early abstinence , maintaining abstinence and recovery . SC are intensive out-patient program services that include 9 - 12 hours of face-to-face contact per week over 2 - 4 days of group and individual therapies plus medication management . MEASUREMENTS Primary outcomes were PTSD severity and substance use severity at 6 months . Secondary outcomes were therapy retention . FINDINGS PTSD symptoms reduced in all conditions with no difference between them . In analyses of covariance , ICBT produced more favorable outcomes on toxicology than IAC or SC [ comparison with IAC , parameter estimate : 1.10 ; confidence interval ( CI ) = 0.17 - 2.04 ; comparison with SC , parameter estimate : 1.13 ; CI = 0.18 - 2.08 ] and had a greater reduction in reported drug use than SC ( parameter estimate : -9.92 ; CI = -18.14 to -1.70 ) . ICBT patients had better therapy continuation versus IAC ( P<0.001 ) . There were no unexpected or study -related adverse events . CONCLUSIONS Integrated cognitive behavioral therapy may improve drug-related outcomes in post-traumatic stress disorder sufferers with substance use disorder more than drug-focused counseling , but probably not by reducing post-traumatic stress disorder symptoms to a greater extent OBJECTIVE To examine the mechanisms of prolonged exposure ( PE ) and naltrexone ( NAL ) that underlie symptom reduction among individuals with comorbid posttraumatic stress disorder ( PTSD ) and alcohol dependence ( AD ) . We hypothesized that ( a ) reduction in negative cognitions mediates PTSD improvement during PE ; ( b ) reduction in alcohol craving mediates reduction in drinking frequency during NAL treatment ; and ( c ) PTSD improvement mediates reduction in craving and alcohol use during PE . METHOD Participants were 159 individuals meeting the DSM-IV diagnosis of PTSD and AD r and omly assigned to 1 of 4 conditions : PE + NAL , PE + placebo ( PBO ) , supportive counseling ( SC ) + NAL ; and SC + PBO . All participants received supportive counseling . RESULTS Lagged multilevel mediational analyses indicated that ( a ) a reciprocal relationship between cognitive change and PTSD improvement was observed in PE + NAL , PE + PBO , and SC + NAL , but not in SC + PBO ; ( b ) reduction in craving significantly mediated subsequent decrease in alcohol use in PE + NAL and SC + PBO , but not in PE + PBO and SC + NAL ; and ( c ) PTSD improvement significantly mediated subsequent reduction of craving in PE + PBO , and mediated decrease in alcohol use in PE + NAL . CONCLUSIONS The efficacy of combining PE and NAL for reducing alcohol use among those with comorbid PTSD/AD seems to be through reduction in both PTSD symptoms and craving . These findings shed light on the mechanism of PE and highlight the central role of PTSD in the maintenance of alcohol craving and use in patients with comorbid PTSD/AD Aims This study aim ed to test the efficacy of integrated cognitive behaviour therapy ( CBT ) for coexisting post traumatic stress disorder ( PTSD ) and alcohol use disorders ( AUD ) . Setting Clinics across Sydney , Australia . Design R and omized controlled trial of 12 once-weekly individual sessions of either integrated CBT for PTSD and AUD(integrated therapy , IT ; n = 33 ) or CBT for AUD plus supportive counselling ( alcohol-support , AS ; n = 29 ) . Blind assessment s were conducted at baseline and post-treatment and at 5 [ st and ard deviation ( SD ) = 2.25 ] and 9.16(SD = 3.45 ) months post-treatment . Participants Sixty-two adults with concurrent PTSD and AUD . Measurements Outcomes included changes in alcohol consumption ( time-line follow-back ) , PTSD severity [ clinician-administered PTSD scale ( CAPS ) ] , alcohol dependence and problems , and depression and anxiety . Findings Reductions in PTSD severity were evident in both groups . IT participants who had received one or more sessions of exposure therapy exhibited a twofold greater rate of clinical ly significant change in CAPS severity at follow-up than AS participants [ IT60 % , AS 39 % , odds ratio ( OR ) : 2.31 , 95 % confidence interval ( CI ) : 1.06 , 5.01 ] . AS participants exhibited larger reductions than IT participants in alcohol consumption , dependence and problems within the context of greater treatment from other services during follow-up . Results lend support to a mutually maintaining effect between AUD and PTSD . Conclusions Individuals with severe and complex presentations of coexisting post-traumatic stress disorder(PTSD ) and alcohol use disorders ( AUD ) can derive substantial benefit from cognitive behaviour therapy targeting AUD , with greater benefits associated with exposure for PTSD . Among individuals with dual disorders , these therapies can generate significant , well-maintained treatment effects on PTSD , AUD and psychopathology INTRODUCTION AND AIMS Despite advances towards integration of care for women with co-occurring substance use disorder ( SUD ) and post-traumatic stress disorder ( PTSD ) , low abstinence rates following SUD/PTSD treatment remain the norm . The utility of investigating distinct substance use trajectories is a critical innovation in the detection and refining of effective interventions for this clinical population . DESIGN AND METHODS The present study reanalysed data from the largest r and omised clinical trial to date for co-occurring SUD and PTSD in women ( National Drug Abuse Treatment Clinical Trials Network ; Women and Trauma Study ) . R and omised participants ( n = 353 ) received one of two interventions in addition to treatment as usual for SUD : ( i ) trauma-informed integrative treatment for PTSD/SUD ; or ( ii ) an active control psychoeducation course on women 's health . The present study utilised latent growth mixture models ( LGMM ) with multiple groups to estimate women 's substance use patterns during the 12-month follow-up period . RESULTS Findings provided support for three different trajectories of substance use in the post-treatment year : ( i ) consistently low likelihood and use frequency ; ( ii ) consistently high likelihood and use frequency ; and ( iii ) high likelihood and moderate use frequency . Covariate analyses revealed improvement in PTSD severity was associated with membership in a specific substance use trajectory , although receiving trauma-informed treatment was not . Additionally , SUD severity , age and after-care efforts were shown to be related to trajectory membership . DISCUSSION AND CONCLUSIONS Findings highlight the necessity of accounting for heterogeneity in post-treatment substance use , relevance of trauma-informed care in SUD recovery and benefits of incorporating method ologies like LGMM when evaluating SUD treatment outcomes The present study investigates the prevalence of comorbid posttraumatic stress disorder ( PTSD ) in a sample of Polish alcohol dependent patients and examines the relationship between comorbid PTSD and alcohol use-related problems . Patients ( n=458 ) were recruited from r and omly chosen clinical setting s and were administered self-report measures of trauma exposure , PTSD symptomatology , and alcohol use-related problems . From this sample , 67 % of the patients reported having experienced at least one criterion A traumatic event , and 60 % of them reported multiple traumas . Approximately 25 % of them met the criteria for current PTSD . The only significant difference between the PTSD and non-PTSD groups was abuse/dependence of other psychoactive substances . However , patients reporting physical assaults committed by a non-stranger reported more frequent PTSD diagnosis , more extensive symptomatology , more conflicts with the law and more physical injuries due to drinking . The findings of the study confirm the importance of assessing trauma and PTSD in alcohol dependent patients OBJECTIVE Despite progress in epidemiologic research on posttraumatic stress disorder ( PTSD ) , little is known about factors that distinguish chronic from nonchronic PTSD . In a previous report , the authors identified a set of personal predispositions associated with PTSD following traumatic events in a general population sample of young adults . The purpose of this analysis was to identify characteristics of chronic PTSD and examine whether any of the suspected risk factors for PTSD was associated specifically with chronic PTSD . METHOD A r and om sample of 1,007 21- to 30-year-old members of a large health maintenance organization in the Detroit area was interviewed , using the National Institute of Mental Health Diagnostic Interview Schedule ( DIS ) , revised for DSM-III-R. The analysis was performed on data from 394 respondents who reported traumatic events , of whom 93 met criteria for PTSD . Chronic PTSD was defined as duration of symptoms for 1 year or more . RESULTS Persons with chronic PTSD ( N = 53 ) had , on the average , a significantly higher total number of PTSD symptoms and higher rates of overreactivity to stimuli that symbolized the stressor and interpersonal numbing than persons with nonchronic PTSD . The rates of one or more additional anxiety or affective disorders and a variety of medical conditions were higher in persons with chronic than nonchronic PTSD . Family history of antisocial behavior and female sex were associated specifically with chronic PTSD . CONCLUSIONS The findings suggest that chronic PTSD may be associated with specific risk factors and clinical features . Longitudinal data on the course of PTSD are needed to determine whether the distinct features and the medical and psychiatric histories of persons with chronic PTSD are complications attendant on a chronic course or coexisting disturbances that inhibit recovery We longitudinally investigated coping among male military veterans ( n = 98 ) with posttraumatic stress disorder ( PTSD ) symptomatology and a co-occurring substance use disorder ( SUD ) who participated in a r and omized controlled trial of seeking safety ( SS ) . Participants were r and omized to SS or intensive treatment-as-usual ( TAU ) for SUD . Coping ( active , avoidant , emotional discharge ) , and PTSD and SUD symptomatology were measured prior to and at the end of treatment , and at 6- and 12-month follow-ups . Among the total sample , we found that : ( a ) avoidant and emotional discharge , but not active , coping tended to be positively associated with PTSD and SUD symptomatology at baseline ; ( b ) active coping increased and avoidant and emotional discharge coping decreased during the 12-month time-period ; and ( c ) avoidant and emotional discharge , but not active , coping longitudinally covaried with PTSD and SUD symptomatology . Results suggest the utility of targeting maladaptive coping in treatments for individuals with co-occurring PTSD and SUD Psychological trauma and post-traumatic stress disorder ( PTSD ) may complicate and reduce the effectiveness of treatment for substance use disorders ( SUDs ) . This study assessed trauma history and symptoms of simple and complex PTSD at baseline in a r and omized trial of contingency management ( CM ) compared to st and ard treatment ( ST ) with 142 cocaine- or heroin-dependent out patients . History of exposure to each of eight types of psychological trauma was unrelated to treatment outcome , except for witnessed assaults and emotional abuse . Complex PTSD symptoms were inversely associated with short-term treatment outcomes , and PTSD symptoms were positively related to long-term outcome , independent of the effects of demographics , psychological distress , baseline substance use status , and treatment modality . Complex PTSD symptoms warrant further study as a potential negative prognostic factor in SUD interventions BACKGROUND AND OBJECTIVES Previous research has been inconclusive about whether adding psychosocial treatment to medication assisted treatment ( MAT ) improves outcomes for patients with co-occurring psychiatric and opioid use disorders . This study evaluated the impact of MAT and psychosocial therapies on treatment outcomes for patients with co-occurring opioid use disorders and PTSD . METHODS Patients meeting criteria for PTSD and substance use disorders were r and omly assigned to one of three treatment conditions : St and ard Care ( SC ) alone , Integrated Cognitive Behavioral Therapy ( ICBT ) plus SC , or Individual Addiction Counseling ( IAC ) plus SC . Substance use and psychiatric symptoms were assessed at baseline and 6 months . Only patients with opioid use disorders were included in the present analyses ( n = 126 ) . Two-way ANOVAS and logistic regression analyses were used to examine associations between treatment conditions and MAT , for substance use and psychiatric outcomes . RESULTS MAT patients receiving ICBT had significantly decreased odds of a positive urine drug screen , compared to non-MAT patients receiving SC alone ( OR = .07 , 95 % CI = .01 , .81 , p = .03 ) . For PTSD symptoms , a significant MAT by psychosocial treatment condition interaction demonstrated that MAT patients had comparable declines in PTSD symptoms regardless of psychosocial treatment type ( F(2 , 88 ) = 4.74 , p = .011 ) . Non-MAT patients in ICBT had significantly larger reductions in PTSD . CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE For patients with co-occurring opioid use disorders and PTSD , MAT plus ICBT is associated with more significant improvement in substance use . For non-MAT patients , ICBT is most beneficial for PTSD symptoms BACKGROUND : Little is known about the impact of childhood trauma ( CT ) on the clinical profile of individuals with co-occurring substance use disorder ( SUD ) and post traumatic stress disorder ( PTSD ) . AIMS : To compare the clinical characteristics of individuals with SUD+PTSD who have a history of CT with SUD+PTSD individuals who have experienced trauma during adulthood only . METHOD : Data were collected on 103 individuals as part of a r and omised controlled trial examining the efficacy of an integrated psychosocial treatment for SUD+PTSD . Participants were recruited from substance use treatment services , community referrals and advertising . Data were collected on demographic characteristics , substance use and treatment histories , lifetime trauma exposure , and current physical and mental health functioning . RESULTS : The vast majority ( 77 % ) of the sample had experienced at least one trauma before the age of 16 , with 55 % of those endorsing childhood sexual abuse . As expected individuals with a CT history , as compared to without , evidence d significantly longer duration of PTSD . Those with a CT history also had more extensive lifetime trauma exposure , an earlier age of first intoxication , and reported more severe substance use ( e.g. , a greater number of drug classes used in their lifetime , higher severity of dependence scores and greater number of drug treatment episodes ) . CONCLUSION : Individuals with co-morbid SUD+PTSD who have experienced CT present with a more severe and chronic clinical profile in relation to a number of trauma and substance use characteristics , when compared to individuals with adulthood only trauma histories . It is therefore important for SUD+PTSD treatment planning that CT be carefully assessed OBJECTIVE This study sought to examine whether a web-delivered brief alcohol intervention ( BAI ) is effective for reducing alcohol misuse in U.S. military veterans presenting to primary care . METHOD Veterans ( N = 167 ) screening positive for alcohol misuse during a routine primary care visit were r and omized to receive a BAI plus treatment as usual ( TAU ) or TAU alone . An assessment of alcohol-related outcomes was conducted at baseline and 3 and 6 months after treatment . RESULTS Veterans in both study conditions showed a significant reduction in alcohol quantity and frequency and alcohol-related problems at 6-month follow-up . No differential treatment effects on outcomes were observed between the two treatment groups . CONCLUSIONS This study is the first to explore whether a web-delivered BAI using normative feedback is effective for veterans with alcohol misuse . Our findings suggest that BAIs using normative feedback may not have any additional benefit beyond TAU for older veterans with high rates of comorbid mental health concerns Abstract Background : The challenges of implementing and sustaining evidence -based therapies into routine practice have been well-documented . Objectives : This study examines the relationship among clinician factors , quality of therapy delivery , and patient outcomes . Methods : Within a r and omized controlled trial , 121 patients with current co-occurring substance use and posttraumatic stress disorders were allocated to receive either manualized Integrated Cognitive Behavioral Therapy ( ICBT ) or Individual Addiction Counseling ( IAC ) . Twenty-two clinicians from seven addiction treatment programs were trained and supervised to deliver both therapies . Clinician characteristics were assessed at baseline ; clinician adherence and competence were assessed over the course of delivering both therapies ; and patient outcomes were measured at baseline and 6-month follow-up . Results : Although ICBT was delivered at acceptable levels , clinicians were significantly more adherent to IAC ( p < 0.05 ) . At session 1 , clinical female gender ( p < 0.05 ) and lower education level ( p < 0.05 ) were predictive of increased clinician adherence and competence across both therapies . Adherence and competence at session 1 in either therapy were significantly predictive of positive patient outcomes . ICBT adherence ( p < 0.05 ) and competence ( p < 0.01 ) were predictive of PTSD symptom reduction , whereas IAC adherence ( p < 0.01 ) and competence ( p < 0.01 ) were associated with decreased drug problem severity . Conclusions : The differential impact of adherence and competence for both therapy types is consistent with their purported primary target : ICBT for PTSD and IAC for substance use . These findings also suggest the benefits of considering clinician factors when implementing manual-guided therapies . Future research should focus on diverse clinician sample s , r and omization of clinicians to therapy type , and prospect i ve design s to evaluate models of supervision and quality monitoring OBJECTIVE This secondary analysis investigated the impact of 12 sessions of Seeking Safety ( SS ) on reducing posttraumatic stress disorder ( PTSD ) symptoms in a sample of dually diagnosed women with physical disabilities versus nondisabled ( ND ) women . SS is an evidence -based and widely implemented manualized therapy for PTSD and /or substance use disorder . It is a present-focused model that promotes coping skills and psychoeducation . DESIGN As part of the National Institute on Drug Abuse Clinical Trials Network ( NIDA CTN ) , 353 participants with current PTSD and substance use disorder ( SUD ) were r and omly assigned to partial-dose SS or Women 's Health Education ( WHE ) group therapy conducted in community-based substance abuse treatment programs . The women were categorized as participants with disabilities ( PWD ; n = 20 ) or ND ( n = 333 ) based on the question , " Do you receive a pension for a physical disability ? " PTSD was assessed on the Clinician-Administered PTSD Scale ( CAPS ) at baseline and follow-ups after treatment ( 1 week , 3 months , 6 months , and 12 months ) . RESULTS PWD experienced sustained reductions in PTSD symptoms when treated with SS but not WHE . Indeed , PTSD symptoms of PWD in WHE returned to baseline levels of severity by 12-month follow-up . This pattern of results was not observed among ND women , who sustained improvements on PTSD in both treatment conditions . IMPLICATION S These results suggest strong potential for using SS to treat PTSD among women with physical disabilities , and speak to the genuine need to address trauma and PTSD more directly with PWD . Our results are also consistent with other findings from the NIDA CTN trial , in which virtually all significant results evidence d SS outperforming WHE Recent federal legislation and a renewed focus on integrative care models underscore the need for economical , effective , and science-based behavioral health care treatment . As such , maximizing the impact and reach of treatment research is of great concern . Behavioral health issues , including the frequent co-occurrence of substance use disorders ( SUD ) and posttraumatic stress disorder ( PTSD ) , are often complex , with a myriad of factors contributing to the success of interventions . Although treatment guides for comorbid SUD/PTSD exist , most patients continue to suffer symptoms following the prescribed treatment course . Further , the study of efficacious treatments has been hampered by method ological challenges ( e.g. , overreliance on " superiority " design s ( i.e. , design s structured to test whether or not one treatment statistically surpasses another in terms of effect sizes ) and short term interventions ) . Secondary analyses of r and omized controlled clinical trials offer potential benefits to enhance underst and ing of findings and increase the personalization of treatment . This paper offers a description of the limits of r and omized controlled trials as related to SUD/PTSD population s , highlights the benefits and potential pitfalls of secondary analytic techniques , and uses a case example of one of the largest effectiveness trials of behavioral treatment for co-occurring SUD/PTSD conducted within the National Drug Abuse Treatment Clinical Trials Network ( NIDA CTN ) and producing 19 publications . The paper concludes with implication s of this secondary analytic approach to improve addiction research ers ' ability to identify best practice s for community-based treatment of these disorders . Innovative methods are needed to maximize the benefits of clinical studies and better support SUD/PTSD treatment options for both specialty and non-specialty healthcare setting s. Moving forward , planning for and description of secondary analyses in r and omized trials should be given equal consideration and care to the primary outcome analysis A controlled trial of Seeking Safety ( SS ) and Male-Trauma Recovery Empowerment Model ( M-TREM ) examined implementation and effectiveness of integrated group therapy for comorbid post-traumatic stress disorder ( PTSD ) and substance use disorder ( SUD ) on PTSD and mental health symptoms plus self-esteem and efficacy for incarcerated men . The study sample ( n=230 ) was male inmates 18 years or older who were primarily non-white , high school graduates or equivalents , had childhood trauma histories , committed violent crimes , had serious mental illnesses , and resided in a maximum security prison . Incarcerated men , who screened positive for PTSD and SUD , were assigned r and omly ( n=142 ) or by preference ( n=88 ) to receive SS or M-TREM , with a waitlist group of ( n=93 ) . Manualized interventions were group-administered for 14 weeks . Primary outcomes were PTSD and other mental health symptoms . Secondary outcomes were self-esteem , coping , and self-efficacy . SUD outcomes can not be measured in a correctional setting . Implementation feasibility was exhibited by the ability to recruit , screen , assign , and retain participants . Effectiveness findings depended on sample , design , and method for analysis . Using a waitlist control group and no follow-up period , we found no aggregate effect of treatment on PTSD symptoms , although , when disaggregated , M-TREM was found to improve PTSD severity and SS improved general mental health symptoms and psychological functioning . Using intent-to-treat and completer analyses , no significant differences were found in the relative performance between SS and M-TREM on primary or secondary outcomes . When longitudinal data were maximized and modeled in ways that reflect the hierarchical nature of the data , we found that SS and M-TREM performed better than no treatment on PTSD severity and secondary outcomes , and that treatment benefits endured . Findings cautiously support implementing either Seeking Safety or M-TREM to treat incarcerated men with co-morbid PTSD and addiction problems OBJECTIVE This study assessed whether adding a telephone care management protocol to usual aftercare improved the outcomes of veterans in the year after they were discharged from residential treatment for posttraumatic stress disorder ( PTSD ) . METHODS In a multisite r and omized controlled trial , 837 veterans entering residential PTSD treatment were assigned to receive either st and ard outpatient aftercare ( N=425 ) or st and ard aftercare plus biweekly telephone monitoring and support ( N=412 ) for three months after discharge . Symptoms of PTSD and depression , violence , substance use , and quality of life were assessed by self-report question naires at intake , discharge , and four and 12 months postdischarge . Treatment utilization was determined from the Department of Veterans Affairs administrative data . RESULTS Telephone case monitors reached 355 participants ( 86 % ) by phone at least once and provided an average of 4.5 of the six calls planned . Participants in the telephone care and treatment-as-usual groups showed similar outcomes on all clinical measures . Time to rehospitalization did not differ by condition . In contrast with prior studies reporting poor treatment attendance among veterans , participants in both telephone monitoring and treatment as usual completed a mental health visit an average of once every ten days in the year after discharge . Many participants had continuing problems despite high utilization of outpatient care . CONCLUSIONS Telephone care management had little incremental value for patients who were already high utilizers of mental health services . Telephone care management could potentially be beneficial in setting s where patients experience greater barriers to engaging with outpatient mental health care after discharge from inpatient treatment OBJECTIVE The purpose of the analysis was to examine the temporal course of improvement in symptoms of posttraumatic stress disorder ( PTSD ) and substance use disorder among women in outpatient substance abuse treatment . METHOD Participants were 353 women r and omly assigned to 12 sessions of either trauma-focused or health education group treatment . PTSD and substance use assessment s were conducted during treatment and posttreatment at 1 week and after 3 , 6 , and 12 months . A continuous Markov model was fit on four defined response categories ( nonresponse , substance use response , PTSD response , or global response [ improvement in both PTSD and substance use ] ) to investigate the temporal association between improvement in PTSD and substance use symptom severity during the study 's treatment phase . A generalized linear model was applied to test this relationship over the follow-up period . RESULTS Subjects exhibiting nonresponse , substance use response , or global response tended to maintain original classification ; subjects exhibiting PTSD response were significantly more likely to transition to global response over time , indicating maintained PTSD improvement was associated with subsequent substance use improvement . Trauma-focused treatment was significantly more effective than health education in achieving substance use improvement , but only among those who were heavy substance users at baseline and had achieved significant PTSD reductions . CONCLUSIONS PTSD severity reductions were more likely to be associated with substance use improvement , with minimal evidence of substance use symptom reduction improving PTSD symptoms . Results support the self-medication model of coping with PTSD symptoms and an empirical basis for integrated interventions for improved substance use outcomes in patients with severe symptoms OBJECTIVES This study examined in- and post-treatment mediation effects of a 12-session dose of Seeking Safety (SS)-an integrative cognitive behavioral treatment for comorbid PTSD and SUDs-on alcohol and cocaine outcomes in comparison to Women 's Health Education ( WHE ) in a seven-site r and omized controlled effectiveness trial . METHODS Women ( n = 353 ) enrolled in outpatient substance abuse treatment , who had experienced multiple traumas in childhood and /or adulthood and who had comorbid PTSD , were r and omly assigned to receive SS or WHE delivered in open enrollment groups for 12 sessions in 6 weeks ( unlike the full 25-topic SS protocol ) . Data were analyzed under two forms of longitudinal mediation analysis , each accounting for changes over time in group membership and group context , respectively . RESULTS Women in SS , compared to WHE , showed significantly steeper decreases in PTSD frequency and severity , which in turn , showed significant impact in reducing both cocaine and alcohol use . This pattern was strongest for those who completed most of the treatment sessions , which was the majority of patients in the trial ; these patterns only emerged during the in-treatment phase . CONCLUSIONS Use of an integrated approach to PTSD/SUD such as SS can be helpful to more rapidly reduce PTSD , which consequently reduce SUD symptoms , particularly for those who attend most of the available treatment sessions . SCIENTIFIC SIGNIFICANCE This is one of the first studies to illustrate such effects in treating comorbid PTSD and SUD in the context of a highly impaired population delivered by community-based providers . ( Am J Addict 2014;23:218 - 225 ) Studies have shown strong associations between intimate partner violence ( IPV ) and both posttraumatic stress disorder ( PTSD ) and substance use disorders ( SUD ) . Despite these linkages , research on the dual diagnosis of PTSD-SUD and its relationship to IPV is in an early stage , and little is known about how PTSD-SUD treatment might influence IPV outcomes . The current study is a secondary analysis of a larger NIDA Clinical Trials Network study exploring the effectiveness of two behavioral interventions for women with comorbid PTSD-SUD . Participants ( n=288 ) were r and omly assigned to Seeking Safety ( SS ) , a cognitive-behavioral treatment that focuses on trauma and substance abuse symptoms , or to Women 's Health Education , a psychoeducational group . Logistic regressions were used to examine how treatment condition , identified risk factors and their interactions were related to IPV . Results showed that participants who were abstinent at baseline were significantly less likely to experience IPV over the 12-month follow-up period , whereas participants living with someone with an alcohol problem were significantly more likely to experience IPV over follow-up . Findings also showed that at a trend level participants with recent interpersonal trauma at baseline and higher total of lifetime trauma exposures were more likely to report IPV during follow-up . Although there was no main effect for treatment condition , a significant interaction between treatment condition and baseline abstinence was found . Participants who were abstinent at baseline and in the SS condition were significantly less likely to report IPV over follow-up . These findings indicate that an integrated treatment for PTSD and SUD was associated with significantly better IPV outcomes for a subset of individuals . The possibility that women with PTSD-SUD may differentially benefit from SS has important clinical implication s. Further research examining the intersection of PTSD , SUD and IPV , and the impact of treatment on a range of outcomes is needed OBJECTIVE The Recovery Management paradigm provides a conceptual framework for the examination of joint impact of a focal treatment and post-treatment service utilization on substance abuse treatment outcomes . We test this framework by examining the interactive effects of a treatment for comorbid PTSD and substance use , Seeking Safety , and post-treatment Twelve-Step Affiliation ( TSA ) on alcohol and cocaine use . METHOD Data from 353 women in a six-site , r and omized controlled effectiveness trial within the NIDA Clinical Trials Network were analyzed under latent class pattern mixture modeling . LCPMM was used to model variation in Seeking Safety by TSA interaction effects on alcohol and cocaine use . RESULTS Significant reductions in alcohol use among women in Seeking Safety ( compared to health education ) were observed ; women in the Seeking Safety condition who followed up with TSA had the greatest reductions over time in alcohol use . Reductions in cocaine use over time were also observed but did not differ between treatment conditions nor were there interactions with post-treatment TSA . CONCLUSIONS Findings advance underst and ing of the complexities for treatment and continuing recovery processes for women with PTSD and SUDs , and further support the chronic disease model of addiction Objective : Co-occurring posttraumatic stress ( PTSD ) and substance use disorders provide clinical challenges to addiction treatment providers . Interventions are needed that are effective , well-tolerated by patients , and capable of being delivered by typical clinicians in community setting s. This is a r and omized controlled trial of integrated cognitive behavioral therapy for co-occurring PTSD and substance use disorders . Methods : Fifty-three participants sample d from seven community addiction treatment programs were r and omized to integrated cognitive behavioral therapy plus st and ard care or individual addiction counseling plus st and ard care . Fourteen community therapists employed by these programs delivered both manual-guided therapies . Primary outcomes were PTSD symptoms , substance use symptoms , and therapy retention . Participants were assessed at baseline , 3- and 6-month follow-up . Results : Integrated cognitive behavioral therapy was more effective than individual addiction counseling in reducing PTSD re-experiencing symptoms and PTSD diagnosis . Individual addiction counseling was comparably effective to integrated cognitive behavioral therapy in substance use outcomes and on other measures of psychiatric symptom severity . Participants assigned to individual addiction counseling with severe PTSD were less likely to initiate and engage in the therapy than those assigned to integrated cognitive behavioral therapy . In general , participants with severe PTSD were more likely to benefit from integrated cognitive behavioral therapy . Conclusions : The findings support the promise of efficacy of integrated cognitive behavioral therapy in improving outcomes for persons in addiction treatment with PTSD . Community counselors delivered both interventions with satisfactory adherence and competence . Despite several limitations to this research , a larger r and omized controlled trial of integrated cognitive behavioral therapy appears to be warranted OBJECTIVE The present study examined predictors and moderators of treatment response among 165 adults meeting Diagnostic and Statistical Manual of Mental Disorders , fourth edition criteria for comorbid posttraumatic stress disorder ( PTSD ) and alcohol dependence ( AD ) , who were r and omized to 24 weeks of Naltrexone ( NAL ) , NAL and prolonged exposure ( PE ) , pill placebo , or pill placebo and PE . All participants received supportive counseling for alcohol use . METHOD Six domains of predictors or moderators ( 23 variables ) were evaluated using measures of PTSD ( Posttraumatic Stress Symptom Scale Interview ) and AD ( days drinking from the timeline follow-back interview ) collected every 4 weeks throughout treatment . Multilevel modeling with the Fournier approach was used to evaluate predictors and moderators of rates of symptom improvement and posttreatment outcomes . RESULTS Combat trauma , sexual assault trauma , and higher baseline anxiety sensitivity predicted slower improvement and poorer PTSD outcome . Combat trauma , White race , and higher baseline drinking severity predicted poorer drinking outcome . PTSD severity moderated the efficacy of PE on PTSD outcomes , such that the benefit of PE over no-PE was greater for participants with higher baseline PTSD severity . Baseline depressive severity moderated the efficacy of PE on drinking outcomes , whereby the benefit of PE over no-PE was greater for participants with higher depressive symptoms . NAL effects were most beneficial for those with the longest duration of AD . CONCLUSION These results suggest that concurrent , trauma-focused treatment should be recommended for PTSD-AD patients who present with moderate or severe baseline PTSD and depressive symptoms . Future research should examine the mechanisms underlying poorer outcome among identified subgroups of PTSD-AD patients OBJECTIVE This study uses data from the largest effectiveness trial to date on treatment of co-occurring posttraumatic stress and substance use disorders , using advances in statistical methodology for modeling treatment attendance and membership turnover in rolling groups . METHOD Women receiving outpatient substance abuse treatment ( N = 353 ) were r and omized to 12 sessions of Seeking Safety or a health education control condition . Assessment s were completed at baseline and at 1 week , 3 , 6 , and 12 months posttreatment . Outcome measures were alcohol and cocaine use in the prior 30 days captured using the Addiction Severity Index . Latent class pattern mixture modeling ( LCPMM ) was used to estimate attendance patterns and to test for treatment effects within and across latent attendance patterns and group membership turnover . RESULTS Across LCPMM analyses for alcohol and cocaine use , similar treatment attendance patterns emerged : Completers never decreased below an 80 % probability of attendance , droppers never exceeded a 41 % probability of attendance , and titrators demonstrated a 50 % to 80 % probability of attendance . Among completers , there were significant decreases in alcohol use from baseline to 1-week posttreatment , followed by nonsignificant increases in alcohol during follow-up . No differences between treatment conditions were detected . Titrators in Seeking Safety had lower rates of alcohol use from 1-week through 12-month follow-up compared with control participants . Droppers had nonsignificant increases in alcohol during both study phases . Cocaine use findings were similar but did not reach significance levels . CONCLUSIONS The impact of client self-modulation of treatment dosage and group membership composition may influence behavioral treatment outcomes among this population Posttraumatic stress disorder ( PTSD ) and alcohol dependence ( AD ) are frequently comorbid and the order in which they develop may affect the clinical presentation and response to treatment . This study compared 73 treatment-seeking participants who developed PTSD prior to developing AD ( " PTSD-first " ) with 64 participants who developed AD prior to developing PTSD ( " AD-first " ) on demographics , clinical presentation , and response to treatment for PTSD and AD . All participants received BRENDA , a medication management and motivational enhancement intervention and were r and omly assigned to either prolonged exposure ( PE ) for PTSD plus BRENDA or BRENDA alone and to either naltrexone ( NAL ) for AD or placebo ( PBO ) . Results showed that participants with AD-first were more likely to report low income , meet criteria for antisocial or borderline personality disorder , report an index trauma of physical assault , compared to those with PTSD-first . Conversely , participants with PTSD-first were more likely to report an index trauma of sexual assault or a combat experience . Notably , no group differences were observed in treatment outcome despite some differences in clinical presentation OBJECTIVE Co-occurring mental and substance use disorders are associated with worse outcomes than a single disorder alone . In this exploratory subgroup analysis of a r and omized trial , the authors hypothesized that providing chronic care management ( CCM ) for substance dependence in a primary care setting would have a beneficial effect among persons with substance dependence and major depressive disorder or posttraumatic stress disorder ( PTSD ) . METHODS Adults ( N=563 ) with alcohol dependence , drug dependence , or both were assigned to CCM or usual primary care . CCM was provided by a nurse care manager , social worker , internist , and psychiatrist . Clinical outcomes ( any use of opioids or stimulants or heavy drinking and severity of depressive and anxiety symptoms ) and treatment utilization ( emergency department use and hospitalization ) were measured at three , six , and 12 months after enrollment . Longitudinal regression models were used to compare r and omized arms within the subgroups of participants with major depressive disorder or PTSD . RESULTS Among all participants , 79 % met criteria for major depressive disorder and 36 % met criteria for PTSD at baseline . No significant effect of CCM was observed within either subgroup for any outcome , including any use of opioids or stimulants or heavy drinking , depressive symptoms , anxiety symptoms , and any hospitalizations or number of nights hospitalized . Among participants with depression , those receiving CCM had fewer days in the emergency department compared with the control group , but the finding was of only borderline significance ( p=.06 ) . CONCLUSIONS Among patients with co-occurring substance dependence and mental disorders , CCM was not significantly more effective than usual care for improving clinical outcomes or treatment utilization To test whether a modified version of prolonged exposure ( mPE ) can effectively treat posttraumatic stress disorder ( PTSD ) in individuals with co-occurring PTSD and substance dependence , an efficacy trial was conducted in which substance dependent treatment-seekers with PTSD ( N = 126 , male = 54.0 % , White = 79.4 % ) were r and omly assigned to mPE , mPE + trauma-focused motivational enhancement session ( mPE + MET-PTSD ) , or a health information-based control condition ( HLS ) . All participants were multiply traumatized ; the median number of reported traumas that satisfied DSM-IV Criterion A for PTSD was 8 . Treatment consisted of 9 - 12 60-min individual therapy sessions plus substance abuse treatment-as-usual . Participants were assessed at baseline , end-of-treatment , and at 3- and 6-months posttreatment . Both the mPE and mPE + MET-PTSD conditions achieved significantly better PTSD outcome than the control condition . The mPE + MET-PTSD and mPE conditions did not differ from one another on PTSD symptoms at end of treatment , 3- , or 6-month follow-up . Substance use outcomes did not differ between groups with all groups achieving 85.7%-97.9 % days abstinent at follow-up . In regard to clinical ly significant improvement in trauma symptoms , 75.8 % of the mPE participants , 60.0 % of the mPE + MET-PTSD participants , and 44.4 % of the HLS participants experienced clinical ly significant improvement at the end-of-treatment . Results indicate mPE , with or without an MET-PTSD session , can effectively treat PTSD in patients with co-occurring PTSD and substance dependence . In addition , mPE session lengths may better suit st and ard clinical practice and are associated with medium effect sizes . ( PsycINFO Data base While there is high level of comorbidity of PTSD and substance use disorders ( SUDs ) , little research has focused on the overlapping symptom constellation characteristic of both PTSD and substance use/withdrawal . This report describes two preliminary investigations that address this area . In the first study , the pattern of PTSD symptoms in a sample of women ( n = 28 ) seeking treatment for a SUD and comorbid with PTSD was compared with the symptom pattern of a sample of women ( n = 28 ) with PTSD only . The PTSD + SUD group evidence d significantly more symptoms in the avoidance and arousal symptom clusters than the PTSD-only group . At the individual symptom level , the PTSD + SUD group reported significantly more sleep disturbance than the PTSD-only group . It was also determined that the PTSD + SUD group reported greater traumatic-event exposure than the PTSD-only group . In the second study , PTSD symptoms were compared in a sample of alcohol- dependent and a sample of cocaine-dependent individuals with PTSD . The alcohol- dependent group exhibited significantly more arousal symptoms than the cocaine-dependent group . Implication s of the results for the assessment of individuals with comorbid PTSD and SUDs are discussed AIMS To determine whether substituting Seeking Safety ( SS ) , a manualized therapy for comorbid substance use disorders ( SUD ) and post-traumatic stress disorder ( PTSD ) for part of treatment-as-usual ( TAU ) improves substance use outcomes . DESIGN R and omized controlled effectiveness trial . SETTING S Out-patient Veterans Administration Health Care System SUD clinic . PARTICIPANTS Ninety-eight male military Veterans with a SUD and co-occurring PTSD symptomatology . MEASUREMENTS Drug and alcohol use and PTSD severity , measured on the first day of treatment , and 3 ( i.e. the planned end of SS sessions ) and 6 months following the baseline assessment . Treatment attendance and patient satisfaction were measured following treatment ( 3-month follow-up ) . Active coping was measured at treatment intake and following treatment . FINDINGS SS compared to TAU was associated with better drug use outcomes ( P < 0.05 ) , but alcohol use and PTSD severity decreased equally under both treatments ( P 's < 0.01 ) . SS versus TAU was associated with increased treatment attendance , client satisfaction and active coping ( all P 's < 0.01 ) . However , neither these factors nor decreases in PTSD severity mediated the effect of treatment on drug use . CONCLUSIONS The manualized treatment approach for substance use disorder , Seeking Safety , is well received and associated with better drug use outcomes than ' treatment as usual ' in male veterans with post-traumatic stress disorder . However , the mechanism of its effect is unclear AIMS The association between substance use disorder ( SUD ) and the perpetration of violence has been well documented . There is some evidence to suggest that the co-occurrence of post traumatic stress disorder ( PTSD ) may increase the risk for violence . This study aims to determine the prevalence of violence perpetration and examine factors related to violence amongst individuals with comorbid SUD and PTSD . DESIGN AND PARTICIPANTS Data was collected via interview from 102 participants recruited to a r and omised controlled trial of an integrated treatment for comorbid SUD and PTSD . MEASUREMENTS The interview addressed demographics , perpetration of violent crime , mental health including aggression , substance use , PTSD , depression , anxiety and borderline personality disorder . FINDINGS Over half of participants reported committing violence in their lifetime and 16 % had committed violence in the past month . Bivariate associations were found between violence perpetration and trait aggression , higher levels of alcohol and cannabis use , lower levels of other opiate use , and experiencing more severe PTSD symptoms , particularly in relation to hyperarousal . When entered into a backward stepwise logistic regression however , only higher levels of physical aggression and more severe PTSD hyperarousal symptoms remained as independent predictors of violence perpetration . CONCLUSIONS These findings highlight the importance of assessing for PTSD amongst those with SUD particularly in forensic setting s. They also indicate that it is the hyperarousal symptoms of PTSD specifically that need to be targeted by interventions aim ed at reducing violence amongst individuals with SUD and PTSD Cognitive processing therapy ( CPT ) is currently applied in military veteran mental health services in many countries . This study tests the effectiveness of community-administered CPT for military-related PTSD under r and omized controlled conditions . Fifty-nine treatment-seeking veterans with military-related PTSD were r and omly allocated to receive 12 twice-weekly 60 min sessions of CPT or an equivalent period of usual treatment at veterans ' community based counseling services . Intent to treat analyses found significantly greater improvement for participants receiving CPT over usual treatment at post-treatment and 3 month follow-up . CPT also produced greater improvements in anxiety , depression , social and dyadic relationships than usual treatment . No CPT related adverse events occurred during the trial . This trial reports the first r and omized controlled trial evidence that CPT is an effective treatment for military PTSD and co-morbid conditions when compared to usual treatment and delivered in community setting s by clinicians from diverse disciplines , preferred treatment orientation and levels of experience |
13,284 | 28,747,293 | No statistically significant differences were found on either outcome between studies using cognitive behavioral therapy ( CBT ) approaches ( as defined by the authors ) compared with other psychological approaches , offering guidance compared with self-guidance , or recruiting from a targeted workplace population compared with a universal workplace population .
In-depth analysis of the interventions identified by the positive deviance approach suggests that interventions that offer guidance are delivered over a shorter time frame ( 6 to 7 weeks ) , utilize secondary modalities for delivering the interventions and engaging users ( ie , emails and text messages [ short message service , SMS ] ) , and use elements of persuasive technology ( ie , self-monitoring and tailoring ) , which may achieve greater engagement and adherence .
Conclusions This review provides evidence that occupational digital mental health interventions can improve workers ’ psychological well-being and increase work effectiveness . | Background Stress , depression , and anxiety among working population s can result in reduced work performance and increased absenteeism .
Although there is evidence that these common mental health problems are preventable and treatable in the workplace , uptake of psychological treatments among the working population is low .
One way to address this may be the delivery of occupational digital mental health interventions .
While there is convincing evidence for delivering digital psychological interventions within a health and community context , there is no systematic review or meta- analysis of these interventions in an occupational setting .
Objective The aim of this study was to identify the effectiveness of occupational digital mental health interventions in enhancing employee psychological well-being and increasing work effectiveness and to identify intervention features associated with the highest rates of engagement and adherence . | Objective The purpose of this study was to develop a new Internet-based computerized cognitive behavior therapy ( iCBT ) program in Manga format , the Japanese cartoon , for workers and to examine the effects of the iCBT program on improving subthreshold depression using a r and omized controlled trial ( RCT ) design among workers employed in private companies in Japan . Method All workers in a company ( n = 290 ) and all workers in three departments ( n = 1,500 ) at the headquarters of another large company were recruited by an invitation e-mail . Participants who fulfilled the inclusion criteria were r and omly allocated to intervention or control groups ( N = 381 for each group ) . A six-week , six-lesson iCBT program using Manga ( Japanese comic ) story was developed . The program included several CBT skills : self-monitoring , cognitive restructuring , assertiveness , problem solving , and relaxation . The intervention group studied the iCBT program at a frequency of one lesson per week . Depression ( Beck Depression Inventory II ; BDI-II ) was assessed as a primary outcome at baseline , and three- and six-month follow-ups for both intervention and control groups were performed . Results The iCBT program showed a significant intervention effect on BDI-II ( t = −1.99 , p<0.05 ) with small effect sizes ( Cohen 's d : −0.16 , 95 % Confidence Interval : −0.32 to 0.00 , at six-month follow-up ) . Conclusions The present study first demonstrated that a computerized cognitive behavior therapy delivered via the Internet was effective in improving depression in the general working population . It seems critical to improve program involvement of participants in order to enhance the effect size of an iCBT program . Trial Registration UMIN Clinical Trials Registry Background Most work sites engage in some form of health promotion programming design ed to improve worker health and reduce health care costs . Although these programs have typically been delivered through combinations of seminars and print material s , workplace health promotion programs are increasingly being delivered through the Internet . Objective The purpose of this research was to evaluate the effectiveness of a Web-based multimedia health promotion program for the workplace , design ed to improve dietary practice s , reduce stress , and increase physical activity . Methods Using a r and omized controlled trial design with pretest-posttest comparisons within each group , 419 employees of a human re sources company were r and omly assigned to the Web-based condition or to a condition that provided print material s on the same topics . All subjects were assessed at pretest and posttest through an online question naire containing multiple measures of health behavior and attitudes . The test period was 3 months . Question naire data were analyzed mainly by analysis of covariance and t tests . Results Retention rates were good for both groups—85 % for the Web-based group and 87 % for the print group . Subjects using the Web-based program performed significantly better than the print group on Attitudes Toward a Healthful Diet ( F1,415 = 7.104 , P = .008 ) and Dietary Stage of Change ( F1,408 = 6.487 , P = .01 ) , but there were no significant group differences on the five other dietary measures . Both groups also showed improvement from pretest to posttest on most dietary measures , as indicated by significant t tests . Within the Web-based group , dosage analyses showed significant effects of the number of times the subject accessed the program on measures of Dietary Self-Efficacy ( F2,203 = 5.270 , P = .003 ) , Attitudes Toward a Healthful Diet ( F2,204 = 2.585 , P = .045 ) , and Dietary Stage of Change ( F2,200 = 4.627 , P = .005 ) . No significant differences were found between the two groups on measures of stress or physical activity , although t tests of pretest-posttest changes indicated that both groups improved on several of these measures . The Web-based group gave significantly higher ratings to the program material s than the print group on all health topics and in their overall evaluation ( F1,410 = 9.808 , P = .002 ) . Conclusions The Web-based program was more effective than print material s in producing improvements in the areas of diet and nutrition but was not more effective in reducing stress or increasing physical activity . The higher ratings given to the Web-based program suggest that workers preferred it to the print material s. Both groups showed numerous pretest-posttest improvements in all health topics , although such improvements might be attributable in part to a Hawthorne effect . Results suggest that a multimedia Web-based program can be a promising means of delivering health promotion material to the workforce , particularly in the area of diet and nutrition Background Depression and anxiety are major causes of absence from work and underperformance in the workplace . Cognitive behavioural therapy ( CBT ) can be effective in treating such problems and online versions offer many practical advantages . The aim of the study was to investigate the effectiveness of a computerized CBT intervention ( MoodGYM ) in a workplace context . Method The study was a phase III two-arm , parallel r and omized controlled trial whose main outcome was total score on the Work and Social Adjustment Scale ( WSAS ) . Depression , anxiety , psychological functioning , costs and acceptability of the online process were also measured . Most data were collected online for 637 participants at baseline , 359 at 6 weeks marking the end of the intervention and 251 participants at 12 weeks post-baseline . Results In both experimental and control groups depression scores improved over 6 weeks but attrition was high . There was no evidence for a difference in the average treatment effect of MoodGYM on the WSAS , nor for a difference in any of the secondary outcomes . Conclusions This study found no evidence that MoodGYM was superior to informational websites in terms of psychological outcomes or service use , although improvement to subthreshold levels of depression was seen in nearly half the patients in both groups Background Work-related stress is highly prevalent among employees and is associated with adverse mental health consequences . Web-based interventions offer the opportunity to deliver effective solutions on a large scale ; however , the evidence is limited and the results conflicting . Objective This r and omized controlled trial evaluated the efficacy of guided Web- and mobile-based stress management training for employees . Methods A total of 264 employees with elevated symptoms of stress ( Perceived Stress Scale-10 , PSS-10≥22 ) were recruited from the general working population and r and omly assigned to an Internet-based stress management intervention ( iSMI ) or waitlist control group . The intervention ( GET.ON Stress ) was based on Lazarus ’s transactional model of stress , consisted of seven sessions , and applied both well-established problem solving and more recently developed emotion regulation strategies . Participants also had the opportunity to request automatic text messages on their mobile phone along with the iSMI . Participants received written feedback on every completed session from an e-coach . The primary outcome was perceived stress ( PSS-10 ) . Web-based self-report assessment s for both groups were scheduled at baseline , 7 weeks , and 6 months . At 12 months , an extended follow-up was carried out for the iSMI group only . Results An intention-to-treat analysis of covariance revealed significantly large effect differences between iSMI and waitlist control groups for perceived stress at posttest ( F 1,261=58.08 , P<.001 ; Cohen ’s d=0.83 ) and at the 6-month follow-up ( F 1,261=80.17 , P<.001 ; Cohen ’s d=1.02 ) . The effects in the iSMI group were maintained at 12-month follow-up . Conclusions This Web- and mobile-based intervention has proven effective in reducing stress in employees in the long term . Internet-based stress management interventions should be further pursued as a valuable alternative to face-to-face interventions . Trial Registration German Clinical Trials Register ( DRKS ) : 00004749 ; http://drks-neu.uniklinik-freiburg.de/ drks_web/setLocale_EN.do ( Archived by WebCite at http://www.webcitation.org/6e8rl98nl PURPOSE Our goal was to evaluate the efficacy of a multimedia support program delivered over the Internet to employed family caregivers of persons with dementia . DESIGN AND METHODS The evaluation of this program involved 299 employed family caregivers participating in a pretest-posttest r and omized clinical trial with a 30-day follow-up and a waitlist control condition . Vali date d instruments include the Center for Epidemiologic Studies -Depression scale , the State-Trait Anxiety Inventory , the Caregiver Strain scale from Benjamin Rose , and Positive Aspects of Caregiving used in the nationwide REACH study . RESULTS Those who viewed Caregiver 's Friend : Dealing with Dementia 30 days postexposure demonstrated significant improvements in depression , anxiety , level and frequency of stress , caregiver strain , self-efficacy , and intention to seek help , as well as perceptions of positive aspects of caregiving . IMPLICATION S Interactive multimedia interventions delivered over the Internet appear to be uniquely suited to provide low-cost , effective , convenient , individually tailored programs that present educational information , cognitive and behavioral skills , and affective learning opportunities . This makes Web-based multimedia a promising avenue for work-life balance programs , employee-assistance providers , and organizations interested in improving family caregiver health and well-being BACKGROUND Depressive disorders are highly prevalent in the working population and are associated with excessive costs . The evidence for effective worker-directed interventions for employees with depressive symptoms is limited . Treating employees with depressive symptoms before sick leave via the Internet could be beneficial and cost saving . OBJECTIVE In this study , we developed and tested the effectiveness of a Web-based guided self-help course for employees with depressive symptoms . We report on the posttreatment effectiveness of the intervention . METHODS This study is a two-arm r and omized controlled trial comparing a Web-based guided self-help course to care as usual ( CAU ) . We recruited employees from 6 different companies via the companies ' intranet and posters . The main inclusion criterion was elevated depressive symptoms as measured by a score of ≥16 on the Center for Epidemiological Studies Depression scale ( CES-D ) . The intervention ( Happy@Work ) was based on problem-solving treatment and cognitive therapy and consisted of 6 weekly lessons . Participants were asked to su bmi t their weekly assignment via the website after completion . They subsequently received feedback from a coach via the website . Self-report question naires on depressive symptoms ( CES-D ; primary outcome ) , anxiety measured by the Hospital Anxiety and Depression Scale ( HADS ) , burnout measured by the Maslach Burnout Inventory ( MBI ) , and work performance measured by the Health and Work Performance Question naire ( HPQ ; secondary outcomes ) were completed at baseline and at posttreatment . RESULTS A total of 231 employees were r and omized to either the intervention group ( n=116 ) or CAU (n=115).The posttreatment assessment was completed by 171 ( 74.0 % ) participants . Both the intervention and the CAU group showed significant improvements in the primary outcome of depressive symptoms , but no differences between the conditions was found ( d=0.16 , 95 % CI -0.10 to 0.41 , P=.29 ) . Significant but small effects in favor of the intervention group were found for anxiety symptoms ( d=0.16 , 95 % CI -0.09 to 0.42 , P=.04 ) and exhaustion ( d=0.17 , 95 % CI -0.09 to 0.43 , P=.02 ) . CONCLUSIONS This study showed that a Web-based guided self-help course for employees with depressive symptoms was not more effective in reducing depressive symptoms among employees than CAU . Large improvements in depressive symptoms in the CAU group were unforeseen and potential explanations are discussed This study evaluated the effectiveness of a computer-based stress management training ( SMT ) program in improving employees ’ psychological well-being and work performance . A total of 12 work units ( N=263 ) were r and omly assigned to either an intervention group ( 8 work units , n=142 ) or to a wait-list control group ( 4 work units , n=121 ) . All participants were requested to answer online question naires assessing psychological well-being as a primary outcome , and coping style , social support , and knowledge about stress management as secondary outcomes at baseline ( T0 ) , immediately after the intervention ( T1 ) , and 2 months after the intervention ( T2 ) . The group × time interaction was tested using a mixed-model repeated measures ANOVA . Results showed a group × time interaction for “ knowledge about stress management ” in the entire sample . Among participants who had more than 3 d of training , a significant group × time interaction was observed for “ problem-solving ” and “ avoidance and suppression ” as well as “ knowledge about stress management . ” Our computer-based stress management program was effective for improving knowledge about stress management . It was also effective for improving coping skills in instances where participants had enough time ( at least 3 d ) to complete all sessions Objective : The objective of this study was to determine whether a mindfulness program , created for the workplace , was both practical and efficacious in decreasing employee stress while enhancing resiliency and well-being . Methods : Participants ( 89 ) recruited from The Dow Chemical Company were selected and r and omly assigned to an online mindfulness intervention ( n = 44 ) or wait-list control ( n = 45 ) . Participants completed the Perceived Stress Scale , the Five Facets of Mindfulness Question naire , the Connor-Davidson Resiliency Scale , and the Shirom Vigor Scale at pre- and postintervention and 6-month follow-up . Results : The results indicated that the mindfulness intervention group had significant decreases in perceived stress as well as increased mindfulness , resiliency , and vigor . Conclusions : This online mindfulness intervention seems to be both practical and effective in decreasing employee stress , while improving resiliency , vigor , and work engagement , thereby enhancing overall employee well-being Objective : To evaluate the effectiveness of a web-based multimedia health promotion program for the workplace , design ed to help reduce stress and to prevent depression , anxiety , and substance abuse . Methods : Using a r and omized controlled trial design , 309 working adults were r and omly assigned to the web-based condition or to a wait-list control condition . All participants were assessed on multiple self-reported outcomes at pretest and posttest . Results : Relative to controls , the web-based group reduced their stress , increased their knowledge of depression and anxiety , developed more positive attitudes toward treatment , and adopted a more healthy approach to alcohol consumption . Conclusions : We found that a brief and easily adaptable web-based stress management program can simultaneously reduce worker stress and address stigmatized behavioral health problems by embedding this prevention material into a more positive stress management framework Background . As distress in society increases , including work environments , individual capacities to compete with stress have to be strengthened . Objective . We examined the impact of a web-based happiness training on psychological and physiological parameters , by self-report and objective means , in an occupational health setting . Methods . R and omized controlled trial with 147 employees . Participants were divided into intervention ( happiness training ) and control groups ( waiting list ) . The intervention consisted of a seven-week online training . Question naires were administered before , after , and four weeks after training . The following scales were included : VAS ( happiness and satisfaction ) , WHO-5 Well-being Index , Stress Warning Signals , Freiburg Mindfulness Inventory , Recovery Experience Question naire , and Flourishing Scale . Subgroup sample s for saliva cortisol and alpha-amylase determinations were taken , indicating stress , and Attention Network Testing for effects on attention regulation . Results . Happiness ( P = 0.000 ; d = 0.93 ) , satisfaction ( P = 0.000 ; d = 1.17 ) , and quality of life ( P = 0.000 ; d = 1.06 ) improved ; perceived stress was reduced ( P = 0.003 ; d = 0.64 ) ; mindfulness ( P = 0.006 ; d = 0.62 ) , flourishing ( P = 0.002 ; d = 0.63 ) , and recovery experience ( P = 0.030 ; d = 0.42 ) also increased significantly . No significant differences in the Attention Network Tests and saliva results occurred ( intergroup ) , except for one saliva value . Conclusions . The web-based training can be a useful tool for stabilizing health/psychological well-being and work/life balance Objectives To examine the efficacy of early intervention on the prevention of long-term sickness absence and major depression among employees at high risk of future sickness absence and with mild to severe depressive complaints . Methods R and omised controlled trial conducted among employees working in an office environment . 139 employees were identified both at high risk of future sickness absence and with mild to severe depressive complaints through screening . Subsequently , they were r and omly assigned to the intervention group ( n=69 ) or the control group ( n=70 ) . Objective sickness absence was analysed at 12 and 18 months of follow-up . Depressive complaints were assessed by the Beck Depression Inventory ( BDI-II ) at baseline , and at 6 and 12 months of follow-up . Results Intention-to-treat analyses showed a significant difference in total sickness absence duration between the intervention ( 27.5 calendar days ( SD 44.7 ) ) and control group ( 50.8 days ( SD 75.8 ) ) over 12 months of follow-up , a reduction of 46 % ( p=0.017 ) . The intervention group showed a non-significantly lower proportion of long-term sickness absence spells compared with the control group ( p=0.127 ) . Statistically significant and clinical ly relevant differences in depressive complaints were found after both 6 months ( p=0.001 ) and 12 months ( p=0.005 ) of follow-up , in favour of the intervention group . Relative risk reductions ( RRR ) were 19.2 % and 19.8 % respectively . Sickness absence data were available for all participants over 18 months of follow-up . Question naire data were available for 99 ( at 6 months ) and 90 participants ( at 12 months ) . No adverse events or side effects occurred . Conclusions Early intervention in employees with mild to severe depressive complaints and high risk of future long-term sickness absence proved to be effective in preventing/reducing both sickness absence and depressive complaints Background Worldwide , depression is rated as the fourth leading cause of disease burden and is projected to be the second leading cause of disability by 2020 . Annual depression-related costs in the United States are estimated at US $ 210.5 billion , with employers bearing over 50 % of these costs in productivity loss , absenteeism , and disability . Because most adults with depression never receive treatment , there is a need to develop effective interventions that can be more widely disseminated through new channels , such as employee assistance programs ( EAPs ) , and directly to individuals who will not seek face-to-face care . Objective This study evaluated a self-guided intervention , using the MoodHacker mobile Web app to activate the use of cognitive behavioral therapy ( CBT ) skills in working adults with mild-to-moderate depression . It was hypothesized that MoodHacker users would experience reduced depression symptoms and negative cognitions , and increased behavioral activation , knowledge of depression , and functioning in the workplace . Methods A parallel two-group r and omized controlled trial was conducted with 300 employed adults exhibiting mild-to-moderate depression . Participants were recruited from August 2012 through April 2013 in partnership with an EAP and with outreach through a variety of additional non-EAP organizations . Participants were blocked on race/ethnicity and then r and omly assigned within each block to receive , without clinical support , either the MoodHacker intervention ( n=150 ) or alternative care consisting of links to vetted websites on depression ( n=150 ) . Participants in both groups completed online self- assessment surveys at baseline , 6 weeks after baseline , and 10 weeks after baseline . Surveys assessed ( 1 ) depression symptoms , ( 2 ) behavioral activation , ( 3 ) negative thoughts , ( 4 ) worksite outcomes , ( 5 ) depression knowledge , and ( 6 ) user satisfaction and usability . After r and omization , all interactions with subjects were automated with the exception of safety-related follow-up calls to subjects reporting current suicidal ideation and /or severe depression symptoms . Results At 6-week follow-up , significant effects were found on depression , behavioral activation , negative thoughts , knowledge , work productivity , work absence , and workplace distress . MoodHacker yielded significant effects on depression symptoms , work productivity , work absence , and workplace distress for those who reported access to an EAP , but no significant effects on these outcome measures for those without EAP access . Participants in the treatment arm used the MoodHacker app an average of 16.0 times ( SD 13.3 ) , totaling an average of 1.3 hours ( SD 1.3 ) of use between pretest and 6-week follow-up . Significant effects on work absence in those with EAP access persisted at 10-week follow-up . Conclusions This r and omized effectiveness trial found that the MoodHacker app produced significant effects on depression symptoms ( partial eta2 = .021 ) among employed adults at 6-week follow-up when compared to subjects with access to relevant depression Internet sites . The app had stronger effects for individuals with access to an EAP ( partial eta2 = .093 ) . For all users , the MoodHacker program also yielded greater improvement on work absence , as well as the mediating factors of behavioral activation , negative thoughts , and knowledge of depression self-care . Significant effects were maintained at 10-week follow-up for work absence . General attenuation of effects at 10-week follow-up underscores the importance of extending program contacts to maintain user engagement . This study suggests that light-touch , CBT-based mobile interventions like MoodHacker may be appropriate for implementation within EAPs and similar environments . In addition , it seems likely that supporting MoodHacker users with guidance from counselors may improve effectiveness for those who seek in-person support . Trial Registration Clinical Trials.gov NCT02335554 ; https:// clinical trials.gov/ct2/show/NCT02335554 ( Archived by WebCite at http://www.webcitation.org/6dGXKWjWE CONTEXT Although guideline -concordant depression treatment is clearly effective , treatment often falls short of evidence -based recommendations . Organized depression care programs significantly improve treatment quality , but employer purchasers have been slow to adopt these programs based on lack of evidence for cost-effectiveness from their perspective . OBJECTIVE To evaluate the effects of a depression outreach-treatment program on workplace outcomes , a concern to employers . DESIGN , SETTING , AND PARTICIPANTS A r and omized controlled trial involving 604 employees covered by a managed behavioral health plan were identified in a 2-stage screening process as having significant depression . Patient treatment allocation was concealed and assessment of depression severity and work performance at months 6 and 12 was blinded . Employees with lifetime bipolar disorder , substance disorder , recent mental health specialty care , or suicidality were excluded . INTERVENTION A telephonic outreach and care management program encouraged workers to enter outpatient treatment ( psychotherapy and /or antidepressant medication ) , monitored treatment quality continuity , and attempted to improve treatment by giving recommendations to providers . Participants reluctant to enter treatment were offered a structured telephone cognitive behavioral psychotherapy . MAIN OUTCOME MEASURES Depression severity ( Quick Inventory of Depressive Symptomatology , QIDS ) and work performance ( World Health Organization Health and Productivity Question naire [ HPQ ] , a vali date d self-report instrument assessing job retention , time missed from work , work performance , and critical workplace incidents ) . RESULTS Combining data across 6- and 12-month assessment s , the intervention group had significantly lower QIDS self-report scores ( relative odds of recovery , 1.4 ; 95 % confidence interval , 1.1 - 2.0 ; P = .009 ) , significantly higher job retention ( relative odds , 1.7 ; 95 % confidence interval , 1.1 - 3.3 ; P = .02 ) , and significantly more hours worked among the intervention ( beta=2.0 ; P=.02 ; equivalent to an annualized effect of 2 weeks of work ) than the usual care groups that were employed . CONCLUSIONS A systematic program to identify depression and promote effective treatment significantly improves not only clinical outcomes but also workplace outcomes . The financial value of the latter to employers in terms of recovered hiring , training , and salary costs suggests that many employers would experience a positive return on investment from outreach and enhanced treatment of depressed workers . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00057590 Objective This r and omised controlled trial ( RCT ) aim ed to evaluate the efficacy of a self-guided internet-based stress management intervention ( iSMI ) for employees compared to a 6-month wait-list control group ( WLC ) with full access for both groups to treatment as usual . Method A sample of 264 employees with elevated symptoms of perceived stress ( Perceived Stress Scale , PSS-10 ≥22 ) was r and omly assigned to either the iSMI or to the WLC . The iSMI consisted of seven sessions and one booster session including problem-solving and emotion regulation techniques . Self-report data were assessed at baseline , at 7 weeks and at 6 months following r and omisation . The primary outcome was perceived stress ( PSS-10 ) . The secondary outcomes included other relevant mental-related and work-related health outcomes . Data were analysed based on intention-to-treat principles . Results The iSMI participants showed a significantly higher reduction in perceived stress from baseline to post-treatment at 7 weeks ( d=0.96 , 95 % CI 0.70 to 1.21 ) and to the 6-month follow-up ( d=0.65 , 95 % CI 0.40 to 0.89 ) compared to the WLC . Significant differences with small to moderate effect sizes were also found for depression , anxiety , emotional exhaustion , sleeping problems , worrying , mental health-related quality of life , psychological detachment , emotion regulation skills and presenteeism , in favour of the experimental group . At the 6 -month follow-up , all outcomes remained significantly better for the experimental group with the exception of work engagement , physical health-related quality of life and absenteeism , which were not found to significantly differ between the iSMI and WLC groups . Conclusions The iSMI investigated in this study was found to be effective in reducing typical mental-related and work-related health symptoms of stressed employees . Internet-based self-guided interventions could be an acceptable , effective and potentially cost-effective approach to reduce the negative consequences associated with work-related stress Objective : The objective of this study is to determine the effectiveness of an 8-week web-based , mindfulness stress management program ( WSM ) in a corporate call center and added benefit of group support . Methods : One hundred sixty-one participants were r and omized to WSM , WSM with group support , WSM with group and expert clinical support , or wait-list control . Perceived stress , burnout , emotional and psychological well-being , mindfulness , and productivity were measured at baseline , weeks 8 and 16 , and 1 year . Results : Online usage was low with participants favoring CD use and group practice . All active groups demonstrated significant reductions in perceived stress and increases in emotional and psychological well-being compared with control . Group support improved participation , engagement , and outcomes . Conclusion : A self-directed mindfulness program with group practice and support can provide an affordable , effective , and scalable workplace stress management solution . Engagement may also benefit from combining web-based and traditional CD delivery OBJECTIVE The primary purpose of this r and omized controlled trial ( RCT ) was to evaluate the efficacy of internet-based problem-solving training ( iPST ) for employees in the educational sector ( teachers ) with depressive symptoms . The results of training were compared to those of a waitlist control group ( WLC ) . METHODS One-hundred and fifty teachers with elevated depressive symptoms ( Center for Epidemiologic Studies Depression Scale , CES-D ≥16 ) were assigned to either the iPST or WLC group . The iPST consisted of five lessons , including problem-solving and rumination techniques . Symptoms were assessed before the intervention began and in follow-up assessment s after seven weeks , three months , and six months . The primary outcome was depressive symptom severity ( CES-D ) . Secondary outcomes included general and work-specific self-efficacy , perceived stress , pathological worries , burnout symptoms , general physical and mental health , and absenteeism . RESULTS iPST participants displayed a significantly greater reduction in depressive symptoms after the intervention ( d=0.59 , 95 % CI 0.26 - 0.92 ) , after three months ( d=0.37 , 95 % CI 0.05 - 0.70 ) and after six months ( d=0.38 , 95 % CI 0.05 - 0.70 ) compared to the control group . The iPST participants also displayed significantly higher improvements in secondary outcomes . However , workplace absenteeism was not significantly affected . CONCLUSION iPST is effective in reducing symptoms of depression among teachers . Disseminated on a large scale , iPST could contribute to reducing the burden of stress-related mental health problems among teachers . Future studies should evaluate iPST approaches for use in other working population The aim of this study was to assess the effects of a 7‐week st and ardized cognitive behavioural treatment of work‐related stress conducted via e‐mail . A total of 342 people applied for treatment in reaction to a newspaper article . Initial screening reduced the sample to a heterogeneous ( sub ) clinical group of 239 participants . Participants were assigned r and omly to a waiting list condition ( n = 62 ) , or to immediate treatment ( n = 177 ) . A follow‐up was conducted 3 years after inception of the treatment . The outcome measures used were the Depression Anxiety Stress Scales ( DASS‐42 ) and the Emotional Exhaustion scale of the Maslach Burnout Inventory – General Survey ( MBI‐GS ) . Fifty participants ( 21 % ) dropped out . Both groups showed statistically significant improvements . Intention‐to‐treat analysis of covariance ( ANCOVAs ) revealed that participants in the treatment condition improved significantly more than those in the waiting control condition ( 0.001<p⩽0.025 ) . In the treatment group , the effects were large to moderate ( 0.9 (stress)⩾d⩾0.5 ( anxiety ) ) . The between‐group effects ranged from d = 0.6 ( stress ) to d = 0.1 ( anxiety ) . At follow‐up , the effects were more pronounced , but this result requires replication in view of high attrition at follow‐up . The results warrant further research on Internet‐driven st and ardized cognitive behavioural therapy for work‐related stress . Such research should include the direct comparison of this treatment with face‐to‐face treatment , and should address the optimal level of therapist contact in Internet‐driven treatment Background Nonadherence to treatment is a prevalent issue in Internet interventions . Guidance from health care professionals has been found to increase treatment adherence rates in Internet interventions for a range of physical and mental disorders . Evaluating different guidance formats of varying intensity is important , particularly with respect to improvement of effectiveness and cost-effectiveness . Identifying predictors of nonadherence allows for the opportunity to better adapt Internet interventions to the needs of participants especially at risk for discontinuing treatment . Objective The goal of this study was to investigate the influence of different guidance formats ( content-focused guidance , adherence-focused guidance , and administrative guidance ) on adherence and to identify predictors of nonadherence in an Internet-based mobile-supported stress management intervention ( ie , GET.ON Stress ) for employees . Methods The data from the groups who received the intervention were pooled from three r and omized controlled trials ( RCTs ) that evaluated the efficacy of the same Internet-based mobile-supported stress management intervention ( N=395 ) . The RCTs only differed in terms of the guidance format ( content-focused guidance vs waitlist control , adherence-focused guidance vs waitlist control , administrative guidance vs waitlist control ) . Adherence was defined by the number of completed treatment modules ( 0 - 7 ) . An ANOVA was performed to compare the adherence rates from the different guidance formats . Multiple hierarchical linear regression analysis was conducted to evaluate predictors of nonadherence , which included gender , age , education , symptom-related factors , and hope for improvement . Results In all , 70.5 % ( 93/132 ) of the content-focused guidance sample , 68.9 % ( 91/132 ) of the adherence-focused guidance sample , and 42.0 % ( 55/131 ) of the participants in the administrative guidance sample completed all treatment modules . Guidance had a significant effect on treatment adherence ( F2,392=11.64 , P<.001 ; ω2=.05 ) . Participants in the content-focused guidance ( mean 5.70 , SD 2.32 ) and adherence-focused guidance sample s ( mean 5.58 , SD 2.33 ) completed significantly more modules than participants in the administrative guidance sample ( mean 4.36 , SD 2.78 ; t223=4.53 , P<.001 ; r=.29 ) . Content-focused guidance was not significantly associated with higher adherence compared to adherence-focused guidance ( t262=0.42 , P=.67 ; r=.03 ) . The effect size of r=.03 ( 95 % CI –0.09 to 0.15 ) did not pass the equivalence margin of r=.20 and the upper bound of the 95 % CI lay below the predefined margin , indicating equivalence between adherence-focused guidance and content-focused guidance . Beyond the influence of guidance , none of the predictors significantly predicted nonadherence . Conclusions Guidance has been shown to be an influential factor in promoting adherence to an Internet-based mobile-supported stress management intervention . Adherence-focused guidance , which included email reminders and feedback on dem and , was equivalent to content-focused guidance with regular feedback while requiring only approximately a quarter of the coaching re sources . This could be a promising discovery in terms of cost-effectiveness . However , even after considering guidance , sociodemographic , and symptom-related characteristics , most interindividual differences in nonadherence remain unexplained . Clinical Trial DRKS00004749 ; http://drks-neu.uniklinik-freiburg.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL _ ID = DRKS00004749 ( Archived by WebCite at http://www.webcitation.org/6QiDk9Zn8 ) ; DRKS00005112 ; http://drks-neu.uniklinik-freiburg . de/drks_web/navigate.do?navigationId = trial . HTML&TRIAL_ID = DRKS00005112 ( Archived by WebCite at http://www.webcitation.org/6QiDysvev ) ; DRKS00005384 ; http://drks-neu.uniklinik-freiburg.de/ drks_web/navigate.do?navigationId = trial . HTML&TRIAL_ID = DRKS00005384 ( Archived by WebCite at http://www.webcitation.org/6QiE0xcpE BACKGROUND Emotional distress has major implication s for employees and employers . Cognitive behavioural therapy ( CBT ) is a recommended treatment , but dem and outstrips supply . CBT is well suited to computerization . Most employee assistance programmes have not been systematic ally evaluated and computerized CBT has not previously been studied in the workplace . AIMS To evaluate the effect of an 8 week computerized cognitive behavioural therapy programme , ' Beating The Blues ' , on emotional distress in employees with recent stress-related absenteeism , and to explore the reasons for non-participation . METHODS An open , r and omized trial in a London NHS occupational health department . Forty-eight public sector employees , with 10 or more cumulative days stress-related absenteeism in the last 6 months , r and omized equally to ' Beating The Blues ' plus conventional care , or conventional care alone . Main outcome measures were Hospital Anxiety and Depression Scale and Attributional Style Question naire scores at end of treatment and 1 , 3 and 6 months later ; and reasons for non-participation . RESULTS At end of treatment and 1 month later , adjusted mean depression scores and adjusted mean negative attributional style scores were significantly lower in the intervention group . One month post-treatment , adjusted mean anxiety scores were also significantly lower in the intervention group . The differences were not statistically significant at 3 and 6 months post-treatment . Non-participation was common and related to access problems , preference for other treatments , time commitment , scepticism about the intervention and the employer connection . CONCLUSIONS ' Beating The Blues ' may accelerate psychological recovery in employees with recent stress-related absenteeism . Greater flexibility and accessibility might improve uptake OBJECTIVE This r and omized controlled trial evaluated the efficacy of an Internet-based intervention , which aim ed to improve recovery from work-related strain in teachers with sleeping problems and work-related rumination . In addition , mechanisms of change were also investigated . METHODS A sample of 128 teachers with elevated symptoms of insomnia ( Insomnia Severity Index [ ISI ] ≥ 15 ) and work-related rumination ( Cognitive Irritation Scale ≥ 15 ) was assigned to either an Internet-based recovery training ( intervention condition [ IC ] ) or to a waitlist control condition ( CC ) . The IC consisted of 6 Internet-based sessions that aim ed to promote healthy restorative behavior . Self-report data were assessed at baseline and again after 8 weeks . Additionally , a sleep diary was used starting 1 week before baseline and ending 1 week after post assessment . The primary outcome was insomnia severity . Secondary outcomes included perseverative cognitions ( i.e. , work-related rumination and worrying ) , a range of recovery measures and depression . An extended 6-month follow-up was assessed in the IC only . A serial multiple mediator analysis was carried out to investigate mechanisms of change . RESULTS IC participants displayed a significantly greater reduction in insomnia severity ( d = 1.37 , 95 % confidence interval : 0.99 - 1.77 ) than did participants of the CC . The IC was also superior with regard to changes in all investigated secondary outcomes . Effects were maintained until a naturalistic 6-month follow-up . Effects on insomnia severity were mediated by both a reduction in perseverative cognitions and sleep effort . Additionally , a greater increase in number of recovery activities per week was found to be associated with lower perseverative cognitions that in turn led to a greater reduction in insomnia severity . CONCLUSIONS This study provides evidence for the efficacy of an unguided , Internet-based occupational recovery training and provided first evidence for a number of assumed mechanisms of change OBJECTIVES The primary purpose of this r and omized controlled trial ( RCT ) was to evaluate the efficacy of a guided internet-based recovery training for employees who suffer from both work-related strain and sleep problems ( GET.ON Recovery ) . The recovery training consisted of six lessons , employing well-established methods from cognitive behavioral therapy for insomnia ( CBT-I ) such as sleep restriction , stimulus control , and hygiene interventions as well as techniques targeted at reducing rumination and promoting recreational activities . METHODS In a two-arm RCT ( N=128 ) , the effects of GET.ON Recovery were compared to a waitlist-control condition ( WLC ) on the basis of intention-to-treat analyses . German teachers with clinical insomnia complaints ( Insomnia Severity Index ≥15 ) and work-related rumination ( Irritation Scale , cognitive irritation subscale ≥15 ) were included . The primary outcome measure was insomnia severity . RESULTS Analyses of covariance ( ANCOVA ) revealed that , compared to the WLC , insomnia severity of the intervention group decreased significantly stronger ( F=74.11 , P<0.001 ) with a d=1.45 [ 95 % confidence interval ( 95 % CI ) 1.06 - 1.84 ] The number needed to treat ( NNT ) was < 2 for reliable change and NNT < 4 for reduction in expert-rated diagnosis of primary insomnia . CONCLUSION The training significantly reduces sleep problems and fosters mental detachment from work and recreational behavior among adult stressed employees at post-test and 6-months follow up . Given the low threshold access this training could reach out to a large group of stressed employees when results are replicated in other studies |
13,285 | 29,426,344 | While education is important , implementation science literature reveals that education is not as effective in generating change . | Background Developed countries , such as the USA , have achieved significant decreases in cervical cancer burden since the introduction of Pap smear-based programs in the 1960s .
Due to implementation barriers and limited re sources , many countries in sub-Saharan Africa ( SSA ) have been unable to attain such reductions .
The purpose of this review is to evaluate implementation strategies used to improve the uptake and sustainability of cervical cancer prevention programs in SSA . | Background Adherence is crucial for public health program effectiveness , though the benefits of increasing adherence must ultimately be weighed against the associated costs . We sought to determine the relationship between investment in community health worker ( CHW ) home visits and increased attendance at cervical cancer screening appointments in Cape Town , South Africa . Methodology /Principal Findings We conducted an observational study of 5,258 CHW home visits made in 2003–4 as part of a community-based screening program . We estimated the functional relationship between spending on these visits and increased appointment attendance ( adherence ) . Increased adherence was noted after each subsequent CHW visit . The costs of making the CHW visits was based on re source use including both personnel time and vehicle-related expenses valued in 2004 R and . The CHW program cost R194,018 , with 1,576 additional appointments attended . Adherence increased from 74 % to 90 % ; 55 % to 87 % ; 48 % to 77 % ; and 56 % to 80 % for 6- , 12- , 24- , and 36-month appointments . Average per-woman costs increased by R14–R47 . The majority of this increase occurred with the first 2 CHW visits ( 90 % , 83 % , 74 % , and 77 % ; additional cost : R12–R26 ) . Conclusions / Significance We found that study data can be used for program planning , identifying spending levels that achieve adherence targets given budgetary constraints . The results , derived from a single disease program , are retrospective , and should be prospect ively replicated Background .We compared vaccine coverage achieved by 2 different delivery strategies for the quadrivalent human papillomavirus ( HPV ) vaccine in Tanzanian schoolgirls . Methods .In a cluster-r and omized trial of HPV vaccination conducted in Tanzania , 134 primary schools were r and omly assigned to class-based ( girls enrolled in primary school grade [ class ] 6 ) or age-based ( girls born in 1998 ; 67 schools per arm ) vaccine delivery . The primary outcome was coverage by dose . Results .There were 3352 and 2180 eligible girls in schools r and omized to class-based and age-based delivery , respectively . HPV vaccine coverage was 84.7 % for dose 1 , 81.4 % for dose 2 , and 76.1 % for dose 3 . For each dose , coverage was higher in class-based schools than in age-based schools ( dose 1 : 86.4 % vs 82.0 % [ P = .30 ] ; dose 2 : 83.8 % vs 77.8 % [ P = .05 ] ; and dose 3 : 78.7 % vs 72.1 % [ P = .04 ] ) . Vaccine-related adverse events were rare . Reasons for not vaccinating included absenteeism ( 6.3 % ) and parent refusal ( 6.7 % ) . School absenteeism rates prior to vaccination ranged from 8.1 % to 23.5 % . Conclusions .HPV vaccine can be delivered with high coverage in schools in sub-Saharan Africa . Compared with age-based vaccination , class-based vaccination located more eligible pupils and achieved higher coverage . HPV vaccination did not increase absenteeism rates in selected schools . Innovative strategies will be needed to reach out-of-school girls . Clinical Trials Registration . NCT01173900 Objective Human papillomavirus ( HPV ) self-sampling ( Self-HPV ) may be used as a primary cervical cancer screening method in a low re source setting . Our aim was to evaluate whether an educational intervention would improve women 's knowledge and confidence in the Self-HPV method . Method Women aged between 25 and 65 years old , eligible for cervical cancer screening , were r and omly chosen to receive st and ard information ( control group ) or st and ard information followed by educational intervention ( interventional group ) . St and ard information included explanations about what the test detects ( HPV ) , the link between HPV and cervical cancer and how to perform HPV self-sampling . The educational intervention consisted of a culturally tailored video about HPV , cervical cancer , Self-HPV and its relevancy as a screening test . All participants completed a question naire that assessed sociodemographic data , women 's knowledge about cervical cancer and acceptability of Self-HPV . Results A total of 302 women were enrolled in 4 health care centers in Yaoundé and the surrounding countryside . 301 women ( 149 in the “ control group ” and 152 in the “ intervention group ” ) completed the full process and were included into the analysis . Participants who received the educational intervention had a significantly higher knowledge about HPV and cervical cancer than the control group ( p<0.05 ) , but no significant difference on Self-HPV acceptability and confidence in the method was noticed between the two groups . Conclusion Educational intervention promotes an increase in knowledge about HPV and cervical cancer . Further investigation should be conducted to determine if this intervention can be sustained beyond the short term and influences screening behavior . Trials Registration International St and ard R and omised Controlled Trial Number ( IS RCT N ) Register IS RCT Background Cervical cancer is a disease of public health importance affecting many women and contributing to avoidably high levels of cancer deaths in Nigeria . In spite of the relative ease of prevention , the incidence is on the increase . This study aim ed to determine the effect of health education on the awareness , knowledge and perception of cervical cancer and screening among women in rural Nigerian communities . Methods The study design was quasi-experimental . The study was carried out among adult women in Odogbolu ( intervention ) and Ikenne ( control ) local government areas ( LGA ) of Ogun state . Three hundred and fifty ( 350 ) women were selected per group by multistage r and om sampling technique . Data was collected by semi structured interviews with the aid of question naire . The intervention consisted of structured health education based on a movie . Result The intervention raised the level of awareness of cervical cancer and screening to 100 % ( p < 0.0001 ) . The proportion of women with very good knowledge of cervical cancer and screening rose from 2 % to 70.5 % ( χ2 = 503.7 , p < 0.0001 ) while the proportion of those with good perception rose from 5.1 % to 95.1 % ( p < 0.0001 ) . The mean knowledge and mean perception scores were also increased ( p < 0.0001 ) . There was increase in the proportion of women who had undertaken cervical screening from 4.3 % to 8.3 % ( p = 0.038 ) . The major reason stated by the women for not having had cervical screening done was lack of awareness about cervical cancer and screening . There was statistically significant difference between the intervention and control groups concerning their knowledge attitude and practice towards cervical and screening ( p < 0.05 ) after the intervention . Conclusion Multiple media health education based on a movie is effective in creating awareness for and improving the knowledge and perception of adult women about cervical cancer and screening . It also improves the uptake of cervical cancer screening . The creation of awareness is very crucial to the success of a cervical cancer prevention programme BACKGROUND Information about women 's acceptance of new screening methods in Sub-Saharan Africa is limited . The aim of this study was to report on women 's acceptance of human papillomavirus ( HPV ) self-sampling following an educational intervention on cervical cancer and HPV . METHODS Women were recruited from the city of Tiko and a low-income neighborhood of Yaoundé , both in Cameroon . Written and oral instructions about how to perform an unsupervised HPV self- sample were given to participants , who performed the test in a private room . Acceptability of HPV self-sampling was evaluated by question naire . Participants previously screened for cervical cancer by a physician were asked additional questions to assess their personal preferences about HPV self-sampling . RESULTS A sample of 540 women were prospect ively enrolled in the study ; median age was 43 years old ( range 30 - 65 years ) . Participants expressed a high level of acceptance of HPV self-sampling as a screening method following information sessions about cervical cancer and HPV . Most expressed no embarrassment , pain , anxiety , or discomfort ( 95.6 % , 87.8 % , 91.3 % , and 85.0 % , respectively ) during the information sessions . Acceptance of the method had no correlation with education , knowledge , age , or socio-professional class . Eighty-six women ( 16 % ) had a history of previous screening ; they also reported high acceptance of HPV self-sampling . CONCLUSION Educational interventions on cancer and HPV were associated with high acceptability of HPV self-testing by Cameroonian women . Further evaluation of the intervention in a larger sample and using a control group is recommended Background Over 85 % of cervical cancer cases and deaths occur in developing countries . HIV-seropositive women are more likely to develop precancerous lesions that lead to cervical cancer than HIV-negative women . However , the literature on cervical cancer prevention in seropositive women in developing countries has not been review ed . The aim of this study is to systematic ally review cervical cancer prevention modalities available for HIV-seropositive women in developing countries . Methods / design This protocol was developed by following the Preferred Reporting Items for Systematic Review s and Meta-Analyses Protocol s ( PRISMA -P ) statement , and the systematic review will be reported in accordance with the PRISMA guidelines . Embase , MEDLINE , PubMed , CINAHL and Cochrane Library will be search ed from inception up to date of final search , and additional studies will be located through citation and reference list tracking . Eligible studies will be r and omised controlled trials , prospect i ve and retrospective cohort studies , case-control and cross-sectional studies carried out in developing countries . Studies will be included if they are published in English and examine cervical cancer prevention modalities in HIV-seropositive women . Results will be summarised in tables and , where appropriate , combined using meta- analysis . Discussion This review will address the gap in evidence by systematic ally review ing the published literature on the different prevention modalities being used to prevent cervical cancer in HIV-seropositive women in developing countries . The findings may be used to inform evidence -based guidelines for prevention of cervical cancer in seropositive women as well as future research . Systematic review registration PROSPERO CRD42017054678 OBJECTIVE To determine the impact of trained community health educators on the uptake of cervical and breast cancer screening , and HPV vaccination in rural communities in southeast Nigeria . METHODS A prospect i ve population -based intervention study , with a before- and -after design , involved four r and omly selected communities in southeast Nigeria from February 2014 to February 2016 . Before the intervention , baseline data were collected on the uptake of cervical and breast cancer prevention services . The intervention was house-to-house education on cervical cancer and breast cancer prevention . Postintervention outcome measures included the uptake of cervical and breast cancer screening , and HPV vaccination within 6 months of intervention . RESULTS In total , 1327 women were enrolled . Before the intervention , 42 ( 3.2 % ) women had undergone cervical cancer screening ; afterwards , 897 ( 67.6 % ) women had received screening ( P<0.001 ) . Clinical breast examination was performed for 59 ( 4.4 % ) women before and 897 ( 67.6 % ) after the intervention ( P<0.001 ) . Only 2 ( 0.9 % ) of 214 children eligible for HPV vaccination had received the vaccine before versus 71 ( 33.2 % ) after the intervention ( P<0.001 ) . CONCLUSION The use of community health educators for house-to-house cervical and breast cancer prevention education was associated with significant increases in the uptake of cervical cancer screening , clinical breast examination , and HPV vaccination BACKGROUND Cervical cancer is one of the most common forms of carcinoma among women worldwide , accounting for about 12 % of all cancers . Tragically , studies have shown generally low awareness levels on its symptoms , risk factors and prevention . This study evaluated the effect of a health education program on knowledge of cervical cancer amongst women at risk in Africa . METHOD This study was conducted in the city of Lagos , Nigeria , using a multistage sampling technique . Two model markets were chosen by simple r and om sampling method from a total of 10 local governments with model markets . One was design ated the intervention/experimental group while the other was the control . Systematic sampling method was used in selecting 350 women comprising of 175 participants from each model market . A baseline survey on cervical cancer awareness and screening practice s was carried out in both sample groups with the aid of interviewer-administered , structured and pre-tested question naires . Thereafter , respondents in the intervention group received sessions of community-based educational messages on cervical cancer and its prevention . Subsequently , participants in both groups were reassessed to evaluate the effect of the educational program . Data analysis was conducted with Epi-info statistical software . RESULTS Knowledge level was low on cervical cancer at baseline ; only about 15 % and 6.9 % of participants in the intervention and control groups respectively had heard of cervical cancer . The most common sources of information were friends and media prior to the intervention . Significant increase in proportions were found in the intervention/experimental group on awareness of cervical cancer ( 61.7 % ) , associated symptoms and risk factors such as early sexual debut , promiscuity and smoking . CONCLUSION It is apparent that efforts must be put in place by all stakeholders in reaching women at risk of cervical cancer through well organized educational campaigns using culturally sensitive information , education and communication Background Cervical cancer incidence and mortality rates in Sub-Saharan Africa ( SSA ) remain high due to several factors including low levels of uptake of cervical cancer screening . Self- collection of cervicovaginal sample s for HPV DNA testing may be an effective modality that can increase uptake of cervical cancer screening in SSA and hard to reach population s in developed countries . We investigated whether self- collection of cervicovaginal sample s for HPV DNA tests would be associated with increased uptake of screening compared with clinic based collection of sample s. Furthermore , we compared the quality of sample s collected by both approaches for use in HPV genotyping . Methods We conducted a community based r and omized trial in a semi-urban district of Abuja , Nigeria with 400 women , aged 30 to 65 years r and omized to either hospital- collection or self- collection of cervicovaginal sample s. We compared cervical cancer screening uptake among the 2 groups and evaluated the concentration of human DNA in the sample s by measuring RNase P gene levels using qPCR . High-risk HPV DNA detection and typing was done using the GP5+/6 + Luminex system . Results Most participants in the self- collection arm ( 93 % , 185/200 ) su bmi tted their sample s while only 56 % ( 113/200 ) of those invited to the hospital for sample collection attended and were screened during the study period ( p value < 0.001 ) . Human genomic DNA was detected in all but five ( 1.7 % ) participants , all of whom were in the self- collection arm . The prevalence of high-risk HPV in the study population was 10 % with types 35 , 52 and 18 being the commonest . Conclusions Our study shows that self-sampling significantly increased uptake of HPV DNA based test for cervical cancer screening in this population and the sample s collected were adequate for HPV detection and genotyping . Cervical cancer screening programs that incorporate self-sampling and HPV DNA tests are feasible and may significantly improve uptake of cervical cancer screening in SSA OBJECTIVE Cervical cancer screening uptake may be influenced by inadequate knowledge in re source -limited setting s. This r and omized trial evaluated a health talk 's impact on cervical cancer knowledge , attitudes , and screening rates in rural Kenya . METHODS 419 women attending government clinics were r and omized to an intervention ( N=207 ) or control ( N=212 ) group . The intervention was a brief health talk on cervical cancer . Participants completed surveys at enrollment ( all ) , immediately after the talk ( intervention arm ) , and at three-months follow-up ( all ) . The primary outcomes were the change in knowledge scores and the final screening rates at three-months follow-up . Secondary outcomes were changes in awareness about cervical cancer screening , perception of personal cervical cancer risk , cervical cancer and HIV stigma , and screening acceptability . RESULTS Mean Knowledge Scores increased by 26.4 % ( 8.7 points increased to 11.0 points ) in the intervention arm compared to only 17.6 % ( 8.5 points increased to 10.0 points ) in the control arm ( p<0.01 ) . Screening uptake was moderate in both the intervention ( 58.9 % ; N=122 ) and control ( 60.9 % ; N=129 ) arms , with no difference between the groups ( p=0.60 ) . CONCLUSION A brief health talk increased cervical cancer knowledge , although it did not increase screening over simply informing women about free screening . PRACTICAL IMPLICATION S Screening programs can increase patient underst and ing with just a brief educational intervention Our objective was ( i ) to assess if a self‐collected test for human papillomavirus ( HPV ) may serve as a primary cervical cancer screening method in a low‐re source setting , ( ii ) to evaluate its implication in a screen and treat approach and ( iii ) to identify the most eligible age group in a screening program . Women were recruited through a cervical cancer screening campaign conducted in Cameroon . Written and oral instructions were given to participants by a health‐care professional to carry out an unsupervised self‐collected HPV‐test ( Self‐HPV ) , followed by a physician‐collected cervical sample for HPV testing ( Physician‐HPV ) and cytology . Differences in performance between Self‐HPV versus Physician‐HPV and their ability to detect abnormal cytology results ( ASC‐US+ ) were evaluated . Descriptive analyses were used to examine the correlation between HPV positivity and cervical abnormalities by age . A sample of 789 women was prospect ively enrolled . HPV prevalence was 14.6 % and 12.7 % for Self‐HPV and Physician‐HPV , respectively ( Cohen 's kappa = 0.74 ) . HPV positivity by cytological diagnosis for ASC‐US+ was similar with the two tests . positive predictive value of the Self‐HPV for ASC‐US+ was 20.4 ; odds ratio and number needed to treat were 6.5 ( 3.2–13.4 ) and 6 ( 4.2–10.9 ) , respectively . We observed a trend of increasing cytological abnormalities in 30–49 year‐old women and a concomitant trend of decreasing HPV prevalence supporting that this age group might be the most eligible group for screening . In conclusion , Self‐HPV can be used as a primary screening test but needs to be followed by a triaging test that would identify the subset of women affected by clinical ly significant precancer or cancer How does increasing access to treatment affect the dem and for preventive testing ? In this paper we present results from a field experiment in Nigeria in which we offered cervical cancer screening to women at r and omly chosen prices . To test our hypothesis , we also offered women a lottery where the payoff was a subsidy towards the cost of cervical cancer treatment ( conditional upon a diagnosis of cervical cancer ) . We find that women r and omly selected to receive the conditional cancer treatment subsidy were about 4 percentage points more likely to take up screening than those in the control group . We also show that reducing the price of screening by 10 cents increased take-up by about 1 percentage point . These results offer compelling evidence that the optimal set of subsidies to increase take-up of preventive testing in developing countries , must include subsidies towards treatment costs ( in addition to price subsidies ) Successful cervical cancer prevention depends on reaching , screening and treating women with pre-invasive disease . We aim ed to evaluate the effectiveness of two media interventions -a photo-comic and a radio-drama-in increasing cervical screening uptake . A r and omized controlled trial compared a photo-comic on cervical cancer screening with a placebo comic . One month after the comics were distributed a radio-drama paralleling the photo-comic was broadcast on the community radio station and a retrospective evaluation was carried out . The trial was set in Khayelitsha , a peri-urban squatter community near Cape Town , South Africa . A r and om sample consisted of 658 women between the ages of 35 and 65 years , from a stratified sample of census areas . The main outcome measure was self-reported cervical screening uptake 6 months after distribution of the comics . Seven percent ( 18 of 269 ) of women who received the intervention photo-comic reported cervical screening during the 6 months follow-up , compared with 6 % ( 25 of 389 ) of controls ( P = 0.89 ) . Women who recalled hearing the radio-drama were more likely to report attending screening ( nine of 53 , 17 % ) than those who did not ( 19 of 429 , 4 % ; P < 0.001 ) . We conclude that the photo-comic was ineffective in increasing cervical screening uptake in this population . The radio-drama may have had more impact , but only a minority of women recalled being exposed to it . Future research must concentrate not only on achieving high level of exposure to health messages , but also on investigating the links between exposure and action The impact of health message framing on cervical cancer screening uptake is poorly understood . In a prospect i ve r and omized control study with 748 females , aged 21–65 years with no Pap smear in the previous 3 years , they r and omly received a loss-framed , gain-framed , or neutral health message ( control ) regarding cervical cancer screening by email . Screening rate in the control group was 9.58 percent ( CI : 9.29%–9.87 % ) , 5.71 percent ( CI : 5.48%–6.98 % ) in the gain-framed group , and 8.53 percent ( CI : 8.24%–8.81 % ) in the loss-framed group . Statistically there was no difference between the three screening rates . Framing of health messages may not be a significant consideration when communicating through emails OBJECTIVE Our purpose was to determine the feasibility of providing a cervical screening facility to the underprivileged communities through an educational program and a mobile clinic in which cytologic smears could be taken , screened immediately , and , when appropriate , the patients treated on site with minimal delay . STUDY DESIGN A prospect i ve study was conducted in two parts on 5045 patients living in squatter areas around Cape Town , South Africa . The patients were educated about cervical cancer and its prevention and were offered a free Papanicolaou smear taken in a fully equipped mobile clinic . These were immediately stained and processed . Patients diagnosed cytologically as having high- grade squamous intraepithelial lesions were assessed colposcopically and , when indicated , immediately treated by large loop excision of the transformation zone under local anesthesia . RESULTS In phase 1 , colposcopy was done in the nearest colposcopy clinic , 20 km from the screening site . The defaulter rate was 66 % . In phase 2 , colposcopy and treatment were offered on site . A total of 97 % of patients referred for colposcopy attended the clinic , and all patients requiring treatment have been adequately treated . CONCLUSION With a rapid turnaround time for the reporting of cytologic results and given a colposcopy and treatment facility available located at the screening site at the time women receive their results , the majority of women will undergo colposcopy and treatment OBJECTIVES Patient financial incentives are being promoted as a mechanism to increase receipt of preventive care , encourage healthy behavior , and improve chronic disease management . However , few empirical evaluations have assessed such incentive programs . STUDY DESIGN In South Africa , a private health plan has introduced a voluntary incentive program which costs enrollees approximately $ 20 per month . In the program , enrollees earn points when they receive preventive care . These points translate into discounts on retail goods such as airline tickets , movie tickets , or cell phones . METHODS We chose 8 preventive care services over the years 2005 to 2011 and compared the change between those who entered the incentive program and those that did not . We used multivariate regression models with individual r and om effects to try to address selection bias . RESULTS Of the 4,186,047 unique individuals enrolled in the health plan , 65.5 % ( 2,742,268 ) voluntarily enrolled in the incentive program . Joining the incentive program was associated with statistically higher odds of receiving all 8 preventive care services . The odds ratio ( and estimated percentage point increase ) for receipt of cholesterol testing was 2.70 ( 8.9 % ) ; glucose testing 1.51 ( 4.7 % ) ; glaucoma screening 1.34 ( 3.9 % ) ; dental exam 1.64 ( 6.3 % ) ; HIV test 3.47 ( 2.6 % ) ; prostate specific antigen testing 1.39 ( 5.6 % ) ; Papanicolaou screening 2.17 ( 7.0 % ) ; and mammogram 1.90 ( 3.1 % ) ( P < .001 for all 8 services ) . However , preventive care rates among those in the incentive program was still low . CONCLUSIONS Voluntary participation in a patient incentive program was associated with a significantly higher likelihood of receiving preventive care , though receipt of preventive care among those in the program was still lower than ideal Objectives : To assess the validity , feasibility , and acceptability of 2 methods of self-sampling compared to clinician sampling during a speculum examination . Goal : To improve screening for reproductive tract infections ( RTIs ) in re source -poor setting s. Study Design : In a public clinic in Cape Town , 450 women underwent a speculum examination and were r and omized to self- sample with either a tampon or vaginal swabs . All specimens were tested for the same pathogens using the same diagnostic tests . Results : Self-sampling result ed in satisfactory validity for N gonorrhoeae , C trachomatis , bacterial vaginosis , and C and ida species ( tampons and swabs ) and high-risk human papillomavirus ( swabs only ) when tested with molecular tests or microscopy , but not for T vaginalis by culture . Self-sampling was feasible and acceptable , but some women preferred speculum examinations , which allow the clinician to view the vagina and cervix . Conclusions : Although self-sampling should not replace speculum examinations in all circumstances , it should be explored further as an RTI screening strategy |
13,286 | 29,587,882 | Conclusion Current evidence is strong for the protective effect of ITN interventions in malaria prevention .
Even though ITNs were found to be the only preventive measure with statistical support for their effectiveness , the role of other malaria control measures may be important adjuncts in the global drive to eliminate malaria | Background Malaria causes significant morbidity and mortality worldwide .
There are several preventive measures that are currently employed , including insecticide-treated nets ( ITNs , including long-lasting insecticidal nets and insecticidal-treated bed nets ) , indoor residual spraying ( IRS ) , prophylactic drugs ( PD ) , and untreated nets ( UN ) .
However , it is unclear which measure is the most effective for malaria prevention .
We therefore undertook a network meta- analysis to compare the efficacy of different preventive measures on incidence of malaria infection . | Background Sequential analysis enables repeated statistical analyses to be performed throughout a trial recruitment period , while maintaining a pre-specified power and type I error . Thus the trial can be stopped as soon as the information accumulated is considered sufficient to reach a conclusion . Sequential tests are easy to use and their statistical properties are especially suitable to trials with very straightforward objectives such as non-comparative phase II trials . We report on a phase II study based on the triangular test ( TT ) aim ing at assessing the effectiveness of azithromycin in preventing Plasmodium vivax relapses . Methods To test whether the P. vivax relapse rate was either < 12 % or ≥ 45 % in patients treated with azithromycin , a sequential analysis based on the TT was as used . Patients infected with P. vivax were treated with azithromycin , 1.2 g daily , for 7 days . The onset of a relapse infection was monitored . Results Five patients presenting with an acute P. vivax infection were included in the study . All the patients were initially cured . Three patients reported mild gastrointestinal adverse effects . When the third patient relapsed , the sample path crossed the upper boundary of the TT , and the trial was stopped . Conclusions Using the triangular test , with only a small number of patients , we concluded that azithromycin was not effective enough in preventing P. vivax relapses to warrant further evaluation in phase III . It is suggested that a wider use of sequential analysis in phase II anti-infective drugs trials may have financial and ethical benefits BACKGROUND In the Sahel and sub-Sahelian regions of Africa , malaria transmission is highly seasonal . During a short period of high malaria transmission , mortality and morbidity are high in children under age 5 years . We assessed the efficacy of seasonal intermittent preventive treatment-a full dose of antimalarial treatment given at defined times without previous testing for malaria infection . METHODS We did a r and omised , placebo-controlled , double-blind trial of the effect of intermittent preventive treatment on morbidity from malaria in three health-care centres in Niakhar , a rural area of Senegal . 1136 children aged 2 - 59 months received either one dose of artesunate plus one dose of sulfadoxine-pyrimethamine or two placebos on three occasions during the malaria transmission season . The primary outcome was a first or single episode of clinical malaria detected through active or passive case detection . Primary analysis was by intention-to-treat . This study is registered with , number NCT00132561 . FINDINGS During 13 weeks of follow-up , the intervention led to an 86 % ( 95 % CI 80 - 90 ) reduction in the occurrence of clinical episodes of malaria . With passive case detection , protective efficacy against malaria was 86 % ( 77 - 92 ) , and when detected actively was 86 % ( 78 - 91 ) . The incidence of malaria in children on active drugs was 308 episodes per 1000 person-years at risk , whereas in those on placebo it was 2250 episodes per 1000 person-years at risk . 13 children were not included in the intention-to-treat analysis , which was restricted to children who received a first dose of antimalarial or placebo . There was an increase in vomiting in children who received the active drugs , but generally the intervention was well tolerated . INTERPRETATION Intermittent preventive treatment could be highly effective for prevention of malaria in children under 5 years of age living in areas of seasonal malaria infection New drugs are needed for preventing drug-resistant Plasmodium falciparum malaria . The prophylactic efficacy of azithromycin against P. falciparum in malaria-immune Kenyans was 83 % . We conducted a double-blind , placebo-controlled trial to determine the prophylactic efficacy of azithromycin against multidrug-resistant P. falciparum malaria and chloroquine-resistant Plasmodium vivax malaria in Indonesian adults with limited immunity . After radical cure therapy , 300 r and omized subjects received azithromycin ( 148 subjects , 750-mg loading dose followed by 250 mg/d ) , placebo ( 77 ) , or doxycycline ( 75 , 100 mg/d ) . The end point was slide-proven parasitemia . There were 58 P. falciparum and 29 P. vivax prophylaxis failures over 20 weeks . Using incidence rates , the protective efficacy of azithromycin relative to placebo was 71.6 % ( 95 % confidence interval [ CI ] , 50.3 - 83.8 ) against P. falciparum malaria and 98.9 % ( 95 % CI , 93.1 - 99.9 ) against P. vivax malaria . Corresponding figures for doxycycline were 96.3 % ( 95 % CI , 85.4 - 99.6 ) and 98 % ( 95 % CI , 88.0 - 99.9 ) , respectively . Daily azithromycin offered excellent protection against P. vivax malaria but modest protection against P. falciparum malaria Background Individual malaria interventions provide only partial protection in most epidemiological situations . Thus , there is a need to investigate whether combining interventions provides added benefit in reducing mortality and morbidity from malaria . The potential benefits of combining IPT in children ( IPTc ) with home management of malaria ( HMM ) was investigated . Methods During the 2008 malaria transmission season , 1,277 children under five years of age resident in villages within the rural Farafenni demographic surveillance system ( DSS ) in North Bank Region , The Gambia were r and omized to receive monthly IPTc with a single dose of sulphadoxine/pyrimethamine ( SP ) plus three doses of amodiaquine ( AQ ) or SP and AQ placebos given by village health workers ( VHWs ) on three occasions during the months of September , October and November , in a double-blind trial . Children in all study villages who developed an acute febrile illness suggestive of malaria were treated by VHWs who had been taught how to manage malaria with artemether-lumefantrine ( Coartem ™ ) . The primary aims of the project were to determine whether IPTc added significant benefit to HMM and whether VHWs could effectively combine the delivery of both interventions . Results The incidence of clinical attacks of malaria was very low in both study groups . The incidence rate of malaria in children who received IPTc was 0.44 clinical attacks per 1,000 child months at risk while that for control children was 1.32 per 1,000 child months at risk , a protective efficacy of 66 % ( 95 % CI -23 % to 96 % ; p = 0.35 ) . The mean ( st and ard deviation ) haemoglobin concentration at the end of the malaria transmission season was similar in the two treatment groups : 10.2 ( 1.6 ) g/dL in the IPTc group compared to 10.3 ( 1.5 ) g/dL in the placebo group . Coverage with IPTc was high , with 94 % of children receiving all three treatments during the study period . Conclusion Due to the very low incidence of malaria , no firm conclusion can be drawn on the added benefit of IPTc in preventing clinical episodes of malaria among children who had access to HMM in The Gambia . However , the study showed that VHWs can successfully combine provision of HMM with provision of IPTc . Trial Registration Clinical Trials.gov Background Recent studies have shown that intermittent preventive malaria treatment ( IPT ) in infants in areas of stable malaria transmission reduces malaria and severe anaemia incidence . However in most areas malaria morbidity and mortality remain high in older children . Methods To evaluate the effect of seasonal IPT with sulphadoxine pyrimethamine ( SP ) on incidence of malaria disease in area of seasonal transmission , 262 children 6 months-10 years in Kambila , Mali were r and omized to receive either IPT with SP twice at eight weeks interval or no IPT during the transmission season of 2002 and were followed up for 12 months . Subjects were also followed during the subsequent transmission season in 2003 to assess possible rebound effect . Clinical malaria cases were treated with SP and followed to assess the in vivo response during both periods . Results The incidence rate of malaria disease per 1,000 person-months during the first 12 months was 3.2 episodes in the treatment group vs. 5.8 episodes in the control group with age-adjusted Protective Efficacy ( PE ) of 42.5 % ; [ 95 % CI 28.6%–53.8 % ] . When the first 16 weeks of follow up is considered age-adjusted PE was 67.5 % [ 95 % CI 55.3 % – 76.6 % ] . During the subsequent transmission season , the incidence of clinical malaria per 1000 persons-days was similar between the two groups ( 23.0 vs 21.5 episodes , age-adjusted IRR = 1.07 [ 95 % CI , 0.90–1.27 ] ) . No significant difference was detected in in vivo response between the groups during both periods . Conclusion Two malaria intermittent treatments targeting the peak transmission season reduced the annual incidence rate of clinical malaria by 42.5 % in an area with intense seasonal transmission . This simple strategy is likely to be one of the most effectives in reducing malaria burden in such areas .Trial Registration Clinical trials.gov Background Insecticide treated nets ( ITNs ) and indoor residual spraying ( IRS ) are effective vector control tools that protect against malaria . There is conflicting evidence regarding whether using ITNs and IRS in combination provides additional benefit over using either of these methods alone . This study investigated factors that may modify the effect of the combined use of IRS and ITNs compared to using ITNs alone on malaria infection prevalence . Methods Secondary analysis was carried out on data from a cluster r and omised trial in north-west Tanzania . 50 clusters received ITNs from a universal coverage campaign ; of these 25 were r and omly allocated to additionally receive two rounds of IRS in 2012 . In cross-sectional household surveys children 0.5–14 years old were tested for Plasmodium falciparum infections ( PfPR ) two , six and ten months after the first IRS round . Results IRS protected those sleeping under nets ( OR = 0.38 , 95%CI 0.26–0.57 ) and those who did not ( OR = 0.43 , 95%CI 0.29–0.63 ) . The protective effect of IRS was not modified by community level ITN use ( ITN use<50 % , OR = 0.39 , 95%CI 0.26–0.59 ; ITN use > = 50 % , OR = 0.46 , 95%CI 0.28–0.74 ) . The additional protection from IRS was similar in low ( < 10 % PfPR , OR = 0.38 , 95%CI 0.19–0.75 ) and high transmission areas ( ≥10 % PfPR , OR = 0.34 , 95%CI 0.18–0.67 ) . ITN use was protective at the individual-level regardless of whether the village had been sprayed ( OR = 0.83 , 95%CI 0.70–0.98 ) . Living in a sprayed village was protective regardless of whether the individual slept under an ITN last night ( OR = 0.41 , 95%CI 0.29–0.58 ) . Interpretation Implementing IRS in addition to ITNs was beneficial for individuals from villages with a wide range of transmission intensities and net utilisation levels . Net users received additional protection from IRS . ITNs were providing some individual protection , even in this area with high levels of pyrethroid insecticide resistance . These results demonstrate that there is a supplementary benefit of IRS even when ITNs are effective . Trial Registration Clinical Trials.gov A malaria intervention study was carried out using permethrin impregnated bed nets in the south- central part of Irian Jaya with perennial transmission , from April 1993 to April 1995 . Malariometric surveys were carried out periodically for parasite prevalence by species and for spleen rates . Prior to intervention , the percentage of Plasmodium falciparum infected inhabitants was significantly higher in Hiripau , where permethrin-impregnated bed nets were used during the study , than in the placebo-treated control village , Kaugapu . After two years of intervention the situation was reversed and figures higher in the control village ( RR 0.19 , 95 % CI 0.10 - 0.36 , p < 0.0001 ) . Similarly , P. vivax infection rates , 12.4 % in Hiripau vs 5.7 % in Kaugapu in April 1993 . were reversed in April 1995 ( 3.6 % in Hiripau and 11.3 % in Kaugapu , p < 0.001 ) . In the treated village , pre-control hyperendemicity was reduced to a low mesoendemic level ( spleen rate 12.5 % ) during two years of intervention , whereas the level was mesoendemic ( spleen rate 35.2 % ) in the control village . Impregnated bed nets were found an effective intervention both in moderate ( April 1993 through April 1994 , 1,626 mm rainfall ) and high ( April 1994 through April 1995/1995 , 3,321 mm ) transmission seasons A r and omized trial reported by Diadier Diallo and colleagues shows that intermittent preventive treatment for malaria in children who are protected from mosquitoes using insecticide-treated bednets provides substantial protection from malaria Background Long-lasting insecticidal hammocks ( LLIHs ) are being evaluated as an additional malaria prevention tool in setting s where st and ard control strategies have a limited impact . This is the case among the Ra-glai ethnic minority communities of Ninh Thuan , one of the forested and mountainous provinces of Central Vietnam where malaria morbidity persist due to the sylvatic nature of the main malaria vector An . dirus and the dependence of the population on the forest for subsistence - as is the case for many impoverished ethnic minorities in Southeast Asia . Methods A social science study was carried out ancillary to a community-based cluster r and omized trial on the effectiveness of LLIHs to control forest malaria . The social science research strategy consisted of a mixed methods study triangulating qualitative data from focused ethnography and quantitative data collected during a malariometric cross-sectional survey on a r and om sample of 2,045 study participants . Results To meet work requirements during the labor intensive malaria transmission and rainy season , Ra-glai slash and burn farmers combine living in government supported villages along the road with a second home at their fields located in the forest . LLIH use was evaluated in both locations . During daytime , LLIH use at village level was reported by 69.3 % of all respondents , and in forest fields this was 73.2 % . In the evening , 54.1 % used the LLIHs in the villages , while at the fields this was 20.7 % . At night , LLIH use was minimal , regardless of the location ( village 4.4 % ; forest 6.4 % ) . Discussion Despite the free distribution of insecticide-treated nets ( ITNs ) and LLIHs , around half the local population remains largely unprotected when sleeping in their forest plot huts . In order to tackle forest malaria more effectively , control policies should explicitly target forest fields where ethnic minority farmers are more vulnerable to malaria BACKGROUND In the context of the increasing resistance to sulfadoxine-pyrimethamine ( SP ) , we evaluated the efficacy of mefloquine ( MQ ) for intermittent preventive treatment during pregnancy ( IPTp ) . METHODS A multicenter , open-label equivalence trial was conducted in Benin from July 2005 through April 2008 . Women of all gravidities were r and omized to receive SP ( 1500 mg of sulfadoxine and 75 mg of pyrimethamine ) or 15 mg/kg MQ in a single intake twice during pregnancy . The primary end point was the proportion of low-birth-weight ( LBW ) infants ( body weight , < 2500 g ; equivalence margin , 5 % ) . RESULTS A total of 1601 women were r and omized to receive MQ (n=802)or SP (n=799).In the modified intention-to-treat analysis , which assessed only live singleton births , 59 ( 8 % ) of 735 women who were given MQ and 72 ( 9.8 % ) of 730 women who were given SP gave birth to LBW infants ( difference between low birth weights in treatment groups , -1.8 % ; 95 % confidence interval [ CI ] , -4.8 % to 1.1 % ] ) , establishing equivalence between the drugs . The per- protocol analysis showed consistent results . MQ was more efficacious than SP in preventing placental malaria ( prevalence , 1.7 % vs 4.4 % of women ; P = .005 ) , clinical malaria ( incidence rate , 26 cases/10,000 person-months vs. 68 cases/10,000 person-months ; P = .007 ) and maternal anemia at delivery ( as defined by a hemoglobin level < 10 g/dL ) ( prevalence , 16 % vs 20 % ; marginally significant at P = .09 ) . Adverse events ( mainly vomiting , dizziness , tiredness , and nausea ) were more commonly associated with the use of MQ ( prevalence , 78 % vs 32 % ; P < 10(-3 ) ) One woman in the MQ group had severe neuropsychiatric symptoms . CONCLUSIONS MQ proved to be highly efficacious -- both clinical ly and parasitologically -- for use as IPTp . However , its low tolerability might impair its effectiveness and requires further investigations Spatial analyses of the effect of insecticide (permethrin)-treated bed nets ( ITNs ) on nearby households both with and without ITNs was performed in the context of a large-scale , group-r and omized , controlled mortality trial in Asembo , western Kenya . Results illustrate a protective effect of ITNs on compounds lacking ITNs located within 300 meters of compounds with ITNs for child mortality , moderate anemia , high-density parasitemia , and hemoglobin levels . This community effect on nearby compounds without nets is approximately as strong as the effect observed within villages with ITNs . This implies that in areas with intense malaria transmission with high ITN coverage , the primary effect of insecticide-treated nets is via area-wide effects on the mosquito population and not , as commonly supposed , by simple imposition of a physical barrier protecting individuals from biting . The strength of the community effect depended upon the proportion of nearby compounds with treated nets . To maximize their public health impact , high coverage with treated nets is essential Background Malaria and anaemia are the leading causes of morbidity and mortality in children in sub-Saharan Africa . We have investigated the effect of intermittent preventive treatment with sulphadoxine-pyrimethamine or artesunate plus amodiaquine on anaemia and malaria in children in an area of intense , prolonged , seasonal malaria transmission in Ghana . Methods 2451 children aged 3–59 months from 30 villages were individually r and omised to receive placebo or artesunate plus amodiaquine ( AS+AQ ) monthly or bimonthly , or sulphadoxine-pyrimethamine ( SP ) bimonthly over a period of six months . The primary outcome measures were episodes of anaemia ( Hb<8.0 g/dl ) or malaria detected through passive surveillance . Findings Monthly artesunate plus amodiaquine reduced the incidence of malaria by 69 % ( 95 % CI : 63 % , 74 % ) and anaemia by 45 % ( 95 % CI : 25%,60 % ) , bimonthly sulphadoxine-pyrimethamine reduced the incidence of malaria by 24 % ( 95 % CI : 14%,33 % ) and anaemia by 30 % ( 95 % CI : 6 % , 49 % ) and bimonthly artesunate plus amodiaquine reduced the incidence of malaria by 17 % ( 95 % CI : 6 % , 27 % ) and anaemia by 32 % ( 95 % CI : 7 % , 50 % ) compared to placebo . There were no statistically significant reductions in the episodes of all cause or malaria specific hospital admissions in any of the intervention groups compared to the placebo group . There was no significant increase in the incidence of clinical malaria in the post intervention period in children who were > 1 year old when they received IPTc compared to the placebo group . However the incidence of malaria in the post intervention period was higher in children who were < 1 year old when they received AS+AQ monthly compared to the placebo group . Interpretation IPTc is safe and efficacious in reducing the burden of malaria in an area of Ghana with a prolonged , intense malaria transmission season . Trial Registration Clinical Trials.gov Background With dwindling malaria cases in Bhutan in recent years , the government of Bhutan has made plans for malaria elimination by 2016 . This study aim ed to determine coverage , use and ownership of LLINs , as well as the prevalence of asymptomatic malaria at a single time-point , in four sub-districts of Bhutan . Methods A cross-sectional study was carried out in August 2013 . Structured question naires were administered to a single respondent in each household ( HH ) in four sub-districts . Four members from 25 HH , r and omly selected from each sub-district , were tested using rapid diagnostic tests ( RDT ) for asymptomatic Plasmodium falciparum and Plasmodium vivax infection . Multivariable logistic regression models were used to identify factors associated with LLIN use and maintenance . Results All blood sample s from 380 participants tested negative for Plasmodium infections . A total of 1,223 HH ( 92.5 % of total HH ) were surveyed for LLIN coverage and use . Coverage of LLINs was 99.0 % ( 1,203/1,223 HH ) . Factors associated with decreased odds of sleeping under a LLIN included : washing LLINs < six months and > nine months compared to washing LLINs every six months ; HH in the least poor compared to the most poor socio-economic quintile ; a HH income of Nu 5,001 - 10,000 ( US$ 1 = Nu 59.55 ) , and Nu > 10,000 , compared to HH with income of < Nu 1,500 ; HH located one to three hours walking distance to a health centre compared to being located closer to a health centre ; a reported lack of knowledge as to what to do in event of LLINs being torn ; and keeping LLINs in a box compared to keeping them hanging in the place of use . Factors associated with use of LLINs for purpose s other than the intended use included : income group Nu 1,501 - 3,000 and HH located one to three hours walking distance from a health centre . Conclusions There was high coverage of LLINs in the study area with regular use of LLINs throughout the year . LLIN use for purpose s other than malaria prevention was low . With high coverage and regular use of LLINs , and a zero prevalence of malaria infection found in historically high-risk communities during the peak malaria season , it appears Bhutan is on course to achieve malaria elimination The effectiveness of village-wide use of permethrin-impregnated bed nets or eave , window , and door curtains as control measures for Plasmodium falciparum malaria was evaluated during two successive high-transmission seasons in western Kenya . Pairs of villages were assigned to one of three study groups : bed net , curtain , or control . Clinical , parasitologic , and entomologic measures were made from March to July 1990 and again 12 months later . When compared with the controls in 1990 and 1991 , we observed a marked reduction in the incidence of P. falciparum infections in children less than six years old in the bed net villages ( reduced by 40 % and 48 % ) and a smaller but still significant reduction in the curtain villages ( 10 % and 33 % ) . Significant reductions were also seen in the incidence of P. falciparum parasitemias greater than 2,500/mm3 in the bed net group ( reduced by 44 % and 49 % ) and curtain group ( 16 % and 32 % ) . Additionally , we observed significant reductions in the incidence of documented fevers in association with P. falciparum parasitemia in bed net ( reduced by 63 % ) and curtain villages ( 53 % ) when compared with controls . Entomologic inoculation rates in both bed net and control villages decreased by more than 50 % below control values during both high transmission seasons . The results of this study , together with a 1988 study in the same area during the low transmission season , show that bed nets offer greater year-round of protection against P. falciparum infection than curtains . However , during the high transmission season , this technique reduces the frequency of P. falciparum infection rather than preventing it entirely Background Intermittent preventive treatment in infants ( IPTi ) with sulphadoxine-pyrimethamine ( SP ) for the prevention of malaria has shown promising results in six trials . However , resistance to SP is rising and alternative drug combinations need to be evaluated to better underst and the role of treatment versus prophylactic effects . Methods Between March 2004 and March 2008 , in an area of western Kenya with year round malaria transmission with high seasonal intensity and high usage of insecticide-treated nets , we conducted a r and omized , double-blind placebo-controlled trial with SP plus 3 days of artesunate ( SP-AS3 ) , 3 days of amodiaquine-artesunate ( AQ3-AS3 ) , or 3 days of short-acting chlorproguanil-dapsone ( CD3 ) administered at routine exp and ed programme of immunization visits ( 10 weeks , 14 weeks and 9 months ) . Principal Findings 1,365 subjects were included in the analysis . The incidence of first or only episode of clinical malaria during the first year of life ( primary endpoint ) was 0.98 episodes/person-year in the placebo group , 0.74 in the SP-AS3 group , 0.76 in the AQ3-AS3 group , and 0.82 in the CD3 group . The protective efficacy ( PE ) and 95 % confidence intervals against the primary endpoint were : 25.7 % ( 6.3 , 41.1 ) ; 25.9 % ( 6.8 , 41.0 ) ; and 16.3 % ( −5.2 , 33.5 ) in the SP-AS3 , AQ3-AS3 , and CD3 groups , respectively . The PEs for moderate-to-severe anaemia were : 27.5 % ( −6.9 , 50.8 ) ; 23.1 % ( −11.9 , 47.2 ) ; and 11.4 % ( −28.6 , 39.0 ) . The duration of the protective effect remained significant for up to 5 to 8 weeks for SP-AS3 and AQ3-AS3 . There was no evidence for a sustained beneficial or rebound effect in the second year of life . All regimens were well tolerated . Conclusions These results support the view that IPTi with long-acting regimens provide protection against clinical malaria for up to 8 weeks even in the presence of high ITN coverage , and that the prophylactic rather than the treatment effect of IPTi appears central to its protective efficacy . Trial Registration Clinical Trials.gov Background Mosquito coils are the most commonly used household insecticidal product in the world with sales exceeding 50 billion coils , used by two billion people worldwide annually . Despite strong evidence that coils prevent mosquito bites a systematic review concluded that there is no evidence that burning mosquito coils prevents malaria acquisition . Therefore , the current trial was design ed to measure and compare prevention of malaria infection by mosquito coils or long-lasting insecticidal net ( LLIN ) or a combination of the two in Yunnan , China in the Greater Mekong sub-region . Methods A four-arm single blind household-r and omized design was chosen as coils emanate insecticide throughout the household . Households enrolled at baseline were r and omly allocated by the lottery method to one of the four intervention arms : ( i ) nothing , ( ii ) 0.03 % transfluthrin coils alone , ( iii ) deltamethrin long-lasting insecticide treated nets , ( LLINs ) alone or ( iv ) a combination of transfluthrin coils and deltamethrin LLINs . All household members were recruited to the study , with only those households excluded with pregnant or breastfeeding mothers , members with chest complaints or allergies or members that regularly slept away from home . The main outcome of interest was Plasmodium falciparum malaria prevalence detected by rapid diagnostic tests ( RDTs ) during six repeated monthly cross-sectional surveys . The secondary outcome of interest was the effect on Plasmodium vivax prevalence detected in the same way . Results A total of 2,052 households were recruited into the study , comprising 7,341 individuals The odds ratios of testing positive by RDT with P. falciparum or P. vivax were > 75 % lower for all intervention arms compared with the control arm . Coils alone provided 77 % protection ( 95 % CI : 50%-89 % ) , LLINs provided 91 % protection ( 95 % CI : 72%-97 % ) and the combination of coils and LLINs provided 94 % protection ( 95 % CI : 77%-99 % ) against P. falciparum compared with the control arm . There was no statistically significant difference between the protective efficacies of the different interventions . Conclusions This is the first robust clinical evaluation of transfluthrin mosquito coils as a means to reduce malaria and the high degree of infection prevented would indicate they represent a potentially highly effective tool , which could be integrated into larger vector control programmes . Trial registration Clinical Trials.gov Identifier : NCT00442442 , March 2007 Tafenoquine is a promising new 8-aminoquinoline drug that may be useful for malaria prophylaxis in nonpregnant persons with normal glucose-6-phosphate dehydrogenase ( G6PD ) function . A r and omized , double-blind , placebo-controlled chemoprophylaxis trial was conducted with adult residents of northern Ghana to determine the minimum effective weekly dose of tafenoquine for the prevention of infection by Plasmodium falciparum . The primary end point was a positive malaria blood smear result during the 13 weeks of study drug coverage . Relative to the placebo , all 4 tafenoquine dosages demonstrated significant protection against P. falciparum infection : for 25 mg/week , protective efficacy was 32 % ( 95 % confidence interval [ CI ] , 20%-43 % ) ; for 50 mg/week , 84 % ( 95 % CI , 75%-91 % ) ; for 100 mg/week , 87 % ( 95 % CI , 78%-93 % ) ; and for 200 mg/week , 86 % ( 95 % CI , 76%-92 % ) . The mefloquine dosage of 250 mg/week also demonstrated significant protection against P. falciparum infection ( protective efficacy , 86 % ; 95 % CI , 72%-93 % ) . There was little difference between study groups in the adverse events reported , and there was no evidence of a relationship between tafenoquine dosage and reports of physical complaints or the occurrence of abnormal laboratory parameters . Tafenoquine dosages of 50 , 100 , and 200 mg/week were safe , well tolerated , and effective against P. falciparum infection in this study population Background Intermittent preventive treatment for malaria in Infants ( IPTi ) has been shown to give effective and safe protection against malaria . It has been suggested that IPTi might have long-lasting beneficial effects but , in most setting s , the protection provided by IPTi appears to be short-lived . Knowledge of the duration of protection given by IPTi would help interpret the results of existing trials and suggest optimal delivery schedules for IPTi . This study investigated how the protective efficacy of IPTi against malaria and anaemia changes over time . Methods and Findings A secondary analysis of data from a cluster-r and omised , placebo-controlled trial of IPTi using sulfadoxine-pyrimethamine ( SP ) in Ghana was conducted . In this trial IPTi was given to 2485 infants at 3 , 4 , 9 and 12 months of age ; children remained in follow-up until two years of age . Poisson regression with a r and om effect to adjust for the cluster-r and omised design was used to determine protective efficacy of IPTi against clinical malaria and anaemia in defined time strata following administration of IPTi . Analysis of first-or-only clinical malaria episode following the individual IPTi doses showed that some protection against malaria lasted between 4 to 6 weeks . A similar pattern was seen when the incidence of all malaria episodes up to 2 years of age was analysed in relation to the most recent IPT , by pooling the incidence of malaria after the individual IPTi doses . Protective efficacy within four weeks of IPTi was 75.2 % ( 95 % CI : 66–82 ) against malaria , 78.9 % ( 95 % CI : 69–86 ) against high parasite density malaria , and 93.8 % ( 95 % CI : 73–99 ) against anaemia . Protection against these outcomes was short-lived , with evidence of any effect lasting for only 6 , 6 and 4 weeks respectively . Protection in children who were parasitaemic when receiving IPTi appeared to be of shorter duration than in uninfected children . There was no evidence of any benefit of IPTi after the immediate period following the IPTi doses . Conclusions Intermittent preventive treatment provides considerable protection against malaria and anaemia for short periods , even in an area of intense seasonal transmission . Due to the relatively short duration of protection provided by each dose of IPTi , this treatment will be of most benefit when delivered at the time of peak malaria incidence BACKGROUND Although many malaria control programmes in sub-Saharan Africa use indoor residual spraying with long-lasting insecticidal nets ( LLINs ) , the two studies assessing the benefit of the combination of these two interventions gave conflicting results . We aim ed to assess whether the addition of indoor residual spraying to LLINs provided a significantly different level of protection against clinical malaria in children or against house entry by vector mosquitoes . METHODS In this two-arm cluster , r and omised , controlled efficacy trial we r and omly allocated clusters of Gambian villages using a computerised algorithm to LLINs alone ( n=35 ) or indoor residual spraying with dichlorodiphenyltrichloroethane plus LLINs ( n=35 ) . In each cluster , 65 - 213 children , aged 6 months to 14 years , were surveyed at the start of the 2010 transmission season and followed in 2010 and 2011 by passive case detection for clinical malaria . Exposure to parasite transmission was assessed by collection of vector mosquitoes with both light and exit traps indoors . Primary endpoints were the incidence of clinical malaria assessed by passive case detection and number of Anopheles gambiae sensu lato mosquitoes collected per light trap per night . Intervention teams had no role in data collection and the data collection teams were not informed of the spray status of villages . The trial is registered at the IS RCT N registry , number IS RCT N01738840 . FINDINGS LLIN coverage in 2011 was 3510 ( 93 % ) of 3777 children in the indoor residual spraying plus LLIN group and 3622 ( 95.5 % ) of 3791 in the LLIN group . In 2010 , 7845 children were enrolled , 7829 completed passive case detection , and 7697 ( 98 % ) had complete clinical and covariate data . In 2011 , 7009 children remained in the study , 648 more were enrolled , 7657 completed passive case detection , and 7545 ( 98.5 % ) had complete data . Indoor residual spraying coverage per cluster was more than 80 % for both years in the indoor residual spraying plus LLIN group . Incidence of clinical malaria was 0.047 per child-month at risk in the LLIN group and 0.044 per child-month at risk in the indoor residual spraying plus LLIN group in 2010 , and 0.032 per child-month at risk in the LLIN group and 0.034 per child-month at risk in the indoor residual spraying plus LLIN group in 2011 . The incident rate ratio was 1.08 ( 95 % CI 0.80 - 1.46 ) controlling for confounders and cluster by mixed-effect negative binomial regression on all malaria attacks for both years . No significant difference was recorded in the density of vector mosquitoes caught in light traps in houses over the two transmission seasons ; the mean number of A gambiae sensu lato mosquitoes per trap per night was 6.7 ( 4.0 - 10.1 ) in the LLIN group and 4.5 ( 2.4 - 7.4 ) in the indoor residual spraying plus LLIN group ( p=0.281 in the r and om-effects linear regression model ) . INTERPRETATION We identified no significant difference in clinical malaria or vector density between study groups . In this area with high LLIN coverage , moderate seasonal transmission , and susceptible vectors , indoor residual spraying did not provide additional benefit . FUNDING UK Medical Research Council The effect of permethrin-treated bed nets ( ITNs ) on malaria vectors was studied as part of a large-scale , r and omized , controlled trial in western Kenya . Indoor resting densities of fed Anopheles gambiae s.l . and An . funestus in intervention houses were 58.5 % ( P = 0.010 ) and 94.5 % ( P = 0.001 ) lower , respectively , compared with control houses . The sporozoite infection rate in An . gambiae s.l . was 0.8 % in intervention areas compared with 3.4 % ( P = 0.026 ) in control areas , while the sporozoite infection rates in An . funestus were not significantly different between the two areas . We estimated the overall transmission of Plasmodium falciparum in intervention areas to be 90 % lower than in control areas . Permethrin resistance was not detected during the study period . As measured by densities of An . gambiae s.l . , the efficacy of bed nets decreased if one or more residents did not sleep under a net or if bed nets had not been re-treated within six months . These results indicate that ITNs are optimally effective if used every night and if permethrin is reapplied at least biannually Background Intermittent preventive treatment ( IPTi ) with sulphadoxine-pyrimethamine ( SP ) in infants result ed in different estimates of clinical malaria protection in two trials that used the same protocol in Ifakara , Tanzania , and Manhiça , Mozambique . Underst and ing the reasons for the discrepant results will help to eluci date the action mechanism of this intervention , which is essential for rational policy formulation . Methods A comparative analysis of two IPTi trials that used the same study design , follow-up , intervention , procedures and assessment of outcomes , in Tanzania and Mozambique was undertaken . Children were r and omised to receive either SP or placebo administered 3 times alongside routine vaccinations delivered through the Exp and ed Program on Immunisation ( EPI ) . Characteristics of the two areas and efficacy on clinical malaria after each dose were compared . Results The most relevant difference was in ITN 's use ; 68 % in Ifakara and zero in Manhiça . In Ifakara , IPTi was associated with a 53 % ( 95 % CI 14.0 ; 74.1 ) reduction in the risk of clinical malaria between the second and the third dose ; during the same period there was no significant effect in Manhiça . Similarly , protection against malaria episodes was maintained in Ifakara during 6 months after dose 3 , but no effect of IPTi was observed in Manhiça . Conclusion The high ITN coverage in Ifakara is the most likely explanation for the difference in IPTi efficacy on clinical malaria . Combination of IPTi and ITNs may be the most cost-effective tool for malaria control currently available , and needs to be explored in current and future studies .Trial Registration Manhiça study registration number : NCT00209795Ifakara study registration number : Background Insecticide-treated bed nets ( ITN ) reduce malaria morbidity and mortality consistently in Africa , but their benefits have been less consistent in Asia . This study ’s objective was to evaluate the malaria protective efficacy of village-wide usage of ITN in Western Myanmar and estimate the cost-effectiveness of ITN compared with extending early diagnosis and treatment services . Methods A cluster-r and omized controlled trial was conducted in Rakhine State to assess the efficacy of ITNs in preventing malaria and anaemia in children and their secondary effects on nutrition and development . The data were aggregated for each village to obtain cluster-level infection rates . In total 8,175 children under 10 years of age were followed up for 10 months , which included the main malaria transmission period . The incidence and prevalence of Plasmodium falciparum and Plasmodium vivax infections , and the biting behaviour of Anopheles mosquitoes in the area were studied concurrently . The trial data along with costs for current recommended treatment practice s were modelled to estimate the cost-effectiveness of ITNs compared with , or in addition to extending the coverage of early diagnosis and treatment services . Results In aggregate , malaria infections , spleen rates , haemoglobin concentrations , and weight for height , did not differ significantly during the study period between villages with and without ITNs , with a weighted mean difference of −2.6 P. falciparum episodes per 1,000 weeks at risk ( 95 % Confidence Interval −7 to 1.8 ) . In areas with a higher incidence of malaria there was some evidence ITN protective efficacy . The economic analysis indicated that , despite the uncertainty and variability in their protective efficacy in the different study sites , ITN could still be cost-effective , but not if they displaced funding for early diagnosis and effective treatment which is substantially more cost-effective . Conclusion In Western Myanmar deployment of ITNs did not provide consistent protection against malaria in children living in malaria endemic villages . Early diagnosis and effective treatment is a more cost effective malaria control strategy than deployment of ITNs in this area where the main vector bites early in the evening , often before people are protected by an ITN BACKGROUND The use of sulfadoxine-pyrimethamine ( SP ) for intermittent preventive treatment in pregnancy ( IPTp ) is threatened by the spread of resistance to SP . Therefore , we studied the efficacy , safety , and tolerance of amodiaquine ( AQ ) or the combination of AQ and SP ( SPAQ ) as possible alternative treatments . METHODS The study was performed in Ghana from June 2004 through February 2007 . Women were individually r and omized to receive IPTp with SP ( n=1328 ) , AQ ( n= 986 ) , or SPAQ ( n=1328 ) . Incidences of anemia , peripheral anemia , and placental parasitemia at delivery were assessed for paucigravidae , as were the birth weights of their infants . Delivery outcomes and the incidence of adverse events were investigated for all women . RESULTS The prevalences of anemia ( as defined by a hemoglobin concentration of < 11.0 g/dL ) at delivery were comparable between the SP and AQ groups and between the SP and SPAQ groups . Similarly , there was no significant difference between the SP and AQ groups or between the SP and SPAQ groups with regard to the incidences of low birth weight ( LBW ) . Women who received AQ or SPAQ were more likely to report adverse events than were those who received SP . CONCLUSION The effects of IPTp with AQ or SPAQ on maternal anemia and LBW were comparable to the effects of IPTp with SP ; however , IPTp regimens that contain AQ are unlikely to be useful as an alternative to IPTp with SP in Ghana , because of a high frequency of associated adverse events . TRIAL REGISTRATION Clinical trials.gov identifier : NCT00146783 Abstract Objective To evaluate the effects of intermittent preventive treatment for malaria in infants ( IPTi ) with sulfadoxine-pyrimethamine in an area of intense , seasonal transmission . Design Cluster r and omised placebo controlled trial , with 96 clusters allocated r and omly to sulfadoxine-pyrimethamine or placebo in blocks of eight . Interventions Children received sulfadoxine-pyrimethamine or placebo and one month of iron supplementation when they received DPT-2 , DPT-3 , or measles vaccinations and at 12 months of age . Main outcome measures Incidence of malaria and of anaemia determined through passive case detection . Results 89 % ( 1103/1242 ) of children in the placebo group and 88 % ( 1088/1243 ) in the IPTi group completed follow-up to 24 months of age . The protective efficacy of IPTi against all episodes of malaria was 24.8 % ( 95 % confidence interval 14.3 % to 34.0 % ) up to 15 months of age . IPTi had no protective effect against malaria between 16 and 24 months of age ( protective efficacy −4.9 % , −21.3 % to 9.3 % ) . The incidence of high parasite density malaria ( ≥ 5000 parasites/μl ) was higher in the IPTi group than in the placebo group between 16 and 24 months of age ( protective efficacy −19.5 % , −39.8 % to −2.2 % ) . IPTi reduced hospital admissions with anaemia by 35.1 % ( 10.5 % to 52.9 % ) up to 15 months of age . IPTi had no significant effect on anaemia between 16 and 24 months of age ( protective efficacy −6.4 % , −76.8 % to 35.9 % ) . The relative risk of death up to 15 months of age in the IPTi group was 1.26 ( 95 % confidence interval 0.81 to 1.96 ; P = 0.31 ) , and from 16 to 24 months it was 1.28 ( 0.77 to 2.14 ; P = 0.35 ) . Conclusions Intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine can reduce malaria and anaemia in infants even in seasonal , high transmission areas , but concern exists about possible rebound in the incidence of malaria in the second year of life BACKGROUND Malaria and anaemia , especially that due to iron deficiency , are two leading causes of morbidity worldwide . Little is known about the relative contribution of Plasmodium falciparum infection and iron deficiency to the aetiology of anaemia in malaria-endemic areas . We undertook a r and omised comparison of different strategies for control of anaemia and malaria in infants , including an assessment of the effect of iron supplementation on malaria susceptibility . METHODS 832 infants born at one hospital in a malaria-hyperendemic area of Tanzania between January and October , 1995 , were r and omly assigned to group DI , receiving daily oral iron ( 2 mg/kg daily ) plus weekly Deltaprim ( 3.125 mg pyrimethamine plus 25 mg dapsone ) ; group IP , receiving iron plus weekly placebo ; group DP , receiving daily placebo plus weekly Deltaprim ; or group PP . supplementation was given from 8 to 24 weeks of age , and the weekly chemoprophylaxis from 8 to 48 weeks . The frequency of severe anaemia ( packed-cell volume < 25 % ) and malaria episodes was assessed through a combination of passive case detection and cross-sectional surveys . FINDINGS The groups that received iron supplementation had a lower frequency of severe anaemia than those that did not receive iron ( 0.62 vs 0.87 cases per person-year ; protective efficacy 28.8 % [ 95 % CI 6.3 - 45.8 ) . Iron supplementation had no effect on the frequency of malaria ( 0.87 vs 1.00 cases per person-year ; protective efficacy 12.8 % [ -12.8 to 32.5 ] ) . The groups that received malaria prophylaxis had lower frequencies of both severe anaemia ( 0.45 vs 1.04 episodes per person-year ; protective efficacy 57.3 % [ 43.0 - 67.9 ] ) and malaria ( 0.53 vs 1.34 episodes per person-year ; protective efficacy 60.5 % [ 48.2 - 69.9 ] ) than the groups that did not receive prophylaxis . After the end of the intervention period , children who had received malaria chemoprophylaxis had higher rates of severe anaemia and malaria than non-chemoprophylaxis groups ( relative risks 2.2 [ 1.3 - 3.7 ] and 1.8 [ 1.3 - 2.6 ] ) . INTERPRETATION Malaria chemoprophylaxis during the first year of life was effective in prevention of malaria and anaemia but apparently impaired the development of natural immunity . Iron supplementation was effective in preventing severe anaemia without increasing susceptibility to malaria . Our findings support iron supplementation of infants to prevent iron-deficiency anaemia , even in malaria-endemic areas A double-blind controlled trial was undertaken from August 1990 to February 1991 among Karen children on the Thai-Burmese border to evaluate the effects on malaria incidence and prevalence of permethrin-treated bed nets . Three hundred and fifty schoolchildren , aged 4 to 15 years , were allocated at r and om to receive either a permethrin-impregnated net or a non-treated net . The incidence of malaria infections , confirmed by a blood film , was assessed during 6 months . Three surveys were conducted , on admission and 3 and 6 months later , to measure the prevalence of infections and spleen rates . Compliance was assessed by monthly home visiting . The use of permethrin-treated bed nets reduced the number of parasitaemic Plasmodium falciparum infections by 38 % and the number of symptomatic episodes by 42 % . The number of P. vivax malaria attacks was similar in each group . The prevalence of positive blood films in the 2 groups did not change significantly during the study . A reduction in spleen rate by 50 % in both groups at the end of the study period could not be related to the overall use of nets . Compliance was high and no side-effect was reported . The long-term effects on morbidity and mortality need to be assessed after distribution of permethrin treated bed nets at the village level In many areas of tropical Africa affected by chloroquine-resistant Plasmodium falciparum , a combination of sulfadoxine and pyrimethamine ( S-P ) is used for alternative medication , especially in young children . In Magoda village in Muheza District , north-eastern Tanzania , 38 children 1 - 10 years of age were enrolled in a therapeutic study of S-P in July 1994 . All had monoinfections of P. falciparum and an asexual parasite count of 1000 - 80,000/microL of blood . S-P was given as a single dose corresponding to 0.8 - 1.4 mg pyrimethamine/kg body weight . Of the 38 children followed up to day 7 , 10 showed an S/RI response , 26 an RII response , and 2 an RIII response . Older children had lower pre-treatment parasitaemia and a better therapeutic response than younger children . Among the various contributory factors responsible for the poor therapeutic result , drug pressure from a prophylactic intervention with weekly dapsone-pyrimethamine between May 1993 and May 1994 seems to have been the most important An intervention trial was undertaken in a rural area of The Gambia to assess the impact on malaria morbidity of the use of bed nets . Bed nets were allocated at r and om among a group of 16 Fula hamlets , where they were previously rarely used . The incidence of febrile episodes with associated malaria parasitaemias throughout the rainy season and the prevalence of splenomegaly and parasitaemia at the end of the rainy season were determined in 233 children aged 1 - 9 years who slept under bed nets and in 163 children who did not . Bed nets were used correctly by the children in the study cohort , but direct observations showed that a significant number of children left their nets for a period during the night . There was no significant difference in the incidence of clinical attacks of malaria or in any other malariometric measurement between the 2 groups . Thus , bed nets were not effective in reducing malaria morbidity in this group of children . The apparent protection from bed nets demonstrated in previous retrospective surveys may have been due to an increased number of infective bites being received by exposed individuals sleeping close to users of bed nets One hundred and ninety students aged 6 to 18 at a boarding school 120 km west of Nairobi in the Rift Valley participated in a comparative trial of malaria prophylaxis . Treatment with a combination of amodiaquine 25 mg/kg over three days plus doxycycline 100 mg twice daily for five days cleared their blood of Plasmodium falciparum . They were then r and omly divided into the following three groups matched for age and sex : one group slept under mosquito nets ; one group received one or two tablets ( 100 mg each ) of proguanil hydrochloride daily according to weight ; one group received one or two placebo tablets daily which were the same size and colour as the proguanil tablets . Malaria was diagnosed when asexual P falciparum were seen on blood films and was treated with pyrimethamine-sulphadoxine . At the end of one school term 188 of the 190 students had completed the study . One new infection was found during 3893 days of follow up in the mosquito net group , eight new infections over 3667 days in the proguanil group , and 35 new infections over 3677 days in the placebo group , representing a reduction of 97.3 % and 77.1 % in attack rates for the mosquito net method and for treatment with proguanil respectively . Both provide effective protection from malaria ABSTRACT Intermittent preventive treatment ( IPT ) is increasingly used to reduce malaria morbidity and mortality in children and pregnant women . The efficacy of IPT depends on the pharmacokinetic and pharmacodynamic properties of the antimalarial drugs used . Healthy adult male volunteers whose occupation put them at high risk of malaria on the Northwest border of Thail and were r and omized to receive a 3-day-treatment dose of dihydroartemisinin-piperaquine monthly ( DPm ) or every 2 months ( DPalt ) or an identical placebo with or without fat ( 6.4g/dose ) over a 9-month period . All volunteers were monitored weekly . One thous and adults were recruited . Dihydroartemisinin-piperaquine was well tolerated . There were 114 episodes of malaria ( 49 Plasmodium falciparum , 63 P. vivax , and 2 P. ovale ) . The protective efficacy against all malaria at 36 weeks was 98 % ( 95 % confidence interval [ CI ] , 96 % to 99 % ) in the DPm group and 86 % ( 95 % CI , 81 % to 90 % ) in the DPalt group ( for both , P < 0.0001 compared to the placebo group ) . As a result , the placebo group also had lower hematocrits during the study ( P < 0.0001 ) . Trough plasma piperaquine concentrations were the main determinant of efficacy ; no malaria occurred in participants with a trough concentration above 31 ng/ml . Neither plasma piperaquine concentration nor efficacy was influenced by the coadministration of fat . DPm is safe to use and is effective in the prevention of malaria in adult males living in an area where P. vivax and multidrug-resistant P. falciparum malaria are endemic ABSTRACT The therapeutic responses to the eight most widely used antimalarial drugs were assessed in 207 adult patients withPlasmodium vivax malaria . This parasite does not cause marked sequestration , so parasite clearance can be used as a direct measure of antimalarial activity . The activities of these drugs in descending order were artesunate , artemether , chloroquine , mefloquine , quinine , halofantrine , primaquine , and pyrimethamine-sulfadoxine ( PS ) . Therapeutic responses to PS were poor ; parasitemias did not clear in 5 of the 12 PS-treated patients , whereas all the other patients made an initial recovery . Of 166 patients monitored for ≥28 days , 35 % had reappearance of vivax malaria 11 to 65 days later and 7 % developed falciparum malaria 5 to 21 days after the start of treatment . There were no significant differences in the times taken for vivax malaria reappearance among the different groups except for those given mefloquine and chloroquine , in which all vivax malaria reappearances developed > 28 days after treatment , suggesting suppression of the first relapse by these slowly eliminated drugs . There was no evidence of chloroquine resistance . The antimalarial drugs vary considerably in their intrinsic activities and stage specificities of action Gambian children who had received malaria chemoprophylaxis for a variable period of time during their first 5 years of life were followed to determine whether they experienced a rebound in mortality or in morbidity from malaria during the period after chemoprophylaxis was stopped . The risk of dying between the ages of 5 years , when chemoprophylaxis was stopped , and 10 years was no higher among children who had received chemoprophylaxis with Maloprim ( pyrimethamine plus dapsone ) for some period during their first 5 years of life than among children who had received placebo ( 21 vs. 24 deaths ) and the beneficial effect of chemoprophylaxis on mortality observed during the first 5 years of life was sustained . The incidence of clinical attacks of malaria during the year after medication was stopped was significantly higher among children who had previously received Maloprim for several years than among children who had previously received placebo . However , at the end of this year , there was no significant difference in spleen rate , parasite rate or packed cell volume between the 2 groups of children . Thus , stopping chemoprophylaxis after a period of several years increased the risk of clinical malaria but did not result in a rebound in mortality in Gambian children . However , the number of deaths recorded was small , so a modest effect on mortality can not be excluded The effectiveness of permethrin-impregnated ( 0.5 g/m2 ) bed-nets and curtains as malaria control measures was evaluated in Uriri , Kenya in 1988 . One hundred five families were r and omly assigned to 1 of 3 study groups ( control , bed-net , or curtain ) . All participants were cured of parasitemia with pyrimethamine/sulfadoxine . Selective epidemiologic and entomologic parameters were measured weekly , while knowledge , attitude , and practice s surveys were conducted at the beginning and end of the 15 week study . Plasmodium falciparum infections per person week at risk were significantly higher in the control group than in either the curtain group ( 5.42 vs. 2.35 cases/100 person weeks risk ) or the bed-net group ( 5.42 vs. 3.77 cases/100 person weeks risk ) . The curtain group had fewer infections per person week at risk than the bed-net group ( 2.35 vs. 3.77 cases/100 person weeks risk ) . A difference was found in clinical malaria among the groups : 45 % of persons in the bed-net and curtain groups vs. 30 % of those in the control group reported no episodes of fever and chills ( chi 2 , P less than 0.05 ) . Indoor resting Anopheles gambiae or An . funestus were found on 94 occasions in the control houses , but only twice in the treated houses during weekly visits to each house over the study period ( chi 2 P less than 0.001 ) . The pyrethrum knockdown method produced similar results with a total of 195 , 23 , and 3 An . gambiae and An . funestus collected in the control , bed-net , and curtain houses during the same period , respectively . ( ABSTRACT TRUNCATED AT 250 WORDS R and omized trials and mathematical modeling suggest that insecticide-treated mosquito nets ( ITNs ) provide community-level protection to both those using ITNs and those without individual access . Using nationally representative household survey data sets from 17 African countries , we examined whether community ITN coverage is associated with malaria infections in children < 5 years old and all-cause child mortality ( ACCM ) among children < 5 years old in households with one or more ITNs versus without any type of mosquito net ( treated or untreated ) . Increasing ITN coverage ( > 50 % ) was protective against malaria infections and ACCM for children in households with an ITN , although this protection was not conferred to children in households without ITNs in these data . Children in households with ITNs were protected against malaria infections and ACCM with ITN coverage > 30 % , but this protection was not significant with ITN coverage < 30 % . Results suggest that ITNs are more effective with higher ITN coverage This paper reports 2 studies . ( i ) After a year of baseline data collection , lambdacyhalothrin-treated bed nets were introduced into 3 of 5 villages in north-west Thail and , the remaining 2 being treated with placebo . Human bait collection s were carried out in each village on 2 nights per month , for 8 months of each year , and the biting densities were compared between the first year and the second year . The treated bed nets did not have any significant impact on the density or parous rates of Anopheles sawadwongporni and A. maculatus s.s . population s. The results for A. dirus s.l . were not conclusive because of the low number caught . Significant reductions in biting and parous rates of A. minimus species A were observed in only one of the 3 treated villages , and there was no overall difference between treated and control groups . However , the trial suffered from the washing of nets by villagers and the low rate of reimpregnation . ( ii ) A short-term study involved 4 villages in a cross-over design , and lasted 48 d. For the first 24 d , residents of 2 villages were given new treated nets while the other 2 villages retained their own untreated nets . For the second 24 d , this situation was reversed . Daily light-trapping revealed no significant difference in the indoor densities or parous rates of A. minimus species A between the periods with treated or untreated nets . ( ABSTRACT TRUNCATED AT 250 WORDS Long lasting insecticide treated nets ( LLINs ) have been advocated as an effective tool for prevention and control of malaria . Olyset net was the first LLINs which became commercially available and obtained WHO approval . According to the national strategic plan on evaluation of Olyset net , a field trial was conducted to determine the efficacy of these nets against malaria vectors in an endemic area in the southeast of Iran . Fourteen villages with similar topographical and epidemiological situations were selected and r and omly assigned to two clusters of the study : Olyset net and untreated net . Distribution of nets was carried out to cover 100 % of the population in Olyset net and untreated net cluster . Anopheline mosquitoes were collected monthly using different WHO st and ard methods in both areas to determine their abundance , feeding pattern and resting behaviour . Human blood index was determined using ELISA test . Additionally , Olyset nets were evaluated for their biological activity using WHO cone bioassay test by susceptible colony of Anopheles stephensi ( Beech strain ) and then for insecticide residues by employing high performance thin layer chromatography . Malaria incidence was measured by passive and active case detection from all study population . In total 2115 adult anopheline mosquitoes were collected and identified using morphological characters . They comprised of seven species : Anopheles dthali ( Liston ) , A. culicifacies ( Giles ) , A. stephensi ( Liston ) , A. superpictus ( Grassi ) , A.fluviatilis ( James ) , A. moghulensis ( Christophers ) and A. turkhudi ( Liston ) . A. dthali , A. culicifacies and A. stephensi were most prevalent species in both areas . In the Olyset net study area , there was a significant reduction of 41.1 % , 54.4 % , 59.39 % and 64.1 % in the indoor-resting density of A. culicifacies , A. stephensi , A. dthali and A. superpictus , respectively , with an overall reduction of 39.3 % in total mosquitoes in comparison with untreated net area . A significant reduction was also observed in human blood index of vector species in the Olyset net villages . Bioefficacy test results of Olyset nets showed that the median knockdown time was 1.48 and 3.25min , while the average mortality rate was 100 % and 72.3%±7.07 in baseline and after 1 year of intervention , respectively . The average permethrin content reached to 68.31 % ( 683.1mg/m(2 ) ) of the initial insecticide dose of 937±21.69mg/m(2 ) ( nearly 1000mg/m(2 ) ) at the end of intervention . Malaria incidence was reduced by 96.6 % and 64.8 % in the village with Olyset nets and in the villages with untreated nets , respectively . During intervention period , there was a reduction of 93.2 % in malaria incidence in Olyset net area as compared to the untreated area . This study indicated that Olyset nets have a major impact on malaria vectors and disease burden ; therefore it could be recommended as an effective personal protection tool for malaria control in malarious areas Long term use of insecticides in malaria vector control has been shown to alter the behavior of vectors . Such behavioral shifts have the potential of undermining the effectiveness of insecticide-based control interventions . The effects of insecticide treated nets ( ITNs ) use on the composition , biting/feeding and sporozoite rates of Anopheles gambiae s.l . mosquitoes in Musilongo village , Vihiga County of western Kenya highl and s were investigated . Adult mosquitoes were collected in selected sleeping spaces inside six r and omly selected houses using miniature Centre for Disease Control and Prevention ( CDC ) light traps . Mosquito sampling in each house was conducted twice every week for 16 consecutive months ( May 2010-August 2012 ) . At each sampling a single trap was set in the selected space inside each house such that it collected mosquitoes alternatively from 18:00 to 21:00h and 21:00 to 06:00h every week . All collected mosquitoes were morphologically identified . Female Anopheles mosquitoes were classified according to their physiological status as unfed , fed , partially gravid and gravid , sorted and counted . Members of the A. gambiae complex were identified using a Polymerase chain reaction ( PCR ) method . Enzyme-linked-immunosorbent assay ( ELISA ) was used to determine blood meal sources and Plasmodium infection rates in A. gambiae s.l . mosquitoes . Blood meal tests were conducted on DNA extracted from gut contents of blood fed A. gambiae s.l . The head and thorax section of dried sample s of A. gambiae s.l . were used in testing for the presence of Plasmodium falciparum ( Pf ) sporozoites . Overall , 735 adult female Anopheles comprising 708 [ 96.3 % ] A. gambiae s.l . and 27 [ 3.7 % ] Anopheles funestus mosquitoes were collected . A. gambiae s.l . population collected comprised , 615 [ 86.9 % ] unfed and 38 [ 5.4 % ] fed adult mosquitoes . The rest were either partially or fully gravid . The proportion of A. gambiae s.l . biting indoors within 18:00 - 21:00h was 15.8 % ( 103/653 ) at a rate of 3.2bites per person per hour compared to 84.2 % biting from 21:00 - 06:00h at a rate of 3.8 bites/per/h . An estimated 97.7 % A. gambiae ss and 2.3 % A. arabiensis constituted the indoor biting A. gambiae s.l . The population of An . gambiae s.l . biting from 18:00 to 21:00h had a Plasmodium faciparum ( pf ) sporozoite rate of 3.8 % compared to 3.5 % observed in population s biting within 21:00 - 06:00h . Human blood constituted 89 % of An . gambiae s.l . blood meal sources . The risk of malaria transmission from 21:00 to 06:00h was approximately 5 fold the risk within 18:00 - 21:00h . Majority of the infective female A. gambiae s.l . adults were biting deep into the night than in the early hours of the night . Humans remain the preferred source of blood meal for A. gambiae s.s . the dominant malaria vector in the highl and s. ITNs remain a fundamental control intervention against malaria transmission since female blood seekers were more during bed time than pre-bed time . Advocacy on enhanced net availability , integrity and usage in Kenyan highl and s can reduce Pf transmission . Additional complementary interventions are required to control the biting and parasite transmission encountered before bed-time A r and omized trial reported by Alassane Dicko and colleagues shows that intermittent preventive treatment for malaria in children who are protected from mosquitoes by insecticide-treated bednets provides substantial protection from malaria Studies were conducted on the efficacy of Olyset nets-a long-lasting insecticidal net ( LLIN ) factory treated with 2 % ( w/w ) permethrin on malaria transmission in an area under the influence of pyrethroid susceptible vector species Anopheles culicifacies and A. fluviatilis in Sundargarh District , Orissa , India . The study area comprised 22 villages that were r and omized into three clusters and design ated as Olyset net , untreated net , and no net area . Malaria incidence in the study population was measured through longitudinal active surveillance at fortnightly intervals . There was a reduction of 65 - 70 % in malaria incidence in Olyset net area as compared to the control areas . The attack rate of Plasmodium falciparum or number of episodes per person per year in different age groups also showed significant reduction in Olyset net area as compared to untreated net and no net areas . Cross-sectional point prevalence surveys showed 45.7 % reduction of malaria prevalence in Olyset net users , whereas there was an increase of 33.3 % and 51 % in untreated net and no net villages respectively . The compliance rate of Olyset net usage in the study population was 80 - 98 % during different months , whereas it was between 70 % and 90 % for untreated nets . There were minimal complains of skin irritation ( 4 % ) , itching ( 8 % ) and eye irritation ( 1.2 % ) . However , these effects were only transitory in nature lasting for few hours of the first usage . Olyset nets also provided collateral benefits in terms of relief not only from mosquitoes and malaria but also from other household pests such as head lice , bed bugs , cockroaches , ants and houseflies . The Olyset nets were found to be safe to humans as no adverse event was recorded in the net users that can be attributed to the use of net . The study showed that Olyset nets are effective personal protection tool that can be used in a community based intervention programme Between 1991 and 1994 , an intervention program with permethrin- and lambdacyhalothrin-impregnated bed nets was carried out over a period of nine months in each of five endemic , malarious areas of Ecuador , Peru , and Colombia . This program was evaluated through household surveys , blood sampling , in-depth longitudinal studies , and entomologic analysis . Eighty-four communities ( including approximately 35,000 individuals ) were paired according to malaria incidence , size , and coverage with bed nets and then r and omly allocated to intervention and control groups . The results showed that peoples ' acceptance of the measure was related to their perception of an immediate protective effect against insects . The effectiveness of the bed nets , measured as a reduction of malaria incidence in intervention communities as against control communities , showed large variations between and within the study areas . The protective efficacy varied between 0 % and 70 % when looking only at the postintervention differences between intervention and control groups . The average protection was 40.8 % when considering a four-month incidence of clinical malaria attacks and 28.3 % when considering a two-week malaria incidence . Important factors for the success of the bed net program were insect susceptibility to pyrethroids , high coverage with impregnated bed nets , high malaria incidence , good community participation , high mosquito densities when people go to bed , and a high proportion of Plasmodium falciparum . In one area , where DDT spraying in the control communities was executed , the effectiveness of bed net impregnation was slightly better than that of spraying A r and omized controlled trial of insecticide-treated bed nets ( ITNs ) was conducted in an area of high malaria transmission in Tanzania in order to assess the effects of ITNs on infection and anaemia . One hundred and twenty-two children , aged 5 to 24 months , were r and omly allocated to 2 groups , one of which received ITNs . Outcome measures were assessed in 6 consecutive months with monthly cross-sectional surveys . These measures were haemoglobin values , Plasmodium falciparum prevalence and density , and multiplicity of infection determined by polymerase chain reaction-restriction fragment length polymorphism analysis ( PCR-RFLP ) of the msp2 locus . There was a significant increase in mean heamoglobin values and a significant decrease of 16.4 % in microscopically determined P. falciparum prevalence in children in the ITN group six months after the start of the trial . Both effects were more pronounced in younger children . However , no significant difference was observed in parasite density or multiplicity of infection among infected children . Comparison with PCR results indicated that microscopically subpatent parasitaemia was more frequently found in children in the ITN group . This , together with the observed similar multiplicity in the 2 groups , suggests that infections are maintained despite ITN use , owing to the chronicity of infections . This study shows that ITNs reduce the risk of anaemia in highly exposed young children . The virtually unchanged multiplicity of infection indicates that the potentially protective concomitant immunity is not compromised A r and omized , double-blind , field trial was carried out to compare the effectiveness of permethrin-treated bed nets with that of untreated nets as a method of malaria control for migrant workers in eastern Thail and . The study was conducted using 261 subjects in eastern rural areas that are known to be highly endemic for multidrug-resistant Plasmodium falciparum infection . One hundred twenty-six subjects used treated nets , while 135 used untreated nets . During the 35 weeks of observation , 23 subjects using treated nets and 33 workers using untreated nets developed 28 and 51 episodes of malaria , respectively ( P = 0.029 ) . The reduction in risk per subject due to treated nets was 0.06 . The residual effects of permethrin were tested using a World Health Organization st and ard bioassay . Anti-mosquito activity was found to be present in the nets for more than 16 months . We conclude that because of the failure of the development of safe , effective , long-lasting prophylactic agents , integrating the use of impregnated nets with large-scale primary health care programs may be a partially effective method for controlling malaria in eastern Thail and An exploratory trial of the efficacy of indoor spraying with malathion on morbidity and mortality in refugee camps in eastern Sudan was conducted during the rainy season of 1997 . The interior walls of houses from a r and omly selected group of five camps were sprayed with malathion in mid-September and morbidity and mortality rates in the camps for the months October to December compared with rates in five controls . Pyrethrum spray collection and human l and ing catches were performed in two collection rounds . An exophagic but endophilic population of Anopheles arabiensis was the most common mosquito collected . The mean human blood index of 242 mosquitoes from eight camps was 0.51 . Only two of 1040 mosquitoes examined harboured sporozoites . Blood sample s of 83 putative malaria patients were examined for parasites by PCR . Mortality rates in the 3 months following spraying were significantly lower in sprayed camps although differences in clinical malaria incidence between sprayed and non-sprayed camps were not significant A field trial of permethrin-impregnated bed nets ( PIBs ) was conducted in 2 Afghan refugee villages in Pakistan . Nets were issued to only 10 % of families (= 1398 people ) ; this simulated a situation in which bed nets are gradually adopted by villagers in Afghanistan . A further 10 % lacking bed nets were selected as controls from the same villages . An initial survey showed that 86 % of household heads were aware that malaria was transmitted by mosquito bites , but only 2 % had used bed nets before . Trial families were encouraged to attend the village health centres if they fell ill . Microscopy records showed that , between July and December 1991 , 22.4 % of the control group became infected with Plasmodium vivax and 13.0 % contracted P. falciparum while in the intervention group only 9.9 % contracted P. vivax ( relative risk 0.58 , confidence interval [ CI ] 95 % 0.49 - 0.68 ) and only 3.8 % contracted P. falciparum ( relative risk 0.39 , 95 % CI 0.29 - 0.53 ) . A single treatment of the nets with permethrin at 0.5g/m2 remained protective throughout the 6 months ' transmission season . 73 % of families cl aim ed to use their nets every night ; members of families who cl aim ed to use nets less regularly showed an incidence similar to that of the control group . There was no sex or age difference in net use or protective efficacy . Headlouse infestation rates were reduced in PIB users . Few nets were washed , given away or sold . The prospect for PIBs as personal protection appears good , despite people 's lack of previous experience A r and omized controlled trial investigated the impact of community-wide use of mosquito nets impregnated with lambda-cyhalothrin alone or with dapsone/pyrimethamine ( d/p ) prophylaxis on clinical malaria due to perennially transmitted Plasmodium falciparum in children in the Bo district of Sierra Leone . The 17 study communities were pair-matched and r and omly allocated to receive treated mosquito nets or no nets and the children ( age range = 3 months-6 years ) in each community were r and omly allocated to receive d/p or placebo individually every two weeks . This result ed in each of the approximately 2,000 children recruited being in one of four study groups ( impregnated mosquito nets and d/p prophylaxis , impregnated mosquito nets , d/p prophylaxis , and controls ) . The intervention phase of the study lasted 12 months . A total of 1,800 children attended more than 25 % of the 48 total weekly morbidity surveillance surveys and were included in the analysis . The effects of the exclusive use of either treated mosquito nets or d/p prophylaxis on protection against clinical malaria due to P. falciparum was significantly similar ( 49 % and 42 % , respectively ) , while in combination this protective efficacy was significantly increased to 72 % ( 95 % confidence interval = 67 - 76 % ) . Children in the control group had an average of 1.3 clinical malaria episodes per child annually compared with 0.65 episodes or 0.78 episodes for those using treated mosquito nets and d/p , respectively . Children using both treated mosquito nets and d/p prophylaxis had an average of 0.37 episodes per child . The interventions significantly reduced spleen rates and increased hematocrit values , and reduced the duration of episodes of clinical malaria ABSTRACT A village-scale trial was conducted on the efficacy of Olyset nets : a long-lasting insecticidal net ( LLIN ) factory treated with 2 % wt : wt permethrin against malaria vectors Anopheles culicifacies Giles and Anopheles fluviatilis James , in Sundargarh District , Orissa , India . The study area comprised 22 villages that were r and omized into three clusters and design ated as Olyset net , untreated net , and no net clusters . Baseline studies showed that both vector species were 100 % susceptible to permethrin . Results of wash resistance and bioefficacy of Olyset nets showed 100 % mortality in An culicifacies up to 11 washings , whereas 100 % mortality was observed in An . fluviatilis even after 20 washings . The median knock-down time for these species ranged between 4.55–6.00 and 4.45–5.45 min , respectively , during 1 yr of intervention . In the Olyset net study area , there was a significant reduction of 80.6 , 94.1 , and 76.7 % in the entry rate of An . culicifacies , An . fluviatilis , and other anopheline species , respectively , with an overall reduction of 63.5 % in total mosquitoes . Floor sheet collection s in houses with Olyset nets indicated 39 % immediate mortality in total mosquitoes . The overall feeding success rate of mosquitoes in the trial village was only 18.0 % in comparison to 44.2 and 79.1 % in villages with untreated nets and no nets , respectively . A significant reduction was also recorded in parity rate and human blood index of vector species in the Olyset net area . This study showed that Olyset nets are an effective personal protection tool that can be used in a community-based intervention program In villages of northern Guadalcanal in the Solomon Isl and s , where the predominant malaria vector is An.farauti No. 1 and An.puctulatus is also involved , malaria transmission rates were compared for three zones : ( 1 ) non-intervention : 438 people in seventeen villages ; ( 2 ) residual DDT house-spraying two cycles per year : 644 people in thirty villages ; ( 3 ) bednets impregnated with permethrin 0.5 g/m2 twice per year , used by 580 people in sixteen villages . Regular DDT spraying in zones 1 and 3 had been withdrawn 18 months previously . Malariological blood smear surveys of children aged 1 - 9 years in August 1986 to January 1987 showed a mean baseline malaria parasite rate of 38 % ( 32/84 ) . By February 1988 , 18 months after introduction of impregnated bednets , the Plasmodium falciparum infection rate in children was lowest in the zone using impregnated bednets ( 21 % of 29 ) , intermediate in the untreated zone ( 29 % of 34 ) and highest in the DDT zone ( 46 % of 53 ) , but these differences were not statistically significant . P. vivax infection rates were 9 - 14 % . Using ELISA tests for malaria circumsporozoite antigen in the vectors , overall positivity rates were 0.7 % of 49,902 An.farauti and 2.54 % of 118 An.punctulatus , comprising 228 P.falciparum and 124 P.vivax infections . In the study zones , vector positivity rates were 0.93 % of 31,615 An.farauti in the untreated zone ; 0.32 % of 16,883 An.farauti in the DDT zone ; 0.07 % of 1404 An.farauti and 2.54 % of 118 An.puctulatus in the impregnated bednet zone . here was no significant correlation between malaria parasite rates in the vectors and the children . ( ABSTRACT TRUNCATED AT 250 WORDS Both insecticide-treated bed nets ( ITNs ) and indoor residual spraying ( IRS ) reduce malaria in high malaria transmission areas . The combined effect of these interventions is unknown . We conducted a non-r and omized prospect i ve cohort study to determine protective efficacy of IRS with ITNs ( ITN + IRS ) compared with ITNs alone ( ITN only ) in preventing Plasmodium falciparum parasitemia . At baseline , participants provided blood sample s for malaria smears , were presumptively treated for malaria , and received ITNs . Blood smears were made monthly and at sick visits . In total , 1,804 participants were enrolled . Incidence of P. falciparum parasitemia in the ITN + IRS and ITN only groups was 18 and 44 infections per 100 persons-years at risk , respectively ( unadjusted rate ratio = 0.41 ; 95 % confidence interval [ CI ] = 0.31 - 0.56 ) . Adjusted protective efficacy of ITN + IRS compared with ITN only was 62 % ( 95 % CI = 0.50 - 0.72 ) . The combination of IRS and ITN might be a feasible strategy to further reduce malaria transmission in areas of persistent perennial malaria transmission BACKGROUND Administration of sulfadoxine-pyrimethamine at times of vaccination-intermittent preventive treatment in infants (IPTi)-is a promising strategy to prevent malaria . However , rising resistance to this combination is a concern . We investigated a shortacting and longacting antimalarial drug as alternative regimens for IPTi . METHODS We undertook a double-blind , placebo-controlled trial of IPTi in an area of high resistance to sulfadoxine-pyrimethamine at sites of moderate ( n=1280 infants enrolled ) and low ( n=1139 ) intensity of malaria transmission in Tanzania . Infants aged 8 - 16 weeks were r and omly assigned in blocks of 16 to sulfadoxine ( 250 mg ) plus pyrimethamine ( 12.5 mg ; n=319 in moderate-transmission and 283 in low-transmission sites ) , chlorproguanil ( 15 mg ) plus dapsone ( 18.75 mg ; n=317 and 285 ) , mefloquine ( 125 mg ; n=320 and 284 ) , or placebo ( n=320 and 284 ) , given at the second and third immunisations for diphtheria , pertussis , and tetanus , and for measles . Research team and child were masked to treatment . Recruitment was stopped early at the low-transmission site because of low malaria incidence . The primary endpoint was protective efficacy against all episodes of clinical malaria at 2 - 11 months of age . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00158574 . FINDINGS All r and omly assigned infants were analysed . At the moderate-transmission site , mefloquine had a protective efficacy of 38.1 % ( 95 % CI 11.8 - 56.5 , p=0.008 ) against clinical malaria in infants aged 2 - 11 months , but neither sulfadoxine-pyrimethamine ( -6.7 % , -45.9 to 22.0 ) nor chlorproguanil-dapsone ( 10.8 % , -24.6 to 36.1 ) had a protective effect . No regimen had any protective efficacy against anaemia or hospital admission . Mefloquine caused vomiting in 141 of 1731 ( 8 % ) doses given on day 1 ( odds ratio vs placebo 5.50 , 95 % CI 3.56 - 8.46 ) . More infants died in the chlorproguanil-dapsone and mefloquine groups ( 18 and 15 , respectively ) than in the sulfadoxine-pyrimethamine or placebo groups ( eight deaths per group ; p=0.05 for difference between chlorproguanil-dapsone and placebo ) . INTERPRETATION IPTi with a longacting , efficacious drug such as mefloquine can reduce episodes of malaria in infants in a moderate-transmission setting . IPTi with sulfadoxine-pyrimethamine has no benefit in areas of very high resistance to this combination . The appropriateness of IPTi should be measured by the expected incidence of malaria and the efficacy , tolerability , and safety of the drug . FUNDING IPTi Consortium and the Gates Malaria Partnership |
13,287 | 20,064,798 | Further , systems that were endorsed by colleagues , minimized perceived threats to professional autonomy , and did not compromise doctor-patient interactions were accepted by users . | There is wide variability in the use and adoption of recommendations generated by computerized clinical decision support systems ( CDSSs ) despite the benefits they may bring to clinical practice .
We conducted a systematic review to explore the barriers to , and facilitators of , CDSS uptake by physicians to guide prescribing decisions . | Abstract Objective : To evaluate the use of a computerised support system for decision making for implementing evidence based clinical guidelines for the management of asthma and angina in adults in primary care . Design : A before and after pragmatic cluster r and omised controlled trial utilising a two by two incomplete block design . Setting : 60 general practice s in north east Engl and . Participants : General practitioners and practice nurses in the study practice s and their patients aged 18 or over with angina or asthma . Main outcome measures : Adherence to the guidelines , based on review of case notes and patient reported generic and condition specific outcome measures . Results : The computerised decision support system had no significant effect on consultation rates , process of care measures ( including prescribing ) , or any patient reported outcomes for either condition . Levels of use of the software were low . Conclusions : No effect was found of computerised evidence based guidelines on the management of asthma or angina in adults in primary care . This was probably due to low levels of use of the software , despite the system being optimised as far as was technically possible . Even if the technical problems of producing a system that fully supports the management of chronic disease were solved , there remains the challenge of integrating the systems into clinical encounters where busy practitioners manage patients with complex , multiple conditions BACKGROUND Although computerized physician order entry reduces medication errors among in patients , little is known about the use of this system in primary care . METHODS We calculated the override rate among 3481 consecutive alerts generated at 5 adult primary care practice s that use a common computerized physician order entry system for prescription writing . For detailed review , we selected a r and om sample of 67 alerts in which physicians did not prescribe an alerted medication and 122 alerts that result ed in a written prescription . We identified factors associated with the physicians ' decisions to override a medication alert , and determined whether an adverse drug event ( ADE ) occurred . RESULTS Physicians overrode 91.2 % of drug allergy and 89.4 % of high-severity drug interaction alerts . In the multivariable analysis using the medical chart review sample ( n = 189 ) , physicians were less likely to prescribe an alerted medication if the prescriber was a house officer ( odds ratio [ OR ] , 0.26 ; 95 % confidence interval [ CI ] , 0.08 - 0.84 ) and if the patient had many drug allergies ( OR , 0.70 ; 95 % CI , 0.53 - 0.93 ) . They were more likely to override alerts for renewals compared with new prescriptions ( OR , 17.74 ; 95 % CI , 5.60 - 56.18 ) . We found no ADEs in cases where physicians observed the alert and 3 ADEs among patients with alert overrides , a nonsignificant difference ( P = .55 ) . Physician review ers judged that 36.5 % of the alerts were inappropriate . CONCLUSIONS Few physicians changed their prescription in response to a drug allergy or interaction alert , and there were few ADEs , suggesting that the threshold for alerting was set too low . Computerized physician order entry systems should suppress alerts for renewals of medication combinations that patients currently tolerate Background : Recent clinical trials indicate that treatment with lipid modifying therapy improves outcomes in patients with ischemic heart disease ( IHD ) and low levels of high density lipoprotein ( HDL ) cholesterol . The results of these trials , however , have not been widely implemented in clinical practice . Objectives : To develop and test an intervention design ed to increase the rate of prescription of lipid modifying therapy and to determine the relative effectiveness of three different prompts ( progress notes , patient letters , or computer chart reminders ) . Methods : The study was conducted in 11 US Department of Veterans Affairs Medical Centers . The effect of the intervention on the proportion of eligible patients receiving lipid modifying therapy was compared between five intervention sites and six matched control sites using a controlled before and after study design . Additionally , 92 providers within the intervention clinics were r and omized to receive one of the three prompts . Data were analyzed using logistic regression modeling which incorporated terms to account for the clustered nature of the data . Results : At the intervention sites the prescription rate increased from 8.3 % during the pre-intervention period to 39.1 % during the intervention ( OR = 6.5 , 95 % CI 5.2 to 8.2 , p<0.0001 ) but remained unchanged at the control sites . The interaction between group ( control v intervention ) and time period was highly significant ( p<0.0001 ) . The adjusted odds of receiving a prescription during the intervention period was 3.1 times higher at the intervention sites than at the control sites ( 95 % CI 2.1 to 4.7 ) . Overall , there was no significant difference in prescription rates among the three prompt groups . However , there was a significant interaction between prompt group and site , indicating that the efficacy of the prompts differed by site . Conclusion : An intervention for primary care providers consisting of an educational workshop , opinion leader influence , and prompts substantially increased the prescription rate of lipid modifying therapy OBJECTIVE The aim of this study was to evaluate the impact of an integrated patient-specific electronic clinical reminder system on diabetes and coronary artery disease ( CAD ) care and to assess physician attitudes toward this reminder system . DESIGN We enrolled 194 primary care physicians caring for 4549 patients with diabetes and 2199 patients with CAD at 20 ambulatory clinics . Clinics were r and omized so that physicians received either evidence -based electronic reminders within their patients ' electronic medical record or usual care . There were five reminders for diabetes care and four reminders for CAD care . MEASUREMENTS The primary outcome was receipt of recommended care for diabetes and CAD . We created a summary outcome to assess the odds of increased compliance with overall diabetes care ( based on five measures ) and overall CAD care ( based on four measures ) . We surveyed physicians to assess attitudes toward the reminder system . RESULTS Baseline adherence rates to all quality measures were low . While electronic reminders increased the odds of recommended diabetes care ( odds ratio [ OR ] 1.30 , 95 % confidence interval [ CI ] 1.01 - 1.67 ) and CAD ( OR 1.25 , 95 % CI 1.01 - 1.55 ) , the impact of individual reminders was variable . A total of three of nine reminders effectively increased rates of recommended care for diabetes or CAD . The majority of physicians ( 76 % ) thought that reminders improved quality of care . CONCLUSION An integrated electronic reminder system result ed in variable improvement in care for diabetes and CAD . These improvements were often limited and quality gaps persist BACKGROUND A cluster r and omized trial of tailored interventions to support the implementation of guidelines for sore throat and urinary tract infection found little or no change in the main outcomes , which were antibiotic prescriptions , use of laboratory tests and use of telephone consultations . There was great variation between the practice s in the change in these outcomes . OBJECTIVES Our aim was to evaluate how the interventions were received and to underst and why practice s did or did not change . METHODS The trial was conducted in general practice s in Norway . Data for this process evaluation were collected from the 120 practice s that completed the trial . Multiple methods were used : observations , semi-structured telephone interviews , a postal survey and data extracted from electronic medical records . We investigated factors that might explain a lack of change , including : agreement with the guidelines ; communication within each practice ; degree of participation in the project ; taking time to discuss the guidelines and their implementation ; use of the components of the interventions ; and routines for telephone consultations . Possible explanatory factors were explored in relation to variation in change and the overall extent of change in rates of use of antibiotics , laboratory tests and telephone consultations . RESULTS Sixty-three per cent of practice s agreed with the guidelines . Only 35 % reported having regular meetings , and 33 % discussed the project before its start , although 75 % reported agreement about participating within the practice . Only 33 % reported meeting to discuss the guidelines . Use of the components of the interventions ranged from 11 % for the increased fee for telephone consultations to 48 % for the computerized decision support . Forty-four per cent reported problems with telephone routines . No single factor explained the observed variation in the extent of change across practice s. CONCLUSIONS Inadequate time , re sources and support were the most salient factors that might explain a lack of change . Problems with internal communication and telephone routines were important contributing factors in many practice OBJECTIVE To assess the effects on health care re source utilization of a network of microcomputer workstations for writing all inpatient orders . DESIGN R and omized controlled clinical trial . SETTING Inpatient internal medicine service of an urban public hospital . SUBJECTS A total of 5219 internal medicine patients and the 68 teams of house officers , medical students , and faculty internists who cared for them . INTERVENTION Microcomputer workstations , linked to a comprehensive electronic medical record system , for writing all inpatient orders . MAIN OUTCOME MEASURES Total inpatient charges for each admission and charges for specific categories of orders . A time-motion study of selected interns assessed the ordering system 's time consumption . RESULTS Intervention teams generated charges that were $ 887 ( 12.7 % ) lower per admission than did control teams ( P = .02 ) . Significant reductions ( P < .05 ) were demonstrated separately for bed charges , diagnostic test charges , and drug charges . Reductions of similar proportion and statistical significance were found for hospital costs . The mean length of stay was 0.89 day shorter for intervention resident teams ( P = .11 ) . Interns in the intervention group spent an average of 33 minutes longer ( 5.5 minutes per patient ) during a 10-hour observation period writing orders than did interns in the control group ( P < .0001 ) . CONCLUSIONS A network of microcomputer workstations for writing all inpatient orders significantly lowered patient charges and hospital costs . This would amount to savings of more than $ 3 million in charges annually for this hospital 's medicine service and potentially tens of billions of dollars nationwide . However , the system required more physician time than did the paper charts . Research at other sites and system advances to reduce time requirements are warranted BACKGROUND Medication errors are frequently related to failure to appropriately select medications or adjust for laboratory parameters . Differences between guideline recommendations and actual frequency of therapeutic laboratory monitoring are substantial . This study evaluated interventions to improve laboratory monitoring at initiation of medication therapy . METHODS This cluster-r and omized trial compared 3 interventions to usual care for 10 medications in 15 primary care clinics in a health maintenance organization with an electronic medical record system . Eligible patients , identified from electronic data bases , had not received recommended laboratory monitoring within 5 days after new dispensing of a study medication . Interventions were an electronic medical record reminder to the prescribing health care professional , an automated voice message to the patient , and a pharmacy team outreach to the patient . Primary outcome was completion of all recommended baseline laboratory monitoring . RESULTS A total of 961 patients participated in the study . At 25 days , 95 ( 48.5 % ) of 196 patients in the electronic medical record reminder group , 177 ( 66.3 % ) of 267 in the automated voice message group , 214 ( 82.0 % ) of 261 in the pharmacy team outreach group , and 53 ( 22.4 % ) of 237 in the usual care group had completed all recommended baseline laboratory monitoring ( P<.001 ) . After adjustments , the hazard ratios for completing laboratory monitoring compared with usual care were 2.5 ( 95 % confidence interval , 1.8 - 3.5 ) for electronic medical record reminder , 4.1 ( 95 % confidence interval , 3.0 - 5.6 ) for automated voice message , and 6.7 ( 95 % confidence interval , 4.9 - 9.0 ) for pharmacy team outreach . CONCLUSIONS All 3 interventions were effective in increasing laboratory monitoring when initiating new medications in primary care . Further work is necessary to determine if these interventions improve patient outcomes Abstract Objective : To underst and the factors influencing the adoption of a computerised clinical decision support system for two chronic diseases in general practice . Design : Practice based , longitudinal , qualitative interview study . Setting : Five general practice s in north east Engl and . Participants : 13 respondents ( two practice managers , three nurses , and eight general practitioners ) gave a total of 19 semistructured interviews . 40 people in practice s included in the r and omised controlled trial ( 34 doctors , three nurses ) and interview study ( three doctors , one previously interviewed ) gave feedback . Results : Negative comments about the decision support system significantly outweighed the positive or neutral comments . Three main areas of concern among clinicians emerged : timing of the guideline trigger , ease of use of the system , and helpfulness of the content . Respondents did not feel that the system fitted well within the general practice context . Experience of “ on-dem and ” information sources , which were generally more positively viewed , informed the comments about the system . Some general practitioners suggested that nurses might find the guideline content more clinical ly useful and might be more prepared to use a computerised decision support system , but lack of feedback from nurses who had experienced the system limited the ability to assess this . Conclusions : Significant barriers exist to the use of complex clinical decision support systems for chronic disease by general practitioners . Key issues include the relevance and accuracy of messages and the flexibility to respond to other factors influencing decision making in primary care . What is already known on this topic R and omised controlled trials of complex computerised decision support systems have found low rates of use and no effects on process and outcomes of care What this study adds Clinicians found a computerised decision support system for chronic disease in general practice to be difficult to use and unhelpful clinical ly It did not fit well into a general practice consultation and compared unfavourably with “ on-dem and ” information “ Active ” decision support can make clinicians aware of gaps between their own practice and “ best ” practice , but computer prompts need to be relevant and BACKGROUND The Clinical Information Access Program ( CIAP ) , an online evidence retrieval system , provides NSW health professionals in public hospitals with 24 h access to information supporting evidence -based practice . AIM To assess the frequency and type of CIAP usage by senior and junior medical staff and doctors ' attitudes to CIAP . METHODS A convenience sample of 25 % of doctors from 65 r and omly selected public hospitals completed a survey . Junior ( n = 392 ) and senior ( n = 684 ) doctors ' responses were compared using chi2 analyses and t-tests . RESULTS Most doctors had heard of CIAP ( 71.8 % ) and 60.6 % had used it . More junior ( 72.4 % ) than senior ( 53.8 % ) doctors had used CIAP and junior doctors found it easier to use . Of the users 93.5 % believed CIAP had the potential to improve patient care ; 55.2 % had directly experienced this . Most usage ( 61.5 % ) occurred at point-of-care ; 74 % of users found all/most of the information they sought and 71.6 % found the search time to be ' good/excellent ' . Users had increased their usage in the past year and predicted increased future usage . The most popular data bases were Medline and MIMS . Age , access to other evidence , and lack of training , time and computer skills were associated with non-usage . Junior and senior users differed in 4 of 15 reasons for using CIAP . CONCLUSIONS CIAP is used and valued by the majority of doctors . Patterns of usage , online experiences and the attitudes toward CIAP of senior doctors who use CIAP are relatively similar to those of junior doctors OBJECTIVE A research prototype Physician Workstation ( PWS ) incorporating a graphical user interface and a drug ordering module was compared with the existing hospital information system in an academic Veterans Administration General Medical Clinic . Physicians in the intervention group received recommendations for drug substitutions to reduce costs and were alerted to potential drug interactions . The objective was to evaluate the effect of the PWS on user satisfaction , on health-related outcomes , and on costs . DESIGN A one-year , two-period , r and omized controlled trial with 37 subjects . MEASUREMENTS Differences in the reliance on noncomputer sources of information , in user satisfaction , in the cost of prescribed medications , and in the rate of clinical ly relevant drug interactions were assessed . RESULTS The study subjects logged onto the workstation an average of 6.53 times per provider and used it to generate 2.8 % of prescriptions during the intervention period . On a five-point scale ( 5 = very satisfied , 1 = very dissatisfied ) , user satisfaction declined in the PWS group ( 3.44 to 2.98 p = 0.008 ) , and increased in the control group ( 3.23 to 3.72 , p < 0.0001 ) . CONCLUSION The intervention physicians did not use the PWS frequently enough to influence information-seeking behavior , health outcomes , or cost . The study design did not determine whether the poor usage result ed from satisfaction with the control system , problems using the PWS intervention , or the functions provided by the PWS intervention . Evaluative studies should include provisions to improve the chance of successful implementation as well as to yield maximum information if a negative study occurs BACKGROUND Decision-support information technology is often adopted to improve clinical decision making , but it is rarely rigorously evaluated . Congress m and ated the evaluation of Problem-Knowledge Couplers ( PKC Corp , Burlington , Vt ) , a decision-support tool proposed for the Department of Defense 's new health information network . METHODS This was a patient-level r and omized trial conducted at 2 military practice s. A total of 936 patients were allocated to the intervention group and 966 to usual care . Couplers were applied before routine ambulatory clinic visits . The primary outcome was quality of care , which was assessed based on the total percentage of any of 24 health care quality process measures ( opportunities to provide evidence -based care ) that were fulfilled . Secondary outcomes included medical re sources consumed within 60 days of enrollment and patient and provider satisfaction . RESULTS There were 4639 health care opportunities ( 2374 in the Coupler group and 2265 in the usual-care group ) , with no difference in the proportion of opportunities fulfilled ( 33.9 % vs 30.7 % ; P = .12 ) . Although there was a modest improvement in performance on screening/preventive measures , it was offset by poorer performance on some measures of acute care . Coupler patients used more laboratory and pharmacy re sources than usual-care patients ( logarithmic mean difference , 71 dollars ) . No difference in patient satisfaction was observed between groups , and provider satisfaction was mixed . CONCLUSION This study provides no strong evidence to support the utility of this decision-support tool , but it demonstrates the value of rigorous evaluation of decision-support information technology OBJECTIVES This study aim ed to assess the uptake and effect in primary care of a computerized decision support system ( DSS ) for the management of hyperlipidaemia . METHOD A prospect i ve controlled trial was conducted in 25 practice s covering a population of 150,000 in the city of Birmingham . The Primed system , a specialist developed , rule based DSS for general practice , was introduced prospect ively after a 3-month baseline data collection . The main outcome measures were nine months ' data on prescribing of lipid lowering agents ; use of laboratory tests ; and referrals to secondary care for the investigation of hyperlipidaemia . RESULTS System use was lower than expected . A shift was observed towards requests for appropriate follow-up of previously abnormal lipid results and a greater emphasis on full lipid profiles , in line with the DSS guidelines . Referrals showed a 55 % decrease on those expected ( NS ) . The prescribing evaluation revealed a large variation between practice s , but no significant alteration following system use . Views of users favoured decision support as a concept , but criticised technical problems with the system . CONCLUSIONS Greater integration of DSS software and practice based data h and ling systems is needed . The mode of data capture , and hence both the content and form of knowledge representation , in DSS must take greater account of the primary care consultation process if such systems are to be of use to practitioners Abstract Objective : To evaluate the potential effect of computer support on general practitioners ' prescribing , and to compare the effectiveness of three different support levels . Design : Crossover experiment with balanced block design . Subjects : R and om sample of 50 general practitioners ( 42 agreed to participate ) from 165 in a geographically defined area of Oxfordshire . Interventions : Doctors prescribed for 36 simulated cases constructed from real consultations . Levels of computer support were control ( alphabetical list of drugs ) , limited support ( list of preferred drugs ) , and full support ( the same list with explanations available for suggestions ) . Main outcome measures : Percentage of cases where doctors ignored a cheaper , equally effective drug ; prescribing score ( a measure of how closely prescriptions matched expert recommendations ) ; interview to elicit doctors ' views of support system . Results : Computer support significantly improved the quality of prescribing . Doctors ignored a cheaper , equally effective drug in a median 50 % ( range 25%-75 % ) of control cases , compared with 36 % ( 8%-67 % ) with limited support and 35 % ( 0 - 67 % ) with full support ( P<0.001 ) . The median prescribing score rose from 6.0 units ( 4.2 - 7.0 ) with control support to 6.8 ( 5.8 to 7.7 ) and 6.7 ( 5.6 to 7.8 ) with limited and full support ( P<0.001 ) . Of 41 doctors , 36 ( 88 % ) found the system easy to use and 24 ( 59 % ) said they would be likely to use it in practice . Conclusions : Computer support improved compliance with prescribing guidelines , reducing the occasions when doctors ignored a cheaper , equally effective drug . The system was easy to operate , and most participating doctors would be likely to use it in practice Abstract Aims /hypothesis . Journals play an important part in continuing medical education and in influencing the prescription of drugs . Because little is known about reading habits and information management of specialists a question naire survey among German diabetologists was conducted . Subjects and methods . A non-r and omised sample of 461 German diabetologists was selected from a data base of German diabetologists ( n=1585 ) . A question naire was developed ( 92 items ) which consisted of eight sections : continuing education in general , decision making and problem solving , use of data bases , reading habits , knowledge of technical terms and critical appraisal skills , personal data . Results . The adjusted response rate was 57 % ( crude 52 % ) . Most influential factors for therapeutic decision making were due to own experience , continuing education events , published material , and colleagues . The influence of industry related factors was perceived low . A relatively high rate of respondents ( 39 % ) perceived the influence by patients as rather low . Overall 90 % had convenient access to the internet , MedLine or EMBASE but only 45 % search ed data bases regularly ( three search es per month ) . Median time for reading journals was 3 h a week . Five journals were read regularly , 25 % of which were diabetological journals and 47 % of the respondents did not read English written journals regularly . The methods section of an article was seldom read whereas the abstract and the discussion were almost always read . Most respondents had some underst and ing of technical terms but reported practice s of appraising articles were inadequate . Conclusion /interpretation . It could be shown that reading expenditures and critical appraisal skills of diabetologists are slightly higher compared with non-specialists . But the concept of evidence -based medicine still does not seem to be incorporated in clinical practice OBJECTIVE To assess the acceptability and usage of a st and alone personal digital assistant (PDA)-based clinical decision-support system ( CDSS ) for the diagnosis and management of acute respiratory tract infections ( RTIs ) in the outpatient setting . DESIGN Observational study performed as part of a larger r and omized trial in six rural communities in Utah and Idaho from January 2002 to March 2004 . Ninety-nine primary care providers received a PDA-based CDSS for use at the point-of-care , and were asked to use the tool with at least 200 patients with suspected RTIs . MEASUREMENTS Clinical data were collected electronically from the devices at periodic intervals . Providers also completed an exit question naire at the end of the study period . RESULTS Providers logged 14,393 cases using the CDSS , the majority of which ( n=7624 ; 53 % ) were from family practitioners . Overall adherence with CDSS recommendations for the five most common diagnoses ( pharyngitis , otitis media , sinusitis , bronchitis , and upper respiratory tract infection ) was 82 % . When antibiotics were prescribed ( 53 % of cases ) , adherence with the CDSS-recommended antibiotic was high ( 76 % ) . By logistic regression analysis , the odds of adherence with CDSS recommendations increased significantly with each ten cases completed ( P=0.001 ) . Question naire respondents believed the CDSS was easy to use , and most ( 44/65 ; 68 % ) did not believe it increased their encounter time with patients , regardless of prior experience with PDAs . CONCLUSION A st and alone PDA-based CDSS for acute RTIs used at the point-of-care can encourage better outpatient antimicrobial prescribing practice s and easily gather a rich set of clinical data PRIMARY OBJECTIVE To investigate whether computer decision support software used in the management of patients with asthma improves clinical outcomes . RESEARCH DESIGN R and omized controlled trial with practice s each reporting on 30 patients with asthma over a 6 month period . METHODS AND PROCEDURES 447 patients were r and omly selected from practice asthma registers managed by 17 general practice s from throughout the UK . Intervention practice s used the software during consultations with these patients throughout the study while control practice s did not . MAIN OUTCOMES AND RESULTS Practice consultations , acute exacerbations of asthma , hospital contacts , symptoms on assessment and medication use . A smaller proportion of patients within the intervention group initiated practice consultations for their asthma : 34 ( 22 % ) vs 111 ( 34 % ) , odds ratio ( OR ) = 0.59 , 95 % confidence interval ( CI ) ( 0.37 - 0.95 ) ; and suffered acute asthma exacerbations : 12 ( 8 % ) vs 57 ( 17 % ) , OR = 0.43 , 95 % CI = 0.21 - 0.85 six months after the introduction of the computer decision support software . There were no discernable differences in reported symptoms , maintenance prescribing or use of hospital services between the two groups . CONCLUSION The use of computer decision support software that implements guidelines during patient consultations may improve clinical outcomes for patients with asthma Factors contributing to low adherence to clinical guidelines by clinicians are not well understood . The user interface of ATHENA-HTN , a guideline -based decision support system ( DSS ) for hypertension , presents a novel opportunity to collect clinician feedback on recommendations displayed at the point of care . We analyzed feedback from 46 clinicians who received ATHENA advisories as part of a 15-month r and omized trial to identify potential reasons clinicians may not intensify hypertension therapy when it is recommended . Among the 368 visits for which feedback was provided , clinicians commonly reported they did not follow recommendations because : recorded blood pressure was not representative of the patient 's typical blood pressure ; hypertension was not a clinical priority for the visit ; or patients were nonadherent to medications . For many visits , current quality -assurance algorithms may incorrectly identify clinical ly appropriate decisions as guideline nonadherent due to incomplete capture of relevant information . We present recommendations for how automated DSSs may help identify " apparent " barriers and better target decision support BACKGROUND A cross-sectional content analysis nested within a r and omized , controlled trial was conducted to collect information on provider responses to computer alerts regarding guideline recommendations for patients with suboptimal hypertension care . METHODS Participants were providers who cared for 1,017 patients with uncontrolled hypertension on a single antihypertensive agent within Veterans Affairs primary care clinics . All reasons for action or inaction were sorted into a framework to explain the variation in guideline adaptation . RESULTS The 184 negative provider responses to computer alerts contained explanations for not changing patient treatment ; 76 responses to the alerts were positive , that is , the provider was going to make a change in antihypertensive regimen . The negative responses were categorized as : inertia of practice ( 66 % ) , lack of agreement with specific guidelines ( 5 % ) , patient-based factors ( 17 % ) , environmental factors ( 10 % ) , and lack of knowledge ( 2 % ) . Most of the 135 providers classified as inertia of practice indicated , " Continue current medications and I will discuss at the next visit . " The median number of days until the next visit was 45 days ( interquartile range , 29 to 78 days ) . DISCUSSION Clinical inertia was the primary reason for failing to engage in otherwise indicated treatment change in a subgroup of patients . A framework was provided as a taxonomy for classification of provider barriers A frustrating time for hospitalized patients and their primary care providers is after discharge from the hospital , because of changes in patients ' medications . We developed a computer program to improve the discharge process , by providing guidance to the physician writing the prescriptions , offering educational material to the patients , and providing electronic notification of medication changes to the primary care providers . During a one-year clinical evaluation of this system , in which use of the program was voluntary , 1000 patients were discharged through the program . House officers tended to use the program more often for patients who were older and in the hospital longer . Both house officers and primary care physicians found the program extremely useful , and the process took no longer than the manual method of creating discharge medication lists . Patients who were discharged using this program may have had better adherence to medication regimens . We conclude that computer-assisted compilation of a discharge medication list is a useful method for improving the discharge process |
13,288 | 24,995,607 | This study suggests a survival benefit of postoperative ChRT over Ch in patients with resected gastric cancer | INTRODUCTION This study conducted a systematic review and meta- analysis ( direct and indirect ) of published r and omised controlled trials ( RCTs ) to compare the effects of postoperative chemo-radiotherapy ( ChRT ) with chemotherapy ( Ch ) on overall and disease-free survival ( DFS ) for patients with resectable gastric cancer . | One hundred forty‐two patients with all stages of gastric carcinoma were prospect ively stratified into two divisions according to T.N.M. stage following , but irrespective of the type of surgical procedure . Division I ( T 1‐3 , N 1‐2 , M O ) was r and omized into a control group , and a treatment group who received 2000 rad in 8 fractions over 10 days with intravenous 5 Fluorouracil ( 5 F.U. ) at a dose of 500 mg daily × 4 days preirradiation and then 12.5 mg/kg daily for 5 days every 28 days for six courses . Division II ( T4 or M1 ) was r and omized into three groups ; a control group , a group who received radiotherapy and 5 F.U. in the same schedule as division one and a group who received Thiotepa 45 mg intravenously daily for three days and then every 28 days for 6 months . Four and one‐half years after commencement of the trial 86 % of the patients had died . There was no difference in survival rate between the treatment and control groups , ( p > 0.5 ) in Division I or II . Survival appeared to correlate with the T.N.M. stage of disease and not therapy . Blind assessment of the quality of life showed no difference between the treatment groups and the controls . In the dose schedules used , this form of oncological therapy had no efect on survival or quality of life in patients with gastric carcinoma . Cancer 44:385‐391 , 1979 In this prospect ively r and om study , the effect of oral Ftorafur as an adjuvant chemotherapy was compared with that of oral placebo in patients with Stage II and Stage III gastric cancer . Patients had undergone a subtotal gastrectomy with a resection margin that should have been free of tumors . Ftorafur ( 10 mg/kg ) was given daily to 59 Group A patients . Multiple vitamins were given twice a week to 56 Group B patients . We found that there was no statistical significance in Stage II patients with regard to survival . In Stage III patients , those treated with oral Ftorafur had better 3-year and 5-year survival rates than those receiving oral placebo . This preliminary report on this ongoing study seems to indicate that long-term postoperative Ftorafur treatment may be beneficial to Stage III gastric cancer patients PURPOSE The first planned interim analysis ( median follow-up , 3 years ) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival , the primary end point . The results were therefore opened at the recommendation of an independent data and safety monitoring committee . We report 5-year follow-up data on patients enrolled onto the ACTS-GC study . PATIENTS AND METHODS Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were r and omly assigned to receive S-1 after surgery or surgery only . S-1 ( 80 to 120 mg per day ) was given for 4 weeks , followed by 2 weeks of rest . This 6-week cycle was repeated for 1 year . The primary end point was overall survival , and the secondary end points were relapse-free survival and safety . RESULTS The overall survival rate at 5 years was 71.7 % in the S-1 group and 61.1 % in the surgery-only group ( hazard ratio [ HR ] , 0.669 ; 95 % CI , 0.540 to 0.828 ) . The relapse-free survival rate at 5 years was 65.4 % in the S-1 group and 53.1 % in the surgery-only group ( HR , 0.653 ; 95 % CI , 0.537 to 0.793 ) . Subgroup analyses according to principal demographic factors such as sex , age , disease stage , and histologic type showed no interaction between treatment and any characteristic . CONCLUSION On the basis of 5-year follow-up data , postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy Background Despite curative resection , 50%–90 % of gastric cancer patients die of disease relapse . Although some clinical trials have indicated that chemotherapy and immunochemotherapy may be effective modalities , more recent studies have not been able to define the st and ard treatment for advanced gastric cancer . The present study evaluated the effect of adjuvant immunochemotherapy with the use of BCG ( bacille Calmette-Guérin ) and FAM ( 5-fluorouracil , adriamycin , mitomycin C ) chemotherapy on the survival of patients with locally advanced resectable gastric cancer . Methods A total of 156 patients with stage III or IV gastric cancer who had undergone curative resection were r and omly assigned to three treatment groups : BCG + FAM ( immunochemotherapy ) , FAM ( chemotherapy ) , and control ( surgery only ) . Treatment was continued for 2 years or until death . Further postsurgical follow up was carried on for up to 10 years . Results Overall 10-year survival was 47.1 % for the immunochemotherapy group ( P < 0.037 vs FAM and P < 0.0006 vs control ) , 30 % for the chemotherapy group ( vs control , NS ) , and 15.2 % for the control group . In patients with pT2/T3 primary tumors , 10-year survival was 55.3 % for BCG + FAM vs 28.2 % for FAM ( P < 0.01 ) and 14.6 % for the control group ( P < 0.00018 ) . BCG + FAM signifi-cantly improved the survival of patients with intestinal-type but not diffuse-type cancer . Immunochemotherapy was well tolerated . Conclusion This study , based on a limited number of patients , indicates that adjuvant immunochemotherapy ( BCG + FAM ) may prolong the survival of gastric cancer patients after curative gastrectomy ; in particular , in patients with pT2/T3 tumors and intestinal-type primary tumors . There was no survival benefit from FAM adjuvant chemotherapy BACKGROUND AND PURPOSE The role of postoperative chemoradiotherapy in the treatment of patients with gastric cancer with D2 lymph node curative dissection is not well established . In this study , we compared postoperative intensity-modulated radiotherapy plus chemotherapy ( IMRT-C ) with chemotherapy-only in this patient population . MATERIAL S AND METHODS We r and omly assigned patients with D2 lymph node dissection in gastric cancer to IMRT-C or chemotherapy-only groups . The adjuvant IMRT-C consisted of 400 mg of fluorouracil per square meter of body-surface area per day plus 20 mg of leucovorin per square meter of body-surface area per day for 5 days , followed by 45 Gy of IMRT for 5 weeks , with fluorouracil and leucovorin on the first 4 and the last 3 days of radiotherapy . Two 5-day cycles of fluorouracil and leucovorin were given 4 weeks after the completion of IMRT . Chemotherapy-only group was given the same chemotherapy regimens as IMRT-C group . RESULTS The median overall survival ( OS ) in the chemotherapy-only group was 48 months , as compared with 58 months in the IMRT-C group ; the hazard ratio for death was 1.24 ( 95 % confidence interval , 0.94 - 1.65 ; P=0.122 ) . IMRT-C was associated with increases in the median duration of recurrence-free survival ( RFS ) ( 36 months vs. 50 months ) , the hazard ratio for recurrence was 1.35 ( 95 % confidence interval , 1.03 - 1.78 ; P=0.029 ) . COX multivariate regression analysis showed that lymph node metastasis and TNM stage were both the independent prognostic factors . Rates of all grade adverse events were similar in the two treatment groups . CONCLUSIONS IMRT-C improved RFS , but did not significantly improve OS among patients with D2 lymph node dissection in gastric cancer . Using IMRT plus chemotherapy was feasible and well tolerated in patients with gastric cancer after D2 resection BACKGROUND The aim of this study was to determine the efficacy of the EAP regimen ( etoposide , adriamycin and cisplatin ) followed by the Machover schedule ( fluorouracil and folinic acid ) given as adjuvant treatment to patients with poor prognostic factors ( N+ or T3/4 ) . PATIENTS AND METHODS Before r and omisation , the subjects were stratified on the basis of node involvement ( N+ or N- ) and the time from surgery to r and omisation ( < or = 21 days or > 22 days ) . The surgical procedures for sub-total or total gastrectomy with D2 dissection were st and ardised among the participating centres . RESULTS Between December 1992 and December 1997 , 274 patients were enrolled : 137 in the treatment arm and 137 in the control arm . The majority of the patients ( 90 % ) were N+ . After a median follow up of 66 months ( range 2 - 83 ) , the 5-year overall survival ( OS ) was 52 % in the treatment arm and 48 % in the control arm [ hazard ratio ( HR ) 0.93 ; 95 % confidence interval ( CI ) 0.65 - 1.34 ] ; the 5-year disease-free survival ( DFS ) was 49 % and 44 % , respectively ( HR : 0.83 ; 95 % CI 0.59 - 1.17 ) . Among the patients with N-/N+ ( 1 - 6 ) , the 5-year OS was 61 % in the treatment group and 60 % in the control group ; in those with N+ ( 1 - 6 ) , it was 42 % and 22 % . The treatment was completed by 87 % of patients . Drug-related grade 3/4 WHO toxicities included leukopenia ( 21 % ) , nausea and vomiting ( 14 % ) , mucositis ( 9 % ) , neutropenia ( 3 % ) and thrombocytopenia ( 2 % ) . There were two deaths due to sepsis . CONCLUSIONS Although our results are not statistically significant , there was a limited relative risk reduction in the patients receiving adjuvant therapy ( 17 % in DFS and 7 % in OS ) . The data suggest that D2 surgery may have a favourable impact on OS BACKGROUND The aim of this study was to evaluate the efficacy of adjuvant chemotherapy after resection for gastric cancer in a r and omized controlled trial . PATIENTS AND METHODS After curative resection , stage II-III-IVM0 gastric cancer patients were r and omly assigned to postoperative chemotherapy or surgery alone . 5-Fluorouracil ( 5-FU ) 800 mg/m(2 ) daily ( 5-day continuous infusion ) was initiated before day 14 after resection . One month later , four 5-day cycles of 5-FU ( 1 g/m(2 ) per day ) plus cisplatin ( 100 mg/m(2 ) on day 2 ) were administered every 4 weeks . RESULTS The study was closed prematurely after enrollment of 260 patients ( 79.7 % N+ ) , owing to poor accrual . At 97.8 months median follow-up , 5- and 7-year overall survival were 41.9 % and 34.9 % in the control group versus 46.6 % and 44.6 % in the chemotherapy group ( P=0.22 ) . Cox model hazard ratios were 0.74 [ 95 % confidence interval ( CI ) 0.54 - 1.02 ; P=0.063 ] for death and 0.70 ( 95 % CI 0.51 - 0.97 ; P=0.032 ) for recurrence . An invaded/removed lymph nodes ratio > 0.3 was the main independent poor prognostic factor identified by multivariate analysis ( P=0.0001 ) . Because of toxicity , only 48.8 % of patients received more than 80 % of the planned dose . CONCLUSION There was no statistically significant survival benefit with this toxic cisplatin-based adjuvant chemotherapy , but a risk reduction in recurrence was observed After en bloc resection of gastric adenocarcinoma , 180 patients were r and omized to 2 years of 5‐fluorouracil ( 5‐FU ) + semustine ( MeCCNU ) chemotherapy or to observation only . After a median follow‐up time of 64 months , 48 of 89 control patients and 51/91 treated patients recurred ( P < 0.71 ) . The sites of recurrent cancer were similar for both groups : liver , 32 % ; local esophagus or stomach , 51 % ; abdominal nodes and peritoneum , 38 % ; and extra‐abdominal nodes , 14 % . The survival curves overlap ; 51/89 controls and 57/91 treated patients died with a median survival of 32.7 and 36.6 months , respectively ( P < 0.73 ) . Treated patients experienced clinical ly important hematologic toxicity and two treated patients died of marrow failure with leukemia . Because of the toxicity and the lack of effectiveness , adjuvant 5‐FU + MeCCNU is not recommended for patients with resectable gastric cancer Sixty-two patients with resectable but poor-prognosis gastric carcinoma were r and omized to either no surgical adjuvant therapy or treatment with 5-fluorouracil ( 15 mg/kg by rapid intravenous injection X 3 ) plus radiation ( 3,750 rad in 24 fractions ) initiated 3 1/2 to six weeks postoperatively . Informed consent was obtained after r and omization and only from the 39 r and omized to treatment . Ten patients refused their treatment assignment . The five-year survival rate for patients r and omized to treatment was 23 % , and for those r and omized to no treatment , 4 % ( P less than .05 ) . Both the survival distributions and the alive-without-recurrence distributions were significantly different for the two groups ( P = .024 ) and favored treatment assignment . When the treatment assignment group was broken down to those patients actually receiving treatment and those refusing , five-year survival rates were : treated , 20 % ; treatment refusal , 30 % ; controls , 4 % ; the three survival distributions were not significantly different . Thirty-nine percent of patients actually treated had a local-regional component of first clinical recurrence compared with 54 % of those who received no treatment . This study does not establish 5-fluorouracil plus radiation as effective surgical adjuvant therapy for gastric cancer but suggests this approach as a possible fruitful area for continued research . This study also illustrates the potential problems that may be encountered in interpreting results when patients are r and omized to a study before consent is obtained In order to evaluate the results on successful adjuvant chemotherapy in resected gastric cancer we performed a r and omised trial on 134 patients in two arms : a control one with no further treatment after surgery versus a treatment arm given mitomycin-C ( MMC ) , 20 mg/m2 intravenously one day every 6 weeks for four courses , starting before the sixth week after surgery . The median follow-up was 105 months . In the control arm , 49 out of 66 patients died due to recurrence , versus 40 out of 68 patients in treatment arm . Actuarial survival curve was statistically significant ( P < 0.025 ) in favour of the treatment group . Liver metastases were lower in adjuvant group than in the control group ( 8/68 versus 19/66 ) . Toxicity was mild . Main toxic effects were thrombocytopenia , leukopenia , nausea and vomiting . A pelvis renal cancer as a second malignancy 8 years after gastric cancer was observed . In that particular case MMC was given after surgery . We conclude that adjuvant chemotherapy based on MMC given in the early period after surgery , improves survival rate in gastric cancer resected patients Abstract A European state of the art in the treatment of gastric cancer is presented from the results of a question naire . Data were obtained from 62 centers , 60 % of which were from abroad and 40 % of which were from Germany , reporting a total of 16,594 patients . A feature was a low portion ( 8.8 % ) of early cancer . The operation preferred was total gastrectomy . Only in the case of antral carcinoma of the intestinal type , according to Laurén , would the majority perform subtotal gastrectomy . Staging of lymph nodes was performed by 84 % of these centers ; however , systematic radical dissection was carried out only by 27 % . The preferred type of reconstruction after total gastrectomy was Roux-en-Y esophagojejunostomy ; 16 % of the European centers used some type of pouch in addition . Splenectomy was carried out depending on location of the tumor . The median in-hospital mortality for early cancer was 0 ; for carcinoma of the antrum , 6.7 % ; corpus , 9.6 % ; and gastroesophageal junction , 11.7 % . The median 5-year survival rate in patients with early cancer was 82.5 % ; for advanced cancer of the antrum , 30.7 % ; corpus , 24 % ; and gastroesophageal junction , 15.5 % . Ten-year survival was 6–10 % less . It is concluded that in Europe there is a high rate of advanced gastric cancer affecting the results . Improved results may be expected if gastric cancer can be detected earlier and if there is radical lymph node dissection . Generally , prospect i ve r and omized studies presented by st and ardized documentation and statistics are urgently needed . RésuméLe point sur la chirurgie du cancer de l'estomac en Europe a été établi à partir des résultats d'un question naire unique . Les données sont parvenues de 62 centres différents , 60 % d'entre eux étant situés en Allemagne et 40 % hors d'Allemagne . Elles concernent 16,954 malades . Un premier point émerge de cette étude : la faible fréquence de cancer précoce ( 8.8 % ) . L'opération de choix fut la gastrectomie totale . C'est seulement en cas de cancer de l'antre de type intestinal ( selon Laurén ) que la gastrectomie subtotale fut préférée par la majorité des auteurs . L'examen histologique des ganglions fut pratiqué dans 84 % de ces centres et c'est seulement dans 27 % des cas que la dissection complète fut réalisée . Dans la majorité des cas la reconstitution du tractus digestif après gastrectomie totale fut réalisée à l'aide d'une oesophago-jéjunostomie avec une anse jéjunale montée en Y à la Roux et c'est seulement dans 16 % des cas qu'une poche de type variable fut constituée . L'opération fut complétée parfois par une splénectomie en fonction du siège de la tumeur . Le taux médian de la mortalité hospitalière fut égal à 0 en cas de cancer précoce et pour les autres stades de 6.7 % pour l'antre , de 9.6 % pour le corps , et de 11.7 % pour la jonction gastro-oesophagienne . Le taux médian de survie à 5 ans fut de 82.5 % pour le cancer précoce ; pour le cancer avancé il fut de 30.7 % ; de 24 % pour le corps et de 15.5 % pour la jonction gastro-oesophagienne . La survie à 10 ans fut de 6–10%.On peut conclure de ces faits qu'en Europe les résultats observés sont en relation avec la découverte et le traitement tardifs . Ils ne pourront être améliorés que par la découverte du cancer à un stade précoce et par la dissection radicale emportant les ganglions . Il est nécessaire de procéder sans retard à des études r and omisées reposant sur une documentation st and ard et des statistiques irréfutables pour atteindre ce but . ResumenSe présenta un “ estado del arte ” europeo sobre el tratamiento del cáncer gâstrico , basado en los result ados de un cuestionario con preguntas específicas sobre indicaciones para la operación , detalles del acto operatorio , incluyendo “ estadificación , ” tipo de disección ganglionar , tipo de reconstrucción , el uso de suturadores automáticos , y esplenectomía . Se obtuvieron datos de 62 centros , 40 % de los cuales son alemanes y 60 % del extranjero , que informaron sobre un total de 16,594 pacientes . Una característica prominente fue la baja proporción del cáncer temprano ( 8.8 % ) . La operación de preferencia fue la gastrectorrua total . Sólo en casos de carcinoma del antro del tipo intestinal ( según Laurén ) la mayoría de los cirujanos realizan gastrectomía subtotal . La “ estadificación ” de los ganglios linfáticos fue realizada en 84 % de estos centros . Sin embargo , la disección radical fue realizada sólo en 27 % . El tipo preferido de reconstrucción después de gastrectomía total fue la esofagoyeyunostomía de Roux-en-Y ; el 16 % de los centros europeos informó el uso de algún tipo de bolsa o reservorio adicional . Se realizó esplenectomía según la ubicación del tumor . La mortalidad hospitalaria para el cáncer temprano fue 0 ; para carcinoma del antro , 6.7 % ; del cuerpo , 9.6 % ; y de la unión gastroesofágica , 11.7 % . La tasa de supervivencia a 5 años en pacientes con cancer temprano fue 82.5 % ; en pacientes con cancer avanzado del antro , 30.7 % ; del cuerpo , 24 % ; y de la unión gastroesofágica , 15.5 % . La supervivencia a 10 años fue 6–10 % menor . Se llega a la conclusión de que en Europa existe una elevada incidencia de cáncer gástrico avanzado que afecta los result ados . Mejores result ados pueden esperarse con una tasa mayor de cancer temprano y posiblemente con disección ganglionar . Es urgente la necesidad de estudios prospect ivos y aleatorizados que se realicen mediante documentación y estadísticas est and arizadas The optimal adjuvant treatment for gastric cancer remains controversial . We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen , in patients with high-risk gastric cancer , with that of the same chemotherapy plus radiation therapy ( RT ) . In addition , we evaluated the prognostic and /or predictive value of a panel of molecular markers . Patients with histologically proven , radically resected gastric cancer , stage ≥T3 and /or N+ were r and omized to 6 cycles of docetaxel with cisplatin , both at 75 mg/m2 every 3 weeks ( arm A ) or the same treatment with RT ( arm B ; 45 Gy ) . Due to excessive nausea and vomiting , cisplatin was substituted by carboplatin at AUC ( area under the curve ) of 5 after the first 45 patients ( 22 group A , 23 group B ) . The prognostic value of EGFR , ERCC1 , HER2 , MET/HGFR , MAP-Tau , and PTEN expression was also studied in a subset of 67 patients using immunohistochemistry on tissue microarrays ( TMAs ) . A total of 147 patients were r and omized . After a median follow-up of 53.7 months , no differences in overall ( OS ) and disease-free survival ( DFS ) were found between the two arms . The most common grade 3/4 toxicities for arms A and B ( excluding alopecia ) were non-febrile neutropenia ( 11 and 17 % , respectively ) , febrile neutropenia ( 9 and 7 % ) and diarrhea ( 7 and 4 % , respectively ) . Patients with ERCC1 positive tumors had significantly longer median DFS ( 33.1 vs. 11.8 months , Wald P = 0.016 ) and OS ( 63.2 vs. 18.8 months , Wald P = 0.046 ) . Our results indicate that the addition of RT to platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in high-risk , radically resected gastric cancer . However , the possibility that a benefit by the addition of RT was not detected due to decreased power of the study should not be excluded This prospect i ve r and omized study compared the survival of patients with tumour node metastasis ( TNM ) stage T2 N1–2 gastric cancer treated by gastrectomy alone or gastrectomy followed by uracil – tegafur After curative resection for gastric adenocarcinoma , 103 patients , all with positive nodes , were r and omised so that 48 received adjuvant chemotherapy of epidoxorubicin ( EPI ) 75 mg m-2 on day 1 , leucovorin ( LV ) 200 mg m-2 on days 1 - 3 and 5-fluorouracil ( 5-FU ) 450 mg m-2 on days 1 - 3 , every 21 days for 7 months , whereas the remaining 55 did not . During the first year of observation , 21 control patients ( 38 % ) and five treated patients had recurrences . After a follow-up period of 36 months , 12 of the treated patients ( 25 % ) and only seven controls ( 13 % ) were still alive . At that point , the median survival was 13.6 months for the 55 untreated patients and 20.4 months for the 48 treated patients , a significant difference . We found a survival advantage for patients treated with the EPI-LV-5-FU regimen and a consistent delay in the appearance of recurrent or metastatic cancer . Acute toxicity was mild and treatment was well accepted by all patients . There was no long-term toxicity or any cardiac toxicity . We conclude that this particular chemotherapy , administered shortly after gastric resection , improves survival rate in node-positive gastric cancer patients , even although final assessment of this particular adjuvant approach must await completion of the trial BACKGROUND Complete surgical resection of gastric cancer is potentially curative , but long-term survival is poor . METHODS Patients with histologically proven adenocarcinoma of the stomach of stages IB , II , IIIA and B , or IV ( T4N2M0 ) and treated with potentially curative surgery were r and omly assigned to follow-up alone or to intravenous treatment with four cycles ( repeated every 21 days ) of PELF ( cisplatin [ 40 mg/m(2 ) , on days 1 and 5 ] , epirubicin [ 30 mg/m(2 ) , days 1 and 5 ] , L-leucovorin [ 100 mg/m(2 ) , days 1 - 4 ] , and 5-fluorouracil [ 300 mg/m(2 ) , days 1 - 4 ] in a hospital setting . Frequencies and severity of adverse events were determined . Overall survival ( OS ) and disease-free survival ( DFS ) were compared between the treatment arms using Kaplan-Meier analysis and a Cox proportional hazards regression model . All statistical tests were two-sided . RESULTS From January 1995 through September 2000 , 258 patients were r and omly assigned to chemotherapy ( n = 130 ) or surgery alone ( n = 128 ) . Patient characteristics were well balanced between the two arms . Among those who received chemotherapy , grade 3 or 4 toxic effects including vomiting , mucositis , and diarrhea were experienced by 21.1 % , 8.4 % , and 11.8 % of patients , respectively . Leucopenia , anemia , and thrombocytopenia of grade 3 or 4 were experienced by 20.3 % , 3.3 % , and 4.2 % of patients , respectively . After a median follow-up of 72.8 months , 128 patients ( 49.6 % ) experienced recurrence and 139 ( 53.9 % ) deaths were observed , one toxicity-related . Relative to treatment with surgery alone , adjuvant chemotherapy did not increase disease-free survival ( hazard ratio [ HR ] of recurrence = 0.92 ; 95 % confidence interval [ CI ] = 0.66 to 1.27 ) or overall survival ( HR of death = 0.90 ; 95 % CI = 0.64 to 1.26 ) . CONCLUSIONS Our results failed to provide proof of an effect of adjuvant chemotherapy with PELF on overall survival or disease-free survival . The estimated effect of chemotherapy ( 10 % reduction in the hazard of death or relapse ) is modest and consistent with the results of meta-analyses of adjuvant chemotherapy without platinum agents Gastric carcinoma is decreasing in incidence in Western Europe and the United States . However , this disease is still a major cause of cancer death [ 1 ] . Extended surgical procedures over the past 20 years have not profoundly altered the poor outcome of patients with gastric carcinoma [ 2 ] . This fact indicates that surgery alone may not be enough to control the disease . In 1978 we began a prospect i ve r and omized , one-center trial to determine , whether postoperative treatment with mitomycin C ( MMC ) , 5-fluorouracil ( 5-FU ) , and cytosine-arabinoside ( Ara-C ) given for three courses could substantially improve the overall survival of patients treated by curative resection for gastric carcinoma . The regimen employed had been shown to be the most effective chemotherapy combination at the time the study started [ 3 ] . At a median follow-up of 5 years we found no significant effect of adjuvant chemotherapy on overall survival compared with an untreated control group . However , in a retrospective subgroup analysis we observed a significant improvement in the overall survival of patients with the intestinal tumor type , but no effect in patients with mucocellular carcinoma . We therefore believe that there is a selective effect of adjuvant chemotherapy in patients with gastric carcinoma with intestinal type of tumors Long-term oral administration of fluoropyrimidines such as 5-fluorouracil ( 5-FU ) or tegafur is commonly used as an adjuvant chemotherapy for gastric cancer , but the optimal period or optimal total doses of fluoropyrimidines have not been studied . Two hundred cases of macroscopical Stage II and III curatively resected gastric cancer patients were entered in this study , and divided into three groups ( 6 months group : mitomycin C was given i.v . at day 0 and day 1 and 5-FU tablets were orally administered at a dose of 200 mg/day for 6 months . 12 months group : MMC was given the same as for the 6 months group and 5-FU tablets were administered for 12 months . Surgery alone group : No chemotherapy , operation only ) . As the result , 185 cases were eligible . There was no significant difference between the 6 months group and the 12 months group among Stage II patients . Although there was also no significant difference between the 2 groups in Stage III patients , the survival curve of 12 months group was always higher than in the 6 months group . When comparing with surgery alone group , 5-year survival of the 12 months group was always higher than in the surgery alone group of Stage III patients ; however , the survival rate in the 6 months group was worse than in the surgery alone group at Stage II and III . These results suggest that MMC i.v . and 12 months or over administration of 5-FU tablets is useful for Stage III gastric cancer patients , and that cooperative study is required comparing with surgery alone in Stage II patients PURPOSE Surgical resection of gastric cancer has produced suboptimal survival despite multiple r and omized trials that used postoperative chemotherapy or more aggressive surgical procedures . We performed a r and omized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure ( LRF ) following surgery . We originally reported results with 4-year median follow-up . This up date , with a more than 10-year median follow-up , presents data on failure patterns and second malignancies and explores selected subset analyses . PATIENTS AND METHODS In all , 559 patients with primaries ≥ T3 and /or node-positive gastric cancer were r and omly assigned to observation versus radiochemotherapy after R0 resection . Fluorouracil and leucovorin were administered before , during , and after radiotherapy . Radiotherapy was given to all LRF sites to a dose of 45 Gy . RESULTS Overall survival ( OS ) and relapse-free survival ( RFS ) data demonstrate continued strong benefit from postoperative radiochemotherapy . The hazard ratio ( HR ) for OS is 1.32 ( 95 % CI , 1.10 to 1.60 ; P = .0046 ) . The HR for RFS is 1.51 ( 95 % CI , 1.25 to 1.83 ; P < .001 ) . Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse . Second malignancies were observed in 21 patients with radiotherapy versus eight with observation ( P = .21 ) . Subset analyses show robust treatment benefit in most subsets , with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect . CONCLUSION Intergroup 0116 ( INT-0116 ) demonstrates strong persistent benefit from adjuvant radiochemotherapy . Toxicities , including second malignancies , appear acceptable , given the magnitude of RFS and OS improvement . LRF reduction may account for the majority of overall relapse reduction . Adjuvant radiochemotherapy remains a rational st and ard therapy for curatively resected gastric cancer with primaries T3 or greater and /or positive nodes Abstract Purpose : To evaluate FAM [ 5-FU ( 5-fluorouracil ) , doxorubicin , mitomycin C ] chemotherapy as adjuvant therapy for patients with resected TNM stage I , II , or III gastric carcinoma . Patients and Methods : One hundred ninety-three eligible patients were accrued from 1978 to 1991 in a phase III trial comparing six cycles ( 1 year ) of postoperative FAM chemotherapy with observation only . Results : The median follow-up on this study was 9.5 years . For all patients , no differences ( log-rank analysis ) in disease-free survival ( p=0.45 ) and overall survival ( p=0.57 ) between FAM therapy ( 93 cases ) and surgery ( 100 cases ) were observed . Quality of surgical resection affected survival irrespective of FAM use . Cases with curative resection , defined in a retrospective review of pathology and surgical reports as cases having no evidence of residual disease in the abdomen and tumor-free margins > 1 cm , had superior survival compared to cases not meeting these requirements ( p<0.001 ) . FAM was well tolerated with 6 % ( five of 90 ) of cases demonstrating grade IV hematologic toxicity . There were two drug-related fatalities ( one cardiomyopathy , one hematolytic uremic syndrome ) . Conclusion : FAM is not effective adjuvant therapy for TNM stage I , II , and III patients with resected gastric cancer . Future adjuvant studies must emphasize prospect i ve surgical quality control to assure enrollment of appropriately staged and resected cases and wide participation to assure adequate case accrual over a reasonable period A group of 243 patients with gastric cancer was subjected to a prospect i ve r and omized trial of adjuvant chemotherapy after curative gastrectomy . One of the three arms ( regimen A ) is induction therapy with a three-drug combination of mitomycin C ( MMC ) , 5-fluorouracil ( 5-FU ) , and cytosine arabinoside ( ara-C ) followed by intermittent oral administration of 5-FU for two years ( MFC + F ) . In regimen B , 5-FU in regimen A is replaced by ftorafur , administered on the same schedule as regimen A ( MF'C + F ' ) . Regimen C is the control , in which patients are treated by surgery alone . Regimen A was proven effective for the suppression of relapse in the limited groups of moderately locally advanced cancer ; five-year survival rates of the subset of stages I , II , and III were 72.1 % with regimen A and 53.1 % with regimen C ( P less than .05 ) . Regimen B yielded a better survival than the control , although the difference did not reach statistical significance . The results seem to favor 5-FU as adjuvant chemotherapy for gastric cancer PURPOSE To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-negative gastric cancer patients ( excluding patients who were T1N0 ) , we conducted a multicenter phase III clinical trial in which 13 cancer centers in Japan participated . PATIENTS AND METHODS From January 1993 to December 1994 , 252 patients were enrolled into the study and allocated r and omly to adjuvant chemotherapy or surgery alone . The chemotherapy comprised intravenous mitomycin 1.33 mg/m2 , fluorouracil ( FU ) 166.7 mg/m2 , and cytarabine 13.3 mg/m2 twice weekly for the first 3 weeks after surgery , and oral FU 134 mg/m2 daily for the next 18 months for a total dose of 67 g/m2 . The primary end point was relapse-free survival . Overall survival and the site of recurrence were secondary end points . RESULTS Ninety-eight percent of patients underwent gastrectomy with D2 or greater lymph node dissection . There were no treatment-related deaths and few serious adverse events . There was no significant difference in relapse-free and overall survival between the arms ( 5-year relapse-free survival 88.8 % chemotherapy v 83.7 % surgery alone ; P = .14 and 5-year survival 91.2 % chemotherapy v 86.1 % surgery alone ; P = .13 , respectively ) . Nine patients ( 7.1 % ) in the chemotherapy arm and 17 patients ( 13.8 % ) in the surgery-alone arm had cancer recurrence . CONCLUSION There was no statistically significant relapse-free or overall survival benefit with this adjuvant chemotherapy for patients with macroscopically serosa-negative gastric cancer after curative resection , and there was no statistical difference between the two arms relating to the types of cancer recurrence . We do not recommend adjuvant chemotherapy with this regimen for this population in clinical practice Following curative resection for gastric adenocarcinoma , 142 patients were r and omized to receive adjuvant chemotherapy of methyl‐CCNU and 5‐FU or to be closely followed without chemotherapy . The median patient has been followed for four years . At the present time , there have been 38 recurrences and 40 deaths among the 71 patients in the control arm and 28 recurrences with 29 deaths in the group of patients r and omized to chemotherapy . Median survival for control patients is 33 months whereas it is estimated to be in excess of four years for the adjuvant therapy group . A survival advantage appears to be associated with adjuvant treatment , a test for treatment difference being significant ( P < 0.03 ) after adjustment for important covariates . Survival and disease‐free intervals are longer in the chemotherapy arm for patients in all prospect i ve stratification subgroups ( proximal and total vs distal subtotal gastrectomy , presence or absence of lymph node metastases , invasion of adjacent organs vs confined to stomach wall and location of tumor within the stomach ) . A final assessment of this surgical adjuvant approach must await complete results of this trial , as well as of others currently in progress evaluating this same concept The overall survival in patients with gastric cancer is low , even among those undergoing resection . It has been hoped that the development of adjuvant therapy might improve survival in patients following surgery when tumour burden was minimal and both chemotherapy and radiotherapy have been proposed as suitable for use in gastric cancer . Their value has been evaluated by the British Stomach Cancer Group Second adjuvant therapy trial . 436 patients entered a prospect i ve , r and omised , controlled trial of adjuvant radiotherapy or cytotoxic chemotherapy with mitomycin , doxorubicin , and fluorouracil after gastrectomy for adenocarcinoma . After at least 5 years , there have been 372 deaths of which 7 were due to surgical complications and 327 from recurrent cancer . Following stratified r and omisation , 145 patients were allocated to surgery alone , 153 to receive adjuvant radiotherapy , and 138 to adjuvant combination chemotherapy . The overall 2-year and 5-year survival were 33 % ( 95 % confidence interval 31 - 35 % ) and 17 % ( 13 - 21 % ) . No survival advantage has been shown for those patients receiving either adjuvant therapy compared to those undergoing surgery alone . The 5-year survival for surgery alone was 20 % , for surgery plus radiotherapy 12 % , and for surgery plus chemotherapy 19 % . Surgery , therefore , remains the st and ard treatment for this condition and the use of adjuvant treatments should be restricted to controlled trials Background The purpose of the current study is to evaluate the efficacy and complications of concurrent chemoradiotherapy ( CCRT ) for the treatment of gastric cancer patients after D1/D2 surgery . Methods Sixty-eight untreated gastric cancer patients ( T3/T4 and /or N+ ) were enrolled . After surgery , they were r and omized into two groups : the CCRT group and the single chemotherapy group . Radiotherapy patients were treated according to the Intergroup 0116 guidelines . The chemotherapy consisted of continuously administered 5-fluorouracil ( 5-FU ) and tetrahydrofolic acid ( LV ) . The CCRT began 28 days after the first cycle of chemotherapy , and chemotherapy was given within the first four and last three days during the CCRT period , at a radiation dosage of 45 Gy/25 f , i.e. , 1.8 Gy 5 times per week . Two cycles of the same chemotherapy were administrated 1 month after the radiotherapy . Five cycles of 5-FU and LV were applied to CG . Results One- , two- , and three-year survival rates were 85.9 , 73.4 , and 67.7 % , respectively , in the CCRT group and 68.0 , 50.0 , and 44.1 % , in the single chemotherapy group ( P < 0.05 ) . The corresponding disease-free survival rates were 73.5 , 64.7 , and 55.8 % in the CCRT group and 61.8 , 38.2 , and 29.4 % in the single chemotherapy group ( P < 0.05 ) . The major side effects were gastrointestinal reactions and neutrocytopenia . In both the CCRT and single chemotherapy groups , the incidence of these side effects was 73.5 % ( 25/34 ) and 44.1 % ( 15/34 ) ( P < 0.05 ) for Grade I and Grade II anorexia , 82.35 % ( 28/34 ) and 73.5 % ( 25/34 ) ( P > 0.05 ) for nausea and vomiting , and 70.6 % ( 24/34 ) and 44.1 % ( 15/34 ) ( P < 0.05 ) for neutrocytopenia , respectively . The other indices showed no significant differences . Conclusions Our findings indicate that CCRT can increase the one- , two- , and three-year total survival rates , as well as the disease-free survival rates of gastric cancer patients ( T3/T4 and /or N+ ) who have been initially treated with surgery . The major adverse reactions were Grade I and Grade II nausea and vomiting , as well as myelosuppression . CCRT is well tolerated PURPOSE Although chemoradiotherapy was considered the st and ard adjuvant treatment for gastric cancer , a recent Phase III trial ( Medical Research Council Adjuvant Gastric Infusional Chemotherapy [ MAGIC ] ) did not include radiotherapy in the r and omization scheme because it was considered expendable . Given radiotherapy 's potential , efforts needed to be made to optimize its use for treating gastric cancer . We assessed whether intensity-modulated radiotherapy ( IMRT ) could improve upon our published results in patients treated with three-dimensional ( 3D ) conformal therapy . METHODS AND MATERIAL S Fourteen patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a noncoplanar four-field arrangement . Subsequently , a nine-field IMRT plan was design ed using a CMS Xio IMRT version 4.3.3 module . Two IMRT beam arrangements were evaluated : beam arrangement 1 consisted of gantry angles of 0 degrees , 53 degrees , 107 degrees , 158 degrees , 204 degrees , 255 degrees , and 306 degrees . Beam arrangement 2 consisted of gantry angles of 30 degrees , 90 degrees , 315 degrees , and 345 degrees ; a gantry angle of 320 degrees /couch , 30 degrees ; and a gantry angle of 35 degrees /couch , 312 degrees . Both the target volume coverage and the dose deposition in adjacent critical organs were assessed in the plans . Dose-volume histograms were generated for the clinical target volume , kidneys , spine , and liver . RESULTS Comparison of the clinical target volumes revealed satisfactory coverage by the 95 % isodose envelope using either IMRT or 3D conformal therapy . However , IMRT was only marginally better than 3D conformal therapy at protecting the spine and kidneys from radiation . CONCLUSIONS IMRT confers only a marginal benefit in the adjuvant treatment of gastric cancer and should be used only in the small subset of patients with risk factors for kidney disease or those with a preexisting nephropathy PURPOSE To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0 ) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection . METHODS AND MATERIAL S The chemotherapy arm received 5 cycles of fluorouracil and leucovorin ( FL ) , and the chemoradiation therapy arm received 1 cycle of FL , then radiation therapy of 45 Gy concurrently with 2 cycles of FL , followed by 2 cycles of FL . Intent-to-treat analysis and per- protocol analyses were performed . RESULTS Between May 6 , 2002 and June 29 , 2006 , a total of 90 patients were enrolled . Forty-four were r and omly assigned to the chemotherapy arm and 46 to the chemoradiation therapy arm . Treatment was completed as planned by 93.2 % of patients in the chemotherapy arm and 87.0 % in the chemoradiation therapy arm . Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival ( LRRFS ) but not disease-free survival . In subgroup analysis for stage III , chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy ( 93.2 % vs 66.8 % , P=.014 ; 73.5 % vs 54.6 % , P=.056 , respectively ) . CONCLUSIONS Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection Objective : The aim of this study was to evaluate the efficacy of adjuvant chemotherapy with etoposide , Adriamycin and cisplatin ( EAP ) after potentially curative resections for gastric cancer . Methods : After surgery , patients were r and omly assigned to the EAP or control arm . Chemotherapy included 3 courses , administered every 28 days . Each cycle consisted of doxorubicin ( 20 mg/m2 ) on days 1 and 7 , cisplatin ( 40 mg/m2 ) on days 2 and 8 , and etoposide ( 120 mg/m2 ) on days 4 , 5 , and 6 . Results : Of 309 eligible patients , 141 were allocated to chemotherapy and 154 to the supportive care group . Four ( 2.8 % ) treatment-related deaths were recorded , including 3 due to septic complications of myelosuppression and 1 due to cardiocirculatory failure . Grade 3 or 4 toxicities were found in 17 ( 22 % ) patients . According to the intention-to-treat analysis , the median survival was 41.3 months ( 95 % confidence interval , 24.5–58.2 ) and 35.9 months ( 95 % confidence interval , 25.5–46.3 ) in the chemotherapy and control group , respectively ( p = 0.398 ) . Subgroup analysis revealed survival benefit from chemotherapy in patients with tumors infiltrating the serosa and in those with 7–15 metastatic lymph nodes . Conclusion : Three cycles of EAP regimen postoperatively offer no survival advantage in gastric cancer patients Three hundred fifteen patients with operable gastric cancer were r and omized to receive fluorouracil , Adriamycin ( doxorubicin ; Adria Laboratories , Columbus , OH ) , and mitomycin ( FAM ) or no adjuvant treatment between September 1981 and July 1984 . After excluding ineligible patients , 281 patients are included in this analysis . Treatment was moderately well tolerated by the majority of patients , the common side effects being nausea and vomiting ( 58 % ) and alopecia ( 57 % ) . Three possible treatment-related deaths were seen , all due to cardiac failure . At median follow-up of 68 months , 164 patients have died , 73 in the treated arm and 91 in the control arm . There was no significant difference in disease-free or overall survival between the two arms of the study ( P = 0.21 ) . There is some evidence that patients with more advanced carcinoma ( T3-T4 ) derived some benefit from treatment ( P = 0.04 ) . The interpretation of this finding must take into account that all subgroups were defined retrospectively , and this could , therefore , be a chance finding . We conclude that adjuvant chemotherapy as given in this trial is not indicated as routine treatment in operable gastric cancer , but that further evaluation in stage T3-T4 patients is warranted One hundred-three patients with a potentially curative operation of a histologically proven gastric cancer were r and omly assigned to a control and chemotherapy group after stratification according to tumor stage II and III . Chemotherapy courses with 5-fluorouracil ( 10 mg/kg/day ) and BCNU ( 40 mg/m2/day ) for 5 days were administered eight times in 6 - 8 week intervals . Age , sex , and tumor location were matched in the chemotherapy and control groups . Five patients declined treatment after r and omization . Three years after initiating the study , the tumor has recurred in 38 of the 103 patients . There were 21 recurrences of 54 controls and 14 recurrences of 44 patients who received chemotherapy , and 17 and ten deaths , respectively , due to tumor relapse . The results of our study to data show a high degree of statistical probability that adjuvant chemotherapy with the regime used has no influence on the recurrence-free interval and survival time in gastric cancer This study evaluated combined 5‐fluorouracil ( 5FU ) and doxorubicin as postoperative adjuvant chemotherapy for patients who had undergone potentially curative resection of a primary gastric adenocarcinoma . One hundred twenty‐five eligible and evaluable patients were stratified according to extent of surgical resection , location of the primary tumor within the stomach , and lymph node status . They were then r and omized to either receive three cycles of chemotherapy or be observed . The median time from patient entry was 7 years . Results showed no significant difference in time to recurrence . The 5‐year survival rate was 33 % for the observation arm and 32 % for the adjuvant therapy arm . The data excluded a 16 % improvement in the 5‐year survival rate for patients receiving chemotherapy with a P value less than 0.05 . There were two drug‐related fatalities due to sepsis . These results demonstrate no substantive benefit for this chemotherapy regimen as postoperative adjuvant treatment of resected gastric cancer From 1975 to 1988 , 120 consecutive patients with locally advanced ( T3/T4 or N1/N2 ) adenocarcinoma of the stomach underwent attempted curative resection . Seventy patients were treated with surgery alone while 50 patients also received adjuvant therapy consisting of either chemotherapy ( 5-FU/FAM ) alone , radiation therapy alone , or chemotherapy+radiation therapy . Adjuvant therapy was tolerated relatively well with only one patient experiencing a grade 3 ( RTOG/EORTC ) toxicity , and none experiencing grade 4/5 toxicity . In patients with T3/T4 tumors , the median survival was 10 months for surgery alone as compared to 18 months for the adjuvant treatment group , and a 5-year survival of 10 % versus 24 % in the adjuvant therapy group ( p = .01 ) . In patients with lymph node positive disease , the median survival was 10 months in patients treated with surgery as compared to 15 months for those treated with adjuvant therapy , and a 5-year survival of 8 % for surgery alone versus 16 % for the adjuvant therapy group ( p = .04 ) . Patients having both T3/T4 tumor and positive lymph nodes had a median survival of 9 months with surgery versus 13 months for the adjuvant therapy group , and a 5-year survival of 4 % versus 22 % ( p = .03 ) for the adjuvant group . Seventy-four patients were evaluable for pattern of relapse . Thirty developed locoregional recurrence ; 17 of 38 ( 45 % ) in the surgery alone group and 13 of 36 ( 36 % ) in the adjuvant therapy group . The improvement in local control in the adjuvant group was totally accounted for by the group receiving both chemotherapy and radiation therapy , in which the recurrence rate was 19 % . Statistically significant improvement in the 2-year local control rate was limited to patients with negative surgical margins who received radiation , 93 % , versus those who did not , 55 % ( p = 0.03 ) . The modest improvement in survival seen in patients receiving adjuvant therapy appears to be related to improved local control . No improvement in the rate of distant failure was seen . Chemotherapeutic regimens used seem to be critical in enhancing the effects of radiation in improving local control and survival . Results may be further improved by the extended use of intraoperative radiation The results of a prospect i ve r and omized trial of adjuvant treatment after curative resection for gastric cancer are reported . The study consisted of three arms : ( 1 ) surgery only ; ( 2 ) chemotherapy ( 5‐fluoro‐uracil ( FU ) and 1‐(2‐chloroethyl)‐3‐(4‐methylcyclohexil)‐1‐nitrosourea ( Me‐CCNU ) ) after surgery ; ( 3 ) chemo‐immunotherapy ( FU , Me‐CCNU and levamisole ) after surgery . Between March 1977 and June 1981 , 235 patients were included in the study by 18 co‐operating institutions . Thirteen per cent of patients in arm 2 and thirteen per cent in arm 3 suffered major toxicity , necessitating interruption of treatment . Two of these patients died of marrow aplasia . Statistical analysis of survival showed that prognosis was influenced by the well‐known prognostic variables , invasion of the wall , nodal status and site of tumour . The different treatments in the three arms , however , did not show any impact on prognosis , even when adjustments were made for the most relevant prognostic variables . Given the lack of effect on survival and the presence of clinical ly important toxicity , FU and Me‐CCNU ± levamisole can not be recommended as adjuvant therapy for resected gastric cancer BACKGROUND To study the survival benefit of adjuvant chemotherapy in gastric cancer , seven cancer centres in Japan carried out a phase III clinical trial of adjuvant chemotherapy after curative gastrectomy for macroscopically serosa-negative gastric cancer . METHODS 579 patients were enrolled in the study , stratified by disease stage ( T1 , n=188 ; T2 , n=323 ) , and allocated r and omly adjuvant chemotherapy or no further treatment . 285 of 288 cases in the treatment group and 288 of 291 in the control group were eligible . Six cases were excluded because they did not fulfill the entry criteria . The treatment group had intravenous mitomycin ( 1.4 mg/m2 ) and fluorouracil ( 166.7 mg/m2 ) twice weekly for 3 weeks after surgery , and oral UFT ( uracil plus tegafur , 300 mg daily ) for 18 months . Analyses were by intention to treat . FINDINGS No serious toxic effects were observed in the treatment group . At median follow-up of 72 months , 59 patients in the control group and 47 in the treatment group had died . There was no significant difference in survival between the groups ( 5-year survival 82.9 % control vs 85.8 % treated ; hazard ratio 0.738 [ 95 % CI 0.498 - 1.093 ] ) . 5-year survival of patients with T1 ( mucosal or submucosal ) cancer in the control and treatment groups was 94.9 % versus 92.0 % , and that of patients with T2 ( muscularis propria or subserosa ) cancer was 76.9 % versus 83.0 % . However , a test for heterogeneity and interaction over T1 and T2 subgroups revealed no significant difference in terms of drug response . INTERPRETATION There was no survival benefit with this adjuvant therapy regimen for patients with macroscopically serosa-negative gastric cancer ( T1 and T2 ) after curative gastrectomy . Patients with T1 cancer can be excluded from future trials , because curative surgery alone yielded a very good survival rate and there seemed no need for adjuvant therapy BACKGROUND A regimen of epirubicin , cisplatin , and infused fluorouracil ( ECF ) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma . We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer . METHODS We r and omly assigned patients with resectable adenocarcinoma of the stomach , esophagogastric junction , or lower esophagus to either perioperative chemotherapy and surgery ( 250 patients ) or surgery alone ( 253 patients ) . Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin ( 50 mg per square meter of body-surface area ) and cisplatin ( 60 mg per square meter ) on day 1 , and a continuous intravenous infusion of fluorouracil ( 200 mg per square meter per day ) for 21 days . The primary end point was overall survival . RESULTS ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer . Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group ( 46 percent and 45 percent , respectively ) , as were the numbers of deaths within 30 days after surgery . The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group . With a median follow-up of four years , 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died . As compared with the surgery group , the perioperative-chemotherapy group had a higher likelihood of overall survival ( hazard ratio for death , 0.75 ; 95 percent confidence interval , 0.60 to 0.93 ; P=0.009 ; five-year survival rate , 36 percent vs. 23 percent ) and of progression-free survival ( hazard ratio for progression , 0.66 ; 95 percent confidence interval , 0.53 to 0.81 ; P<0.001 ) . CONCLUSIONS In patients with operable gastric or lower esophageal adenocarcinomas , a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival . ( Current Controlled Trials number , IS RCT N93793971 [ controlled-trials.com ] . ) PURPOSE The ARTIST ( Adjuvant Chemoradiation Therapy in Stomach Cancer ) trial was the first study to our knowledge to investigate the role of postoperative chemoradiotherapy therapy in patients with curatively resected gastric cancer with D2 lymph node dissection . This trial was design ed to compare postoperative treatment with capecitabine plus cisplatin ( XP ) versus XP plus radiotherapy with capecitabine ( XP/XRT/XP ) . PATIENTS AND METHODS The XP arm received six cycles of XP ( capecitabine 2,000 mg/m2 per day on days 1 to 14 and cisplatin 60 mg/m2 on day 1 , repeated every 3 weeks ) chemotherapy . The XP/XRT/XP arm received two cycles of XP followed by 45-Gy XRT ( capecitabine 1,650 mg/m2 per day for 5 weeks ) and two cycles of XP . RESULTS Of 458 patients , 228 were r and omly assigned to the XP arm and 230 to the XP/XRT/XP arm . Treatment was completed as planned by 75.4 % of patients ( 172 of 228 ) in the XP arm and 81.7 % ( 188 of 230 ) in the XP/XRT/XP arm . Overall , the addition of XRT to XP chemotherapy did not significantly prolong disease-free survival ( DFS ; P = .0862 ) . However , in the subgroup of patients with pathologic lymph node metastasis at the time of surgery ( n = 396 ) , patients r and omly assigned to the XP/XRT/XP arm experienced superior DFS when compared with those who received XP alone ( P = .0365 ) , and the statistical significance was retained at multivariate analysis ( estimated hazard ratio , 0.6865 ; 95 % CI , 0.4735 to 0.9952 ; P = .0471 ) . CONCLUSION The addition of XRT to XP chemotherapy did not significantly reduce recurrence after curative resection and D2 lymph node dissection in gastric cancer . A subsequent trial ( ARTIST-II ) in patients with lymph node-positive gastric cancer is planned PURPOSE In a r and omized clinical trial ( European Organization for the Research and Treatment of Cancer [ EORTC ] no. 40813 ) on adjuvant chemotherapy in gastric cancer , results obtained after administration of the FAM2 regimen ( fluorouracil [ 5-FU ] , doxorubicin , and mitomycin ) were compared with results obtained after surgery alone to assess the effect of this regimen on overall survival , time to progression , and disease-free interval . PATIENTS AND METHODS Three hundred fourteen patients who had undergone curative resection for stage II or stage III ( International Union Against Cancer [ UICC ] 1978 ) gastric adenocarcinoma were r and omized to receive chemotherapy ( treatment arm ) or no further treatment ( control arm ) . The chemotherapy schedule was repeated every 43 days for seven cycles . The log-rank test and the Cox model were used for statistical analysis . RESULTS Of 314 patients , 159 comprised the control group and 155 the FAM2 group . Nineteen FAM2 patients never received chemotherapy . The median number of cycles was five . Of the patients started on adjuvant treatment , severe hematologic and nonhematologic toxicity ( grade s 3 or 4 , World Health Organization [ WHO ] scale ) occurred , respectively , in 6 % to 9 % and in 1 % to 29 % of cases . The overall 5-year survival rate was 70 % for stage II and 32 % for stage III patients . No statistically significant difference was found between overall survival of the two treatment arms ( P = .295 ) . However , time to progression was significantly delayed in the FAM2 arm ( P = .020 ) and disease-free survival showed borderline significance ( P = .068 ) . CONCLUSION FAM2 , in view of its high toxicity , can not be advocated as st and ard adjuvant treatment for gastric cancer . Large-scale clinical trials using more active , less toxic regimens are required to demonstrate whether adjuvant chemotherapy provides any real benefit PURPOSE The efficacy of adjuvant chemotherapy in gastric cancer is controversial . We conducted a phase III , r and omized , multicentric clinical trial with the goal of assessing the efficacy of the combination of mitomycin plus tegafur in prolonging the disease-free survival and overall survival of patients with resected stage III gastric cancer . PATIENTS AND METHODS Patients with resected stage III gastric adenocarcinoma were r and omly assigned , using sealed envelopes , to receive either chemotherapy or no further treatment . Chemotherapy was started within 28 days after surgery according to the following schedule : mitomycin 20 mg/m(2 ) intravenously ( bolus ) at day 1 of chemotherapy ; 30 days later , oral tegafur at 400 mg bid daily for 3 months . Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis and the Cox proportional hazards model . RESULTS Between January 1988 and September 1994 , 148 patients from 10 hospitals in Catalonia , Spain , were included in the study . The median follow-up period was 37 months . The tolerability of the treatment was excellent . The overall survival and disease-free survival were higher in the group of patients treated with chemotherapy ( P = .04 for survival and P = .01 for disease-free survival in the log-rank test ) . The overall 5-year survival rate and the 5-year disease-free survival rate were , respectively , 56 % and 51 % in the treatment group and 36 % and 31 % in the control group . CONCLUSION Our positive results are consistent with the results of recent studies ; which conclude that there is a potential benefit from adjuvant chemotherapy in resected gastric cancer 411 patients were entered into a prospect i ve , r and omised controlled trial of adjuvant chemotherapy after gastrectomy for adenocarcinoma . After a follow-up of at least 5 1/2 years there has been no survival advantage for those receiving adjuvant 5-fluorouracil and mitomycin C with or without an induction course of 5-fluorouracil , vincristine , cyclophosphamide , and methotrexate compared with those undergoing surgery only . There have been 366 deaths , including 22 from treatment-related conditions . A multivariate analysis of prognostic factors demonstrated that stage of disease , nodal and resection margin involvement , and the presence of residual disease are significant determinants of survival . Weight loss before surgery had a significant independent influence on survival . The combination of preoperative symptoms and intraoperative findings may be used to select patients for radical or palliative procedures |
13,289 | 20,525,214 | Conclusion The combination of bevacizumab and irinotecan might improve outcome in patients with recurrent malignant glioma . | Background The combination of bevacizumab and irinotecan is a new chemotherapy protocol increasingly used for recurrent malignant glioma .
Results from phase II trials suggest this drug combination is beneficial to patients , but no conclusive comparisons between this and other treatment protocol s have been published .
Methods We performed a systematic review and survival gain analysis of phase II studies to evaluate the efficacy and safety of bevacizumab plus irinotecan treatment . | The purpose of this study was to determine the response to CPT-11 administered every three weeks to adults with progressive malignant glioma , treated with or without enzyme-inducing antiepileptic drug ( EIAED ) therapy , at the recommended phase 2 dose determined from a previous phase 1 study . Adult patients age 18 or older with a KPS of 60 or higher who had measurable recurrent grade III anaplastic glioma ( AG ) or grade IV glioblastoma multiforme ( GBM ) were eligible . No more than one prior chemotherapy was allowed , either as adjuvant therapy or for recurrent disease . The CPT-11 dose was 350 mg/m(2 ) i.v . every three weeks in patients not on EIAED and 750 mg/m(2 ) in patients on EIAED therapy . Patients with stable or responding disease could be treated until tumor progression or a total of 12 months of therapy . The primary end point of the study was to determine whether CPT-11 could significantly delay tumor progression , using the rate of six-month progression-free survival ( PFS-6 ) . The trial was sized to be able to discriminate between a 15 % and 35 % rate for the GBM group alone and between a 20 % and 40 % rate for the entire cohort . There were 51 eligible patients , including 38 GBM and 13 AG patients , enrolled . The median age was 52 and 42 years , respectively . PFS-6 for the entire cohort was 17.6 % . PFS-6 was 15.7 % ( 95 % confidence interval [ CI ] , 0.07 - 0.31 ) for the GBM patients and 23 % ( 95 % CI , 0.07 - 0.52 ) for AG patients . Toxicity for the group included diarrhea and myelosuppression . We conclude that the recommended phase 2 dose of CPT-11 for patients with or without EIAED was ineffective on this schedule , in this patient population Purpose : Although patients with newly diagnosed WHO grade 3 malignant glioma have a more favorable prognosis than those with WHO grade 4 malignant glioma , salvage therapies following recurrence offer essentially palliative benefit . We did a phase II trial of bevacizumab , a monoclonal antibody to vascular endothelial growth factor , in combination with irinotecan for patients with recurrent grade 3 malignant glioma . Experimental Design : Upon documentation of adequate safety among an initial cohort of nine patients treated with bevacizumab ( 10 mg/kg ) and irinotecan every 14 days , a second cohort ( n = 24 ) was treated with bevacizumab ( 15 mg/kg ) every 3 weeks with irinotecan on days 1 , 8 , 22 , and 29 of each 42-day cycle . For both cohorts , the dose of irinotecan was 340 mg/m2 for patients on enzyme-inducing antiepileptic drugs ( EIAED ) and 125 mg/m2 for patients not on EIAEDs . After each 6-week cycle , patients were evaluated with a physical examination and magnetic resonance imaging . Results : The 6-month progression-free survival was 55 % ( 95 % confidence interval , 36 - 70 % ) . The 6-month overall survival was 79 % ( 95 % confidence interval , 61 - 89 % ) . Twenty patients ( 61 % ) had at least a partial response . Outcome did not differ between the two treatment cohorts . Significant adverse events were infrequent and included a central nervous system hemorrhage in one patient , and one patient who developed thrombotic thrombocytopenic purpura . Conclusion : Bevacizumab and irinotecan is an active regimen with acceptable toxicity for patients with recurrent WHO grade 3 malignant glioma PURPOSE Evaluation of treatment effects in malignant brain tumors is challenging because of the lack of reliable response predictors of tumor response . This study examines the predictive value of positron emission tomography ( PET ) using [ 18F ] fluorothymidine ( FLT ) , an imaging biomarker of cell proliferation , in patients with recurrent malignant gliomas treated with bevacizumab in combination with irinotecan . PATIENTS AND METHODS Patients with recurrent malignant gliomas treated with biweekly cycles of bevacizumab and irinotecan were prospect ively studied with FLT-PET at baseline , after 1 to 2 weeks , and after 6 weeks from start of treatment . A more than 25 % reduction in tumor FLT uptake as measured by st and ardized uptake value was defined as a metabolic response . FLT responses were compared with response as shown by magnetic resonance imaging ( MRI ) and patient survival . RESULTS Twenty-one patients were included , and 19 were assessable for metabolic response evaluation with FLT-PET . There were nine responders ( 47 % ) and 10 nonresponders ( 53 % ) . Metabolic responders survived three times as long as nonresponders ( 10.8 v 3.4 months ; P = .003 ) , and tended to have a prolonged progression-free survival ( P = .061 ) . Both early and later FLT-PET responses were more significant predictors of overall survival ( 1 to 2 weeks , P = .006 ; 6 weeks , P = .002 ) , compared with the MRI responses ( P = .060 for both 6-week and best responses ) . CONCLUSION FLT-PET as an imaging biomarker seems to be predictive of overall survival in bevacizumab and irinotecan treatment of recurrent gliomas . Whether FLT-PET performed as early as 1 to 2 week after starting treatment is as predictive as the study indicates at 6 weeks warrants further investigation Our objective is to assess treatment efficacy , safety and pattern of response and recurrence in patients with recurrent high- grade glioma treated with bevacizumab and irinotecan . We review ed retrospectively 51 patients with recurrent high- grade glioma treated with this combination at the Henry Ford Hermelin Brain Tumor Center from 11/15/2005 to 04/01/2008 . The 6-month progression-free survival ( PFS ) for anaplastic gliomas ( AGs ) was 78.6 and 63.7 % for glioblastoma . The median PFS was 13.4 months for AG and 7.6 months for those with glioblastoma . The overall survival rate ( OS ) at 6 months was 85.7 % for AG and 78.0 % for glioblastoma . The 12-month OS was 77.9 % for AG and 42.6 % for glioblastoma . The median OS time for AGs was not reached and was 11.5 months for those with glioblastoma . Thirty-six out of 51 ( 70.59 % ) patients demonstrated partial ( 32/51 ) or complete ( 4/51 ) radiographic response to treatment and 8/51 ( 15.69 % ) remained stable . Of the 38 who demonstrated progression on post-gadolinium studies , 23 showed distant progression with or without local recurrence . Seven patients showed progression on FLAIR without concordant findings on post-Gd sequences . Six patients ( 11.76 % ) discontinued treatment due to a treatment-emergent adverse event , including one with end-stage renal failure and another with gastric perforation . No symptomatic intracranial hemorrhages were reported . Patients with recurrent high- grade glioma treated with bevacizumab plus irinotecan demonstrate an excellent radiographic response rate and improved clinical outcome when compared to historical data . The high rate of distant tumor progression suggests that tumors may adapt to inhibition of angiogenesis by increased infiltration and vascular co-option Purpose : Recurrent grade III-IV gliomas have a dismal prognosis with minimal improvements in survival seen following currently available salvage therapy . This study was conducted to determine if the combination of a novel antiangiogenic therapy , bevacizumab , and a cytotoxic agent , irinotecan , is safe and effective for patients with recurrent grade III-IV glioma . Experimental Design : We conducted a phase II trial of bevacizumab and irinotecan in adults with recurrent grade III-IV glioma . Patients with evidence of intracranial hemorrhage on initial brain magnetic resonance imaging were excluded . Patients were scheduled to receive bevacizumab and irinotecan i.v . every 2 weeks of a 6-week cycle . Bevacizumab was administered at 10 mg/kg . The dose of irinotecan was determined based on antiepileptic use : patients taking enzyme-inducing antiepileptic drugs received 340 mg/m2 , whereas patients not taking enzyme-inducing antiepileptic drugs received 125 mg/m2 . Toxicity and response were assessed . Results : Thirty-two patients were assessed ( 23 with grade IV glioma and 9 with grade III glioma ) . Radiographic responses were noted in 63 % ( 20 of 32 ) of patients ( 14 of 23 grade IV patients and 6 of 9 grade III patients ) . The median progression-free survival was 23 weeks for all patients ( 95 % confidence interval , 15 - 30 weeks ; 20 weeks for grade IV patients and 30 weeks for grade III patients ) . The 6-month progression-free survival probability was 38 % and the 6-month overall survival probability was 72 % . No central nervous system hemorrhages occurred , but three patients developed deep venous thromboses or pulmonary emboli , and one patient had an arterial ischemic stroke . Conclusions : The combination of bevacizumab and irinotecan is an active regimen for recurrent grade III-IV glioma with acceptable toxicity PURPOSE OF REVIEW To critically assess the role of irinotecan ( Camptosar , CPT-11 ) and bevacizumab ( Avastin ) as a new treatment for glioblastoma and other malignant gliomas ( anaplastic forms of astrocytomas and oligodendrogliomas ) . RECENT FINDINGS Two prospect i ve phase II trials of bevacizumab and irinotecan have been reported . The observed high response rates ( 30 - 60 % ) had never been seen in this disease before . Gains in progression-free survival and overall survival ( OS ) were less impressive ( 6-month progression-free survival 30 - 50 % ; median OS : 9 - 10 months ) , but are still superior to historical controls . SUMMARY Bevacizumab is a welcome new weapon in the treatment of malignant gliomas and should be favored as a salvage treatment over cytotoxic chemotherapy for recurrent disease . However , survival results remain far from satisfactory . Once failure to treatment with bevacizumab is diagnosed by conventional radiographic methods , most patients experience rapid deterioration and die shortly afterward . New methods and radiographic criteria for detecting disease progression are needed . Patients willing to explore new treatment strategies through participation in clinical trials should do so prior to starting bevacizumab , as this may not be an option once treatment fails . Cost-effectiveness of bevacizumab in gliomas deserves further investigation . The role of irinotecan in this combination remains unclear . At this time , bevacizumab should only be used in newly diagnosed malignant gliomas in the setting of a clinical trial PURPOSE To evaluate single-agent activity of bevacizumab in patients with recurrent glioblastoma . PATIENTS AND METHODS Patients with recurrent glioblastoma were treated with bevacizumab 10 mg/kg every 2 weeks . After tumor progression , patients were immediately treated with bevacizumab in combination with irinotecan 340 mg/m(2 ) or 125 mg/m(2 ) every 2 weeks , depending on use of enzyme-inducing antiepileptic drugs . Complete patient evaluations were repeated every 4 weeks . RESULTS Forty-eight heavily pretreated patients were accrued to this study . Thromboembolic events ( 12.5 % ) , hypertension ( 12.5 % ) , hypophosphatemia ( 6 % ) , and thrombocytopenia ( 6 % ) were the most common drug-associated adverse events . Six patients ( 12.5 % ) were removed from study for drug-associated toxicity ( five thromboembolic events , one bowel perforation ) . Thirty-four patients ( 71 % ) and 17 patients ( 35 % ) achieved radiographic response based on Levin and Macdonald criteria , respectively . Median progression-free survival ( PFS ) was 16 weeks ( 95 % CI , 12 to 26 weeks ) . The 6-month PFS was 29 % ( 95 % CI , 18 % to 48 % ) . The 6-month overall survival was 57 % ( 95 % CI , 44 % to 75 % ) . Median overall survival was 31 weeks ( 95 % CI , 21 to 54 weeks ) . Early magnetic resonance imaging response ( first 96 hours and 4 weeks ) was predictive of long-term PFS , with the Levin criteria being more predictive than Macdonald criteria . Of 19 patients treated with bevacizumab plus irinotecan at progression , there were no objective radiographic responses . Eighteen patients ( 95 % ) experienced disease progression by the second cycle , and the median PFS was 30 days . CONCLUSION We conclude that single-agent bevacizumab has significant biologic and antiglioma activity in patients with recurrent glioblastoma OBJECT Endothelial proliferation has been recognized as a marker of high- grade or aggressive glioma . Bevacizumab is a humanized immunoglobulin G1 monoclonal antibody to vascular endothelial growth factor that has been shown to have activity in malignant gliomas when combined with irinotecan . The authors report on a case series of 13 patients with recurrent heavily pretreated malignant glioma that was treated with the combination of bevacizumab and irinotecan . METHODS St and ard therapy with primary resection followed by adjuvant chemotherapy and radiation had failed in all patients . The median number of therapies applied , including initial surgery , was 5 ( range 3 - 7 therapies ) . Nine patients were started on bevacizumab at a dose of 5 mg/m2 every 2 weeks . Four patients received bevacizumab at a dose of 10 mg/m2 ; irinotecan was given at a dose of 125 mg/m2 every week for 3 weeks . RESULTS Of the 13 treated patients , 10 ( 77 % ) had a radiologically demonstrated partial response and 3 ( 23 % ) had stable disease . Six patients ( 46 % ) had a clinical response . The median time to disease progression while on treatment was 24 weeks . The median overall survival was 27 weeks . The disease progressed in 8 patients , despite an initial response . Five patients are still responding to therapy . Six of the 8 patients whose disease progressed have died . Bevacizumab was discontinued in 2 patients because of nonfatal intracranial bleeding . CONCLUSIONS The combination of bevacizumab and irinotecan is safe and has excellent activity even in this relapsed , heavily pretreated population of patients with high- grade malignant glioma , most of whom would not be c and i date s for clinical trials PURPOSE The prognosis for patients with recurrent glioblastoma multiforme is poor , with a median survival of 3 to 6 months . We performed a phase II trial of bevacizumab , a monoclonal antibody to vascular endothelial growth factor , in combination with irinotecan . PATIENTS AND METHODS This phase II trial included two cohorts of patients . The initial cohort , comprising 23 patients , received bevacizumab at 10 mg/kg plus irinotecan every 2 weeks . The dose of irinotecan was based on the patient 's anticonvulsant : Patients taking enzyme-inducing antiepileptic drugs ( EIAEDs ) received 340 mg/m2 , and patients not taking EIAEDs received 125 mg/m2 . After this regimen was deemed safe and effective , the irinotecan schedule was changed to an accepted brain tumor regimen of four doses in 6 weeks , in anticipation of a phase III r and omized trial of irinotecan versus irinotecan and bevacizumab . The second cohort , comprising 12 patients , received bevacizumab 15 mg/kg every 21 days and irinotecan on days 1 , 8 , 22 , and 29 . Each cycle was 6 weeks long and concluded with patient evaluations , including magnetic resonance imaging . RESULTS The 6-month progression-free survival among all 35 patients was 46 % ( 95 % CI , 32 % to 66 % ) . The 6-month overall survival was 77 % ( 95 % CI , 64 % to 92 % ) . Twenty of the 35 patients ( 57 % ; 95 % CI , 39 % to 74 % ) had at least a partial response . One patient developed a CNS hemorrhage , which occurred in his 10th cycle . Four patients developed thromboembolic complications ( deep venous thrombosis and /or pulmonary emboli ) . CONCLUSION Bevacizumab and irinotecan is an effective treatment for recurrent glioblastoma multiforme and has moderate toxicity A r and omized , multicentre , open-label , phase II study compared temozolomide ( TMZ ) , an oral second-generation alkylating agent , and procarbazine ( PCB ) in 225 patients with glioblastoma multiforme at first relapse . Primary objectives were to determine progression-free survival ( PFS ) at 6 months and safety for TMZ and PCB in adult patients who failed conventional treatment . Secondary objectives were to assess overall survival and health-related quality of life ( HRQL ) . TMZ was given orally at 200 mg/m2/day or 150 mg/m2/day ( prior chemotherapy ) for 5 days , repeated every 28 days . PCB was given orally at 150 mg/m2/day or 125 mg/m2/day ( prior chemotherapy ) for 28 days , repeated every 56 days . HRQL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30 [ + 3 ] ) and the Brain Cancer Module 20 ( BCM20 ) . The 6-month PFS rate for patients who received TMZ was 21 % , which met the protocol objective . The 6-month PFS rate for those who received PCB was 8 % ( P = 0.008 , for the comparison ) . Overall PFS significantly improved with TMZ , with a median PFS of 12.4 weeks in the TMZ group and 8.32 weeks in the PCB group ( P = 0.0063 ) . The 6-month overall survival rate for TMZ patients was 60 % vs. 44 % for PCB patients ( P = 0.019 ) . Freedom from disease progression was associated with maintenance of HRQL , regardless of treatment received . TMZ had an acceptable safety profile ; most adverse events were mild or moderate in severity . © 2000 Cancer Research BACKGROUND Bevacizumab , a monoclonal antibody against vascular endothelial growth factor , has been shown to benefit patients with a variety of cancers . METHODS Between July 2001 and April 2004 , the Eastern Cooperative Oncology Group ( ECOG ) conducted a r and omized study in which 878 patients with recurrent or advanced non-small-cell lung cancer ( stage IIIB or IV ) were assigned to chemotherapy with paclitaxel and carboplatin alone ( 444 ) or paclitaxel and carboplatin plus bevacizumab ( 434 ) . Chemotherapy was administered every 3 weeks for six cycles , and bevacizumab was administered every 3 weeks until disease progression was evident or toxic effects were intolerable . Patients with squamous-cell tumors , brain metastases , clinical ly significant hemoptysis , or inadequate organ function or performance status ( ECOG performance status , > 1 ) were excluded . The primary end point was overall survival . RESULTS The median survival was 12.3 months in the group assigned to chemotherapy plus bevacizumab , as compared with 10.3 months in the chemotherapy-alone group ( hazard ratio for death , 0.79 ; P=0.003 ) . The median progression-free survival in the two groups was 6.2 and 4.5 months , respectively ( hazard ratio for disease progression , 0.66 ; P<0.001 ) , with corresponding response rates of 35 % and 15 % ( P<0.001 ) . Rates of clinical ly significant bleeding were 4.4 % and 0.7 % , respectively ( P<0.001 ) . There were 15 treatment-related deaths in the chemotherapy-plus-bevacizumab group , including 5 from pulmonary hemorrhage . CONCLUSIONS The addition of bevacizumab to paclitaxel plus carboplatin in the treatment of selected patients with non-small-cell lung cancer has a significant survival benefit with the risk of increased treatment-related deaths . ( Clinical Trials.gov number , NCT00021060 . PURPOSE The combination of a vascular endothelial growth factor ( VEGF ) -neutralizing antibody , bevacizumab , and irinotecan is associated with high radiographic response rates and improved survival outcomes in patients with recurrent malignant gliomas . The aim of these retrospective studies was to evaluate tumor vascularity and expression of components of the VEGF pathway and hypoxic responses as predictive markers for radiographic response and survival benefit from the bevacizumab and irinotecan therapy . PATIENTS AND METHODS In a phase II trial , 60 patients with recurrent malignant astrocytomas were treated with bevacizumab and irinotecan . Tumor specimens collected at the time of diagnosis were available for further pathologic studies in 45 patients ( 75 % ) . VEGF , VEGF receptor-2 , CD31 , hypoxia-inducible carbonic anhydrase 9 ( CA9 ) , and hypoxia-inducible factor-2alpha were semiquantitatively assessed by immunohistochemistry . Radiographic response and survival outcomes were correlated with these angiogenic and hypoxic markers . RESULTS Of 45 patients , 27 patients had glioblastoma multiforme , and 18 patients had anaplastic astrocytoma . Twenty-six patients ( 58 % ) had at least partial radiographic response . High VEGF expression was associated with increased likelihood of radiographic response ( P = .024 ) but not survival benefit . Survival analysis revealed that high CA9 expression was associated with poor survival outcome ( P = .016 ) . CONCLUSION In this patient cohort , tumor expression levels of VEGF , the molecular target of bevacizumab , were associated with radiographic response , and the upstream promoter of angiogenesis , hypoxia , determined survival outcome , as measured from treatment initiation . Validation in a larger clinical trial is warranted PURPOSE We evaluated the efficacy of bevacizumab , alone and in combination with irinotecan , in patients with recurrent glioblastoma in a phase II , multicenter , open-label , noncomparative trial . PATIENTS AND METHODS One hundred sixty-seven patients were r and omly assigned to receive bevacizumab 10 mg/kg alone or in combination with irinotecan 340 mg/m(2 ) or 125 mg/m(2 ) ( with or without concomitant enzyme-inducing antiepileptic drugs , respectively ) once every 2 weeks . Primary end points were 6-month progression-free survival and objective response rate , as determined by independent radiology review . Secondary end points included safety and overall survival . RESULTS In the bevacizumab-alone and the bevacizumab-plus-irinotecan groups , estimated 6-month progression-free survival rates were 42.6 % and 50.3 % , respectively ; objective response rates were 28.2 % and 37.8 % , respectively ; and median overall survival times were 9.2 months and 8.7 months , respectively . There was a trend for patients who were taking corticosteroids at baseline to take stable or decreasing doses over time . Of the patients treated with bevacizumab alone or bevacizumab plus irinotecan , 46.4 % and 65.8 % , respectively , experienced grade > or = 3 adverse events , the most common of which were hypertension ( 8.3 % ) and convulsion ( 6.0 % ) in the bevacizumab-alone group and convulsion ( 13.9 % ) , neutropenia ( 8.9 % ) , and fatigue ( 8.9 % ) in the bevacizumab-plus-irinotecan group . Intracranial hemorrhage was noted in two patients ( 2.4 % ) in the bevacizumab-alone group ( grade 1 ) and in three patients ( 3.8 % ) patients in the bevacizumab-plus-irinotecan group ( grade s 1 , 2 , and 4 , respectively ) . CONCLUSION Bevacizumab , alone or in combination with irinotecan , was well tolerated and active in recurrent glioblastoma PURPOSE To determine whether increased uptake on 11C-methionine-PET ( MET-PET ) imaging obtained before radiation therapy and temozolomide is associated with the site of subsequent failure in newly diagnosed glioblastoma multiforme ( GBM ) . METHODS Patients with primary GBM were treated on a prospect i ve trial with dose- escalated radiation and concurrent temozolomide . As part of the study , MET-PET was obtained before treatment but was not used for target volume definition . Using automated image registration , we assessed whether the area of increased MET-PET activity ( PET gross target volume [ GTV ] ) was fully encompassed within the high-dose region and compared the patterns of failure for those with and without adequate high-dose coverage of the PET-GTV . RESULTS Twenty-six patients were evaluated with a median follow-up of 15 months . Nineteen of 26 had appreciable ( > 1 cm(3 ) ) volumes of increased MET-PET activity before treatment . Five of 19 patients had PET-GTV that was not fully encompassed within the high-dose region , and all five patients had non central failures . Among the 14 patients with adequately covered PET-GTV , only two had non central treatment failures . Three of 14 patients had no evidence of recurrence more than 1 year after radiation therapy . Inadequate PET-GTV coverage was associated with increased risk of non central failures . ( p < 0.01 ) . CONCLUSION Pretreatment MET-PET appears to identify areas at highest risk for recurrence for patients with GBM . It would be reasonable to test a strategy of incorporating MET-PET into radiation treatment planning , particularly for identifying areas for conformal boost PURPOSE Vascular endothelial growth factor ( VEGF ) is a potent molecule that mediates tumor angiogenesis primarily through VEGF receptor 2 ( VEGFR2 ) . Bevacizumab , a recombinant humanized monoclonal antibody to VEGF , was administered to previously untreated patients to evaluate parameters of angiogenesis . PATIENTS AND METHODS Twenty-one patients with inflammatory and locally advanced breast cancer were treated with bevacizumab for cycle 1 ( 15 mg/kg on day 1 ) followed by six cycles of bevacizumab with doxorubicin ( 50 mg/m(2 ) ) and docetaxel ( 75 mg/m(2 ) ) every 3 weeks . After locoregional therapy , patients received eight cycles of bevacizumab alone , and hormonal therapy when indicated . Tumor biopsies and dynamic contrast-enhanced magnetic resonance imaging ( DCE-MRI ) were obtained at baseline , and after cycles 1 , 4 , and 7 . RESULTS A median decrease of 66.7 % in phosphorylated VEGFR2 ( Y951 ) in tumor cells ( P = .004 ) and median increase of 128.9 % in tumor apoptosis ( P = .0008 ) were seen after bevacizumab alone . These changes persisted with the addition of chemotherapy . There were no significant changes in microvessel density or VEGF-A expression . On DCE-MRI , parameters reflecting reduced angiogenesis , a median decrease of 34.4 % in the inflow transfer rate constant ( P = .003 ) , 15.0 % in the backflow extravascular- extracellular rate constant ( P = .0007 ) and 14.3 % in extravascular-extracellular volume fraction ( P = .002 ) were seen after bevacizumab alone . CONCLUSION Bevacizumab has inhibitory effects on VEGF receptor activation and vascular permeability , and induces apoptosis in tumor cells Material and Methods . We retrospectively determined the efficacy and safety of a combination of bevacizumab and irinotecan in a consecutive series of 52 heavily pre-treated patients with recurrent high- grade brain tumours . Patients received bevacizumab ( 10 mg/kg ) and irinotecan [ 340 mg/m2 for those receiving enzyme-inducing antiepileptic drugs ( EIAEDs ) and 125 mg/m2 for those not receiving EIAEDs ] every 2 weeks . Fifty-two patients were included and 47 were evaluable for response . Results . Complete or partial response was observed in 25 % of all cases ( 30 % response in grade IV glioma and 15 % in grade III glioma ) . Estimated median progression-free survival ( PFS ) for both grade IV and grade III glioma was 22 weeks . The 6-month PFS was 32 % for all patients , 40 % for grade IV glioma and 33 % for grade III glioma . Estimated median overall survival was 30 weeks for all patients , 28 weeks for grade IV glioma and 32 weeks for grade III glioma . Four patients discontinued treatment because of unmanageable toxicity : cerebral haemorrhage , cardiac arrhythmia , intestinal perforation and diarrhoea , the latter result ing in death . Discussion . We conclude that the combination of bevacizumab and irinotecan shows acceptable safety and is a clinical ly relevant choice of therapy in heavily pre-treated patients with recurrent high- grade brain tumours Common end points for phase II trials in patients with glioblastoma multiforme ( GBM ) are six-month progression-free survival ( PFS6 ) and 12-month overall survival ( OS12 ) . OS12 can be accurately measured but may be confounded with subsequent therapies upon progression , whereas the converse is true for PFS6 . Our goal was to assess the relationship between these end points separately for phase II trials in patients with newly diagnosed GBM and patients with recurrent GBM . Data were pooled from 11 North Central Cancer Treatment Group trials for patients with newly diagnosed GBM ( n = 1348 ) . All patients received radiotherapy and pharmaceutical therapy ( before , during , or after radiotherapy ) . Data were pooled from 16 trials that used various pharmaceuticals in treating patients for recurrent GBM ( n = 345 ) . All trial regimens were declared nonefficacious by predefined criteria . Overall per-patient concordance was estimated with a kappa statistic . The relationship between OS12 and PFS6 across study arms was assessed by weighted linear regression and Pearson 's correlation . Simulation was used to determine the agreement of study outcomes when using PFS6 versus OS12 end points . Cox models with progression status as a time-dependent variable and Kaplan-Meier estimators were used to ascertain the association between progression-free survival status and overall survival . At present , 97 % of the patients with newly diagnosed GBM and 95 % of those with recurrent GBM have died . The PFS6 and OS12 were 43 % and 41 % , respectively , for patients with newly diagnosed disease and 9 % and 14 % for patients with recurrent disease . There was only moderate concordance between the end points on both the patient level and the study level . For the simulation studies , we established phase II efficacy criteria for each end point by using the pooled estimates of OS12 ( PFS6 ) as historical controls . The study decisions made using PFS6 and OS12 were in agreement 88 % and 90 % of the time for the trials of newly diagnosed and recurrent disease , respectively . Finally , there was a strong association between progression-free survival status and overall survival . PFS6 seems to be a reasonable end point for phase II trials in patients with recurrent glioblastoma PURPOSE To determine the activity , toxicity , and pharmacokinetics of irinotecan ( CPT-11 , Camptosar ; Pharmacia & Upjohn , Kalamazoo , MI ) in the treatment of adults with progressive , persistent , or recurrent malignant glioma . PATIENTS AND METHODS Patients with progressive or recurrent malignant gliomas were enrolled onto this study between October 1996 and August 1997 . CPT-11 was given as a 90-minute intravenous ( i.v . ) infusion at a dose of 125 mg/m2 once weekly for 4 weeks followed by a 2-week rest , which comprised one course . Plasma concentrations of CPT-11 and its metabolites , SN-38 and SN-38 glucuronide ( SN-38 G ) , were determined in a subset of patients . RESULTS All 60 patients who enrolled ( 36 males and 24 females ) were treated with CPT-11 and all were assessable for toxicity , response , and survival . Pharmacokinetic data were available in 32 patients . Nine patients ( 15 % ; 95 % confidence interval , 6 % to 24 % ) had a confirmed partial response , and 33 patients ( 55 % ) achieved stable disease lasting more than two courses ( 12 weeks ) . Toxicity observed during the study was limited to infrequent neutropenia , nausea , vomiting , and diarrhea . CPT-11 , SN-38 , and SN-38 G area under the plasma concentration-time curves through infinite time values in these patients were approximately 40 % , 25 % , and 25 % , respectively , of those determined previously in patients with metastatic colorectal cancer not receiving antiepileptics or chronic dexamethasone treatment . CONCLUSION Response results document that CPT-11 , given with a st and ard starting dose and treatment schedule , has activity in patients with recurrent malignant glioma . However , the low incidence of severe toxicity and low plasma concentrations of CPT-11 and SN-38 achieved in this patient population suggest that concurrent treatment with anticonvulsants and dexamethasone enhances drug clearance BACKGROUND Glioblastoma , the most common primary brain tumor in adults , is usually rapidly fatal . The current st and ard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible , followed by adjuvant radiotherapy . In this trial we compared radiotherapy alone with radiotherapy plus temozolomide , given concomitantly with and after radiotherapy , in terms of efficacy and safety . METHODS Patients with newly diagnosed , histologically confirmed glioblastoma were r and omly assigned to receive radiotherapy alone ( fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks , for a total of 60 Gy ) or radiotherapy plus continuous daily temozolomide ( 75 mg per square meter of body-surface area per day , 7 days per week from the first to the last day of radiotherapy ) , followed by six cycles of adjuvant temozolomide ( 150 to 200 mg per square meter for 5 days during each 28-day cycle ) . The primary end point was overall survival . RESULTS A total of 573 patients from 85 centers underwent r and omization . The median age was 56 years , and 84 percent of patients had undergone debulking surgery . At a median follow-up of 28 months , the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone . The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 ( 95 percent confidence interval , 0.52 to 0.75 ; P<0.001 by the log-rank test ) . The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone . Concomitant treatment with radiotherapy plus temozolomide result ed in grade 3 or 4 hematologic toxic effects in 7 percent of patients . CONCLUSIONS The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma result ed in a clinical ly meaningful and statistically significant survival benefit with minimal additional toxicity |
13,290 | 28,617,801 | Methylpheni date increases the risks of decreased appetite , weight loss , and abdominal pain in children and adolescents with attention deficit hyperactivity disorder .
No differences in the risks of gastrointestinal adverse events according to type , dose , or duration of administration were found | OBJECTIVES To study in more depth the relationship between type , dose , or duration of methylpheni date offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review . | OBJECTIVE To evaluate the short-term efficacy and side effects associated with two methylpheni date hydrochloride ( MPH ) dosing patterns . METHODS Twenty-five boys with attention deficit hyperactivity disorder ( ADHD ) participated in a 5-week , triple-blind , placebo-controlled , crossover evaluation of MPH administered twice ( b.i.d . ) versus thrice ( t.i.d . ) per day ( mean dose = 8.8 + /- 5 mg , .30 + /- .1 mg/kg/dose ) . Four dosing conditions ( placebo , titration [ gradual increase to target dose ] , b.i.d . , and t.i.d . ) were used . Dependent measures obtained on a weekly basis included : parent and teacher ratings of child behavior , parent-child conflicts , parent report of stimulant side effects , child self-report of mood symptoms , a sleep log , laboratory measures of attention , and actigraphic recording of sleep activity . RESULTS All dosing conditions result ed in significant effects on ADHD symptoms when compared with baseline . Relative to placebo , t.i.d . dosing was characterized by improvement on the greatest number of behavioral measures , and both b.i.d . and t.i.d . were generally more effective than titration . Direct comparisons of b.i.d . and t.i.d . dosing revealed that t.i.d . was associated with greater improvement on the Conners Parent Rating Scale Impulsivity/Hyperactivity factor , with a similar marginally significant effect for the ADD-H Teacher Rating Scale Hyperactivity factor . The analysis of clinical ly significant change favored a three-times-a-day dosing schedule over placebo on both parent and teacher ratings of impulsivity/hyperactivity and attention . Compared with placebo , appetite suppression was rated , on average , as more severe in the t.i.d . and titration conditions , but not in the b.i.d . condition . However , the number of subjects who exhibited any or severe appetite suppression did not differ significantly between the b.i.d . and t.i.d . schedules . Although there was no difference in sleep duration for children on b.i.d . and t.i.d . schedules , total sleep time appeared to decrease slightly on t.i.d . relative to placebo according to both parent ratings and actigraphic assessment . There were no significant differences between b.i.d . and t.i.d . on any other side effects or sleep variables . CONCLUSIONS For many children with ADHD , t.i.d . dosing may be optimal . There are few differences in acute side effects between b.i.d . and t.i.d . MPH dosing . The dosing schedule should be selected according to the severity and time course of ADHD symptoms rather than in anticipation of dosing schedule-related side effects Background This study examined augmenting atomoxetine with extended-release methylpheni date in children whose attention-deficit/hyperactivity disorder ( ADHD ) previously failed to respond adequately to stimulant medication . Methods Children with ADHD and prior stimulant treatment ( N = 25 ) received atomoxetine ( 1.2 mg/kg/day ) plus placebo . After 4 weeks , patients who were responders ( n = 4 ) were continued on atomoxetine/placebo while remaining patients were r and omly assigned to either methylpheni date ( ATX/MPH ) ( 1.1 mg/kg/day ) or placebo augmentation ( ATX/PB ) for another 6 weeks . Patients and sites were blind to timing of active augmentation . Safety measures included vital signs , weight , and adverse events . Efficacy was assessed by ADHD rating scales . Results Categorical increases in vital signs occurred for 5 patients ( 3 patients in ATX/MPH , 2 patients in ATX/PBO ) . Sixteen percent discontinued the study due to AE , but no difference between augmentation groups . Atomoxetine treatment was efficacious on outcome measures ( P ≤ .001 ) , but methylpheni date did not enhance response . Conclusion Methylpheni date appears to be safely combined with atomoxetine , but conclusions limited by small sample . With atomoxetine treatment , 43 % of patients achieved normalization on ADHD ratings Abstract Hypotheses concerning unexpected , psychostimulant-related effects reported in previous studies were examined by separating behavioral/physical complaints highly specific to methylpheni date ( MPH ) from those that ( a ) may mimic core/ secondary symptoms of the disorder , or ( b ) are commonly reported by unmedicated children in the general population . Sixty-five children with attention-deficit/hyperactivity disorder ( ADHD ) participated in a double-blind , placebo-controlled , within-subject ( crossover ) experimental design and received a placebo and four MPH doses in counterbalanced order following baseline assessment . Behavioral and physical complaints were significantly higher under baseline relative to placebo and the four immediate-release MPH conditions ( 5 mg , 10 mg , 15 mg , and 20 mg ) across three symptom categories : ADHD core/ secondary symptoms ; symptoms commonly reported in the general population , including unmedicated children with ADHD ; and symptoms highly specific to MPH . No significant differences were found among active drug conditions . Past unexpected findings of psychostimulant effects in ADHD may be due to the inclusion of scale items that reflect core/ secondary features of ADHD and normally occurring behavioral/physical complaints in children OBJECTIVE To evaluate the efficacy and safety of osmotic-release methylpheni date ( OROS-MPH ) compared with placebo for attention-deficit/hyperactivity disorder ( ADHD ) , and the impact on substance treatment outcomes in adolescents concurrently receiving cognitive-behavioral therapy ( CBT ) for substance use disorders ( SUD ) . METHOD This was a 16-week , r and omized , controlled , multi-site trial of OROS-MPH + CBT versus placebo + CBT in 303 adolescents ( aged 13 through 18 years ) meeting DSM-IV diagnostic criteria for ADHD and SUD . Primary outcome measures included the following : for ADHD , clinician-administered ADHD Rating Scale ( ADHD-RS ) , adolescent informant ; for substance use , adolescent-reported days of use in the past 28 days . Secondary outcome measures included parent ADHD-RS and weekly urine drug screens ( UDS ) . RESULTS There were no group differences on reduction in ADHD-RS scores ( OROS-MPH : -19.2 , 95 % confidence interval [ CI ] , -17.1 to -21.2 ; placebo , -21.2 , 95 % CI , -19.1 to -23.2 ) or reduction in days of substance use ( OROS-MPH : -5.7 days , 95 % CI , 4.0 - 7.4 ; placebo : -5.2 days , 95 % CI , 3.5 - 7.0 ) . Some secondary outcomes favored OROS-MPH , including lower parent ADHD-RS scores at 8 ( mean difference = 4.4 , 95 % CI , 0.8 - 7.9 ) and 16 weeks ( mean difference = 6.9 ; 95 % CI , 2.9 - 10.9 ) and more negative UDS in OROS-MPH ( mean = 3.8 ) compared with placebo ( mean = 2.8 ; p = .04 ) . CONCLUSIONS OROS-MPH did not show greater efficacy than placebo for ADHD or on reduction in substance use in adolescents concurrently receiving individual CBT for co-occurring SUD . However , OROS-MPH was relatively well tolerated and was associated with modestly greater clinical improvement on some secondary ADHD and substance outcome measures . Clinical Trial Registration Information-Attention Deficit Hyperactivity Disorder ( ADHD ) in Adolescents with Substance Use Disorders ( SUD ) ; http://www . clinical trials.gov ; NCT00264797 The frequency and severity of 17 side effects presumably associated with stimulant medication were assessed during a rigorous , triple-blind , placebo-controlled , crossover evaluation of methylpheni date , 0.3 and 0.5 mg/kg twice a day , in 83 children with attention deficit hyperactivity disorder . Side effects were rated by parents and teachers at the end of each weekly drug condition . Three children ( 3.6 % ) had side effects that were sufficiently serious to warrant immediate discontinuation of medication . Parent ratings indicated that only the side effects of decreased appetite , insomnia , stomachaches , and headaches increased significantly in frequency and severity during the two active medication doses as compared with the placebo condition . Fewer than half of the children experienced these side effects and among those who did , ratings of mean severity remained in the mild range . Teacher ratings showed little change over drug conditions , except on ratings of staring , sadness , and anxiety , which declined with increasing dose of medication . Parent ratings indicated that only the side effects of decreased appetite , insomnia , stomachaches , and headaches increased significantly in frequency and severity during the two active medication doses as compared with the placebo condition . Fewer than half of the children experienced these side effects and among those who did , ratings of mean severity remained in the mild range . Teacher ratings showed little change over drug conditions , except on ratings of staring , sadness , and anxiety , which declined with increasing dose of medication . Surprisingly , a high frequency of these behavior side effects were reported during the placebo condition . Stimulant medication within this therapeutic range , therefore , results in few , generally mild side effects . ( ABSTRACT TRUNCATED AT 250 WORDS In clinical sample s , juvenile bipolar disorder ( JBPD ) is frequently accompanied by co-morbid attention-deficit/hyperactivity disorder ( ADHD ) . Clinical trials assessing combined psychopharmacological interventions in this population are scarce , and methylpheni date ( MPH ) may worsen manic symptoms . We conducted a r and omized crossover trial with MPH and placebo ( 2 weeks each ) combined with aripiprazole in children and adolescents ( n = 16 ; 8 - 17 years old ) with JBPD and ADHD who had a significant response in manic symptoms with aripiprazole but still presented clinical ly significant symptoms of ADHD . ADHD , manic , and depressive symptoms were assessed by means of st and ard scales . Fourteen out of the 16 subjects completed the trial . No significant differences between the effects of methylpheni date and placebo were detected in ADHD ( F(1 , 43.22 ) = 0.00 ; p = 0.97 ) or manic ( F(1 , 40.19 ) = 0.93 ; p = 0.34 ) symptoms . Significant improvement in depressive symptoms was observed in the MPH group ( F(1,19.03 ) = 7.75 ; p = 0.01 ) according to a secondary self-reported outcome measure . One patient using aripiprazole and MPH discontinued the trial due to the onset of a severe mixed episode . No other significant adverse events were observed . Although MPH did not worsen manic symptoms , it was not more effective than placebo in improving ADHD symptoms in children and adolescents with JBPD co-morbid with ADHD stabilized with aripiprazole . Further investigations are warranted . This study is registered at www . clinical trials.gov under the identifier NCT00305370 OBJECTIVE The purpose of this study was to investigate clinical gains from including both dextroamphetamine and methylpheni date in stimulant trials . METHOD Thirty-six medication-naïve children ages 9 - 14 years diagnosed with attention-deficit/hyperactivity disorder ( ADHD ) were enrolled for 6 weeks in a crossover trial , with 2 weeks of methylpheni date , dextroamphetamine , and placebo , in a r and omly assigned , counterbalanced sequence . Outcome measures constituted a computer-based continuous performance test combined with a motion tracking system ( Qb Test ) and an ADHD question naire rated by parents and teachers . RESULTS Group analyses found significant treatment effects of similar size for the two stimulants on both outcome measures . Single-subject analyses revealed that each stimulant produced a favourable response in 26 children ; however , an individual child frequently responded qualitatively or quantitatively differently to the two stimulants . By including both stimulants in the trial , the number of favorable responders increased from 26 ( 72 % ) to 33 ( 92 % ) . In children with favorable responses of unequal strength to the two stimulants , a shift from inferior drug to best drug was associated with a 64 % mean increase in the overall response strength score , as measured by the ADHD question naire . CONCLUSIONS The likelihood of a favorable response and optimal response strength is increased by including both stimulants in the stimulant trial . The study was first registered in clinical trials 28 September 2010 . Clinical Trials.gov Identifier : NCT01220440 OBJECTIVE To determine the efficacy and safety of clonidine , used alone or in combination with methylpheni date , in treating attention-deficit/hyperactivity disorder ( ADHD ) . METHOD A 16-week , r and omized , double-blind , placebo-controlled clinical trial was conducted in 122 children , ages 7 to 12 , with any subtype of ADHD , r and omly assigned to clonidine , methylpheni date , clonidine in combination with methylpheni date , or placebo according to a 2 x 2 factorial design . In two successive 4-week titration periods , clonidine ( or matching placebo ) and added methylpheni date ( or matching placebo ) were adjusted to optimal doses and then continued for 8 weeks . The primary efficacy outcome was changed from baseline to week 16 on the Conners Teachers Abbreviated Symptom Question naire . Secondary outcomes included the Conners Abbreviated Symptom Question naire for Parents and the Children 's Global Assessment Scale . RESULTS On the Conners Teachers Abbreviated Symptom Question naire , clonidine was not found to improve ADHD symptoms , whereas subjects treated with methylpheni date showed significant improvement compared to those not treated with methylpheni date . Subjects treated with clonidine had greater improvements on the Conners Abbreviated Symptom Question naire for Parents and Children 's Global Assessment Scale , but also a higher rate of sedation compared with subjects not treated with clonidine . CONCLUSIONS Based on the Conners Teachers Abbreviated Symptom Question naire , methylpheni date offers the best combination of efficacy and tolerability for ADHD . Clonidine was well tolerated despite the frequency of sedation and did offer some benefit Published evidence suggests that aspects of trial design lead to biased intervention effect estimates , but findings from different studies are inconsistent . This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials . Outcome measures were classified as " mortality , " " other objective , " " or subjective , " and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity . Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear ( vs. adequate ) r and om-sequence generation ( ratio of odds ratios , 0.89 [ 95 % credible interval { CrI } , 0.82 to 0.96 ] ) and with inadequate or unclear ( vs. adequate ) allocation concealment ( ratio of odds ratios , 0.93 [ CrI , 0.87 to 0.99 ] ) . Lack of or unclear double-blinding ( vs. double-blinding ) was associated with an average of 13 % exaggeration of intervention effects ( ratio of odds ratios , 0.87 [ CrI , 0.79 to 0.96 ] ) , and between-trial heterogeneity was increased for such studies ( SD increase in heterogeneity , 0.14 [ CrI , 0.02 to 0.30 ] ) . For each characteristic , average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes , with little evidence of bias in trials with objective and mortality outcomes . This study is limited by incomplete trial reporting , and findings may be confounded by other study design characteristics . Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes |
13,291 | 22,057,019 | There was little evidence of EPS-differences between SGAs , possibly reflecting use of low doses .
We conclude that SGAs offer an EPS advantage over FGAs in FEP though the evidence largely relates to comparisons with haloperidol . | This systematic review aim ed to determine whether the risk of extrapyramidal side effects ( EPS ) differed between antipsychotic drugs used in first episode psychosis ( FEP ) . | Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics , and to be more sensitive to developing extrapyramidal side-effects . The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol . Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms . Patients were r and omly assigned under double-blind conditions to receive risperidone ( n=143 ) or haloperidol ( n=146 ) for 8 wk . The primary efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom Scale ( PANSS ) negative score between treatment groups ; secondary efficacy criteria were changes on the PANSS total score and other PANSS subscores , and several other measures of psychopathology and general functioning . The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of extrapyramidal side-effects measured with the Simpson-Angus Scale ( SAS ) compared between treatment groups . The main hypothesis was that risperidone would be superior in terms of improving negative symptoms and lowering the risk of extrapyramidal symptoms . Secondary tolerability criteria were the other extrapyramidal symptoms , measured with the Hillside Akathisia Scale ( HAS ) and the Abnormal Involuntary Movement Scale ( AIMS ) . The average mean daily doses were 3.8 mg ( s.d.=1.5 ) for risperidone and 3.7 mg ( s.d.=1.5 ) for haloperidol . There were similar , significant improvements in both treatment groups in the primary and secondary efficacy criteria . At week 8 nearly all scores of extrapyramidal side-effects indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with risperidone [ SAS : risperidone 36.5 % of patients ; haloperidol 51.5 % of patients ; likelihood ratio test , chi2(1)=7.8 , p=0.005 ] . There were significantly fewer drop-outs [ risperidone n=55 , drop-out rate=38.5 % ; haloperidol n=79 , drop-out rate=54.1 % , chi2(1)=7.1 , p=0.009 ] and a longer non-discontinuation time [ risperidone : average of 50.8 d to drop-out ; haloperidol : average of 44.0 d to drop-out ; log rank test , chi2(1)=6.4 , p=0.011 ] in the risperidone group . Risperidone and haloperidol appear to be equally effective in treating negative and other symptoms of first-episode schizophrenia . Risperidone has better extrapyramidal tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients BACKGROUND The differential effects of so-called ' first- and second generation ' antipsychotic medications , when given in the first episode , on the long-term outcome of schizophrenia remain to be eluci date d. AIMS We compared the 9-year outcomes of individuals initially r and omised to clozapine or chlorpromazine . METHOD One-hundred and sixty individuals with treatment-naive , first episode schizophrenia or schizophreniform disorder in a mental health centre in Beijing , China were r and omised to clozapine or chlorpromazine treatment for up to 2 years , followed by up to an additional 7 years of naturalistic treatment . The primary outcome was remission status for individuals in each group . RESULTS Individuals in both groups spent essentially equal amounts of time in each clinical state over the follow-up time period(remission , 78 % ; intermediate , 8 % ; relapse , 14 % ) . There were no significant differences on other measures of illness severity . The clozapine group was more likely than the chlorpromazine group to remain on the medication to which they were originally assigned ( 26 % v. 10 % , P = 0.01 ) . There were no significant differences between the two groups on other secondary efficacy outcomes . CONCLUSIONS These findings support the comparability in effectiveness between antipsychotic medications but with slightly greater tolerability of clozapine in the treatment of first-episode psychosis An international , multicenter , double-blind study was conducted in 183 patients with a first psychotic episode ( provisional schizophreniform disorder or schizophrenia ; DSM-III-R ) treated with flexible doses of risperidone or haloperidol for 6 weeks . At endpoint , 63 percent of risperidone-treated patients and 56 percent of haloperidol-treated patients were clinical ly improved ( > or = 50 % reduction in Positive and Negative Syndrome Scale total scores ) . Risperidone was better tolerated than haloperidol : the severity of extrapyramidal symptoms was significantly lower in the risperidone-treated patients ; significantly fewer risperidone-treated patients required antiparkinsonian medication ; and significantly fewer discontinued treatment because of adverse events . A post hoc analysis revealed that low doses of these antipsychotics were efficacious in some patients . Furthermore , the severity of extrapyramidal symptoms and the use of antiparkinsonian medications were significantly lower in patients receiving low doses ( maximum , < or = 6 mg/day ) than high doses ( maximum , > 6 mg/day ) of risperidone or haloperidol . These findings are consistent with the suggestion that patients with a first psychotic episode may require low doses of antipsychotic medications . Studies design ed specifically to compare low and high doses of antipsychotics are warranted to help optimize treatment for these patients The present study examined basal ganglia volumes in drug-naive first-episode schizophrenic patients before and after treatment with either a specific typical or atypical antipsychotic compound . Sixteen antipsychotic drug-naive and three minimally medicated first-episode schizophrenic patients and 19 matched controls participated . Patients were r and omly assigned to treatment with either low doses of the typical antipsychotic drug , zuclopenthixol , or the atypical compound , risperidone . High-resolution magnetic resonance imaging ( MRI ) scans were obtained in patients before and after 12 weeks of exposure to medication and in controls at baseline . Cau date nucleus , nucleus accumbens , and putamen volumes were measured . Compared with controls , absolute volumes of interest ( VOIs ) were smaller in patients at baseline and increased after treatment . However , with controls for age , gender and whole brain or intracranial volume , the only significant difference between patients and controls was a Hemisphere x Group interaction for the cau date nucleus at baseline , with controls having larger left than right cau date nuclei and patients having marginally larger right than left cau date volumes . Within patients , the two medication groups did not differ significantly with respect to volume changes after 3 months of low dose treatment in any of the VOIs . Nevertheless , when medication groups were examined separately , a significant volume increase in the putamen was evidence d in the risperidone group . The altered asymmetry in cau date volume in patients suggests intrinsic basal ganglia pathology in schizophrenia , most likely of neurodevelopmental origin OBJECTIVE R and omized controlled drug trials have demonstrated that antipsychotic medication is effective to rapidly improve psychotic symptomatology in first-episode psychosis . However , these results may not be generalizable to routine clinical practice . We evaluated the effectiveness , tolerability , and safety of olanza-pine , risperidone , and haloperidol in individuals with first-episode nonaffective psychosis who are representative of clinical practice and who are treated in routine clinical setting s. METHOD 172 patients participated in a practical clinical trial and were r and omly assigned to haloperidol ( N = 56 ) , risperidone ( N = 61 ) , and olanzapine ( N = 55 ) . The mean modal daily doses were 5.4 mg/day for halo-peridol , 4 mg/day for risperidone , and 15.3 mg/day for olanzapine ; 98.3 % of subjects were drug naive at baseline . Data from clinical measures of treatment response and tolerability and safety data from the 6-week acute phase of a large epidemiologic and longitudinal ( February 2001 to February 2005 ) intervention program of first-episode psychosis ( schizophrenia spectrum disorders , DSM-IV criteria ) are reported . RESULTS All 3 treatments showed similar effectiveness in reducing the severity of general , negative , and positive symptomatology after 6 weeks of treatment , as reported by mean change in total Clinical Global Impressions-Severity of Illness scale , Brief Psychiatric Rating Scale ( BPRS ) , Scale for the Assessment of Positive Symptoms , and Scale for the Assessment of Negative Symptoms scores between baseline and 6 weeks . The proportion of study subjects responding , defined as 40 % or greater BPRS total score improvement from baseline , was 57.1 % ( N = 32 of 56 ) haloperidol , 52.5 % ( N = 32 of 61 ) risperidone , and 63.6 % ( N = 35 of 55 ) olanzapine , with no statistical differences among groups . The frequency of extrapyramidal symptoms ( chi(2 ) = 24.519 ; p < .001 ) and concomitant anticholinergic medication use ( chi(2 ) = 57.842 ; p < .0001 ) was greater with haloperidol than olanzapine or risperidone . Olanzapine-treated patients had significantly more weight gain compared with the haloperidol and risperidone groups ( p < .001 ) . CONCLUSION Relatively low doses of haloperidol , risperidone , and olanzapine are equally effective for the acute treatment of first-episode nonaffective psychosis under usual conditions of real clinical practice BACKGROUND Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia ; however , their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated . We aim ed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol , in first-episode schizophrenia . METHODS We did an open r and omised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites , in 14 countries . Eligible patients were aged 18 - 40 years , and met diagnostic criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder . 498 patients were r and omly assigned by a web-based online system to haloperidol ( 1 - 4 mg per day ; n=103 ) , amisulpride ( 200 - 800 mg per day ; n=104 ) , olanzapine ( 5 - 20 mg per day ; n=105 ) , quetiapine ( 200 - 750 mg per day ; n=104 ) , or ziprasidone ( 40 - 160 mg per day ; n=82 ) ; follow-up was at 1 year . The primary outcome measure was all-cause treatment discontinuation . Patients and their treating physicians were not blinded to the assigned treatment . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N68736636 . FINDINGS The number of patients who discontinued treatment for any cause within 12 months was 63 ( Kaplan-Meier estimate 72 % ) for haloperidol , 32 ( 40 % ) for amisulpride , 30 ( 33 % ) for olanzapine , 51 ( 53 % ) for quetiapine , and 31 ( 45 % ) for ziprasidone . Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride ( hazard ratio [ HR ] 0.37 , [ 95 % CI 0.24 - 0.57 ] ) , olanzapine ( HR 0.28 [ 0.18 - 0.43 ] ) , quetiapine ( HR 0.52 [ 0.35 - 0.76 ] ) , and ziprasidone ( HR 0.51 [ 0.32 - 0.81 ] ) . However , symptom reductions were virtually the same in all the groups , at around 60 % . INTERPRETATION This pragmatic trial suggests that clinical ly meaningful antipsychotic treatment of first-episode of schizophrenia is achievable , for at least 1 year . However , we can not conclude that second-generation drugs are more efficacious than is haloperidol , since discontinuation rates are not necessarily consistent with symptomatic improvement BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P<0.001 ) or risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism OBJECTIVE Few long-term studies have compared the efficacy and safety of typical and atypical antipsychotic medications directly in patients with a first episode of psychosis who met the criteria for schizophrenia or a related psychotic disorder . This study compared the acute and long-term effectiveness of haloperidol with that of olanzapine in patients with first-episode psychosis in a large , controlled clinical trial . METHOD Patients with first-episode psychosis ( N=263 ) were r and omly assigned under double-blind conditions to receive haloperidol or olanzapine and were followed for up to 104 weeks . Domains measured included psychopathology , psychosocial variables , neurocognitive functioning , and brain morphology and metabolism . This report presents data from clinical measures of treatment response and safety data from the 12-week acute treatment phase . RESULTS Haloperidol and olanzapine were associated with substantial and comparable baseline-to-endpoint reductions in symptom severity , which did not differ significantly in last-observation-carried-forward analyses . However , in a mixed-model analysis , olanzapine-treated subjects had significantly greater decreases in symptom severity as measured by the Positive and Negative Syndrome Scale total score and negative and general scales and by the Montgomery-Asberg Depression Rating Scale but not as measured by the Positive and Negative Syndrome Scale positive scale and by the Clinical Global Impression severity rating . Olanzapine-treated patients experienced a lower rate of treatment-emergent parkinsonism and akathisia but had significantly more weight gain , compared with the haloperidol-treated patients . Overall , significantly more olanzapine-treated subjects than haloperidol-treated subjects completed the 12-week acute phase of the study ( 67 % versus 54 % ) . CONCLUSIONS As expected on the basis of previous studies , both olanzapine and haloperidol were effective in the acute reduction of psychopathological symptoms in this group of patients with first-episode psychosis . However , olanzapine had several relative advantages in therapeutic response . Although the nature of adverse events differed between the two agents , retention in the study was greater with olanzapine . Retention in treatment is important in this patient population , given their risk of relapse . Longer-term results are needed to determine whether treatment with atypical antipsychotics results in superior outcomes for a first episode of schizophrenia OBJECTIVE It has been hypothesized that the morbidity and mortality associated with schizophrenia can be prevented by providing effective treatment during the first episode of psychosis . Hence , the authors examined patients with first-episode psychosis to determine the efficacy and safety of olanzapine and haloperidol treatment . METHOD A sub population of first-episode patients ( N=83 ) from a large prospect i ve , multicenter , international , double-blind , 6-week acute treatment study was evaluated . These patients were selected from a pool of 1,996 patients who had a DSM-III-R diagnosis of schizophrenia , schizoaffective disorder , or schizophreniform disorder and who also met the following criteria : 1 ) the length of their current psychotic episode had to be 5 or fewer years , and 2 ) patients had to be 45 years of age or younger at onset of first psychotic symptoms . RESULTS Compared to haloperidol , olanzapine showed a statistically significantly greater reduction in the Brief Psychiatric Rating Scale ( BPRS ) total and negative scores and in the Positive and Negative Syndrome Scale total and positive scores . Clinical response ( defined as 40 % or greater improvement in BPRS total score from baseline ) was also statistically significantly higher in olanzapine-treated patients ( 67.2 % ) than in haloperidol-treated patients ( 29.2 % ) . Olanzapine-treated patients further showed statistically significant improvements in the Simpson-Angus scale and Barnes Akathisia Scale scores , while haloperidol-treated patients showed a worsening on both measures . Compared to olanzapine-treated multiple-episode patients in the parent study , olanzapine-treated first-episode patients achieved an even statistically significantly higher response . Haloperidol-treated first-episode patients experienced statistically significantly more extrapyramidal symptoms than haloperidol-treated multiple-episode patients . CONCLUSIONS In patients experiencing first-episode psychosis , olanzapine had a risk-benefit profile significantly superior to that of haloperidol . The study results suggest that novel antipsychotic agents such as olanzapine should be considered as a preferred option in first-episode psychosis , on the basis of both safety and efficacy advantages The purported advantages of second-generation or ‘ atypical ’ antipsychotics relative to first-generation antipsychotics have not been examined in patients with a first episode of schizophrenia . This flexible-dose study examined efficacy and safety in a r and omized , double-blind , 52-week trial , comparing chlorpromazine ( CPZ ) and clozapine ( CLZ ) in treatment naive patients experiencing their first episode of schizophrenia . In all , 160 in patients with first-episode schizophrenia or schizophreniform disorder were r and omized to CPZ or CLZ and followed them for 52 weeks or until dropout . The primary efficacy measure was time to first remission and proportion of time remaining in remission . The analysis was supplemented by comparisons on a profile of clinical symptoms and side effects . Of these first-episode patients , 80 % achieved remission within 1 year ( 79 % CPZ , 81 % CLZ ) . The Kaplan – Meier estimated median time to first remission was 8 weeks for CLZ vs 12 weeks for CPZ ( χ2(1)=5.56 , p=0.02 ) . Both the rate of first achieving remission and the odds for being in remission during the trial were almost doubled for the CLZ group in comparison with the CPZ group . At 12 weeks , CLZ was superior on many rating scale measures of symptom severity while CPZ was not superior on any . These symptom differences remained significant when controlling for EPS differences . By 52 weeks many of the symptom differences between groups were no longer significantly different . Generally , CLZ produced fewer side effects than CPZ , particularly extrapyramidal side effects . There was no significant difference between treatments in weight change or glucose metabolism . For each prior year of untreated psychosis , there was a 15 % decrease in the odds of achieving remission ( OR=0.85 ; CI 0.75–0.95 ) . A high proportion of first-episode patients remitted within 1 year . We detected no difference in the proportion of first-episode patients receiving CLZ or CPZ that achieved remission . However , first-episode patients receiving CLZ remitted significantly faster and remained in remission longer than subjects receiving CPZ . While the CLZ group showed significantly less symptomatology on some measures and fewer side effects at 12 weeks , the two treatment groups seemed to converge by 1 year . Longer duration of untreated psychosis was associated with lower odds of achieving remission OBJECTIVES To describe the incidence of tardive dyskinesia ( TD ) in the Yale TD Study and to identify demographic , treatment , and clinical risk factors for TD occurrence . DESIGN An ongoing prospect i ve cohort study in which subjects have been examined every 6 months since 1985 . SETTING The outpatient division of the Connecticut Mental Health Center in New Haven . SUBJECTS Three hundred ninety-eight adult out patients who had been maintained with neuroleptics for 3 months to 33 years at intake and who were free of persistent TD at intake with no history of persistent TD movements . OUTCOME MEASURE New cases of persistent TD were defined as the presence of mild or more severe dyskinetic movements at two successive follow-up visits , using the Abnormal Involuntary Movement Scale . RESULTS As of July 1 , 1990 , there were 62 new persistent cases of TD , yielding an average incidence rate of 0.053 per year and a 5-year risk of 20 % . The TD rate was positively affected by age , being nonwhite , and neuroleptic dose , and it was inversely affected by years of previous exposure . Little or no effects were found for age at first neuroleptic exposure , type of neuroleptic , use of other psychiatric medications , and psychiatric diagnosis . CONCLUSIONS For out patients maintained for many years with neuroleptics , dose should be minimized to reduce the risk of TD . This strategy does not appear to be negated by prescribing frequent changes in dosage . Although the TD rate is greatest during the first 5 years of neuroleptic treatment , new persistent cases continue to occur many years after first exposure OBJECTIVE Second-generation antipsychotics ( SGAs ) have proven superior to first-generation antipsychotics regarding relapse prevention , mainly in multiple-episode patients . Practice guidelines recommend SGAs as first-line treatment particularly in first-episode patients , although evidence for this group is still limited . Accordingly , the hypothesis of whether 1-year relapse rate in first-episode schizophrenia under maintenance treatment with risperidone is lower compared to haloperidol in low dose was tested . METHOD Between November 2000 and May 2004 , 1372 patients had been screened for eligibility in the inpatient facilities of 13 German psychiatric university hospitals . 159 remitted patients were enrolled after treatment of an acute first episode of schizophrenia according to ICD-10 F20 criteria . In the r and omized controlled trial , double-blind antipsychotic treatment with risperidone or haloperidol was maintained in a targeted dose of 2 to 4 mg/day for 1 year . 151 patients were eligible for analysis . For 127 patients , this was a continuation trial after 8 weeks of r and omized , double-blind , acute treatment with the same drugs ; 24 patients were additionally r and omly assigned after open acute treatment . RESULTS With both antipsychotics ( risperidone , N = 77 ; haloperidol , N = 74 ) , no relapse evolved . Additionally , according to 2 post hoc defined measures of " marked clinical deterioration , " significant differences occurred neither in the 2 respective deterioration rates ( risperidone = 9%/23 % ; haloperidol = 8%/22 % ) nor in time until deterioration . Both antipsychotics were equally effective regarding significant symptom reduction and improvement in quality of life . Extrapyramidal symptoms were slightly higher with haloperidol . The overall dropout rate of 68 % , however , was not significantly different between the 2 drug groups . CONCLUSION Against the background of an overall favorable outcome , the hypothesized difference between risperidone and low-dose haloperidol regarding relapse prevention could not be supported for this sample of patients with first-episode schizophrenia . Possible design -related reasons for this finding are discussed . With regard to the high dropout rate , special programs are needed to keep schizophrenia patients who are in their early acute and postacute illness course in effective and safe treatment . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier : NCT00159081 OBJECTIVE This 52-week r and omized , double-blind , flexible-dose , multicenter study evaluated the overall effectiveness ( as measured by treatment discontinuation rates ) of olanzapine , quetiapine , and risperidone in patients early in the course of psychotic illness . METHOD Patients were r and omly assigned to treatment with olanzapine ( 2.5 - 20 mg/day ) , quetiapine ( 100 - 800 mg/day ) , or risperidone ( 0.5 - 4 mg/day ) administered in twice-daily doses . Statistical analyses tested for noninferiority in all-cause treatment discontinuation rates up to 52 weeks ( primary outcome measure ) based on a prespecified noninferiority margin of 20 % . RESULTS A total of 400 patients were r and omly assigned to treatment with olanzapine ( N=133 ) , quetiapine ( N=134 ) , or risperidone ( N=133 ) . The mean modal prescribed daily doses were 11.7 mg for olanzapine , 506 mg for quetiapine , and 2.4 mg for risperidone . At week 52 , all-cause treatment discontinuation rates were 68.4 % , 70.9 % , and 71.4 % for olanzapine , quetiapine , and risperidone , respectively . Reductions in total score on the Positive and Negative Syndrome Scale ( PANSS ) were similar for the three treatment groups , but reductions in PANSS positive subscale scores were greater in the olanzapine group ( at 12 weeks and at 52 weeks or withdrawal from study ) and the risperidone group ( at 12 weeks ) . The most common elicited adverse events for olanzapine were drowsiness ( 53 % ) , weight gain ( 51 % ) , and insomnia ( 38 % ) ; for quetiapine , drowsiness ( 58 % ) , increased sleep hours ( 42 % ) , and weight gain ( 40 % ) ; and for risperidone , drowsiness ( 50 % ) , menstrual irregularities in women ( 47 % ) , and weight gain ( 41 % ) . CONCLUSIONS Olanzapine , quetiapine , and risperidone demonstrated comparable effectiveness in early-psychosis patients , as indicated by similar rates of all-cause treatment discontinuation OBJECTIVE This international , multicenter double-blind trial was design ed to compare the therapeutic profile of an atypical antipsychotic , olanzapine , with that of a conventional dopamine D2 antagonist , haloperidol . METHOD A total of 1,996 patients at 174 sites in Europe and North America were r and omly assigned to treatment with olanzapine ( N = 1,336 ) or haloperidol ( N = 660 ) over 6 weeks . The primary efficacy analysis involved the mean change from baseline to endpoint in total scores on the Brief Psychiatric Rating Scale ( BPRS ) . Secondary analyses included comparisons of the mean change in positive and negative symptoms , comorbid depression , extrapyramidal symptoms , and overall drug safety . RESULTS Olanzapine demonstrated clinical results superior to those of haloperidol on overall improvement according to the BPRS and on every secondary measure , including depression . Olanzapine was also associated with significantly fewer discontinuations of treatment due to lack of drug efficacy or adverse events . Substantially more olanzapine-treated patients ( 66.5 % ) than haloperidol-treated patients ( 46.8 % ) completed 6 weeks of therapy . Statistically significant advantages of olanzapine treatment were related to 1 ) change in negative symptoms , 2 ) extrapyramidal symptom profile , 3 ) effect on prolactin levels , and 4 ) response rate . CONCLUSIONS Olanzapine shows a superior and broader spectrum of efficacy in the treatment of schizophrenic psychopathology , with a substantially more favorable safety profile , than haloperidol . It meets several of the criteria for a novel atypical antipsychotic agent Few studies have assessed the comparative efficacy and safety of atypical and typical antipsychotic medications in patients within their first episode of psychosis . This study examined the effectiveness of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol in patients experiencing their first episode of a schizophrenia-related psychotic disorder over a 2-year treatment period . Two hundred and sixty-three patients were r and omized to olanzapine or haloperidol in a doubleblind , multisite , international 2-year study . Clinical symptoms and side effects were assessed at baseline and longitudinally following r and omization for the duration of the study . Olanzapine and haloperidol treatment were both associated with substantial and comparable reductions in symptom severity ( the primary outcome measure ) over the course of the study . However , the treatment groups differed on two secondary efficacy measures . Patients were less likely to discontinue treatment with olanzapine than with haloperidol : mean time ( in days ) in the study was significantly greater for those treated with olanzapine compared to haloperidol ( 322.09 vs. 230.38 , p<0.0085 ) . Moreover , remission rates were greater in patients treated with olanzapine as compared to those treated with haloperidol ( 57.25 % vs. 43.94 % , p<0.036 ) . While extrapyramidal side effects were greater in those treated with haloperidol , weight gain , cholesterol level and liver function values were greater in patients treated with olanzapine . The data from this study suggest some clinical benefits for olanzapine as compared to haloperidol in first episode patients , which must be weighed against those adverse effects that are more likely with olanzapine The aim of this study was to investigate the long-term effectiveness and efficacy of haloperidol , risperidone and olanzapine in first-episode schizophrenia-spectrum disorders . This was a prospect i ve , r and omized , open-label study . Data for the present investigation were obtained from a large epidemiological and 3-year longitudinal intervention programme of first-episode psychosis conducted at the University Hospital Marques de Valdecilla , Sant and er , Spain . One hundred and seventy-four patients were r and omly assigned to haloperidol ( N = 56 ) , olanzapine ( N = 55 ) , or risperidone ( N = 63 ) and followed up for 1 year . The primary effectiveness measure was all causes of treatment discontinuation . Effectiveness analyses were based on intend-to-treat population s. In addition , an analysis based on per protocol population s was conducted in the analysis for clinical efficacy . The treatment discontinuation rate for any cause was higher with haloperidol than with risperidone and olanzapine ( χ2 = 8.517 ; p = 0.014 ) . The difference in discontinuation rate between risperidone and olanzapine was not significant ( χ2 = 0.063 ; p = 0.802 ) . There were no significant advantages of any of the three treatments in reducing the severity of psychopathology . Risperidone and olanzapine demonstrated higher effectiveness relative to haloperidol , but the three antipsychotics were equally effective in reducing the severity of psychopathology . Specific clinical programmes and the use of second-generation antipsychotics may enhance the effectiveness of antipsychotic treatments BACKGROUND Recent literature documents a stronger association between nonfasting triglycerides ( TG ) and cardiovascular risk compared to fasting TG . Given concerns over antipsychotic effects on serum TG , this analysis explored changes in nonfasting TG in phase 1 of the CATIE Schizophrenia Trial . METHODS Change in nonfasting TG , adjusted for baseline value , was compared between antipsychotic treatment groups using subjects with nonfasting laboratory assessment s at baseline and 3 months . RESULTS Among the 246 subjects there were significant treatment differences in 3-month change from baseline ( p=0.009 ) . The greatest increases in median and adjusted mean nonfasting TG levels were seen among those r and omized to quetiapine ( mean+54.7 mg/dl , median+26 mg/dl ) and olanzapine ( mean+23.4 mg/dl , median+26.5 mg/dl ) , while ziprasidone was neutral ( mean+0.0 mg/dl , median+8 mg/dl ) , and decreases were seen with risperidone ( mean -18.4 mg/dl , median -6.5 mg/dl ) and perphenazine ( mean -1.3 mg/dl , median -22 mg/dl ) . Pairwise comparisons indicated a significant between-group difference for perphenazine vs. olanzapine ( p=0.002 ) and a trend for perphenazine vs. quetiapine ( p=0.006 ) . CONCLUSIONS This analysis provides further evidence for differential antipsychotic metabolic liabilities , and confirms signals for the effects of olanzapine and quetiapine on serum TG seen in earlier CATIE analyses . Future consensus recommendations will clarify the role of nonfasting TG monitoring in routine clinical practice OBJECTIVE The first episode of psychotic illness is a key intervention point . The initial experience with medication can affect willingness to accept treatment . Further , relapse prevention is a treatment cornerstone during the first years of illness because active psychotic illness may affect lifetime outcomes . Thus , initial treatment of active symptoms and subsequent relapse prevention are central goals of pharmacotherapy . This study compared long-term effectiveness of risperidone versus haloperidol in first-episode psychosis patients . METHOD First-episode psychosis patients ( N=555 , mean age=25.4 years ) participated in a double-blind , r and omized , controlled flexible-dose trial that compared risperidone ( mean modal dose=3.3 mg ) and haloperidol ( mean modal dose=2.9 mg ) . The median treatment length was 206 days ( maximum=1,514 ) . RESULTS Positive and Negative Syndrome Scale scores and Clinical Global Impression ratings improved significantly relative to baseline , with no significant differences between groups . Three-quarters of the patients achieved initial clinical improvement , defined as > 20 % reduction in total Positive and Negative Syndrome Scale score . However , among those who achieved clinical improvement , 42 % of the risperidone group experienced a relapse compared with 55 % of the haloperidol group . The median time to relapse was 466 days for risperidone-treated subjects and 205 days for those given haloperidol . These differences were statistically significant based on Kaplan-Meier survival analysis . Adverse effects distinguished the treatments : there were significantly more extrapyramidal signs and symptoms and adjunctive medication use in the haloperidol group and greater prolactin elevation in the risperidone group . There was less weight gain with haloperidol initially but no significant differences between groups at endpoint . CONCLUSIONS Relatively low doses of antipsychotic drugs lead to significant symptom amelioration in the majority of first-episode psychosis patients . In the long term , risperidone prevents relapse in more patients and for a longer time and also induces less abnormal movements than haloperidol OBJECTIVE The authors compared 4-month treatment outcomes for olanzapine versus risperidone in patients with first-episode schizophrenia spectrum disorders . METHOD One hundred twelve subjects ( 70 % male ; mean age=23.3 years [ SD = 5.1 ] ) with first-episode schizophrenia ( 75 % ) , schizophreniform disorder ( 17 % ) , or schizoaffective disorder ( 8 % ) were r and omly assigned to treatment with olanzapine ( 2.5 - 20 mg/day ) or risperidone ( 1 - 6 mg/day ) . RESULTS Response rates did not significantly differ between olanzapine ( 43.7 % , 95 % CI=28.8%-58.6 % ) and risperidone ( 54.3 % , 95 % CI=39.9%-68.7 % ) . Among those responding to treatment , more subjects in the olanzapine group ( 40.9 % , 95 % CI=16.8%-65.0 % ) than in the risperidone group ( 18.9 % , 95 % CI=0%-39.2 % ) had subsequent ratings not meeting response criteria . Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications . Extrapyramidal symptom severity scores were 1.4 ( 95 % CI=1.2 - 1.6 ) with risperidone and 1.2 ( 95 % CI=1.0 - 1.4 ) with olanzapine . Significantly more weight gain occurred with olanzapine than with risperidone : the increase in weight at 4 months relative to baseline weight was 17.3 % ( 95 % CI=14.2%-20.5 % ) with olanzapine and 11.3 % ( 95 % CI=8.4%-14.3 % ) with risperidone . Body mass index at baseline and at 4 months was 24.3 ( 95 % CI=22.8 - 25.7 ) versus 28.2 ( 95 % CI=26.7 - 29.7 ) with olanzapine and 23.9 ( 95 % CI=22.5 - 25.3 ) versus 26.7 ( 95 % CI=25.2 - 28.2 ) with risperidone . CONCLUSIONS Clinical outcomes with risperidone were equal to those with olanzapine , and response may be more stable . Olanzapine may have an advantage for motor side effects . Both medications caused substantial rapid weight gain , but weight gain was greater with olanzapine A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors Sixty-two first-episode psychotic patients who were neuroleptic-naive were studied to examine predictors of acute dystonia after treatment with haloperidol . Twenty-three patients developed dystonia , two of them despite being treated with biperiden . Biperiden significantly prevented dystonic reactions . Dystonia development was significantly related to younger age , severity of illness , and negative symptoms at baseline and showed a trend to be related to positive symptoms as well . No significant effect of gender or diagnosis was found . The authors suggest that young , severely ill patients in their first psychotic episode who have never been treated with neuroleptics might be at higher risk to develop dystonia |
13,292 | 24,210,066 | This review concluded that chronic statin user may be less prone to contrast-induced nephropathy ( CIN ) compared with statin non-users .
Short-term high dose statin administration may also reduce the incidence of CIN in statin naïve patients .
This renoprotective effect of statins against CIN is seen in low risk patients with normal kidney function or mild kidney dysfunction , but probably not in patients with moderate to severe renal dysfunction . | Drug-induced nephrotoxicity ( DIN ) accounts for up to 60 % of hospital acquired acute kidney injury with considerable morbidity and mortality .
Several efforts have been made to reduce drug-induced nephrotoxicity ; however , DIN remains a matter of concern .
Statins with their antioxidant , anti-inflammatory and anti-apoptotic effects may have the potential to protect kidney against DIN .
The present review evaluated all of the available in vitro and in vivo studies that examined the use of statins as renoprotective agents against nephrotoxic drugs . | Contrast-induced nephropathy ( CIN ) is an important cause of mortality and morbidity in patients undergoing angiography . This study investigated whether statins decrease incidence of CIN in the setting of percutaneous coronary intervention ( PCI ) and evaluated the influence of such potential benefit on long-term outcome . Four-hundred thirty-four patients undergoing PCI were prospect ively enrolled and followed up to 4 years . Patients were stratified according to preprocedural statin therapy ( 260 statin treated , 174 statin naive ) . CIN was defined as a postprocedural increase in serum creatinine of > or=0.5 mg/dl or>25 % from baseline . Follow-up assessment included 4-year occurrence of major adverse cardiac events . Statin-treated patients had a significantly lower incidence of CIN ( 3 % vs 27 % , p<0.0001 ; 90 % risk decrease ) and had better postprocedural creatinine clearance ( 80+/-20 vs 65+/-16 ml/min , p<0.0001 ) . Benefit of statin before treatment was observed in all subgroups , except in patients with a pre-existing creatinine clearance<40 ml/min . During follow-up , CIN was a predictor of poorer outcome ; 4-year survival free of major adverse cardiac events was highest in statin-treated patients without CIN ( 95 % , p < or=0.015 ) and lowest in statin-naive patients with CIN ( 53 % , p < or=0.018 ) . In conclusion , patients receiving statins before PCI have a significant decrease of CIN ; this early protective effect translates into better long-term event-free survival . These results may lend further support to utilization of statins as adjuvant pharmacologic therapy before PCI Contrast-induced nephropathy limits the outcomes of percutaneous coronary intervention ( PCI ) . The present study compared the protective effects of different statin doses on renal function . A total of 228 patients with acute coronary syndrome undergoing selective PCI were r and omly divided into simvastatin 20-mg group ( S20 , n = 115 ) and simvastatin 80-mg group ( S80 , n = 113 ) . Serum creatinine was measured at admission , the day of PCI , and 24 and 48 hours after PCI . The creatinine clearance was calculated using the Cochcroft-Gault formula . High-sensitive C-reactive protein , P-selectin , and intercellular adhesion molecule-1 were also measured before and after the procedure . Contrast-induced nephropathy was defined as a postprocedure increase in serum creatinine of > or = 0.5 mg/dl or > 25 % from baseline . The serum creatinine significantly increased after PCI , with the peak value occurring at 24 hours , and then began to decrease . At 48 hours , the serum creatinine had decreased to the baseline level in the S80 group , but it had failed to do so in the S20 group . At 24 and 48 hours after PCI , the serum creatinine was lower in the S80 group than in the S20 group ( p < 0.05 and p < 0.001 , respectively ) . The creatinine clearance significantly decreased after PCI , with the lowest value occurring at 24 hours , and then it began to increase . In the S80 group , the creatinine clearance recovered to baseline level at 48 hours , but it failed to do so in the S20 group . The creatinine clearance was greater at 24 and 48 hours in the S80 group than that in the S20 group . Although the procedure caused a significant increase in high-sensitive C-reactive protein , P-selectin , and intercellular adhesion molecule-1 levels , the value was lower in the S80 group than in the S20 group ( p < 0.001 ) . In conclusion , pretreatment with simvastatin 80 mg before PCI could further decrease the occurrence of contrast-induced nephropathy compared with simvastatin 20 mg . This benefit was associated with the lowering of high-sensitive C-reactive protein , P-selectin , and intercellular adhesion molecule-1 levels We investigated the efficacy of short-term high-dose atorvastatin in decreasing the risk of contrast-induced nephropathy ( CIN ) in patients with chronic kidney disease ( CKD ) subjected to coronary angiography and /or angioplasty . CIN occurs in up to 15 % of patients with pre-existing CKD and affects clinical outcome . The protective effect of statin therapy against CIN is still controversial . A prospect i ve , single-center study of 304 patients with baseline estimated creatinine clearance < 60 ml/min were r and omized to receive atorvastatin 80 mg/day or placebo for 48 hours before and 48 hours after contrast medium administration . All patients received intravenous saline hydration and oral N-acetylcysteine 1,200 mg 2 times/day . Iso-osmolar contrast medium was used . CIN was defined as an absolute increase of serum creatinine > or = 0.5 mg/dl within 5 days after the procedure . CIN occurred in 31 patients ( 10 % ) , 16 ( 11 % ) in the placebo group and 15 ( 10 % ) in the atorvastatin group ( p = 0.86 ) . Mean increase in creatinine was not significantly different in the 2 groups ( 0.59 + or - 0.17 in placebo group vs 0.72 + or - 0.26 mg/dl in atorvastatin group , p = 0.31 ) . Persistent kidney injury , defined as 1-month increase from baseline creatinine value > or = 25 % , was observed in 30 % in the placebo group and in 31 % in the atorvastatin group ( p = 0.58 ) . In conclusion , a short-term administration of high doses of atorvastatin before and after contrast exposure , in addition to st and ard intravenous hydration and oral N-acetylcysteine , does not decrease CIN occurrence in patients with pre-existing CKD Objectives : To investigate whether preprocedural high-dose atorvastatin decreases the incidence of contrast-induced nephropathy ( CIN ) and protects the renal function after emergency percutaneous coronary intervention ( PCI ) . Methods : Statin-naive patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) undergoing emergency PCI ( n = 161 ) r and omly received atorvastatin ( 80 mg , n = 78 , ATOR group ) or placebo [ n = 83 , control ( CON ) group ] followed by long-term atorvastatin ( 40 mg/day ) . The primary end point was incidence of CIN . Results : In the ATOR group , 2.6 % of the patients developed CIN versus 15.7 % in the CON group ( p = 0.01 ) . In the ATOR group , postprocedural serum creatinine was significantly lower ( 93.4 ± 17.1 vs. 112.6 ± 23.3 µmol/l at 48 h and 84.2 ± 14.2 vs. 95.3 ± 17.7 µmol/l at 72 h , both p < 0.0001 ) and in the CON group , peak serum cystatin C was lower ( 0.51 ± 0.14 vs. 0.61 ± 0.13 mg/l , p < 0.0001 ) . Atorvastatin pretreatment was independently associated with a decreased risk of CIN ( OR 0.084 , 95 % CI 0.015–0.462 , p = 0.004 ) . The proportion of alanine aminotransferase > 3 × upper limit of the normal value within 1 month was 3.85 versus 1.20 % ( ATOR vs. CON group , p = 0.57 ) . Conclusion : Preprocedural high-dose atorvastatin prevents CIN and protects the renal function in patients with acute STEMI undergoing emergency PCI Background and aims . Gentamicin ( GM ) is still considered to be an important antibiotic against life-threatening , gram-negative bacterial infections despite its known nephrotoxic effects . We aim ed to evaluate the potential protective effect of atorvastatin ( ATO ) against GM-induced nephrotoxicity in rats . Material s and methods . The rats were r and omly divided into five groups of six animals each : control , GM ( 100 mg/kg/day ) , ATO ( 10 mg/kg/day ) , GM + ATO , and GM + Vehicle . Kidney function tests , tissue oxidative stress parameters , and histopathological and immunohistochemical studies clarified GM nephrotoxicity . Results . GM caused a marked reduction in renal functions and increased oxidative stress parameters . Histopathological examination revealed tubular necrosis especially in the renal cortex in GM rats . On immunohistochemical evaluation , GM rat showed more intense expressions of mitogen-activated protein kinase ( MAPK ) , nuclear factor kappa B ( NF‐kB ) , and inducible nitric oxide synthase ( iNOS ) compared with control . Kidney function tests and tissue oxidative stress parameters were normalized in the GM + ATO group . Histopathological and immunohistochemical pictures were also greatly ameliorated . Conclusions . ATO acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM via the inhibition of MAPK and NF-kB signaling pathways and iNOS expression A decline in kidney function after contrast exposure is associated with a high risk of morbidity and mortality during hospitalization and over long-term periods . Several retrospective and recent prospect i ve clinical trials have shown that statin therapy might prevent contrast-induced nephropathy in patients undergoing percutaneous coronary intervention . In this study , we aim ed to assess the effects of statin therapies on renal function parameters in patients undergoing elective coronary angiography . One hundred and sixty patients undergoing elective coronary angiography were r and omized equally into two groups : atorvastatin 40 mg/day group ( statin started 3 days before coronary angiography ) and an untreated control group . An additional 80 patients were included as a chronic statin therapy group . Serum creatinine , serum cystatin C , and glomerular filtration rate ( GFR ) were measured before and 48 h after coronary angiography . Cockcroft – Gault and Modification of Diet in Renal Disease ( MDRD ) equations were used to determine GFR . After coronary angiography , serum creatinine and GFR determined by MDRD were significantly better in patients using atorvastatin than those in controls ( P = 0.002 and P = 0.004 , respectively ) . Postprocedure serum creatinine , cystatin C , and GFR determined by MDRD were also significantly better in chronic statin therapy group than those in controls ( P = 0.006 , P = 0.003 , and P = 0.004 , respectively ) . There were no differences in renal function parameters between the short-term atorvastatin group and the chronic statin therapy group . Our data demonstrate that the use of short-term atorvastatin and chronic statin therapy may have a role in protecting renal function after elective coronary angiography Contrast-induced nephropathy ( CIN ) impairs clinical outcome in patients undergoing angiographic procedures . The aim of this study was to investigate whether short-term high-dose atorvastatin load decreases the incidence of CIN after percutaneous coronary intervention ( PCI ) . Statin-naive patients with acute coronary syndrome undergoing PCI ( n = 241 ) r and omly received atorvastatin ( 80 mg 12 hours before intervention with another 40-mg preprocedure dose , n = 120 ) or placebo ( n = 121 ) . All patients had long-term atorvastatin treatment thereafter ( 40 mg/day ) . Primary end point was incidence of CIN defined as postintervention increase in serum creatinine ≥0.5 mg/dl or > 25 % from baseline . Five percent of patients in the atorvastatin arm developed CIN versus 13.2 % of those in the placebo arm ( p = 0.046 ) . In the atorvastatin group , postprocedure serum creatinine was significantly lower ( 1.06 ± 0.35 vs 1.12 ± 0.27 mg/dl in placebo , p = 0.01 ) , creatinine clearance was decreased ( 80.1 ± 32.2 vs 72.0 ± 26.6 ml/min , p = 0.034 ) , and C-reactive protein peak levels after intervention were decreased ( 8.4 ± 10.5 vs 13.1 ± 20.8 mg/l , p = 0.01 ) . Multivariable analysis showed that atorvastatin pretreatment was independently associated with a decreased risk of CIN ( odds ratios 0.34 , 95 % confidence interval 0.12 to 0.97 , p = 0.043 ) . Prevention of CIN with atorvastatin was paralleled by a shorter hospital stay ( p = 0.007 ) . In conclusion , short-term pretreatment with high-dose atorvastatin load prevents CIN and shortens hospital stay in patients with acute coronary syndrome undergoing PCI ; anti-inflammatory effects may be involved in this renal protection . These results lend further support to early use of high-dose statins as adjuvant pharmacologic therapy before percutaneous coronary revascularization Lipophilic statins purportedly exert anti-tumoral effects on breast cancer by decreasing proliferation and increasing apoptosis . HMG-CoA reductase ( HMGCR ) , the rate-limiting enzyme of the mevalonate pathway , is the target of statins . However , data on statin-induced effects on HMGCR activity in cancer are limited . Thus , this pre-operative study investigated statin-induced effects on tumor proliferation and HMGCR expression while analyzing HMGCR as a predictive marker for statin response in breast cancer treatment . The study was design ed as a window-of-opportunity trial and included 50 patients with primary invasive breast cancer . High-dose atorvastatin ( i.e. , 80 mg/day ) was prescribed to patients for 2 weeks before surgery . Pre- and post-statin paired tumor sample s were analyzed for Ki67 and HMGCR immunohistochemical expression . Changes in the Ki67 expression and HMGCR activity following statin treatment were the primary and secondary endpoints , respectively . Up-regulation of HMGCR following atorvastatin treatment was observed in 68 % of the paired sample s with evaluable HMGCR expression ( P = 0.0005 ) . The average relative decrease in Ki67 expression following atorvastatin treatment was 7.6 % ( P = 0.39 ) in all paired sample s , whereas the corresponding decrease in Ki67 expression in tumors expressing HMGCR in the pre-treatment sample was 24 % ( P = 0.02 ) . Furthermore , post-treatment Ki67 expression was inversely correlated to post-treatment HMGCR expression ( rs = −0.42 ; P = 0.03 ) . Findings from this study suggest that HMGCR is targeted by statins in breast cancer cells in vivo , and that statins may have an anti-proliferative effect in HMGCR-positive tumors . Future studies are needed to evaluate HMGCR as a predictive marker for the selection of breast cancer patients who may benefit from statin treatment Gentamicin nephrotoxicity is one of the most common causes of acute renal failure . Simvastatin is one of the antioxidative drugs , which has anti-inflammatory and anabolic effects and modulates the immune system . The present study was conducted to assess the effect of simvastatin on ameliorating the gentamicin-induced renal injury in 87 Sprague-Dawley rats , which were allocated r and omly to 11 study groups : ( A ) and ( B ) groups with only gentamicin in 2 dosages ; ( C ) , ( D ) , and ( E ) gentamicin 50 mg/kg/day and simvastatin with different dosage ; ( F ) , ( G ) , and ( H ) gentamicin 80 mg/kg/day and simvastatin with different dosage ; ( I ) only simvastatin ; ( J ) Injected normal saline ; ( K ) control ( no gentamicin and no simvastatin ) group . Our study intervention period for injection of drugs was 12 days . Serum creatinine level and clearance were measured in all groups . At the end of the study , the rats were killed and both kidneys were removed and processed for histopathologic examination using the st and ard methods . The 50 mg/kg/day dose was utilized because it induces a mild form of renal toxicity , whereas the 80 mg/kg/day dose cause a more severe degree of renal injury . Morphologic examination of specimens from all rats was qualitatively assessed with blindness to treatment groups and proximal tubular profiles that were presented in each file were counted . The results demonstrated amelioration of gentamicin-induced renal toxicity in rats by simvastatin due to its antioxidant drug dose-related effect BACKGROUND Contrast media cause oxidative stress , which has been suggested as one possible mechanism responsible for contrast-induced nephropathy . Statins appear to have pleiotropic effects , including antioxidant properties . We investigated to determine whether simvastatin pretreatment reduces the risk of contrast-induced nephropathy in a high-risk population of patients with renal insufficiency undergoing coronary angiography . METHODS We conducted a prospect i ve , r and omized , double-blind , placebo-controlled , 2-center trial , involving 247 consecutive patients with chronic renal insufficiency ( calculated creatinine clearance < or = 60 mL/min and /or serum creatinine > or = 1.1 mg/dL ) undergoing coronary angiography . Patients were r and omized to simvastatin ( n = 124 ; 160 mg total , 40 mg orally every 12 hours starting the evening before and ending the morning after the procedure ) or placebo ( n = 123 ) . All patients received pre - and postprocedure hydration . The iso-osmolar contrast agent iodixanol was used for coronary angiography in all patients . RESULTS There was no difference between simvastatin and placebo in mean peak increase in serum creatinine measured within 48 hours after coronary angiography , the primary study end point ( 0.002 + /- 0.164 vs 0.017 + /- 0.230 mg/mL respectively , P = .559 ) . The incidence of contrast-induced nephropathy , a secondary end point defined as increase of either > or = 25 % or > or = 0.5 mg/dL in serum creatinine , was 2.5 % in simvastatin-treated patients ( 3/118 ) and 3.4 % in placebo-treated patients ( 4/118 ) , a nonsignificant difference ( P = 1.00 ) . There were also no differences between the 2 groups in length of hospital stay or 1- and 6-month clinical outcomes . CONCLUSIONS Simvastatin pretreatment for short-term at high dose do not prevent renal function deterioration after administration of contrast medium in patients with baseline renal insufficiency undergoing coronary angiography AIM Oxidative stress and ischaemia are suggested as possible mechanisms of contrast-induced nephropathy ( CIN ) . Statins may offer renoprotection in both acute and chronic kidney diseases because of their antioxidant and anti-inflammatory properties . We investigated whether use of statins before non-emergent percutaneous coronary intervention ( PCI ) reduces the incidence of CIN . METHODS We retrospectively evaluated 540 consecutive adult patients who underwent non-emergent PCI over a 3 year period at a tertiary care centre . CIN was defined as 25 % or 44 mmol/L increase from baseline creatinine at 48 - 72 h. In addition , we classified patients based on Mehran score for risk of development of CIN and analysed the effect of statins . RESULTS Three-hundred and fifty-three patients met inclusion criteria . Two-hundred and thirty-nine patients were taking statins before PCI and 114 were not . Baseline characteristics were similar for both groups . CIN occurred in 75 patients ( 21.2 % ) . There was a higher incidence of CIN in patients on statins as compared with patients not on statins ( 24.7 % vs 14 % ; 95 % CI : 1.09 - 3.67 ; P = 0.02 ) . However , propensity-based adjustment for receipt of statins revealed no significant differences in CIN between both groups ( OR : 1.6 ; 95 % CI : 0.87 - 3.22 ; P = 0.12 ) . Multivariate logistic regression revealed Mehran score to be independently predictive of CIN . None of the patients who developed CIN required dialysis . CONCLUSIONS Statin use before non-emergent PCI is not associated with reduction in CIN . Further r and omized controlled trials based on proper risk adjustment for development of CIN are needed |
13,293 | 29,139,105 | There was no evidence of differences in preoperative complications .
There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume , and increases preoperative haemoglobin levels , although GnRHa increases the incidence of hot flushes .
During hysterectomy , blood loss , operation time and complication rates were also reduced . | BACKGROUND Uterine fibroids occur in up to 40 % of women aged over 35 years .
Some are asymptomatic , but up to 50 % cause symptoms that warrant therapy .
Symptoms include anaemia caused by heavy menstrual bleeding , pelvic pain , dysmenorrhoea , infertility and low quality of life .
Surgery is the first choice of treatment .
In recent years , medical therapies have been used before surgery to improve intraoperative and postoperative outcomes .
However , such therapies tend to be expensive .
Fibroid growth is stimulated by oestrogen .
Gonadotropin-hormone releasing analogues ( GnRHa ) induce a state of hypo-oestrogenism that shrinks fibroids , but has unacceptable side effects if used long-term .
Other potential hormonal treatments , include progestins and selective progesterone-receptor modulators (SPRMs).This is an up date of a Cochrane Review published in 2000 and 2001 ; the scope has been broadened to include all preoperative medical treatments .
OBJECTIVES To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids .
AUTHORS ' CONCLUSIONS A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier . | BACKGROUND The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear . METHODS In this double-blind noninferiority trial , we r and omly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate ( at a dose of either 5 mg or 10 mg ) or once-monthly intramuscular injections of leuprolide acetate ( at a dose of 3.75 mg ) . The primary outcome was the proportion of patients with controlled bleeding at week 13 , with a prespecified noninferiority margin of -20 % . RESULTS Uterine bleeding was controlled in 90 % of patients receiving 5 mg of ulipristal acetate , in 98 % of those receiving 10 mg of ulipristal acetate , and in 89 % of those receiving leuprolide acetate , for differences ( as compared with leuprolide acetate ) of 1.2 percentage points ( 95 % confidence interval [ CI ] , -9.3 to 11.8 ) for 5 mg of ulipristal acetate and 8.8 percentage points ( 95 % CI , 0.4 to 18.3 ) for 10 mg of ulipristal acetate . Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate , 5 days for those receiving 10 mg of ulipristal acetate , and 21 days for those receiving leuprolide acetate . Moderate-to-severe hot flashes were reported for 11 % of patients receiving 5 mg of ulipristal acetate , for 10 % of those receiving 10 mg of ulipristal acetate , and for 40 % of those receiving leuprolide acetate ( P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate ) . CONCLUSIONS Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes . ( Funded by PregLem ; Clinical Trials.gov number , NCT00740831 . ) OBJECTIVE To investigate the effect of 2 medications ; Diphereline and Cabergoline , on uterine leiomyoma growth , and its histologic , sonographic , and intra-operative changes . METHODS In an effort to treat large uterine leiomyoma in symptomatic patients in the Gynecology Clinics of the Alzahra Teaching Hospital of Tabriz University of Medical Sciences , Tabriz , Iran , from September 2007 to November 2008 , 60 c and i date s r and omized to receive Diphereline 3.75 mg , 4 times every 28 days ( group I ) , and Cabergoline 0.5 mg , once a week for 6 weeks ( group II ) , were included in this study . Clinical symptoms , feasibility of intra-operative dissection , intraoperative complications , sonographic , and pathologic characteristics of the tumor were evaluated . RESULTS Thirteen patients from group I , and 10 patients from group II underwent surgery . There was a significant difference between the groups in the rate of lymphocyte infiltration ( p=0.003 ) , but not in other pathologic features . In both groups , the mitotic index was between 0 - 10 . While there was no significant difference between the groups in the number ( p=0.30 ) , and volume of leiomyomas ( p=0.65 ) , however , changes in the uterine artery circulation was significant ( p=0.001 [ group I ] , p=0.026 [ group II ] ) . In addition , there was a significant difference between the groups for intra-operative hemorrhage and adhesion of leiomyomas to the uterine wall . CONCLUSION This study found that Cabergoline is as effective as Diphereline in the shrinkage of myomas , accompanied by improvement in the sonographic , clinical , and intra-operative outcomes without any adverse pathological changes , and could be a good medical regimen as an adjunct to surgical management Fifty premenopausal patients requiring hysterectomy as treatment for symptomatic uterine leiomyomas , which were the size of 14 to 18 weeks ' gestation , were r and omized into two groups to determine whether preoperative gonadotropin-releasing hormone agonist would increase the feasibility of vaginal rather than abdominal hysterectomy . The control group ( group A ; n = 25 ) did not receive preoperative gonadotropin-releasing hormone agonist , but patients in Group B ( n = 25 ) received 2 months of gonadotropin-releasing hormone agonist before undergoing hysterectomy . Patients in the two groups were similar with respect to age , gravidity , parity , pretreatment uterine size , and hemoglobin and hematocrit levels . Patients in group B had an increase in hemoglobin levels ( 10.75 to 12.12 gm/dl , p less than 0.05 ) and a decrease in uterine volume ( 1086.7 to 723.4 ml , p less than 0.05 ) after 8 weeks of agonist therapy and were more likely to undergo vaginal hysterectomy ( 76.0 % vs 16 % ) . Patients in group B also had shorter hospitalizations ( 5.2 vs 3.8 days , p less than 0.05 ) . We conclude that the administration of gonadotropin-releasing hormone agonist for 2 months followed by vaginal hysterectomy is preferable to abdominal hysterectomy in selected patients with uterine leiomyomas A. J. M. AUDEBERT , P. MADENELAT * , D. Q U E R L E U ? , G. P O N T O N N I E R ~ , C . R A C I N E T ~ , R.R E N A U D ~ , J.-Y. GILLET * * , D. R A U D R A N T ? ~ , J. LANSAC:~ , J.-P. B R E T T E ~ Cnbitiet Medical . Bordeaus : * Hdpital Bichat , Paris ; ? Centre Hospitalier , Roubai.r ; 1 Hdpital de la Grave , Toulouse ; $ Centre Hospiialier Sud , Ecliirolles : Hfipital Central , Strasbourg ; * * Hi?pital Saint Roch , Nice ; ttH6pital de I'Hdtel Dieu , Lyon ; : $ Hdpital de Tours , Tours ; and # Hipito1 Monwti . Brest . OBJECTIVE Our purpose was to examine the effects of RU 486 and leuprolide acetate on uterine artery blood flow and uterine volume . STUDY DESIGN Patients were r and omly assigned to group A ( eight patients ) receiving 25 mg of RU 486 daily for 3 months or group B ( six patients ) receiving 3.75 mg of leuprolide acetate monthly for 3 months . Uterine artery blood flow change was determined by resistive index by means of vaginal color Doppler ultrasonography . Uterine volume was measured before and during the study with abdominal ultrasonography . RESULTS Both groups showed an increase in resistive index . Patients receiving RU 486 had uterine artery blood flow decreased by 40 % , and those receiving leuprolide acetate had a 21 % decrease . We noted a significant decrease in uterine volume compared with pretreatment in both groups at 3 months . There was no significant decrease between groups . CONCLUSION Both RU 486 ( 25 mg daily ) and leuprolide acetate ( 3.75 mg monthly ) are effective in decreasing blood flow to the uterus ( increasing resistive index ) and decreasing uterine volume at 3 months . A significant decrease in uterine artery blood flow may provide a mechanism for the decrease in uterine size and the decrease in uterine blood loss at the time of surgery Background Fibroma , the most common benign pelvic tumor in women , affects 25 to 30 % of women of reproductive age . Primary treatment for patients with symptomatic or large fibroma is surgery . Objective The purpose of this study was to investigate the effect of a single rectal dose of Misoprostol on bleeding during abdominal hysterectomy . Methods This double blind r and omized clinical trial was conducted with 80 c and i date s for abdominal hysterectomy , due to uterine myoma , in the Shahid Sadoughi hospital of Yazd in 2012 . The aim of this study was to assess the effect of single rectal dose of Misoprostol on peri-operational abdominal hysterectomy bleeding . Following administration of 400 micrograms of Misoprostol in the case group ( n=40 ) , predetermined criteria were compared with control group ( n=40 ) . Results Volume of bleeding during the operation was significantly lower in cases where Misoprostol was used . ( 268.71 ± 156.85 vs. 350.38 ± 152.61 cc in the case and control groups , respectively ) . Our findings also showed that Hemoglobin ( Hb ) levels before , 8 , and 30 hours following the operation differed significantly ( p=0.001 ) , but these changes were similar in both groups . Pre-operative Hb levels were 11.90 ± 1.7 and 11.90 ± 2.0 in the case and control groups , respectively . Conclusion A single rectal dose of Misoprostol has positive effect on reducing peri-operational bleeding in women undergoing abdominal hysterectomy due to symptomatic leiomyoma Summary . Twenty‐four women with symptomatic multiple uterine myomas were allocated r and omly to treatment with buserelin , 1200μg/day intranasally , for 3 months followed by myomectomy ( n = 8) or to immediate myomectomy ( n = 16 ) . Pre‐operative treatment with buserelin reduced the mean uterine volume from 432 ( SD 165 ) to 242 ( SD 82 ) ml ( P < 0.01 ) but intra‐operative blood loss and postoperative morbidity were not significantly less in this group . Six months after operation , pelvic examination was normal in all the patients . However , ultrasonography with transvaginal probe demonstrated the presence of myomas of < 1.5 cm in five women ( 63 % ) treated pre‐operatively with the analogue and in two women ( 13 % ) who underwent immediate surgery ( P < 0.05 ) . Induction of a period of hypo‐oestrogenism before myomectomy seems to favour short‐term recurrence of uterine myomas , limiting the efficacy of surgery STUDY OBJECTIVE To evaluate whether tibolone modifies the effectiveness of gonadotropin-releasing hormone ( GnRH ) analog administered before laparoscopic myomectomy . DESIGN Prospect i ve , r and omized , open , placebo-controlled clinical trial ( Canadian Task Force classification I ) . SETTING University-affiliated hospital . PATIENTS Sixty-six women with symptomatic leiomyomas . INTERVENTIONS Patients received 2 months of treatment with GnRH analog and iron plus tibolone ( group A ) or placebo ( group B ) ; group C received only iron . Laparoscopic myomectomy was performed after medical treatment . MEASUREMENTS AND MAIN RESULTS Uterine volume , number and volume of leiomyomas , echogenicity and volume of the largest leiomyomas , hematologic values , and myoma-related symptoms were evaluated at baseline , 1 week before , and 1 week after surgery . We observed significant ( p < 0.05 ) reductions in uterine and leiomyomata volume , myoma-related symptoms , and improvement in hematologic values before surgery in groups A and B , without significant difference between groups compared with baseline values and group C. Operating time and blood loss were significantly ( p < 0.05 ) lower in groups A and B , without significant difference compared with group C. After surgery , significant numbers of women in group C had worsening of hematologic values ( p < 0.05 ) . CONCLUSION Adding tibolone to the GnRH analog regimen before laparoscopic myomectomy does not modify the effectiveness of GnRH analog administered alone BACKGROUND Vaginal hysterectomy is considered the method of choice for removal of the uterus but most gynecologists still prefer the abdominal route for removal of benign uteri > 14 weeks in size . Conversion of an abdominal to a potential vaginal hysterectomy by uterine size reduction would be advantageous . Gonadotrophin-releasing hormone ( GnRH ) agonists can reduce uterine bulk by up to 50 % . OBJECTIVE To evaluate the efficacy of the preoperative administration of a GnRH agonist for women with enlarged non-prolapsing uteri in order to facilitate vaginal hysterectomy , in comparison with patients with enlarged uteri who underwent direct total abdominal hysterectomy ( TAH ) for the same indication ( menorrhagia ) . STUDY DESIGN R and omized controlled study . Women scheduled for hysterectomy for menorrhagia with a non-prolapsing uterus of ≥14 weeks size ( by clinical and sonographic assessment s ) were offered a trial of vaginal hysterectomy after pre-treatment with a GnRH agonist ( goserelin ) for 3 months ( study group = Group 1=40 ) . A group of women with uteri of comparable size who underwent abdominal hysterectomy for similar indications served as controls ( Group 2=40 ) . Pre- and post-operative data such as hemoglobin , myoma size , uterine weight , duration of procedure and complications , pain score and length of hospital stay were collected prospect ively . RESULTS The weight of the uterine specimen was significantly lower in Group 1 ( 511.7±217 g ) compared to Group 2 ( 736.8±212 g ) ; P<0.001 . The mean objective decrease in clinical uterine bulk preoperatively in Group 1 was 20.1 % . The duration of surgery was nearly 1.5 times as long in vaginal ( 119.6±41.7min ) compared to abdominal hysterectomy ( 81.1±34.1min ) , P<0.001 , but analgesia use and the length of inpatient stay were significantly lower in Group 1 ( 2.6±1.3 days ) compared to Group 2 ( 4.12±1.7 days ) , P<0.001 . There was no significant difference between the two groups as regards the rate of occurrence of surgical complications . CONCLUSIONS In women with ≥14 week size uteri , treatment with a GnRH agonist reduces uterine size sufficiently to allow safe vaginal hysterectomy . Although duration of surgery was longer , women who underwent vaginal hysterectomy required less analgesia and had a shorter inpatient stay OBJECTIVE To ascertain whether adjuvant gonadotropin-releasing hormone ( GnRH ) agonist therapy decreases blood loss during abdominal myomectomy . DESIGN R and omized controlled trial . SETTING Academic reproductive surgery center . PATIENT(S ) One hundred premenopausal women requiring first-line conservative surgery for symptomatic intramural or subserous fibroids . INTERVENTION(S ) Eight weeks of treatment with depot triptorelin before myomectomy or immediate surgery . MAIN OUTCOME MEASURES Intraoperative blood loss , operating time , degree of difficulty of the procedure , and short-term rate of fibroid recurrence . RESULT ( S ) Mean ( + /-SD ) intraoperative blood loss was 265 + /- 181 mL in triptorelin recipients and 296 + /- 204 in patients who had immediate surgery ( mean difference , -31 mL [ 95 % CI , -108 to 46 mL ] ) . No significant differences were observed in blood loss according to uterine volume , number of fibroids removed , or total length of myometrial incisions . Most procedures in either group were of routine difficulty . On ultrasonography 6 months after myomectomy , four women in the GnRH agonist group and one in the immediate surgery group had tumor recurrence . CONCLUSION ( S ) Treatment with a GnRH agonist before abdominal myomectomy has no significant effect on intraoperative blood loss . Thus , systematic use of medical therapy before abdominal myomectomy does not seem to be justified OBJECTIVE Aims of our study were as follows : ( 1 ) to evaluate the therapeutic efficacy of the preoperative administration of a gonadotropin-releasing hormone analog before laparoscopic myomectomy and ( 2 ) to assess whether any ultrasonographic parameter of the fibroids ( number , size , Doppler velocimetry , or echogenicity ) was of prognostic value . STUDY DESIGN A prospect i ve r and omized study was performed on 67 patients with symptomatic uterine fibroids that were mainly intramural ; these patients were undergoing laparoscopic myomectomy . Patients were r and omized either to preoperative administration of two injections of a depot formulation of leuprolide acetate 28 days apart ( group A , n = 35 ) or to direct surgery ( group B , n = 32 ) . In each group we studied the number , volume , and echogenicity of the larger fibroids ; the resistance index of uterine arteries and of fibroid vessels ; hematologic parameters ; operative time ; and blood loss . RESULTS The two groups did not differ significantly in basal ultrasonographic parameters and hematologic data . Postoperatively , the red blood cell count and the serum hemoglobin and iron levels were significantly ( p < 0.05 ) lower in group B. Both blood loss ( p < 0.01 ) and operative time ( p < 0.05 ) were significantly lower in group A. However , the operative time was significantly longer when the main fibroid was markedly hypoechoic , probably because the increased softness of the tumor after leuprolide acetate pretreatment makes its enucleation much more cumbersome . CONCLUSION Our data confirm the therapeutic efficacy of preoperative administration of a gonadotropin-releasing hormone analog before laparoscopic myomectomy in reducing the blood loss and in decreasing the operative time . This preoperative course of leuprolide acetate in hypoechoic fibroids , because of the further reduction of the density of the myomas , causes a significant ( p < 0.05 ) increase in operative time BACKGROUND The authors examined 33 patients with symptomatic uterine leiomyomas due to undergo total hysterectomy in order to evaluate the effects of treatment with GnRH analogues on leiomyoma and estrogen and progesterone receptors . METHODS The patients were divided into two groups : one group was treated with leuprolide acetate ( Group A ) and the other did not receive treatment ( Group B ) . RESULTS A significant reduction in the volume of leiomyomas and estrogen and progesterone receptors was noted in patients in Group A. CONCLUSIONS Treatment with GnRH analogues therefore represents a valid aid for patients with uterine leiomyomas and sideropenic anemia awaiting surgery Objective To investigate the effect of the gonadotrophin releasing hormone (GnRH)‐agonist goserelin , given by monthly subcutaneous injection for three months prior to total abdominal hysterectomy for uterine leiomyomata , on the pre‐operative symptoms , difficulty of operation and operative blood loss OBJECTIVE To compare danazol and gestrinone treatment as preoperative endometrial preparation for operative hysteroscopy . DESIGN Prospect i ve , r and omized clinical study . SETTING University department of gynecological , obstetrical sciences and reproductive medicine . PATIENT(S ) One hundred thirty-five patients with endouterine pathologies ( endometrial polyps , submucous myoma , septate uterus ) . INTERVENTION(S ) Patients pretreated with gestrinone ( n = 68 ) and with danazol ( n = 67 ) underwent operative hysteroscopy . MAIN OUTCOME MEASURE(S ) Endometrial response to the medical pretreatment , side effects , procedure time , intraoperative bleeding , infusion volume , patient satisfaction . RESULT ( S ) Side effects were infrequent in both groups , though the patients ' personal satisfaction was in favor of gestrinone . The rate of endometrial response was higher for the gestrinone group ( 97.1 % vs. 83.6 % ) . Operative time ( mean + /- SD ) was 12 + /- 1.8 and 15.2 + /- 1.9 minutes for the gestrinone and danazol groups , respectively . The gestrinone group showed a lower incidence of moderate bleeding ( 3 % vs. 22.4 % ) and a lower infusion volume ( 2,100 + /- 200 mL vs. 2,400 + /- 250 mL ) . Regarding cervical dilatation time , no significant difference was found between the two groups ( 1.6 + /- 0.3 minutes vs. 1.5 + /- 0.4 minutes ) . CONCLUSION ( S ) Both treatments are good ways to prepare the endometrium for operative hysteroscopy . However , the data suggest that gestrinone pretreatment is preferable to danazol Abstract The aim of this r and omised prospect i ve study was to investigate the impact of preoperative gonadotrophin-releasing hormone agonist ( GnRHa ) compared with a control group with myomectomy . A total of 36 women ( n = 36 , group 1 ) with fibroids were r and omised to receive either two monthly doses ( n = 18/36 , group 1a ) or three monthly doses of goserelin ( n = 18/36 , group 1b ) prior to myomectomy . The 32 women who received no treatment ( group 2 ) comprised the controls . All patients had similar demographic features . There were no significant differences among the three groups with respect to : ( 1 ) mean intraoperative blood loss ; ( 2 ) preoperative and postoperative blood transfusion or ( 3 ) length of hospital stay . The only advantage of administering GnRHa prior to myomectomy for symptomatic fibroids in our population was a higher haemoglobin level prior to surgery among the women who received three doses of the drug On 30 women suffering from uterine fibroids , the monthly subcutaneous administration of goserelin depot ( 3.6 mg ) for 6 ( n = 22 ) or 12 months ( n = 8) induced an about 50 % shrinkage of uterus and fibroid volume , and within 3 months , an increase in the haematocrit value , with no metabolic side effects or detectable bone demineralization , evaluated by single photon absortiometry at distal radius . Both uterine and fibroid volumes reversed to pretreatment values after 3 months of goserelin depot withdrawal . In comparison with untreated subjects , on another 10 patients a three month administration of goserelin depot reduced the loss of blood during the surgical removal of the uterus or fibroids . Present data indicate that goserelin depot is effective and relatively safe in the medical management of uterine fibroids . Although , goserelin depot can not yet be proposed as a definite medical therapy , it may represent a useful instrument in the presurgical management of uterine fibroids OBJECTIVE To evaluate the effects of raloxifene administration on uterine leiomyoma size in premenopausal women . DESIGN Prospect i ve , r and omized , open-label , controlled clinical trial . SETTING Tertiary care unit , University of Vienna , Austria . PATIENT(S ) Twenty-five premenopausal women with uterine leiomyomas . INTERVENTION(S ) Three months of treatment with raloxifene ( 180 mg/d ) or no treatment . MAIN OUTCOME MEASURE(S ) Baseline to end point percent change difference in leiomyoma volume between the therapy and control groups . RESULT ( S ) Raloxifene treatment prevented the progression of uterine leiomyomas . Compared with no medical intervention , raloxifene result ed in a decrease of myoma volume . Raloxifene was clinical ly well tolerated . No significant differences were detected in symptoms related to leiomyomas and hormonal status . CONCLUSION ( S ) In premenopausal women , high-dose raloxifene is well tolerated and inhibits the growth of leiomyomas OBJECTIVE : To evaluate whether 3-month administration of CDB-2914 , a selective progesterone receptor modulator , reduces leiomyoma size and symptoms . METHODS : Premenopausal women with symptomatic uterine leiomyomata were r and omly assigned to CDB-2914 at 10 mg ( T1 ) or 20 mg ( T2 ) daily or to placebo ( PLC ) for 3 cycles or 90–102 days if no menses occurred . The primary outcome was leiomyoma volume change determined by magnetic resonance imaging at study entry and within 2 weeks of hysterectomy . Secondary outcomes included the proportion of amenorrhea , change in hemoglobin and hematocrit , ovulation inhibition , and quality -of-life assessment . RESULTS : Twenty-two patients were allocated , and 18 completed the trial . Age and body mass index were similar among groups . Leiomyoma volume was significantly reduced with CDB-2914 administration ( PLC 6 % ; CDB-2914 –29 % ; P=.01 ) , decreasing 36 % and 21 % in the T1 and T2 groups , respectively . During treatment , hemoglobin was unchanged , and the median estradiol was greater than 50 pg/mL in all groups . CDB-2914 eliminated menstrual bleeding and inhibited ovulation ( % ovulatory cycles : CDB-2914 , 20 % ; PLC , 83 % ; P=.001 ) . CDB-2914 improved the concern scores of the uterine leiomyoma symptom quality -of-life subscale ( P=.04 ) . One CDB-2914 woman developed endometrial cystic hyperplasia without evidence of atypia . No serious adverse events were reported . CONCLUSION : Compared with PLC , CDB-2914 significantly reduced leiomyoma volume after three cycles , or 90–102 days . CDB-2914 treatment result ed in improvements in the concern subscale of the Uterine Fibroid Symptom Quality of Life assessment . In this small study , CDB-2914 was well-tolerated without serious adverse events . Thus , there may be a role for CDB-2914 in the treatment of leiomyomata . Clinical Trial Registration : Clinical Trials.gov , www . clinical trials.gov , NCT00290251 LEVEL OF EVIDENCE : The present study was undertaken in order to evaluate the usefulness or otherwise of preoperative gonadotrophin-releasing hormone ( GnRH ) analogue treatment prior to laparoscopic myomectomy . From June 1993 through December 1996 , 60 premenopausal women aged between 25 and 42 years and with a sonographic diagnosis of intramural or subserous myomas were selected for laparoscopic myomectomy at the Department of Obstetrics and Gynaecology of the Catholic University of The Sacred Heart , Rome . According to a computer-generated sequence , 30 patients were su bmi tted to three cycles of GnRH analogue treatment prior to surgery , whereas no preoperative treatment was prescribed to the other 30 patients . Laparoscopic myomectomy was successfully performed in all patients for a total of 174 myomas excised laparoscopically . The patients ' mean age , the number of myomas per patient , the mean diameter of the myomas , parity and estimated blood loss were similar in both groups . The operative time was significantly longer in the group of patients su bmi tted to GnRH analogue treatment than that of the group of patients not su bmi tted to any preoperative medical therapy ( 157.5 + /- 74.71 versus 112.33 + /- 54.71 min ; P = 0.01 ) . No intra-operative complications occurred . In no case was blood transfusion necessary . Two patients developed post-operative fever ( temperature > 38 degrees C. ) . The mean length of hospital stay was 2.39 days and was similar in both groups . Thirteen spontaneous pregnancies occurred among 24 infertile patients ( 54.1 % ) . The pregnancy rate for these patients was similar in both groups . The viable term delivery rate was 45.8 % . The authors conclude that laparoscopic myomectomy is a feasible and safe procedure . The post-operative pregnancy rate for infertile patients is similar to that following laparotomic myomectomy . The present study suggests that preoperative GnRH analogue treatment does not offer any significant advantages for laparoscopic myomectomy BACKGROUND Uterine leiomyomas are widely prevalent and frequently cause menorrhagia . The major therapeutic option today is hysterectomy . Medical options are of highest interest . METHODS A total of 30 women with uterine leiomyomas scheduled for surgical intervention were r and omized to receive either 50 mg mifepristone or placebo every other day during 3 months prior to surgery . Uterine blood flow and leiomyoma volume were evaluated once a month until surgery . Endometrial biopsies were obtained prior to and at end of treatment . Relevant biochemistry , symptoms and bleeding were recorded . Primary outcome was reduction in uterine leiomyoma size . RESULTS There was a significant percentual decrease ( P = 0.021 ) in the total leiomyoma volume in the mifepristone-treated group , -28 ( -48 , -8 ) % ( mean + /- 0 , 95 confidence interval ) , compared with the control group values 6 ( -13 , 25 ) % . Mifepristone treatment significantly reduced the bleeding days ( P = 0.001 ) and increased serum haemoglobin values ( P = 0.046 ) . Serum cortisol levels remained unchanged , while a mild increase in serum and rogens was noted . Endometrial biopsies showed no premalignant changes or changes in mitotic indices . CONCLUSION Mifepristone may offer an effective treatment option for women with uterine leiomyoma and the associated pronounced uterovaginal bleeding . Clinical Trials identifier : www . clinical trials.gov : NCT00579475 OBJECTIVE To determine if 3 months of preoperative gonadotropin-releasing hormone agonist ( GnRH-a ) treatment decreases postoperative uterine adhesions after open abdominal surgery for the removal of uterine fibroids . DESIGN Prospect i ve , r and omized , clinical study . SETTING A tertiary care medical center . PATIENT(S ) Women of reproductive age with symptomatic uterine fibroids not amenable to hysteroscopic removal . INTERVENTION(S ) Twenty patients underwent an initial abdominal myomectomy followed by a second-look laparoscopy for evaluating uterine adhesions after r and om allocation to groups receiving either GnRH analog or placebo for 3 months before the initial surgery . MAIN OUTCOME MEASURE(S ) Adhesion formation between treatment groups and by incision number and aggregate length . RESULT ( S ) Presurgical GnRH-a treatment did not decrease adhesion formation compared with placebo . For every additional centimeter of incision length , the total adhesion area over the uterine serosal surface increased by 0.55 cm(2 ) . The number of myomas removed and the number of incisions were positively correlated with total adhesion area . CONCLUSION ( S ) Preoperative treatment with GnRH-a for 3 months before open abdominal myomectomy did not decrease postoperative uterine adhesions . Following the st and ards of good surgical technique , adhesions are minimized with fewer and smaller incisions OBJECTIVE To assess the efficacy of preoperative treatment with aromatase inhibitors ( AIs ) in premenopausal women undergoing laparoscopic myomectomy of large uterine myomas . STUDY DESIGN Prospect i ve non-r and omized assessor-blind comparative trial . RESULTS This study included 80 patients undergoing laparoscopic myomectomy of large uterine myomas ( ≥8 cm ) . Forty patients were treated with a combination of oral letrozole ( 2.5mg/day ) and norethindrone acetate ( 2.5mg/day ) continuously in the three months prior to surgery ( group A ) and 40 patients received no treatment before surgery ( group B ) . The total operative time ( mean±SD , range ) was significantly lower in group A ( 121.5±19.9min ; 89 - 181min ) than in group B ( 134.4±16.8min ; 111 - 185min ; p<0.001 ) . The time required to close the hysterotomies ( mean±SD , range ) was lower in group A ( 27.1±5.1min ; 16 - 39min ) than in group B ( 37.1±9.6min ; 17 - 57min ; p<0.001 ) . The intraoperative blood loss ( mean±SD , range ) was lower in group A ( 271.0±125.6ml ; 95 - 625ml ) than in group B ( 460.4±205.7ml ; 180 - 1115ml ; p<0.001 ) . No major complication occurred in any case . The cleavage plane was better defined in group B compared with group A ( p<0.001 ) . The quality of the myometrial scar , defined by ultrasound evaluation , was similar in the two study groups both at one-week ( p=0.356 ) and at 3-month follow-up ( p=0.201 ) . CONCLUSIONS The total operative time , the time required to close the hysterotomies and the intraoperative blood loss significantly decrease after preoperative treatment with letrozole . Future r and omized studies should compare the efficacy of preoperative administration of AIs and GnRHa prior to laparoscopic myomectomy OBJECTIVE Uterine leiomyoma , or fibroid tumors , are the leading indication for hysterectomy in the United States , but the proportion of women in whom fibroid tumors develop is not known . This study screened for fibroid tumors , independently of clinical symptoms , to estimate the age-specific proportion of black and white women in whom fibroid tumors develop . STUDY DESIGN R and omly selected members of an urban health plan who were 35 to 49 years old participated ( n = 1364 women ) . Medical records and self-report were used to assess fibroid status for those women who were no longer menstruating ( most of whom had had hysterectomies ) . Premenopausal women were screened by ultrasonography . We estimated the age-specific cumulative incidence of fibroid tumors for black and white women . RESULTS Thirty-five percent of premenopausal women had a previous diagnosis of fibroid tumors . Fifty-one percent of the premenopausal women who had no previous diagnosis had ultrasound evidence of fibroid tumors . The estimated cumulative incidence of tumors by age 50 was > 80 % for black women and nearly 70 % for white women . The difference between the age-specific cumulative incidence curves for black and white women was highly significant ( odds ratio , 2.9 ; 95 % CI , 2.5 - 3.4 ; P < .001 ) . CONCLUSION The results of this study suggest that most black and white women in the United States develop uterine fibroid tumors before menopause and that uterine fibroid tumors develop in black women at earlier ages than in white women OBJECTIVE To examine and compare the efficacy and safety of GnRH agonist ( GnRHa ) vs. aromatase inhibitor in premenopausal women with leiomyomas . DESIGN Multicenter , r and omized , controlled clinical trial . SETTING University hospitals . PATIENT(S ) A total of 70 subjects with a single uterine myoma measuring > or=5 cm . Subjects were r and omized into two groups with use of a r and om table . They were treated with aromatase inhibitor ( group A ) or GnRHa ( group B ) . INTERVENTION(S ) Group A received letrozole ( 2.5 mg/d ) for 12 weeks . Group B received triptorelin ( 3.75 mg/mo ) for 12 weeks . MAIN OUTCOME MEASURE(S ) Measurement of myoma volume and E(2 ) , FSH , LH , and T levels . RESULT ( S ) Total myoma volume decreased by 45.6 % in group A and 33.2 % in group B. Reductions in myoma volume in the two groups were statistically significant . There was no significant change in hormonal milieu in group A. The serum level of hormones significantly decreased in group B by the 12th week of treatment . CONCLUSION ( S ) Uterine myoma volume was successfully reduced by use of an aromatase inhibitor . Rapid onset of action and avoidance of initial gonadotropin flare with an aromatase inhibitor may be advantageous for short-term management of women with myomas of any size who are to be managed transiently and who wish to avoid surgical intervention , specifically women with unexplained infertility having uterine myoma Objective . To investigate the usefulness of a routine short term treatment with gonadotropin releasing hormone agonist ( D‐Trp‐6‐LHRH depot ) before abdominal hysterectomy for leiomyoma OBJECTIVE To evaluate the efficacy of GnRH analogue treatment before hysteroscopic resection of submucous myomas in patients with abnormal uterine bleeding . DESIGN Multicenter , prospect i ve , r and omized , clinical study . SETTING Tertiary-care university hospitals . PATIENT(S ) Thirty-nine consecutive patients with submucous myomas grade d as G0 or G1 according to the European Society for Gynecological Endoscopy classification ( myoma size 10 - 35 mm ) . INTERVENTION(S ) Patients were r and omized to either direct surgery or 2 months of GnRH analogues before undergoing hysteroscopic resection of the submucous myoma . MAIN OUTCOME MEASURE(S ) Operating times , fluid absorption , difficulty of the operation , surgeon satisfaction with the procedure , intra- and postoperative complications , postoperative pain , and patient satisfaction were recorded . RESULT ( S ) Patients treated with GnRH analogue had significantly shorter operative times ( 15.9+/-3.1 minutes vs. 21.3+/-4.0 minutes ) and significantly reduced fluid absorption ( 378+/-137 mL vs. 566+/-199 mL ) compared with no preoperative medical treatment . Operative difficulty and overall surgeon satisfaction were significantly better in the GnRH analogue group . Patient satisfaction was similar in the two groups . CONCLUSION ( S ) GnRH analogue treatment before hysteroscopic resection of G0-G1 10 - 35 mm submucous myomas was effective in reducing operative times , fluid absorption , and difficulty of the procedure STUDY OBJECTIVE To evaluate the efficacy of preoperative treatment with ulipristal acetate ( UPA ) in patients undergoing high complexity hysteroscopic myomectomy . DESIGN Retrospective analysis of a prospect ively collected data base ( Canadian Task Force classification II-2 ) . SETTING University teaching hospital . PATIENTS Patients of reproductive age requiring hysteroscopic myomectomy with STEPW ( size , topography , extension , penetration , and wall ) score 5 or 6 . INTERVENTIONS Patients included in the study either underwent direct surgery ( group S ) or received a 3-month preoperative treatment with UPA ( group UPA ) . Based on a power calculation , 25 patients were required in each study group . MEASUREMENTS AND MAIN RESULTS Myoma characteristics were similar in the 2 study groups . The 3-month UPA treatment caused a 21.9 % ( ±10.3 % ) mean ( ±SD ) percentage decrease in myoma volume . The number of complete resections ( primary outcome of the study ) was higher in group UPA ( 92.0 % ) than in group S ( 68.0 % ; p = .034 ) . The operative time was lower in group UPA than in group S ( p = .048 ) , whereas there was no significant difference in fluid balance between the 2 study groups ( p = .256 ) . The incidence of complications was similar in the 2 groups ( p = .609 ) . Patient satisfaction at 3 months from surgery was higher in group UPA than in group S ( p = .041 ) . CONCLUSION A 3-month preoperative treatment with UPA increases the possibility of complete resection in high complexity hysteroscopic myomectomy . It decreases the operative time and improves patient satisfaction at 3 months from surgery OBJECTIVE To investigate the efficacy and safety of ulipristal acetate ( UPA ) for long-term treatment of symptomatic uterine fibroids . DESIGN Repeated intermittent open-label UPA courses , each followed by r and omized double-blind norethisterone acetate ( NETA ) or placebo . SETTING European clinical gynecology centers . PATIENT(S ) Two hundred and nine women with symptomatic fibroids including heavy menstrual bleeding . INTERVENTION(S ) Patients received up to four 3-month courses of UPA 10 mg daily , immediately followed by 10-day double-blind treatment with NETA ( 10 mg daily ) or placebo . MAIN OUTCOME MEASURE(S ) Amenorrhea , fibroid volume , endometrial histology . RESULT ( S ) After the first UPA course , amenorrhea occurred in 79 % of women , with median onset ( from treatment start ) of 4 days ( interquartile range , 2 - 6 days ) . Median fibroid volume change was -45 % ( interquartile range , -66 % ; -25 % ) . Amenorrhea rates were 89 % , 88 % , and 90 % for the 131 , 119 , and 107 women who received treatment courses 2 , 3 , and 4 , respectively . Median times to amenorrhea were 2 , 3 , and 3 days for treatment courses 2 , 3 , and 4 , respectively . Median fibroid volume changes from baseline were -63 % , -67 % , and -72 % after treatment courses 2 , 3 , and 4 , respectively . All endometrial biopsies showed benign histology without hyperplasia ; NETA did not affect fibroid volume or endometrial histology . CONCLUSION ( S ) Repeated 3-month UPA courses effectively control bleeding and shrink fibroids in patients with symptomatic fibroids . CLINICAL TRIAL REGISTRATION Clinical Trials.gov ( www . clinical trials.gov ) registration numbers NCT01156857 ( PEARL III ) and NCT01252069 ( PEARL III extension ) OBJECTIVE To investigate the effect of cabergoline ( Dostinex , a dopamine agonist ) on the myoma growth compared to Diphereline ( a gonadotropin-releasing hormone agonist ) . METHODS This study took place in the Department of Obstetrics and Gynecology of Tabriz University of Medical Sciences , Tabriz , Iran from July 2004 to December 2005 . Fifty women with uterine myoma , who met the criteria of the study thoroughly , were r and omly allocated into 2 equal groups to take either Diphereline or Cabergoline . The first Group took 3.75 mg of Diphereline 4 times every 28 days and the second group took 0.5 mg of Cabergoline once a week for 6 weeks . RESULTS The Cabergoline was well tolerated and fewer adverse effects were noted . The tumor regressed significantly and volume reduction rate of individual tumor nodule varied from 46 - 53 % . The gonadotropin releasing hormone agonist group all responded to the treatment , and volume reduction rate of the individual tumor nodule varied from 21 - 97 % . The extent of tumor shrinkage was positively correlated to the number of nodules ( p=0.881 , p<0.005 and 0.701 , p<0.005 ) . CONCLUSION In light of therapeutic efficacy and few adverse effects , the dopamine agonists may hold promise as novel treatment modalities for leiomyoma . Further studies are warranted to determine the optimal strategy for the treatment of leiomyoma through these agents The recurrence of myomas and myoma-related symptoms was evaluated in women participating in a r and omized , double-blind , P-controlled study of the efficacy of LA depot before myomectomy . After 27 to 38 months of follow-up , the recurrence of myomas was found to be greater when at least four myomas were resected . Myoma recurrence was not associated with pretreatment or preoperative uterine volume , resected myoma mass , or preoperative medical therapy INTRODUCTION Asoprisnil , a novel orally active selective progesterone receptor modulator , is being studied for the management of symptomatic uterine leiomyomata . The exact mechanism of action is not yet discerned . The primary objectives of this double-blind , r and omized , placebo-controlled study included evaluation of the effect of asoprisnil on uterine artery blood flow . Furthermore , we assessed effects of asoprisnil on leiomyoma symptoms . PATIENTS AND METHODS Thirty-three premenopausal patients scheduled for hysterectomy due to symptomatic uterine leiomyomata were recruited in four centers and treated with 10 or 25 mg asoprisnil or placebo for 12 wk before surgery . At baseline and before hysterectomy , all patients underwent sonographic assessment to measure impedance to uterine artery blood flow , determined by resistance index and pulsatility index , as well as volumes of largest leiomyoma and uterus . In addition , patients recorded intensity and frequency of menstrual bleeding on a menstrual pictogram . Each asoprisnil treatment was compared with placebo . RESULTS The increased pulsatility index in both asoprisnil groups and the statistically significantly increased resistance index within the 25-mg asoprisnil group suggest a moderately decreased uterine artery blood flow . Analysis of menstrual pictogram scores showed a statistically significant larger decrease in frequency and intensity of bleeding for both asoprisnil groups compared with placebo . Bleeding was suppressed by asoprisnil 25 mg in 91 % of patients . Asoprisnil treatment was well tolerated when administered daily for a 12-wk period , and no serious adverse events occurred . CONCLUSION Asoprisnil moderately reduced uterine artery blood flow . This effect may contribute in part to the clinical effects of asoprisnil To determine whether pre-operative treatment with gonadotrophin-releasing hormone ( GnRH ) analogue may have a beneficial effect on surgery outcome , 53 patients with symptomatic fibroid uteri awaiting myomectomy or transabdominal hysterectomy ( TAH ) , were r and omly divided into a study group ( n = 29 ) and a control group ( n = 24 ) . The study group of patients were treated by an i.m . injection of D-Trp6 LHRH microcapsules at 2 months and 1 month prior to surgery . The control group had no pre-operative treatment . Haemoglobin concentration and oestradiol , follicle-stimulating hormone and luteinizing hormone concentrations were measured at 2 months and 1 month prior to surgery , and at surgery . The duration of surgery was shorter in the study group ( 49 versus 70 min in the hysterectomy group ) and intra-operative blood loss was less ( 208 versus 309 ml in the hysterectomies and 320 versus 476 ml in the myomectomies ) . Pre-operative treatment with GnRH-agonists which induces shrinkage of the uterus and fibroids is therefore efficient in shortening the duration of surgery , and diminishing the intra-operative blood loss in surgery for fibroid uteri . Such pre-operative treatment is therefore a useful addition to surgery in cases with symptomatic fibroid uteri OBJECTIVE To analyze the impact of the diameter ( myoma-φ ) and the uterine cavity protruding proportion ( protruding % ) of the submucous myoma on serum hemoglobin ( Hb ) level . DESIGN Retrospective descriptive study . SETTING Tertiary university hospital . PATIENT(S ) Two hundred fifty-nine women with a single submucous myoma . INTERVENTION(S ) Transvaginal ultrasound examination and office hysteroscopy . MAIN OUTCOME MEASURE(S ) Myoma-φ and protruding % were determined with transvaginal ultrasound scan and office hysteroscopy . Menorrhagic period ( months ) and serum Hb were recorded within 2 weeks of these examinations . RESULT ( S ) Serum Hb negatively correlated with myoma-φ , protruding % , and menorrhagic period . The negative association between serum Hb and protruding % was even more prominent after adjusting for myoma-φ . Multivariate regression analysis revealed that myoma-φ and protruding % , after adjusting for the confounding effect of menorrhagic period , maintained a strongly negative correlation with serum Hb level . When myoma-φ was < 2 cm , however , the serum Hb levels were similar regardless of the protruding % . CONCLUSION ( S ) For women with a single submucous myoma , myoma-φ and protruding % can determine the serum Hb level significantly . As myoma-φ and protruding % increased , the serum Hb level decreased accordingly STUDY OBJECTIVE To evaluate whether uterine shrinkage induced by gonadotropin-releasing hormone ( GnRH ) agonists in women with a large uterus ( > 14 wks ) may facilitate total laparoscopic hysterectomy . DESIGN R and omized , prospect i ve study ( Canadian Task Force classification I ) . SETTING University-affiliated hospital . PATIENTS Sixty-two women with symptomatic uterine myomas ( size 16 - 20 wks ) . INTERVENTIONS Total laparoscopic hysterectomy for benign pathology . MEASUREMENTS AND MAIN RESULTS Before surgery , women were assigned , at a ratio of 1:1 by r and om selection , to receive injections of triptorelin depot 11.25 mg 3 months before surgery ( group A ) or no treatment ( group B ) . Uterine volume , mean operating time , uterine weight , drop in hemoglobin , intraoperative complications , conversions to laparotomy , and hospital stay were recorded . Triptorelin decreased uterine volume , calculated by ultrasonography , by 26.5 % in group A , whereas the volume remained unchanged in group B. Statistical differences were found between groups concerning uterine weight , operating time , and drop in hemoglobin level . Three patients in group B were converted to laparotomy because of uterine size . CONCLUSION In women with a large uterus , a 3-month preoperative course of GnRH may facilitate laparoscopic hysterectomy , decreasing uterine size , operating time , and blood loss OBJECTIVE To evaluate whether administration of tibolone changes the effectiveness of GnRH analogue administered before laparoscopic myomectomy . DESIGN Prospect i ve , r and omized , open , placebo-controlled clinical trial . SETTING Department of Gynecology and Obstetrics , University of Naples Federico II , Naples , Italy . PATIENT(S ) 66 women with symptomatic uterine leiomyomas . INTERVENTION(S ) Treatment for 2 months with leuprolide acetate and iron tablets , plus tibolone ( group A ) or placebo tablets ( group B ) ; or with leuprolide acetate and iron tablets ( group C ) . MAIN OUTCOME MEASURE(S ) Laparoscopic myomectomy at the end of treatment . Operative time and blood loss during surgery were recorded . Uterine volume , volume and number of uterine leiomyomas , volume and echogenicity of the largest uterine leiomyomas , hematologic data , and myoma-related symptoms were evaluated at baseline and 1 week before and after surgery . RESULT ( S ) Uterine and leiomyomata volume and myoma-related symptoms were significantly reduced and hematologic variables improved significantly in groups A and B , compared with baseline values and with group C. Operative time and blood loss were significantly less in groups A and B than in group C. After surgery , hematologic variables were significantly worse in group C compared with groups A and B. During the study no significant difference was detected between groups A and B. CONCLUSIONS Administration of tibolone administration in patients treated with GnRH analogue before laparoscopic myomectomy does not change the effectiveness of the analogue administered alone OBJECTIVE To compare the use of a new antiestrogen fulvestrant with goserelin in reducing uterine fibroid growth before hysterectomy . DESIGN An international , multicenter , r and omized , placebo-controlled study . SETTING Departments of obstetrics and gynecology . PATIENT(S ) Premenopausal women ( n = 307 ) diagnosed with uterine fibroids requiring hysterectomy . INTERVENTION(S ) Over a 12-week period , patients received fulvestrant ( 50 mg , 125 mg , or 250 mg ) as an i.m . injection , goserelin ( 3.6 mg ) as a s.c . injection , or an injection-matched placebo once every 4 weeks . Patients underwent a hysterectomy at week 13 . MAIN OUTCOME MEASURES Efficacy endpoints included changes in fibroid growth , endometrial thickness , and uterine volume . The excretion of urinary markers of bone resorption was also examined . RESULT ( S ) Goserelin significantly reduced fibroid growth and endometrial thickness compared with placebos . Fulvestrant did not significantly alter fibroid volume or endometrial thickness or change endpoints such as endometrial histology or vaginal bleeding . Fulvestrant was associated with fewer postmenopause-related adverse events than goserelin . Goserelin , but not fulvestrant , significantly increased markers of bone resorption . CONCLUSION ( S ) At doses equivalent to those used for the treatment of breast cancer in postmenopausal women , fulvestrant did not significantly inhibit fibroid growth and , of particular note , did not lead to bone resorption OBJECTIVE To compare the effects of goserelin acetate treatment with or without iron with iron alone . DESIGN Multinational , multicenter , prospect i ve , r and omized , double-blind study . PATIENTS Premenopausal women with menorrhagia or metrorrhagia and anemia associated with uterine leiomyomata awaiting hysterectomy . INTERVENTION Patients were r and omized to one of three 12-week treatment groups namely goserelin acetate 3.6 mg once monthly plus placebo iron ; 3.6 mg goserelin acetate once monthly plus 600 mg/d iron ; or sham injection once monthly plus 600 mg/d iron . MAIN OUTCOME MEASURE Preoperative hemoglobin concentration ; preoperative uterine and fibroid volumes and operative blood loss . RESULTS Considering the entry and preoperative hemoglobin concentrations , there was a difference in least square means of just over 1 g/dL between the goserelin acetate plus iron and iron only groups and 2.6 g/dL between the goserelin acetate plus iron and goserelin acetate only group . These differences were both statistically significant . Uterine and fibroid volumes were decreased in the goserelin acetate-treated patients by between 37 % and 40 % and 44 % and 47 % , respectively , compared with 7 % decreases for both in the iron only group . The differences in absolute changes were statistically significant for both the goserelin acetate-treated groups versus the iron-treated group . The least square geometric mean operative blood loss was greatest in the iron only group . CONCLUSION In the patient with uterine leiomyomata and anemia , goserelin acetate in combination with iron therapy has shown significant advantages over the iron alone in restoring hematologic normality , decreasing uterine and fibroid volumes , and reducing operative blood loss OBJECTIVE To compare the mechanism of action of raloxifene and gosereline induced shrinkage of leiomyomas via estrogen receptor , progesterone receptor , bcl-2 and p53 expression immunohistochemically . STUDY DESIGN Thirty-two premenopausal women affected by uterine leiomyomas were r and omized into two equal groups . Group A was treated with gosereline ( 3.6 mg subcutaneous injection monthly ) and group B was treated with raloxifene ( 60 mg daily per os ) for 3 months before undergoing surgery . At entry and at the end of the treatment the leiomyoma volume was measured ultrasonografically and the volume change was calculated . Immunohistochemical detection of estrogen receptor ( ER ) , progesterone receptor ( PR ) , bcl-2 and p53 were performed on leiomyoma tissue sample s from group A , group B and the matched-control group . H-scores for ER , PR , bcl-2 and p53 were calculated . The mean volume changes of leiomyomas and immunohistochemical H-score differences of ER , PR , bcl-2 and p53 were compared between groups . RESULTS The leiomyoma volume decreased significantly after treatment in gosereline group from baseline of 65 cm(3 ) to 35 cm(3 ) , and in raloxifene group from 68 cm(3 ) to 50 cm(3 ) , p<0.05 . The difference between the before and after treatment leiomyoma volumes between the two treatments was not statistically significant . H-score of ER expression was significantly lower in gosereline group compared to control group ( 54.4 versus 113.2 , p = 0.001 ) , whereas H-score of PR expression was significantly lower with both gosereline and raloxifene groups compared to control group ( 64.8 for gosereline versus 94.6 for control , 73.6 for raloxifene versus 94.6 for control , p = 0.001 ) . The bcl-2 expression was higher in both gosereline and raloxifene groups compared to control group ( 173.7 for gosereline versus 94.7 for control , 179.7 for raloxifene versus 94.7 for control , p = 0.001 ) . The p53 expression was only lower with gosereline than the control group ( 169.4 versus 205.6 , p = 0.001 ) , whereas there was no significant change between the raloxifene group and the control group ( 201.9 versus 205.6 ) ( p>0.05 ) . CONCLUSION Raloxifene was as effective as gosereline in reducing leiomyoma volumes . Decreased PR expression may be a mechanism for tumor growth reduction in raloxifene treatment . In both treatment modalities , the mechanism of shrinkage of leiomyomas could not be increased apoptosis mediated by bcl-2 and p53 expression and should be investigated by further studies Objective To determine the effectiveness of leuprolide acetate depot plus iron compared with iron alone in the preoperative treatment of anemia due to prolonged or excessive bleeding associated with uterine leiomyomas . Methods This was a phase III , stratified , r and omized , double-blind , placebo-controlled , parallel-group , 12-week multicenter study . Enrolled patients had hemoglobin levels of 10.2 g/dL or less and /or hematocrit values of 30 % or less . Patients were entered into one of two strata based on their pre- study hematocrit level : stratum A , hematocrit less than or equal to 28 % , and stratum B , hematocrit greater than 28 % . Patients within each stratum were r and omized to one of three treatment arms : leuprolide acetate depot 7.5 mg , leuprolide acetate depot 3.75 mg , or placebo . All patients received iron orally . Response was defined as a hemoglobin level of 12 g/dL or more and a hematocrit value of 36 % or greater . Results Three hundred nine patients were entered into the study , of whom 265 were evaluated . Using our response criteria , a significantly greater number of patients in both leuprolide acetate groups ( combined strata ) responded to therapy than did those in the placebo group : 74 % in each leuprolide acetate group versus 46 % in the placebo group ( P < .001 ) . Gonadotropin-releasing hormone agonist-treated patients had a significant reduction in uterine and myoma volume when compared with the placebo group ( P < .01 ) . Hot flashes and vaginitis were reported significantly more often ( P < .001 ) in the leuprolide acetate-treated groups than in the placebo group . Conclusion Both dosages of GnRH agonist plus iron were more effective than iron alone in treating the anemia of patients with uterine leiomyomas , in reducing uterinemyoma volume , and in alleviating bleeding and other leiomyoma-related symptoms OBJECTIVE To evaluate if pre-operative GnRH-a modify uterine leiomyoma pseudocapsule and the possible clinical effects of these changes . STUDY DESIGN The study was performed at the University Federico II of Naples on 33 premenopausal patients su bmi tted to laparotomic myomectomy after treatment with triptorelin depot . 29 untreated patients formed the control group . The operating time , the intraoperative bleeding and the prompt identification of the cleavage plan between myoma and myometrium were evaluated . The pseudocapsule features and the immunoexpression of PCNA and CD34 in this area were studied . RESULTS Treated patients showed lower blood loss and not clearly identifiable cleavage plan , but without any significant increase in the operating time . Treated lesions showed less evident border between myoma and myometrium and lower PCNA and CD34 pseudocapsule immunoexpression than untreated ones . CONCLUSION We propose the changes of leiomyoma pseudocapsule as partial explanations of the reported clinical and surgical findings after pre-operative GnRH-a Objective To compare the size of arterial vessels in myomas from women treated with GnRH agonist ( GnRH-a ) or given placebo . Methods Our study group included 46 women about to undergo myomectomy or hysterectomy ; 30 were treated with leuprolide acetate ( 3.75 or 7.5 mg ) in three monthly doses , and 16 were given placebo . Arterial diameters of the intramyomatous vessels were measured using an ocular micrometer on hematoxylin and eosin-stained slides . Results Clinical ly and radiologically , the uterine volume of GnRH-a-treated patients decreased by an average of 30 % , and the diameter of the largest myoma decreased by 27 % . The average diameter of intramyomatous arteries was 24 % smaller in GnRH-a subjects compared with those receiving placebo ( 136 ± 42 versus 178 ± 60 μm , P < .01 ) . In addition , arteriosclerotic changes , including intimal and medial fibrosis , were seen more often in the GnRH-a-treated subjects ( 48 versus 25 % , P < .05 ) . Conclusion Intramyomatous arteries were smaller and more often showed arteriosclerotic changes in leiomyomas removed from women treated with GnRH-a compared with those given placebo . The estrogen deprivation induced by GnRH-a may cause a relative vasoconstriction of myomatous vessels . Whether this decreased vessel size is the principal contributor to decreased myoma size will require further study Aim of the study is to compare the effects of preoperative therapy with tibolone plus gonadotropin-releasing hormone analogue ( GnRH-a ) in premenopausal women with those of GnRH-a alone on clinical response , uterine volume , immunohistochemical expression of platelet-derived growth factor ( PDGF ) , vascular endothelial growth factor ( VEGF ) and basic fibroblast growth factor ( bFGF ) and vascular features of myomas . Seventy women with symptomatic uterine fibromatosis were treated for four months with leuprorelin acetate alone or plus tibolone . Untreated patients were su bmi tted to uterine surgery directly . Uterine volume , hematological data , BMD , myoma-related symptoms and hot flushes were evaluated at the admission and before surgery . Immunohistochemical expression of PDGF , bFGF and VEGF , vascular changes and CD105 expression , as a marker of angiogenesis , were evaluated in myomas obtained after surgery . Uterine volume and myoma-related symptoms reduced and hematological variables increased in treated patients . BMD decreased in patients treated with GnRH-a alone . Hot flushes were less in GnRH-a plus tibolone group than in GnRH-a group . Immunohistochemical expression of PDGF , bFGF and VEGF , vascularization and angiogenesis reduced in treated patients in comparison with untreated ones . In conclusion , the administration of tibolone plus GnRH-a before uterine surgery does not change the clinical and immunohistochemical effects of GnRH-a alone To evaluate the efficacy and safety of nafarelin before hysterectomy in a prospect i ve placebo-controlled trial , we r and omized 188 pre-menopausal women with uterine fibroids ( n = 111 ) , menometrorrhagia ( n = 58 ) or pelvic pain ( n = 19 ) to receive either nafarelin ( 200 micrograms twice daily as a nasal spray ) or a placebo for 3 months before abdominal hysterectomy . The data analysis could be performed in 166 women , of whom 107 received nafarelin and 59 a placebo . Nafarelin led to a rise in blood haemoglobin ( 5.5 g/l ) and to a decrease in uterine volume ( 23.7 % ) . This , however , gave no objective benefit during surgery ( similar operative duration s and blood losses ) . The uteri from patients treated with nafarelin ( 255.5 + /- 12.6 g , mean + /- SD ) were significantly lighter ( P = 0.029 ) than those from patients treated with a placebo ( 346.2 + /- 35.7 g ) . Histological examination of the fibroids or uteri revealed changes typical for hypo-oestrogenism , but no specific histological pattern could be established . The endometrium was proliferative in 56 % and showed mild hyperplastic features in 10 % of patients given nafarelin , whereas the respective figures for the placebo group were 41 and 0 % . Hot flushes were the most common side-effects , being reported by 61 % in the nafarelin group and 35 % in the placebo group . Nafarelin can be useful as a pre-surgical adjunct in a patient scheduled for abdominal hysterectomy if there is a need to raise the haemoglobin concentration or to reduce the size of the uterus OBJECTIVE To evaluate the role of three-monthly pre-treatment with gonadothropin releasing hormone ( GnRH ) analogues prior to myomectomy for women in comparison with control group of patients with no application . Analysis is focused on peroperative and postoperative results of surgery treatment for women with clinical ly symptomatic uterine fibroids in reproductive age with interest in getting pregnant . DESIGN Prospect i ve clinical study . SETTING Gynecological and Obstetric Clinic of Medical Faculty of Masaryk University and the University Hospital Brno . MAIN MEASURES The group of 212 patients with symptomatic uterine fibroids detected by ultrasound . 90 patients ( 42.5 % ) underwent laparoscopic myomectomy ( LM ) and 122 patients ( 57.5 % ) underwent open laparotomic myomectomy ( OM ) . In the selected group we were observing the common number of exstirpated uterine fibroids , their size , anatomical localisation , depth of invasion of dominant exstirpated uterine fibroid in relation to uterine wall . METHODS Both groups of patients were r and omised into two parts . The group LM with GnRH pretreatment contained 42 patients ( 19,8 % ) and control group with no pre-treatment 48 patients ( 22.7 % ) . Laparotomic part of study was divided into two groups with preoperative application of GnRH analogues 44 patients ( 36,7 % ) and control group OM with no application 44 patients ( 20.8 % ) . The main outcome measures were peroperative blood loss , duration of surgery , the length of hospital stay , evidence of per- and postoperative complications and the final results by second look laparoscopy ( SLL ) . RESULTS In the observed group LM with pre-treatment of GnRh analogues there was significantly higher volume of blood loss ( p = 0.0003 ) , significantly longer duration of surgery ( p = 0.0063 ) and significantly higher lenght of hospital stay ( p = 0.0025 ) compared with control group . We have not found a significant difference in the incidence of peroperational converse to laparotomy , final result of neoformation of uterus wall and occurrence of postoperative adhesions by SLL in observed LM group compared with control group . In the observed OM group with pre-treatment of GnRH analogues there was no significant difference in : peroperative blood loss ( p = 0.5324 ) , duration of surgery ( p = 0.3927 ) neither average length of hospital stay compared with control group . In the OM group , there was significantly lower incidence of recidives of uterine fibroids observed by SLL ( p = 0.0025 ) and no significant difference of occurrence of postoperative adhesions compared with control group . We have not found significant difference in the incidence of peroperative complications , early and late postoperative complications in group of LM and OM in comparison with control groups . CONCLUSION Application of GnRH analogues in observed group of patients before LM and OM have not lead to improvement of peroperative results in comparison with control group . Pre-treatment of GnRh analogues before OM have lead to significant drop in recidives of uterine fibroids observed by SLL ( p = 0.0025 ) compared with control group BACKGROUND Submucous fibroids are common benign tumours responsible for menorrhagia , subfertility and miscarriage . They can be readily removed by hysteroscopic transcervical resection of myoma ( TCRM ) . To facilitate resection , pre-operative GnRH analogues have been suggested , but the value of this treatment is uncertain . Our aim was to assess the value of pre-operative GnRH analogues for the resection of submucous fibroids . METHODS This was a prospect i ve , double-blind , placebo-controlled , r and omized trial . Women found to have submucous fibroids on three-dimensional saline infusion sonohysterography ( 3D SIS ) were r and omized to receive GnRH or placebo . Following treatment patients underwent TCRM by a single operator blinded to the group allocation . Women were followed up 6 weeks after their operation to ascertain resolution of symptoms . The primary outcome measure of the study was completeness of fibroid resection . Secondary outcome measures included the duration of the TCRM , the fluid deficit recorded at TCRM , the resolution of symptoms post-operatively and the number of subsequent fibroid related operations . RESULTS Forty-seven women were r and omized to GnRH or placebo . On the basis of intention-to-treat analysis , there was no significant difference in the number of complete fibroid resections between women who received GnRH analogues [ 14/24 , 58.3 % ( 95 % CI 38.6 - 78.1 ) ] and those who received placebo [ 16/23 , 69.6 % ( 50.8 - 88.4 ) ] ( RR 0.84 , 95 % CI 0.54 - 1.29 ; P = 0.43 ) . Similarly there was no significant difference between the groups in any of the secondary outcome measures . CONCLUSIONS Our study does not support routine administration of GnRH analogues before transcervical resection of fibroid as we did not identify any benefit in such treatment OBJECTIVES To compare the effect of the gonadotrophin-releasing hormone agonist leuprorelin and progestin lynestrenol , given prior to surgical treatment of symptomatic uterine myomas , on the pre-operative symptoms , tolerance , and operative blood loss . STUDY DESIGN Fifty-six women were r and omly selected to receive , during 16 weeks , either monthly subcutaneous injections of leuprorelin 3.75 mg sustained release ( n=33 ) or lynestrenol 5 mg two tabs per day ( 5th to the 25th menstrual cycle ) ( n=23 ) . RESULTS Intent-to-treat analysis of the main efficacy criterion , namely ultrasonographic reduction of myoma(s ) diameter , showed a significant difference in favour of leuprorelin ( P=0.02 ) with a mean decrease of 26.5+/-4.5 % ( n=29 ) as opposed to 7.3+/-5 % in the lynestrenol group ( n=17 ) . Clinical improvement was satisfactory in both groups . Hematocrit decrease between the preoperative value and the value measured 48 h postoperatively was significantly lower in the leuprorelin group than in the lynestrenol one ( P=0.02 ) ( for hemoglobin : P=0.07 ) . CONCLUSION Leuprorelin was more effective than lynestrenol because of its more intense antigonadotropic activity . The tolerance was good , reflecting each drug mechanism of action Objective : To evaluate the clinical features and the expression of transforming grwoth factor-β3 ( TGF-β3 ) and connective tissue growth factor ( CTGF ) in myometrium and uterine leiomyomas after preoperative treatment with gonadotropin-releasing hormone-analogs ( GnRH-a ) and tibolone . Methods : Twenty-three patients received 3.75 mg leuprolide acetate depot for 4 months . Twenty-two ptients received the same therapy plus 2.5 mg tibolone daily . Patients underwent uterine surgery after therapy . Twenty-two untreated patients underwent surgery directly . Hematologic tests , bone mineral density ( BMD ) measurement , and ultrasonographic evaluation of uterine volume were performed before and after treatment . Menorrhagia and pelvic pain were evaluated with a visual analog scale . Hot flushes were recorded in daily diaries . Immunohistochemical expression of TGF-β3 and CTGF in myometrium and myoma sample s was evaluated semiquantitatively . Results : After therapy , hemoglobin and iron levels similarly increased in both groups . BMD significantly decreased only in the GnRH-a group . Uterine volume similarly decreased in both groups . No patient had menorrhagia or pelvic pain at the end of therapy . The number of hot flushes increased after the first month in the GnRH-a group ; in the GnRH-a plus tibolone group , it remained constant and was lower . In untreated cases , TGF-β3 and CTGF smooth muscle cell immunoexpression was lower in myometrium than in leiomyomas . After medical treatment , growth factor immunoexpression remained unchanged in myometrial sample s and was reduced in leiomyomas . Endothelial cells showed strong immunopositivity , both in untreated and in treated cases . Conclusion : This study focuses on the effects of GnRH-a and tibolone on TGF-β3 and CTGF expression in myometrium and myomas and supports the hypothesis of a pathogenetic role of these growth factors in uterine fibromatosis OBJECTIVES Our purpose was to assess the changes in uterine volume and uterine artery pulsatility index in response to gonadotropin-releasing hormone agonist treatment in women undergoing hysterectomy for nonfibroid-related uterine bleeding . STUDY DESIGN A double-blind , placebo-controlled r and omized trial of 51 women awaiting hysterectomy in a gynecology outpatient clinic was conducted . The women were treated for 8 weeks with either leuprolide acetate depot or placebo . Vaginal ultrasonographic examinations were performed before and after treatment . The paired t test was used for statistical analysis . RESULTS In those allocated to therapy with gonadotropin-releasing hormone agonist the mean uterine volume decreased by 34 % and the uterine artery pulsatility index increased from 2.25 to 2.7 . No significant changes were seen in the placebo group . The intersonographer variability was low and there was a high correlation between uterine size as measured by ultrasonography before hysterectomy and that measured postoperatively . CONCLUSIONS Treatment with gonadotropin-releasing hormone agonists leads to uterine shrinkage and an increase in the uterine artery pulsatility index even in the absence of uterine fibroids OBJECTIVE To compare the usefulness of preoperative treatment with triptorelin , letrozole or ulipristal acetate or no treatment before hysteroscopic removal of uterine submucosal myomas . STUDY DESIGN Single center prospect i ve non-r and omized comparative pilot study . The study included consecutive premenopausal patients undergoing hysteroscopic resection of myomas grade d as type 0 , type 1 or type 2 according to the FIGO classification with diameter between 20 and 35 mm . Exclusion criteria were : associated polyps , associated non-hysteroscopic surgical procedures , > 2 myomas requiring hysteroscopic resection . This study enrolled patients who underwent either direct surgery ( group S ; n=23 ) or 3-month preoperative treatment with triptorelin ( 3.75 mg every 28 days ; group T ; n=20 ) , letrozole ( 2.5 mg/day ; group L ; n=11 ) or ulipristal acetate ( 5 mg/day ; group U ; n=7 ) . Patients underwent hysteroscopic resection of the myomas . RESULTS All medical treatments caused a significant decrease in the volume of myomas ( group T , p<.001 ; group L , p<.001 ; group U , p=.006 ) ; however , the percentage decrease in myoma volume was lower in group U than in group T ( p=.001 ) and in group L ( p=.010 ) . The hysteroscopy time was higher in group S than in group T ( p<.001 ) and in group L ( p=.001 ) ; there was no significant difference in the hysteroscopy time between group S and group U ( p=.206 ) . Fluid absorption was lower in group T than in group S ( p=.002 ) and in group L than in group S ( p=.048 ) ; fluid absorption was similar in group S and group U ( p=.110 ) . Intra- and postoperative complications , postoperative pain , and patient satisfaction were similar in the four study groups . Surgeon 's evaluation of operative difficulty was better in group T than in group S ( p<.005 ) . CONCLUSIONS Preoperative treatment with triptorelin and letrozole decreases the hysteroscopy time and the volume of fluid absorbed during hysteroscopic resection of uterine submucosal myomas Two hundred and forty-seven patients with uterine fibroids were r and omized to surgery alone or 3 months ' Zoladex ( Zeneca , Macclesfield , Ches . , UK ) followed by surgery . Zoladex significantly reduced uterine and fibroid volumes ( p = 0.0001 ) . There was a significantly ( p = 0.002 ) greater mean rise in haemoglobin from entry to preoperation in the Zoladex group ( 1 g/dl ) compared with the surgery-alone group ( 0.3 g/dl ) as well as a tendency towards easier surgery , and reduced operative blood loss . Zoladex-treated patients had a significantly ( p = 0.016 ) shorter hospital stay and pelvic pain and abdominal pressure symptoms were significantly ( p < 0.0001 ) reduced in this group . Zoladex was well tolerated OBJECTIVE To evaluate leuprolide acetate ( LA ) depot ( Enantone Depot , Takeda , Italy ) when administered preoperatively in hysteroscopic surgery . DESIGN Prospect i ve , comparative study . SETTING University Clinic of Obstetrics and Gynecology . PATIENTS One hundred ninety-three patients ( 114 pretreated with LA depot and 79 controls ) who underwent hysteroscopic surgery for uterine septa ( group A ) , submucous fibroids ( group B ) , and abnormal uterine bleeding ( group C ) . RESULTS In groups B and C there was a significant reduction in the operating time , bleeding during the operation , and the amount of distention medium required after LA depot administration , but no significant differences in surgical feasibility or efficacy were found in group A patients after treatment . CONCLUSION Preoperative treatment with LA depot is effective in making hysteroscopic surgery easier Short-term treatment with gonadotropin-releasing hormone agonist ( GnRHa ) is a useful preoperative medical therapy of uterine leiomyomas . However , adverse effects caused by the hypo-estrogen state sometimes appear , suggesting the necessity of add-back therapy . In this study , we investigated effects of three kinds of add-back therapies on the proliferative activity of uterine leiomyoma cells by examining the expression of Ki-67 in leiomyoma cells by immunostaining . Thirty patients who were to undergo hysterectomy or myomectomy were injected with 3.75 mg depot leuprolide acetate every four weeks until the end of the 12th week . Twenty patients underwent add-back therapy from the 5th week to the end of the 12th week , 8 patients receiving 0.625 mg of conjugated equine estrogen ( CEE ) /day , 6 patients 5.0 mg of medroxyprogesterone acetate (MPA)/day , 6 patients 0.625 mg CEE plus 2.5 mg of MPA /day . The add-back of CEE or CEE plus MPA suppressed decreases in the proliferative activity of leiomyoma cells caused by GnRHa therapy , but that of MPA did not . These results suggest that the add-back therapy with MPA is of use in preventing the adverse effects caused by hypo-estrogen in the preoperative short-term GnRHa therapy Gonadotropin-releasing hormone agonists induce a reversible hypogonadotropic hypogonadal environment . Leiomyomas are common , estrogen-sensitive , benign neoplasms that decrease in size by 40 % to 50 % during gonadotropin-releasing hormone agonist treatment . During gonadotropin-releasing hormone agonist therapy most women are amenorrheic . After discontinuation of gonadotropin-releasing hormone agonist treatment , uterine and myoma size increase and a return to pretreatment menstrual patterns often occurs . Concerns about the safety of long-term hypoestrogenism have made long-term gonadotropin-releasing hormone agonist administration an undesirable treatment strategy . This article focuses on the use of gonadotropin-releasing hormone agonists as preoperative therapy in selected women undergoing hysterectomy or myomectomy and the combination of a gonadotropin-releasing hormone agonist with estrogen-progestin " add-back " treatment as a potential long-term medical therapy for women with symptomatic leiomyomas . Finally , an estrogen threshold hypothesis to assess the effects of circulating estrogen concentrations on different tissues , is presented It has been amply demonstrated that uterine leiomyoma possess estrogen receptors . On the basis of this presupposition , it is considered logical to use GnRH-agonists which , by reducing the level of estrogen , also reduce the volume of the leiomyoma , although to a varying extent . The maximum reduction which can be obtained occurs , according to published data , between 3 and 6 months of treatment , attaining mean values of approximately 50 % . In the author 's experience the treatment period was shortened even further by administering only 2 vials of leuprolide depot each month to women who subsequently underwent hysterectomy . The sample group comprised 30 women with uterine leiomyomatosis , of whom 15 were treated with a GnRH analogue and 15 with placebo . The reduction of uterine volume was evaluated by echography and was found to be 40 % in the treated group , whereas non change was detected in the " placebo-group " BACKGROUND Women with symptomatic uterine leiomyomas ( fibroids ) may have iron-deficiency anemia ( IDA ) ; therefore , surgery places them at risk of blood-borne morbidity from perioperative transfusions . Such women might benefit from a preoperative treatment that restores hematologic normality and alleviates fibroid symptoms . OBJECTIVE The purpose of this study was to examine the effects of a single preoperative depot injection of goserelin acetate plus iron treatment compared with iron monotherapy , in premenopausal women with IDA due to uterine leiomyomas . METHODS This Phase III , r and omized , multicenter , double-blind , controlled trial ( 12 weeks of treatment plus a 24-week follow-up period ) was conducted from October 1997 to August 1999 . Patients received an injection of goserelin acetate 10.8 mg ( 3-month formulation ) or a sham , with both groups receiving PO iron ( ferrous sulfate ) 325-mg tablets TID during the 12-week treatment period . Surgery ( hysterectomy or myomectomy ) was planned for week 12 . Hemoglobin ( Hb ) level , symptoms of uterine leiomyomas , requirement for blood transfusion throughout , ability to donate blood for autologous transfusion , and leiomyoma and uterine volume were assessed for efficacy . The tolerability assessment included bone mineral density measurements and subjective symptomatology ( ie , menstrual bleeding [ uterine hemorrhage ] , fatigue , pelvic pain , and pelvic pressure ) . RESULTS A total of 110 women received treatment ( n = 54 , goserelin acetate 10.8 mg ; n = 56 , sham ) . The majority of patients ( 69.1 % ) were black and the mean age at study entry was 39.9 years , with a mean weight of 80.1 kg . At approximately 12 weeks , Hb levels were significantly higher in the goserelin group compared with the sham group ( difference of least squares mean , 1.17 g/dL ; 95 % CI , 0.68 - 1.66 ; P < 0.001 ) , and significantly more patients in the goserelin group had an increase in Hb concentration of > or=2 g/dL ( odds ratio 6.36 ; 95 % CI , 2.00 - 20.18 ; P < 0.001 ) . A nonsignificant decrease in both uterine and leiomyoma volume was experienced by patients who administered goserelin compared with increases in the sham group . Uterine hemorrhage was also experienced numerically less often by goserelin-treated patients compared with those given the sham injection ( 9.3 % vs 28.6 % , respectively ) . One or more adverse events ( AEs ) were reported by 89 % of patients in each treatment group . Goserelin acetate 10.8 mg was generally well tolerated by patients , with no serious drug-related AEs reported during this 36-week trial . CONCLUSION A single , preoperative injection of goserelin acetate 10.8 mg in addition to PO iron 325 mg TID was associated with improved Hb levels in these premenopausal women with IDA due to uterine leiomyomas Eighteen premenopausal women with symptomatic leiomyomata uteri were enrolled in a stratified , r and omized , double-blind , placebo-controlled study evaluating the efficacy of leuprolide acetate ( LA ) depot treatment before myomectomy . Stratification was based on pretreatment uterine volume ( less than 600 cm3 versus greater than or equal to 600 cm3 ) . Nine women received intramuscular ( IM ) depot LA 3.75 mg every 4 weeks for 12 weeks ( group A ) ; nine women received IM placebo with the same injection schedule ( group B ) . All women underwent myomectomy within 4 weeks of their last injection . Mean total intraoperative blood loss was 213 + /- 44 mL ( mean + /- st and ard error of the mean [ SEM ] ) in group A and 302 + /- 43 mL in group B. When data from patients with large uteri ( pretreatment uterine volumes of 600 cm3 or greater ) were analyzed , mean total blood loss was 189 + /- 44 mL in group A and 390 + /- 20 mL in group B. These data suggest that leuprolide depot treatment before myomectomy may decrease intraoperative blood loss in women with large leiomyomata uteri Objective To evaluate the use of pre‐operative leuprorelin acetate for reducing the morbidity from hysterectomy for nonfibroid menorrhagia BACKGROUND The efficacy and safety of oral ulipristal acetate for the treatment of symptomatic uterine fibroids before surgery are uncertain . METHODS We r and omly assigned women with symptomatic fibroids , excessive uterine bleeding ( a score of > 100 on the pictorial blood-loss assessment chart [ PBAC , an objective assessment of blood loss , in which monthly scores range from 0 to > 500 , with higher numbers indicating more bleeding ] ) and anemia ( hemoglobin level of ≤10.2 g per deciliter ) to receive treatment for up to 13 weeks with oral ulipristal acetate at a dose of 5 mg per day ( 96 women ) or 10 mg per day ( 98 women ) or to receive placebo ( 48 women ) . All patients received iron supplementation . The co primary efficacy end points were control of uterine bleeding ( PBAC score of < 75 ) and reduction of fibroid volume at week 13 , after which patients could undergo surgery . RESULTS At 13 weeks , uterine bleeding was controlled in 91 % of the women receiving 5 mg of ulipristal acetate , 92 % of those receiving 10 mg of ulipristal acetate , and 19 % of those receiving placebo ( P<0.001 for the comparison of each dose of ulipristal acetate with placebo ) . The rates of amenorrhea were 73 % , 82 % , and 6 % , respectively , with amenorrhea occurring within 10 days in the majority of patients receiving ulipristal acetate . The median changes in total fibroid volume were -21 % , -12 % , and + 3 % ( P=0.002 for the comparison of 5 mg of ulipristal acetate with placebo , and P=0.006 for the comparison of 10 mg of ulipristal acetate with placebo ) . Ulipristal acetate induced benign histologic endometrial changes that had resolved by 6 months after the end of therapy . Serious adverse events occurred in one patient during treatment with 10 mg of ulipristal acetate ( uterine hemorrhage ) and in one patient during receipt of placebo ( fibroid protruding through the cervix ) . Headache and breast tenderness were the most common adverse events associated with ulipristal acetate but did not occur significantly more frequently than with placebo . CONCLUSIONS Treatment with ulipristal acetate for 13 weeks effectively controlled excessive bleeding due to uterine fibroids and reduced the size of the fibroids . ( Funded by PregLem ; Clinical Trials.gov number , NCT00755755 . ) Selective progesterone receptor modulators ( SPRMs ) have beneficial effects in reducing the size of uterine fibroids and the amount of bleeding , but their endometrial effects have not been seen with other agents . This report describes the morphology of the endometrium after 3 mo of treatment with the SPRM , ulipristal acetate ( UPA ) . In 2 Phase III r and omized double-blind controlled clinical trials , 546 patients with uterine myomas were treated with 5 or 10 mg of UPA daily for 13 wk or placebo or gonadotropin-releasing hormone agonist . Endometrial biopsies were taken at screening , end of treatment ( 13 wk ) , and after treatment-free follow-up ( 38 wk ) . Biopsies were assessed independently by 3 pathologists according to a preset morphologic scheme . After 13 wk , the UPA-treated endometrium showed altered architectural gl and ular features including extensive cystic dilatation . The gl and ular epithelium appeared inactive or contained abortive subnuclear vacuolization , occasional mitoses , and apoptosis . Abnormal stromal vessels were commonly seen . There was a high level of agreement between pathologists on the presence or the absence of nonphysiological changes . One case of hyperplasia without atypia and 4 polyps were seen at 13 wk of UPA treatment . Six months after treatment , the endometrium returned to normal histology in the majority of the patients , with 1 polyp and no cases of hyperplasia in the UPA-treated groups , and 2 hyperplasias ( 1 with and 1 without atypia ) in the placebo or the gonadotropin-releasing hormone-agonist groups . Mild reversible thickening of the endometrium occurs in a minority of cases . It is important that pathologists are aware of the spectrum of changes induced by SPRMs to avoid misdiagnoses of endometrial hyperplasia or polyps |
13,294 | 30,509,548 | Conclusions Most of the studies reported clinical ly acceptable values for marginal adaptation .
The performance of a CAD‐CAM system is influenced by the type of restorative material .
A nonretentive cavity preparation exhibited better adaptation than a retentive preparation .
Most studies showed that thermomechanical loading affected the quality of marginal adaptation .
Cementation increased marginal discrepancies .
No statistically significant difference was found for marginal fit of onlays between intraoral and extraoral optical scans using a stone die .
The number of milling axes , the type of digital camera , and the region measured were statistically significant in relation to marginal/internal adaptation .
Values of adaptation recorded failed to reproduce the preestablished spacer parameters in the software . | Statement of problem Different parameters can influence the adaptation of computer‐assisted design and computer‐assisted manufacturing ( CAD‐CAM ) inlay/onlay restorations .
However , systematic review s to identify and discuss these parameters are lacking .
Purpose The purpose of this systematic review was to summarize the scientiÜc literature investigating all parameters that can influence both the marginal and internal adaptation of CAD‐CAM inlay/onlay restorations . | The aim of this study was to evaluate the internal fit , marginal adaptation , and bond strengths of inlays made of computer-aided design /computer-aided manufacturing feldspathic ceramic and polymer-infiltrated ceramic . Twenty molars were r and omly selected and prepared to receive inlays that were milled from both material s. Before cementation , internal fit was achieved using the replica technique by molding the internal surface with addition silicone and measuring the cement thicknesses of the pulpal and axial walls . Marginal adaptation was measured on the occlusal and proximal margins of the replica . The inlays were then cemented using resin cement ( Panavia F2.0 ) and subjected to two million thermomechanical cycles in water ( 200 N load and 3.8-Hz frequency ) . The restored teeth were then cut into beams , using a lathe , for microtensile testing . The contact angles , marginal integrity , and surface patterns after etching were also observed . Statistical analysis was performed using two-way repeated measures analysis of variance ( p<0.05 ) , the Tukey test for internal fit and marginal adaptation , and the Student t-test for bond strength . The failure types ( adhesive or cohesive ) were classified on each fractured beam . The results showed that the misfit of the pulpal walls ( p=0.0002 ) and the marginal adaptation ( p=0.0001 ) of the feldspathic ceramic were significantly higher when compared to those of the polymer-infiltrated ceramic , while the bond strength values of the former were higher when compared to those of the latter . The contact angle of the polymer-infiltrated ceramic was also higher . In the present study , the hybrid ceramic presented improved internal and marginal adaptation , but the bond strengths were higher for the feldspathic ceramic Objectives This study was conducted to evaluate a self-adhesive resin luting cement [ RelyX Unicem 3MESPE – RXU ] for luting partial ceramic crowns ( PCCs ) with and without selective enamel etching in a prospect i ve , r and omized clinical trial . Material s and methods Thirty-four patients had received the intended treatment . Two PCCs ( Vita Mark II ; Cerec 3D ; Sirona ) had been placed in a split-mouth design : one with RXU without enamel etching ( RXU ) , the other with RXU with selective enamel etching ( RXU + E ) . Restorations were evaluated at baseline ( BL ) and after 12 , 24 , and 36 months ( USPHS criteria ) . For statistical analysis , the Chi-square test was applied ( α = 0.05 ) . Clinical survival of all restorations ( n = 68 ) after 3 years was determined using Kaplan – Meier analysis . Results Twenty three patients ( 12 male/11 female ) were available for clinical evaluation after 3 years . 19 RXU-PCCs were placed in molars , four in premolars , 18 RXU + E – PCCs in molars , five in premolars . Concerning clinical changes , no significant differences were found between luting strategies RXU/RXU + E at all recalls . Statistically significant changes over time were observed for marginal adaptation and marginal discoloration between BL and 36 m for RXU and RXU + E. For RXU + E , postoperative hypersensitivities decreased significantly from BL ( n = 6 ) to 36 m ( n = 0 ) . Of the 68 restorations originally included , eight RXU and four RXU + E restorations failed . At 3 years , Kaplan – Meier survival of RXU was 72.9 % , that of RXU + E 87.6 % . Survival rates were not statistically significant different . Conclusions Although clinical survival of RXU + E is slightly better at 3 years , restorations of both groups perform similar with respect to clinical changes over time as evaluated by modified USPHS criteria . Clinical relevance The self-adhesive resin cement RXU can be used in conjunction with selective enamel etching , because survival rates of PCCs in the RXU + E group were not lower but , as a trend , even better than without enamel etching Statement of problem Trials comparing the overall performance of digital with that of conventional workflows in restorative dentistry are needed . Purpose The purpose of the third part of a series of investigations was to test whether the marginal and internal fit of monolithic crowns fabricated with fully digital workflows differed from that of crowns fabricated with the conventional workflow . Material and methods In each of 10 participants , 5 monolithic lithium disilicate crowns were fabricated for the same abutment tooth according to a r and omly generated sequence . Digital workflows were applied for the fabrication of 4 crowns using the Lava , iTero , Cerec inLab , and Cerec infinident systems . The conventional workflow included a polyvinyl siloxane impression , manual waxing , and heat‐press technique . The discrepancy between the crown and the tooth was registered using the replica technique with polyvinyl siloxane material . The dimensions of the marginal discrepancy ( Discrepancymarginal ) and the internal discrepancy in 4 different regions of interest ( Discrepancyshoulder , Discrepancyaxial , Discrepancycusp , and Discrepancyocclusal ) were assessed using light microscopy . Post hoc Student t test with Bonferroni correction was applied to detect differences ( & agr;=.05 ) . Results Discrepancymarginal was 83.6 ±51.1 & mgr;m for the Cerec infinident , 90.4 ±66.1 & mgr;m for the conventional , 94.3 ±58.3 & mgr;m for the Lava , 127.8 ±58.3 & mgr;m for the iTero , and 141.5 ±106.2 & mgr;m for the Cerec inLab workflow . The differences between the treatment modalities were not statistically significant ( P>.05 ) . Discrepancyshoulder was 82.2 ±42.4 & mgr;m for the Cerec infinident , 97.2 ±63.8 & mgr;m for the conventional , 103.4 ±52.0 & mgr;m for the Lava , 133.5 ±73.0 & mgr;m for the iTero , and 140.0 ±86.6 & mgr;m for the Cerec inLab workflow . Only the differences between the Cerec infinident and the Cerec inLab were statistically significant ( P=.036 ) . The conventionally fabricated crowns revealed significantly lower values in Discrepancycusp and Discrepancyocclusal than all the crowns fabricated with digital workflows ( P<.05 ) . Conclusions In terms of marginal crown fit , no significant differences were found between the conventional and digital workflows for the fabrication of monolithic lithium disilicate crowns . In the occlusal regions , the conventionally manufactured crowns revealed better fit than the digitally fabricated crowns . Chairside milling result ed in less favorable crown fit than central ized milling production Background Evaluation of the marginal fit of cemented zirconia copings manufactured after digital impression with Lava ™ Chairside Oral Scanner in comparison to that of zirconia copings manufactured after conventional impressions with polyvinyl siloxane . Methods A prepared typodont tooth # 36 , was replicated 40 times with a vinyl silicone and precise model resin . The dies were r and omly divided into two groups according to the impression taking technique . Digital impressions with Lava ™ C.O.S. and conventional impressions were taken according to the group . Subsequently zirconia copings were manufactured and cemented on their respective dies with zinc oxide phosphate cement . After embedding in resin , mesio-distal section of each coping was performed with a diamond saw in order to obtain two slices . One half of the specimen was used for evaluation with an optical microscope ( OM ) and the other half for evaluation with a scanning electron microscope ( SEM ) . Marginal gap ( MG ) and absolute marginal discrepancy ( AMD ) were measured mesial and distal on each slice . Results No significant difference of the marginal parameters between the digital and the conventional group was found . The mean values for MG in the digital group were 96.28 μm ( + /−43.21 μm ) measured with the OM and 99.26 μm ( + /−48.73 μm ) measured with the SEM , respectively . AMD mean values were 191.54 μm ( + /−85.42 μm ) measured with the optical microscope and 211.6 μm ( + /−96.55 μm ) with the SEM . For the conventional group the mean MG values were 94.84 μm ( + /−50.77 μm ) measured with the OM and 83.37 μm ( + /−44.38 μm ) measured with the SEM , respectively . AMD mean values were 158.60 μm ( + /−69.14 μm ) for the OM and 152.72 μm ( + /−72.36 ) for the SEM . Conclusions Copings manufactured after digital impression with Lava ™ C.O.S. show comparable marginal parameters with the copings manufactured after conventional impression with polyvinyl syloxane . The mean MG values of both groups fit in the clinical ly acceptable range OBJECTIVES The aim of the study was to evaluate the marginal and internal fit of heat-pressed and CAD/CAM fabricated all-ceramic onlays before and after luting as well as after thermo-mechanical fatigue . MATERIAL S AND METHODS Seventy-two caries-free , extracted human m and ibular molars were r and omly divided into three groups ( n=24/group ) . All teeth received an onlay preparation with a mesio-occlusal-distal inlay cavity and an occlusal reduction of all cusps . Teeth were restored with heat-pressed IPS-e.max-Press * ( IP , * Ivoclar-Vivadent ) and Vita-PM9 ( VP , Vita-Zahnfabrik ) as well as CAD/CAM fabricated IPS-e.max-CAD * ( IC , Cerec 3D/InLab/Sirona ) all-ceramic material s. After cementation with a dual-polymerising resin cement ( VariolinkII * ) , all restorations were subjected to mouth-motion fatigue ( 98 N , 1.2 million cycles ; 5 ° C/55 ° C ) . Marginal fit discrepancies were examined on epoxy replicas before and after luting as well as after fatigue at 200 × magnification . Internal fit was evaluated by multiple sectioning technique . For the statistical analysis , a linear model was fitted with accounting for repeated measurements . RESULTS Adhesive cementation of onlays result ed in significantly increased marginal gap values in all groups , whereas thermo-mechanical fatigue had no effect . Marginal gap values of all test groups were equal after fatigue exposure . Internal discrepancies of CAD/CAM fabricated restorations were significantly higher than both press manufactured onlays . CONCLUSIONS Mean marginal gap values of the investigated onlays before and after luting as well as after fatigue were within the clinical ly acceptable range . Marginal fit was not affected by the investigated heat-press versus CAD/CAM fabrication technique . Press fabrication result ed in a superior internal fit of onlays as compared to the CAD/CAM technique . CLINICAL RELEVANCE Clinical requirements of 100 μm for marginal fit were fulfilled by the heat-press as well as by the CAD/CAM fabricated all-ceramic onlays . Superior internal fit was observed with the heat-press manufacturing method . The impact of present findings on the clinical long-term behaviour of differently fabricated all-ceramic onlays warrants further investigation STATEMENT OF PROBLEM Gap measurements along margins are frequently used to assess the quality of single crowns . However , the number of gap measurements required for clinical ly relevant results in laboratory studies is not known . PURPOSE This study estimated the minimum number of gap measurements on margins of single crowns to produce relevant results for gap analysis . METHODS AND MATERIAL Ten all-ceramic crowns were fabricated on a master steel die . Gaps along crown margins were investigated in a scanning electron microscope on the master steel die without cementation and on replica dies after conventional cementation . Measurements were made in 100 microm steps according to 3 gap definitions . The initial number of measurements per crown ( n = 230 ) was reduced to smaller subsets using both systematic and r and om approaches to determine the impact on the quality of results . RESULTS On the data of gap definition 1 , reduction from 230 to about 50 measurements caused less than + /-5 microm variability for arithmetic means . Analysis of st and ard errors showed slowly increasing values smaller than 3 microm , both indicating no relevant impact on the quality of results . Smaller data sizes yielded accelerated increase of st and ard errors and divergent variabilities of mean . The minimum of 50 measurements did not depend on gap definition or on cementation condition . CONCLUSION Fifty measurements are required for clinical ly relevant information about gap size regardless of whether the measurement sites are selected in a systematic or r and om manner , which is far more than what current in vitro studies use Objective This study examined the fit of two types of all-ceramic single crowns and indirect composite resin full coverage crowns . Material and Methods Thirty intact human m and ibular first premolars were selected for this study and prepared using a machine to st and ardize the dimensions and r and omly divided into 3 groups . Slip cast ( IC ) ( In-Ceram Zirconia , Vita Zahnfabrik ) , copy-milled zirconia ( CM ) ( ICE , Zirkonzahn ) and indirect composite resin crowns ( NECO , HeraeusKulzer , Hanau , Germany ) , ( N=30 , 10 per group ) were fabricated according to each manufacturer 's recommendations . Before cementation , discrepancies were measured at the marginal zone in each crown . Crowns were then cemented with G-Cem capsule self-adhesive luting cement ( GC Corporation , Tokyo , Japan ) . Four positions were marked for each zone ( mid-facial , mid-mesial , mid-distal , and mid-lingual ) and three measurements were made at each of the four positions yielding to a total of 12 measurements per crown before and after cementation . The measurements were performed at a different magnification using a stereo microscope ( SZ11 , Olympus , Japan ) . Marginal , axial and occlusal zone discrepancies ( µm ) were evaluated after cementation . The data were statistically analyzed using two-way ANOVA and Tukey 's test . Results Before cementation , significantly less marginal discrepancies were noted compared with after cementation in all groups ( p<0.05 ) . No significant differences were found within each zone ( Marginal= IC : 84.2 , NECO : 95.22 , CM : 84.22 ; Axial= IC : 54.22 , NECO : 64.2 , CM : 55.22 ; Occlusal= IC : 119.97 , NECO : 129.18 , CM : 121.15 ) in the three crown systems ( p>0.05 ) . Occlusal zone discrepancies were significantly higher than those of the marginal and axial zones in all groups ( p<0.05 ) . Conclusions Slip cast and copy-milled zirconia crowns showed comparable fit to composite resin crowns in all marginal , axial and occlusal areas PURPOSE Evaluating the effect of a proximal margin elevation technique on marginal adaptation of ceramic inlays . METHODS Class II MOD-cavities were prepared in 40 human molars and r and omly distributed to four groups ( n = 10 ) . In group EN ( positive control ) proximal margins were located in enamel , 1 mm above the cementoenamel junction , while 2 mm below in groups DE-1In , DE-2In and DE . The groups DE-1In , DE-2In and DE simulated subgingival location of the cervical margin . In group DE-1In one 3 mm and in group DE-2In two 1.5 mm composite layers ( Tetric ) were placed for margin elevation of the proximal cavities using Syntac classic as an adhesive . The proximal cavities of group DE remained untreated and served as a negative control . In all groups , ceramic inlays ( Cerec 3D ) were adhesively inserted . Replicas were taken before and after thermomechanical loading ( 1.200.000 cycles , 50/5 ° C , max . load 49 N ) . Marginal integrity ( tooth-composite , composite-inlay ) was evaluated with scanning electron microscopy ( 200 × ) . Percentage of continuous margin ( % of total proximal margin length ) was compared between groups before and after cycling using ANOVA and Scheffé post-hoc test . RESULTS After thermomechanical loading , no significant differences were observed between the different groups with respect to the interface composite-inlay and tooth-composite with margins in dentin . The interface tooth-composite in enamel of group EN was significantly better compared to group DE-2In , which was not different to the negative control group DE and DE-1In . CONCLUSION Margin elevation technique by placement of a composite filling in the proximal box before insertion of a ceramic inlay results in marginal integrities not different from margins of ceramic inlays placed in dentin Objectives This study aims to evaluate the effect of a minimally invasive mesial – occlusal – distal ( mod ) preparation on the marginal adaptation of ceramic and composite inlays with the aim of saving sound dental substance . Material s and methods Class II mod cavities were prepared in 50 extracted human molars and r and omly allocated to five groups ( n = 10 ) . In all groups , the mesial – proximal box margins were located in the dentin , 1 mm below the cementoenamel junction ( CEJ ) , while the distal box margins were 1 mm above the CEJ . In groups A and B , conventional st and ard preparations with a divergent angle of α = 6 ° were prepared . In groups C , D , and E , minimally invasive st and ard preparations with a convergent angle of α = 10 ° were prepared . In groups A and D , composite inlays and , in groups B and C , ceramic inlays were fabricated ( chairside economical restoration of esthetic ceramics ( CEREC ) ) and adhesively inserted . In group E , a direct composite filling using the incremental technique was placed . Replicas were taken before and after thermomechanical loading ( 1,200,000 cycles , 50/5 ° C , max . load 49 N ) . Marginal integrity ( tooth – luting composite , luting composite – inlay ) was evaluated by scanning electron microscopy ( ×200 ) . The percentage of continuous margins in the different locations was compared between and within groups before and after cycling , using ANOVA and Scheffé post hoc test . Results After the thermomechanical loading , no significant differences were observed between the different groups with respect to the interface of luting composite – inlay . At the interface of tooth – luting composite for preparations involving the dentin , groups A and B behaved significantly better compared to the control group E , which in turn were not different to groups C and D. Conclusion Composite and ceramic inlays inserted in minimally invasive prepared mod cavities result in margins not different from those of inlays placed in conventional mod preparations . Direct composite filling margins , however , were inferior to those attained by conventional indirect restorations . Clinical relevance Minimally invasive preparations for mod inlays with undercuts show marginal adaptation equal to that of conventional inlay preparation design PURPOSE The aim of this prospect i ve clinical cohort study was to determine the success rate of 3- to 5-unit zirconia frameworks for posterior fixed partial dentures ( FPDs ) after 5 years of clinical observation . MATERIAL S AND METHODS Forty-five patients who needed at least 1 FPD to replace 1 to 3 posterior teeth were included in the study . Fifty-seven 3- to 5-unit FPDs with zirconia frameworks were cemented with 1 of 2 resin cements ( Variolink or Panavia TC ) . The following parameters were evaluated at baseline , after 6 months , and 1 to 5 years after cementation at test ( abutments ) and control ( contralateral ) teeth : probing pocket depth , probing attachment level , Plaque Index , bleeding on probing , and tooth vitality . Intraoral radiographs of the FPDs were taken . Statistical analysis was performed using descriptive statistics , Kaplan-Meier survival analysis , and the McNemar test . RESULTS Twenty-seven patients with 33 zirconia FPDs were examined after a mean observation period of 53.4 + /- 13 months . Eleven patients with 17 FPDs were lost to follow-up . After the 3-year recall visit , 7 FPDs in 7 patients were replaced because they were not clinical ly acceptable due to biologic or technical complications . After 5 years of clinical observation , 12 FPDs in 12 patients had to be replaced . One 5-unit FPD fractured as a result of trauma after 38 months . The success rate of the zirconia frameworks was 97.8 % ; however , the survival rate was 73.9 % due to other complications . Secondary caries was found in 21.7 % of the FPDs , and chipping of the veneering ceramic in 15.2 % . There were no significant differences between the periodontal parameters of the test and control teeth . CONCLUSIONS Zirconia offers sufficient stability as a framework material for 3- and 4-unit posterior FPDs . The fit of the frameworks and veneering ceramics , however , should be improved Statement of problem . Proper marginal , axial , and occlusal adaptation of dental restorations is essential for their long‐term success . Production protocol s including digital impression systems have been developed , but little information is available on the adaptation of zirconia restorations produced via them . Purpose . The purpose of this in vitro study was to compare the effects of digital impression protocol s on the marginal , axial , and occlusal adaptation of zirconia copings . Material and methods . Thirty extracted human maxillary premolar teeth without caries or defects were used . The teeth were prepared for zirconia crowns and r and omly divided into 3 groups . Zirconia copings were design ed at a thickness of 0.5 mm with 30 & mgr;m of simulated die spacer starting 1 mm from the margin of preparations . They were produced using computer‐aided design ‐computer‐aided manufacture ( CAD‐CAM ) protocol with a conventional impression ( group Cn ) and 2 different production protocol s with digital impressions ( group C ) and group Tr . The marginal , axial , and occlusal discrepancies of these copings were measured using the silicone replica technique with stereomicroscopy at ×50 magnification , and the data were analyzed with 1‐way ANOVAs ( & agr;=.05 ) . Results . The mean marginal discrepancy values were 85.6 & mgr;m for group Cn , 58.7 & mgr;m for group C , and 47.7 & mgr;m for the Tr group . Significant differences were found among the production protocol s in marginal , axial , and occlusal discrepancies ( P<.05 ) . Copings fabricated with the aid of digital impressions had significantly fewer marginal discrepancies than those of group Cn ( P<.05 ) . Group Tr exhibited the lowest marginal discrepancy , whereas groups Cn and C demonstrated similar axial adaptations ( P>.05 ) , and group Tr revealed the lowest axial discrepancy ( P<.05 ) . With regard to the occlusal discrepancy evaluation , group Tr had the lowest discrepancy . However , no significant differences was found between groups C and Cn ( P>.05 ) . Conclusions . The copings produced with the aid of digital impression systems exhibited better marginal and occlusal adaptation than those of the copings produced with the aid of conventional impression Objectives The purpose of this clinical study was to compare the marginal fit of dental crowns based on three different intraoral digital and one conventional impression methods . Methods Forty-nine teeth of altogether 24 patients were prepared to be treated with full-coverage restorations . Digital impressions were made using three intraoral scanners : Sirona CEREC AC Omnicam ( OCam ) , Heraeus Cara TRIOS and 3 M Lava True Definition ( TDef ) . Furthermore , a gypsum model based on a conventional impression ( EXA’lence , GC , Tokyo , Japan ) was scanned with a st and ard laboratory scanner ( 3Shape D700 ) . Based on the data set obtained , four zirconia copings per tooth were produced . The marginal fit of the copings in the patient ’s mouth was assessed employing a replica technique . Results Overall , seven measurement copings did not fit and , therefore , could not be assessed . The marginal gap was 88 μm ( 68–136 μm ) [ median/interquartile range ] for the TDef , 112 μm ( 94–149 μm ) for the Cara TRIOS , 113 μm ( 81–157 μm ) for the laboratory scanner and 149 μm ( 114–218 μm ) for the OCam . There was a statistically significant difference between the OCam and the other groups ( p < 0.05 ) . Conclusion Within the limitations of this study , it can be concluded that zirconia copings based on intraoral scans and a laboratory scans of a conventional model are comparable to one another with regard to their marginal fit . Clinical relevance Regarding the results of this study , the digital intraoral impression can be considered as an alternative to a conventional impression with a consecutive digital workflow when the finish line is clearly visible and it is possible to keep it dry PURPOSE This in vitro study was design ed to evaluate and compare the marginal gap , internal fit , and fracture load of resin-bonded , leucite-reinforced glass ceramic mesio-occlusal-distal ( MOD ) inlays fabricated by computer-aided design /manufacturing ( CAD/CAM ) or hot pressing . MATERIAL S AND METHODS Fifty caries-free extracted human molars were prepared for st and ardized MOD inlays . Impressions of each specimen were made and poured using type IV dental stone . Dies were r and omly divided into two equal groups . Twenty-five ceramic inlays were fabricated by the hot-pressed technique using IPS Empress leucite-reinforced glass ceramics , and the other 25 ceramic inlays were produced by CAD/CAM technology using ProCAD leucite-reinforced ceramic blocks and CEREC inLab facilities . Inlays were bonded to the teeth using a dual-cured resin cement . The specimens were stored in distilled water at 37 ° C for 24 hours and then thermocycled for 5000 cycles . The marginal gap measurements were taken with a stereomicroscope . Specimens in each group of inlay systems were r and omly divided into two subgroups of 10 and 15 specimens each . Ten specimens in each subgroup were sectioned mesiodistally for evaluation of the internal fit . The fracture load of specimens in the second subgroup ( n = 15 ) of the two inlay systems was determined under compressive load in a universal testing machine . Data were analyzed using Student 's t-test at a significance level of p < 0.05 . RESULTS The mean marginal and internal gap size in both IPS Empress and ProCAD inlays were less than 100 μm ; however , the marginal gap for the IPS Empress restorations was significantly higher than that of ProCAD restorations ( p < 0.05 ) . There was no significant difference in the mean internal fit or the fracture load between the two glass ceramic inlays ( p > 0.05 ) . CONCLUSIONS The leucite-reinforced glass ceramic inlay restorations fabricated by CEREC inLab ( CAD/CAM ) and the hot-pressed technique provided clinical ly acceptable marginal and internal fit with comparable fracture loads after luting PURPOSE To evaluate the marginal and internal cement thicknesses of inlay restorations made of various CAD/CAM material s using 3D X-ray micro-computed tomography ( micro-CT ) technique . MATERIAL S AND METHODS Caries-free extracted m and ibular molars ( N = 30 ) with similar size were r and omly assigned to three groups ( N = 10 per group ) . Mesio-occlusal-distal ( MOD ) cavities were prepared , and inlay restorations were obtained by milling out CAD/CAM material s namely , ( a ) IPS : monolithic lithium disilicate ( control ) , ( b ) VE : polymer-infiltrated ceramic , and ( c ) CS : nano-ceramic using a CAM unit . Marginal and internal cement thicknesses were measured using 3D micro-CT . Data were analyzed using 1-way ANOVA and Tukey 's tests ( alpha = 0.05 ) . RESULTS The mean marginal and internal cement thickness were not significant in all inlay material s ( p > 0.05 ) . Mean marginal cement thickness ( μm ) was the lowest for the IPS group ( 67.54 ± 10.16 ) followed by VE ( 84.09 ± 3.94 ) and CS ( 95.18 ± 10.58 ) ( p > 0.05 ) . The internal cement thickness ( μm ) was the lowest in the CS group ( 54.85 ± 6.94 ) followed by IPS ( 60.58 ± 9.22 ) and VE ( 77.53 ± 12.13 ) ( p > 0.05 ) . CONCLUSION Marginal and internal cement thicknesses of MOD inlays made of monolithic lithium disilicate , polymer-infiltrated ceramic , and nano-ceramic CAD/CAM material s were similar and all less than 100 μm , which could be considered clinical ly acceptable . CLINICAL SIGNIFICANCE MOD inlays made of different CAD/CAM material s presented similar cement thickness , less than 100 μm Among the material s used for luting indirect restorations , growing interest has been directed towards the use of self-adhesive resin cements . The aim of this prospect i ve r and omized controlled clinical trial was to evaluate the clinical performance of the self-adhesive resin cement RelyX Unicem ( RXU ) for luting partial ceramic crowns ( PCCs ) . In addition , the influence of selective enamel etching prior to luting ( RXU+E ) was assessed . Two-year results are reported . Thirty-four patients ( 68 PCCs ) had originally received the intended treatment at baseline ( BL ) . Twenty-nine patients ( 14 male , 15 female ) with a total of 58 PCCs participated in the 2-year recall . In each patient , one PCC had been placed with RXU , one PCC with RXU+E. Restorations were evaluated at BL and 24 months after placement using modified United States Public Health Service criteria for postoperative hypersensitivity , anatomic form , marginal adaptation , marginal discoloration , surface texture and recurrent caries . Additionally , the “ percentage failure ” within the 2-year recall period for all restorations ( n = 68 ) was calculated according to ADA Program Guidelines . Target value for acceptability of each procedure was < 5 % failure within 24 m. For statistical analysis of the data , the chi-square test was applied ( α = 0.05 ) . The median patient age was 41 years ( 24–59 years ) . Median PBI was 8 % ( 5–10 % ) . Twenty-two RXU PCCs were placed in molars , seven in premolars . Twenty-one RXU+E PCCs were placed in molars , eight in premolars . Statistically significant changes were observed for marginal adaptation ( MA ) and marginal discoloration ( MD ) between BL and 2 years but not between the two groups ( RXU , RXU+E ) . Percentage of alfa values at BL for MA ( RXU , 97 % and RXU+E , 100 % ) and for MD ( RXU , 97 % and RXU+E , 97 % ) decreased to RXU , 14 % and RXU+E , 28 % for MA and to RXU , 50 % and RXU+E , 59 % for MD after 24 months . Within the observation period , three failures were recorded with RXU ( 5.1 % failure ) , one failure was recorded for RXU+E ( 1.7 % failure ) , but a significant influence of selective enamel etching on failure could not be verified . Although the results of the present study reveal a slight tendency for more favourable results if selective enamel etching is applied prior to insertion of ceramic PCCs with a self-adhesive luting material , longer-term evaluation is needed to confirm this . Additional selective enamel etching with a self-adhesive luting material does not considerably improve clinical performance of the restorations within the observation period reported , neither does it impose a hazard with respect to postoperative hypersensitivity Objectives This study investigated the influence of proximal box elevation ( PBE ) with composite resin when applied to deep proximal defects in root-filled molars with mesio-occluso-distal ( MOD ) cavities , which were subsequently restored with computer-aided design ed/computer-aided manufacturing ( CAD/CAM ) ceramic or composite restorations . Material s and method Root canal treatment was performed on 48 human m and ibular molars . St and ardized MOD cavities were prepared with the distal box located 2 mm below the cemento-enamel junction ( CEJ ) . The teeth were r and omly assigned to one of four experimental groups ( n = 12 ) . In groups G1 and G2 , the distal proximal box was elevated up to the level of the CEJ with composite resin ( PBE ) . No elevation was performed in the remaining two groups ( G3 , G4 ) . CAD/CAM restorations were fabricated with feldspathic ceramic ( Vita Mark II , CER ) in groups G1 ( PBE-CER ) and G3 ( CER ) or with resin nano-ceramic blocks ( Lava Ultimate , LAV ) in groups G2 ( PBE-LAV ) and G4 ( LAV ) . Replicas were taken before and after thermomechanical loading ( TML ; 1.2 Mio cycles ; 49 N ; 3,000 thermocycles between 50 ° C and 5 ° C ) . Following TML , load was applied until failure . Fracture analysis was performed under a stereomicroscope ( ×16 ) . Marginal quality before and after TML ( tooth restoration , composite restoration ) was evaluated using scanning electron microscopy ( ×200 ) . Results After TML , lower percentages of continuous margins were observed in groups G1–G3 compared with pre-TML assessment s ; however , the differences were not statistically significant . For group G4-LAV , the marginal quality after TML was significantly better than in any other group . The highest mean fracture value was recorded for group G4 . No significant difference was found for this value between the groups with PBE compared with the groups without PBE , regardless of the material used . The specimens restored with ceramic onlays exhibited fractures that were mainly restricted to the restoration while , in teeth restored with composite onlays , the percentage of catastrophic failures ( fractures beyond bone level ) was increased . Conclusion PBE had no impact on either the marginal integrity or the fracture behavior of root canal-treated m and ibular molars restored with feldspathic ceramic onlays . CAD/CAM-fabricated composite onlays were more favorable than ceramic onlays in terms of both marginal quality and fracture resistance , particularly in specimens without PBE . Clinical relevance Composite onlays with or without PBE may be a viable approach for the restoration of root-filled molars with subgingival MOD cavities PURPOSE To evaluate the effect of different curing protocol s on marginal adaptation of ceramic inlays after thermomechanical loading ( TML ) . MATERIAL S AND METHODS Forty-eight human molars were r and omly divided into 6 groups ( n = 8) . After Class II cavity preparation ( mod ) , ceramic inlays ( Cerec ) were fabricated . In groups I to IV , the cavities were conditioned with XP Bond mixed with Self Cure Activator ( SCA ) and the inlays were placed with the luting composite ( LC ) Calibra Mix ( dual curing ) . The teeth in groups V and VI were conditioned with XP Bond without SCA and the inlays were placed with Calibra base ( only light curing ) . In groups III , IV and V the adhesive was separately light cured prior to , and in groups II , IV , V and VI , after the inlay insertion . Before and after TML , marginal adaptation was measured using scanning electron microscopy ( 200X ) . Continuous margins ( % of the total ) were compared between groups using analysis of variance ( ANOVA ) . A Bonferroni correction was applied to correct for multiple testing ( alpha < 0.005 ) . RESULTS Light curing after inlay insertion improved marginal adaptation on the occlusal interface between LC and enamel significantly , regardless of the LC 's curing mode . Separate light polymerization of XP Bond did not result in superior marginal quality . Investigation of the interface between LC and proximal dentin margins showed improved adaptation by dual curing the adhesive and LC , irrespective of light application . CONCLUSION Light curing after inlay insertion showed improved marginal adaptation . Using dual-curing adhesive and LC , advantages in marginal adaptation between LC and dentin were observed OBJECTIVES Midterm-evaluation of a 5-year prospect i ve clinical splitmouth-investigation on survival rate and long-term behavior of all-ceramic partial coverage restorations ( PCRs ) on molars . Pressed ceramic and CAD/CAM fabricated PCRs were compared . METHODS 80 vital molars of 25 patients were restored with all-ceramic PCRs ( 40 IPS e.max Press*[IP ] and 40 ProCAD*[PC ] ) . IP-PCRs were heat pressed following the lost-wax method . PC-PCRs were fabricated with Cerec 3 * * and Cerec InLab * * CAD/CAM system ( * * Sirona Dental Systems , Bensheim , Germany ) . All PCRs were adhesively luted with a light-polymerizing composite ( Syntac*/Tetric * ) ( * Ivoclar Vivadent , Schaan , Liechtenstein ) . Clinical reevaluations were performed at baseline and 13 , 25 , and 36 months after insertion of the PCRs according to the modified United States Public Health Services ( USPHS ) criteria . Absolute failures were demonstrated by Kaplan-Meier survival rate . RESULTS After an observation time up to 3 years , survival rate of IP-PCRs was 100 % and 97 % for PC-PCRs due to one severe fracture . The PC-PCR had to be replaced after 9 months . Secondary caries and endodontic complications did not occur . Increased clinical service time result ed in significant decrease of marginal adaptation ( p=0.031 ) and enhanced marginal discoloration ( p<0.0001 ) . Both PCR ceramic material s demonstrated significant deteriorations in color match ( p<0.0001 ) and surface roughness ( p<0.0001 ) , IP-PCRs were significantly more affected ( p < or = 0.005 ) . Regarding anatomic form IP-PCRs performed significantly better ( p=0.0012 ) . CONCLUSION Pressed ceramic and CAD/CAM fabricated partial coverage restorations exhibited a reliable treatment option to restore larger defects in posterior teeth . Marginal degradation of the resin cement and deterioration of the all-ceramic material s during clinical function determine the clinical long-term performance of partial coverage restorations |
13,295 | 30,993,648 | Conclusion Adherence to physical activity , dietary , and multiple lifestyle behaviours recommendations was low amongst cancer survivors .
Recent cancer survivors were relatively more adherent to WCRF/AICR recommendations compared to long-term survivors .
Implication s for Cancer SurvivorsHealth promotion programs help support healthy lifestyle behaviours of cancer survivors . | Purpose Multiple health behaviours ( not smoking , minimal alcohol consumption , and maintaining a healthy weight by having a healthy diet and regular physical activity ) improve quality of life and longevity of cancer survivors .
Despite international guidelines , there are no existing review s that synthesis e cancer survivors ’ adherence to healthy lifestyle recommendations . | There is limited evidence on the association between adherence to guidelines for cancer survivors and health-related quality of life ( HRQoL ) . In a cross-sectional study of Korean breast cancer survivors , we examined whether adherence to the guidelines of the American Cancer Society ( ACS ) and World Cancer Research Fund/American Institute for Cancer Research ( WCRF/AICR ) for cancer survivors was related to levels of HRQoL , assessed by the Korean version of Core 30 ( C30 ) and Breast cancer module 23 ( BR23 ) of the European Organization for Research and Treatment of Cancer- Quality of Life Question naire ( EORTC-QLQ ) . We included a total of 160 women aged 21 to 79 years who had been diagnosed with breast cancer according to American Joint Committee on Cancer ( AJCC ) stages I to III and had breast cancer surgery at least six months before the interview . Increasing adherence to ACS guidelines was associated with higher scores of social functioning ( p for trend = 0.05 ) , whereas increasing adherence to WCRF/AICR recommendations was associated with higher scores of arm symptoms ( p for trend = 0.01 ) . These associations were limited to those with stage II or III cancer . Diet may be an important factor in relation to quality of life among Korean breast cancer survivors , however our findings warrant further prospect i ve studies to evaluate whether healthy diet improves survivors ’ quality of life Background The relationship between colorectal cancer ( CRC ) risk and physical activity and dietary habits has been well-established , but less is known about the relationship between these behaviours and quality of life ( QOL ) post-diagnosis . Moreover , it is unknown whether this relationship is consistent across cancer stage or treatment setting . Thus , the purpose of this study was to assess current diet and physical activity behaviour in CRC survivors receiving systemic chemotherapy , and to examine potential associations between these behaviours and quality of life . A secondary purpose was to examine the association between social support , diet , and physical activity behaviour in this population . Methods Using a cross-sectional survey , 67 CRC survivors currently receiving chemotherapy in Calgary , Alberta completed the survey package . Measures included demographic and medical data , physical activity levels , diet behaviour , QOL , and social support . Results In a largely metastatic sample ( 63 % ) , approximately half were meeting national dietary guidelines ( 58 % ) , less were meeting national physical activity guidelines ( 26 % ) , and a small number were meeting both ( 17 % ) . However , only 12.3 % ( n = 8) reported completely sedentary behaviour , and 7 of these 8 participants were receiving metastatic treatment . Neither behaviour was significantly associated with QOL or perceived social support . Furthermore , there were no significant QOL differences between those treated with palliative intent or adjuvant therapy . Important group differences emerged between those meeting and not meeting the guidelines , and associations between QOL , age , BMI , and provisions of social support . Conclusion These findings provide insight into lifestyle behaviours of CRC survivors currently receiving systemic chemotherapy , and the differences in perceived QOL as affected by severity of disease and treatment setting . Prospect i ve studies in a larger sample of CRC survivors on chemotherapy are needed to confirm lifestyle behaviour patterns and identify factors related to QOL that are unique to this population , especially during metastatic treatment PURPOSE Single-variable analyses have associated physical activity , diet , and obesity with survival after breast cancer . This report investigates interactions among these variables . PATIENTS AND METHODS A prospect i ve study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000 . Enrollment was an average of 2 years postdiagnosis . Only seven women were lost to follow-up through December 2005 . RESULTS In univariate analysis , reduced mortality was weakly associated with higher vegetable-fruit consumption , increased physical activity , and a body mass index that was neither low weight nor obese . In a multivariate Cox model , only the combination of consuming five or more daily servings of vegetables-fruits , and accumulating 540 + metabolic equivalent tasks-min/wk ( equivalent to walking 30 minutes 6 d/wk ) , was associated with a significant survival advantage ( hazard ratio , 0.56 ; 95 % CI , 0.31 to 0.98 ) . The approximate 50 % reduction in risk associated with these healthy lifestyle behaviors was observed in both obese and nonobese women , although fewer obese women were physically active with a healthy dietary pattern ( 16 % v 30 % ) . Among those who adhered to this healthy lifestyle , there was no apparent effect of obesity on survival . The effect was stronger in women who had hormone receptor-positive cancers . CONCLUSION A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables-fruits and moderate levels of physical activity . The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival Objective With increases in cancer survival , promotion of healthy lifestyle behaviors among survivors is receiving considerable attention . This study compared health behaviors among a large sample of Australian adult cancer survivors with an age- and sex-matched cohort of people with no cancer history . Methods Using the Australian National Health Survey , 968 cancer survivors were identified , and r and omly matched by age and sex to 5,808 respondents without a history of cancer . Six health behaviors were compared ( smoking , physical activity , servings of vegetables , servings of fruit , alcohol use , skin checks ) , along with overweight and obesity , using polytomous logistic regression analyses controlling for selected chronic conditions . Models were applied across both groups and by tumor site . Results Compared to the non-cancer comparison group , cancer survivors were significantly more likely to be current ( OR = 1.35 ) smokers , particularly those under 40 years ( OR = 1.69 ) , and more likely to have regular skin checks ( OR = 1.76 ) . Although not significant , there was consistent evidence that cancer survivors were slightly more likely to be overweight or obese ( p = 0.065 ) and have higher levels of alcohol consumption ( p = 0.088 ) . There was no evidence of differences between survivors and controls for levels of physical inactivity , vegetable consumption or fruit consumption . Women with a history of gynecological cancers were much more likely to be current smokers ( OR = 2.37 ) , while other differences by sex and cancer site were consistent with overall patterns . Cancer survivors were also significantly more likely to report having a range of co-morbid chronic medical conditions . Conclusion Given their increased risk of second cancers and co-morbid chronic conditions , the lack of difference in behavioral risk factors confirms the need for a focus on improving the health behaviors of cancer survivors . Collaborative chronic disease management models may be particularly appropriate in this regard AIMS To assess self-reported lifetime prevalence of cardiovascular disease ( CVD ) among colorectal cancer survivors , and examine the cross-sectional and prospect i ve associations of lifestyle factors with co-morbid CVD . METHODS Colorectal cancer survivors were recruited ( n=1966 ) . Data were collected at approximately 5 , 12 , 24 and 36 months post-diagnosis . Cross-sectional findings included six CVD categories ( hypercholesterolaemia , hypertension , diabetes , heart failure , kidney disease and ischaemic heart disease ( IHD ) ) at 5 months post-diagnosis . Longitudinal outcomes included the probability of developing ( de novo ) co-morbid CVD by 36 months post-diagnosis . Lifestyle factors included body mass index , physical activity , television ( TV ) viewing , alcohol consumption and smoking . RESULTS Co-morbid CVD prevalence at 5 months post-diagnosis was 59 % , and 16 % of participants with no known CVD at the baseline reported de novo CVD by 36 months . Obesity at the baseline predicted de novo hypertension ( odds ratio [OR]=2.20 , 95 % confidence intervals [CI]=1.09 , 4.45 ) and de novo diabetes ( OR=6.55 , 95 % CI=2.19 , 19.53 ) . Participants watching > 4h of TV/d at the baseline ( compared with < 2h/d ) were more likely to develop ischaemic heart disease by 36 months ( OR=5.51 , 95 % CI=1.86 , 16.34 ) . CONCLUSION Overweight colorectal cancer survivors were more likely to suffer from co-morbid CVD . Interventions focusing on weight management and other modifiable lifestyle factors may reduce functional decline and improve survival PURPOSE Colorectal cancer survivors are at risk for poor health outcomes because of unhealthy lifestyles , but few studies have developed translatable health behavior change interventions . This study aim ed to determine the effects of a telephone-delivered multiple health behavior change intervention ( CanChange ) on health and behavioral outcomes among colorectal cancer survivors . METHODS In this two-group r and omized controlled trial , 410 colorectal cancer survivors were r and omly assigned to the health coaching intervention ( 11 theory-based telephone-delivered health coaching sessions delivered over 6 months focusing on physical activity , weight management , dietary habits , alcohol , and smoking ) or usual care . Assessment of primary ( ie , physical activity [ Godin Leisure Time Index ] , health-related quality of life [ HRQoL ; Short Form-36 ] , and cancer-related fatigue [ Functional Assessment of Chronic Illness Therapy Fatigue Scale ] ) and secondary outcomes ( ie , body mass index [ kg/m(2 ) ] , diet and alcohol intake [ Food Frequency Question naire ] , and smoking ) were conducted at baseline and 6 and 12 months . RESULTS At 12 months , significant intervention effects were observed for moderate physical activity ( 28.5 minutes ; P = .003 ) , body mass index ( -0.9 kg/m(2 ) ; P = .001 ) , energy from total fat ( -7.0 % ; P = .006 ) , and energy from saturated fat ( -2.8 % ; P = .016 ) . A significant intervention effect was reported for vegetable intake ( 0.4 servings per day ; P = .001 ) at 6 months . No significant group differences were found at 6 or 12 months for HRQoL , cancer-related fatigue , fruit , fiber , or alcohol intake , or smoking . CONCLUSION The CanChange intervention was effective for improving physical activity , dietary habits , and body mass index in colorectal cancer survivors . The intervention is translatable through existing telephone cancer support and information services in Australia and other countries Purpose Differences in health status and behavioral risk factors may explain racial/ethnic breast cancer disparities . We examined racial/ethnic differences in health status and behaviors among female breast cancer survivors compared to females without breast cancer . Methods Using cross-sectional data from the 2009 Behavioral Risk Factor Surveillance System , a national state-based , r and om sample telephone survey , we explored differences in self-rated health , obesity and selected behaviors ( physical activity , smoking , alcohol use , fruit , and vegetable consumption ) among females aged 18 years and older , who reported a previous breast cancer diagnosis ( survivors , n = 10,035 ) and those who reported no breast cancer history ( n = 234,375 ) by race/ethnicity . Adjusted prevalences of health status and behaviors , accounting for sociodemographics , comorbidities and health care access , were estimated by race/ethnicity . Results Compared to all other racial/ethnic groups , more white females reported heavy alcohol consumption and more black females reported obesity regardless of their breast cancer status . Among breast cancer survivors , more whites ( 33.7 % ) were former smokers compared to blacks ( 24.5 % ) , “ others ” ( 20.5 % ) , and Hispanics ( 16.2 % ) ( p = 0.001 ) . Racial/ethnic differences in obesity also varied by reported time since diagnosis ( p value = 0.018 ) . Among long-term survivors ( diagnosed > 5 years before interview ) , more black survivors ( 34.8 % ) reported obesity compared to white survivors ( 23.0 % ) . Also , among “ other ” race survivors , long-term survivors ( 22.0 % ) reported more obesity than survivors diagnosed less than 5 years before interview ( 7.8 % ) . Conclusions These findings suggest opportunities to increase health behaviors and reduce racial disparities among breast cancer survivors . Implication s for Cancer SurvivorsEngaging in healthy behaviors can play a significant role in enhancing health outcomes and quality of life of breast cancer survivors . More research is needed to better underst and racial differences in obesity , smoking and alcohol consumption in order to develop effective , culturally appropriate interventions to promote a healthy lifestyle after a breast cancer diagnosis Purpose The effectiveness of survivorship care plans has not been widely tested . We evaluated whether a one-time brief lifestyle consultation as part of a broader survivorship care plan was effective at changing diet and lifestyle patterns . Methods A diverse sample of women with stage 0-III breast cancer were r and omized to control or intervention groups within 6 weeks of completing adjuvant treatment . Both groups received the National Cancer Institute publication , “ Facing Forward : Life after Cancer Treatment . ” The intervention group also met with a nurse ( 1 h ) and a nutritionist ( 1 h ) to receive personalized lifestyle recommendations based upon national guidelines . Diet , lifestyle , and perceived health were assessed at baseline , 3 and 6 months . Linear regression analyses evaluated the effects of the intervention adjusted for covariates . Results A total of 126 women completed the study ( 60 control/66 intervention , 61 Hispanic/65 non-Hispanic ) . At 3 months , the intervention group reported greater knowledge of a healthy diet ( P = 0.047 ) , importance of physical activity ( P = 0.03 ) , and appropriate use of dietary supplements ( P = 0.006 ) and reported lower frequency of alcohol drinking ( P = 0.03 ) than controls . At 6 months , only greater knowledge of a healthy diet ( P = 0.01 ) persisted . The intervention was more effective among non-Hispanics than Hispanics on improving attitude towards healthy eating ( P = 0.03 ) and frequency of physical activity ( P = 0.006 ) . Conclusions The intervention changed lifestyle behaviors and knowledge in the short-term , but the benefits did not persist . Implication s for Cancer SurvivorsCulturally competent long-term behavioral interventions should be tested beyond the survivorship care plan to facilitate long-term behavior change among breast cancer survivors A healthy diet and physical activity are recommended for prostate cancer survivors . Interdependence theory suggests that the spousal relationship influences those health behaviours and the degree of correspondence may be an indicator of this influence . This study evaluated the correspondence between prostate cancer survivors and spouses regarding physical activity and fruit/vegetable consumption . Baseline data from an ongoing r and omised control trial were utilised . Men who had been treated for prostate cancer within the past year and their partners ( N = 132 couples ) completed self-report measures of physical activity , fruit/vegetable consumption , relationship satisfaction and support for partner 's healthy diet and physical activity . Couples reported similar fruit/vegetable consumption and physical activity as indicated by high levels of correspondence . Greater fruit/vegetable correspondence was related to higher relationship satisfaction ( F = 4.14 , P = 0.018 ) and greater patient ( F = 13.29 , P < 0.001 ) and spouse-rated support ( F = 7.2 , P < 0.001 ) . Greater physical activity correspondence was related to greater patient ( F = 3.57 , P = 0.028 ) and spouse-rated support ( F = 4.59 , P = 0.031 ) . Prostate cancer survivors and spouses may influence each other 's diet and exercise behaviours . Couple-based interventions may promote healthy behaviours among this population PURPOSE To determine whether a low-fat diet high in vegetables , fruit , and fiber differentially affects prognosis in breast cancer survivors with hot flashes ( HF ) or without HF after treatment . PATIENTS AND METHODS A secondary analysis was conducted on 2,967 breast cancer survivors , age 18 to 70 years , who were r and omly assigned between 1995 and 2000 in a multicenter , controlled trial of a dietary intervention to prevent additional breast cancer events and observed through June 1 , 2006 . We compared the dietary intervention group with a group who received five-a-day dietary guidelines . RESULTS Independent of HF status , a substantial between-group difference among those who did and did not receive dietary guidelines was achieved and maintained at 4 years in intake of vegetable/fruit servings per day ( 54 % higher ; 10 v 6.5 servings/d , respectively ) , fiber ( 31 % higher ; 25.5 v 19.4 g/d , respectively ) , and percent energy from fat ( 14 % lower ; 26.9 % v 31.3 % , respectively ) . Adjusting for tumor characteristics and antiestrogen treatment , HF-negative women assigned to the intervention had 31 % fewer events than HF-negative women assigned to the comparison group ( hazard ratio [ HR ] = 0.69 ; 95 % CI , 0.51 to 0.93 ; P = .02 ) . The intervention did not affect prognosis in the women with baseline HFs . Furthermore , compared with HF-negative women assigned to the comparison group , HF-positive women had significantly fewer events in both the intervention ( HR = 0.77 ; 95 % CI , 0.59 to 1.00 ; P = .05 ) and comparison groups ( HR = 0.65 ; 95 % CI , 0.49 to 0.85 ; P = .002 ) . CONCLUSION A diet with higher vegetable , fruit , and fiber and lower fat intakes than the five-a-day diet may reduce risk of additional events in HF-negative breast cancer survivors . This suggestive finding needs confirmation in a trial in which it is the primary hypothesis Background Physical activity levels among breast cancer survivors are typically low , and knowledge of the correlates of increased physical activity among cancer survivors is limited . The purpose of this study was to examine factors that are associated with physical activity or inactivity among breast cancer survivors . Methods Data from 3088 women participating in the Women ’s Healthy Eating and Living ( WHEL ) Study , collected prior to r and omization , were the focus of the current analyses . Self-reports of physical activity levels , quality of life , depression , and dietary intakes were collected . Pearson correlation analyses were employed to examine the associations among these variables , and multiple regression analyses were performed to examine the relationship between selected health behaviors and physical activity levels , after controlling for demographic , breast cancer-related , and psychosocial variables . Results Demographic and psychosocial variables were related to physical activity levels ( P < 0.001 for all ) . Cancer treatment type and cancer stage were correlated with survivors ’ physical activity levels ( P < 0.01 ) , but the associations were no longer significant after controlling for demographic variables . Physical activity levels were strongly associated with other health behaviors , especially dietary intakes ( P < 0.001 ) , even after controlling for demographic , cancer-related , and psychosocial factors . Conclusion Low physical activity levels in breast cancer survivors are associated with specific behavioral and other factors , which can be considered as indicators of women at higher risk . Findings of significant differences in physical activity levels based on demographic characteristics suggest the importance of promoting physical activity particularly among breast cancer survivors of ethnic minority or lower education levels Objective To investigate the prospect i ve relationships between television viewing time and weight gain in the 3 years following colorectal cancer diagnosis for 1,867 colorectal cancer survivors ( body mass index ( BMI ) ≥ 18.5 kg/m2 ) . Methods BMI , television viewing time , physical activity , and socio-demographic and clinical covariates were assessed at baseline ( 5 months ) , 24 months and 36 months post-diagnosis . Multiple linear regression was used to study independent associations between baseline television viewing time and BMI at 24 and 36 months post-diagnosis . Results At both follow-up time points , there was a significant increase in mean BMI for participants reporting ≥5 h/day of television viewing compared to those watching <3 h/day at baseline ( 24 months : 0.72 kg/m2 ( 0.31 , 1.12 ) , p < 0.001 ; 36 months : 0.61 kg/m2 ( 0.14 , 1.07 ) , p = 0.01 ) , independent of baseline BMI , gender , age , education , marital status , smoking , cancer site , cancer disease stage , treatment mode and co-morbidities . Additional adjustment for baseline physical activity did not change results . Conclusions These findings suggest that a greater emphasis on decreasing television viewing time could help reduce weight gain among colorectal cancer survivors . This , in turn , could contribute to a risk reduction for co-morbid conditions such as type 2 diabetes and cardiovascular disease PURPOSE / OBJECTIVES To describe health behaviors of cancer survivors by cancer diagnosis and to compare them to people without a personal or family cancer history . DESIGN Cross-sectional secondary data analysis . SETTING A national , list-assisted telephone survey using r and om-digit dialing of U.S. adults about use of cancer-related information and cancer beliefs . SAMPLE 619 cancer survivors and 2,141 participants without a history of cancer from the original 6,369 Health Information National Trends Survey ( HINTS ) respondents . METHODS Using the National Cancer Institute 's 2003 HINTS , further analyses were conducted . MAIN RESEARCH VARIABLES Cancer history , current smoking , fruit and vegetable consumption , physical activity , and body mass index ( BMI ) . FINDINGS When controlling for demographic variables , no differences were found in self-reported health behaviors between survivors and those without cancer : 22.5 % of survivors and 18.4 % of those without cancer were current smokers , 18 % of survivors and 14.9 % of those without cancer consumed at least five fruits or vegetables per day , 45.3 % of survivors and 53 % of those without cancer were physically active at least weekly , and 58 % of survivors and 54.9 % of those without cancer were overweight or obese ( i.e. , BMI > 25 ) . Only 7.4 % of survivors and 6.4 % of participants without cancer reported positively on all three health behaviors and had a healthy or normal weight . CONCLUSIONS Survivors did not have different health behaviors when compared to participants without a history of cancer . Neither group met the American Cancer Society or Healthy People 2010 objectives for these behaviors . Adoption of healthy lifestyle behaviors should be addressed in cancer survivors . IMPLICATION S FOR NURSING Cancer survivors need to be assessed for current smoking , dietary habits , physical activity , and weight . Information and re sources should be made available , if needed , to promote the adoption of healthy lifestyle behaviors ABSTRACT Alternatives to individual behavior change methods have been proposed ; however , little has been done to investigate how these methods compare . To explore the four methods that quantify change in multiple risk behaviors targeting four common behaviors , we utilized data from two cluster-r and omized , multiple behavior change trials conducted in two setting s : small businesses and health centers . Methods used were ( 1 ) summative , ( 2 ) z-score , ( 3 ) optimal linear combination , and ( 4 ) impact score . In the small business study , methods 2 and 3 revealed similar outcomes . However , physical activity did not contribute to method 3 . In the health centers study , similar results were found with each of the methods . Multivitamin intake contributed significantly more to each of the summary measures than other behaviors . Selection of methods to assess multiple behavior change in intervention trials must consider study design and the targeted population when determining the appropriate method /s to use PURPOSE / OBJECTIVES To determine whether cancer survivors engage in health-promotion behaviors , to evaluate the extent of their experience of psychological distress , and to investigate the relationship between the practice of health-promotion behaviors and psychological distress . DESIGN Cross-sectional secondary data analysis . SETTING A national , face-to-face interview conducted by personnel of the U.S. Census Bureau using a r and om sampling of American adults . SAMPLE 1,784 survey respondents who reported a previous cancer diagnosis . METHODS Data from the 2009 National Health Interview Survey were used to examine the prevalence of smoking , physical inactivity , alcohol use , and reports of psychosocial distress . Interviews pertained to the amount and distribution of illness , its effects in terms of disability and chronic impairments , and the kinds of health services people receive . MAIN RESEARCH VARIABLES Age , current smoking prevalence , alcohol consumption , physical activity , and the experience of feeling hopelessness , sadness , and anxiety . FINDINGS Cancer survivors continue to smoke at a rate similar to the national average . Overall , most respondents reported no symptoms of psychological distress . However , age appears to play a major role , showing significant differences in the prevalence of current smoking , participation in physical activity , alcohol use , and reported level of distress . CONCLUSIONS This study provides estimates of the prevalence of health-promotion behaviors and experience of psychological distress among American cancer survivors . The results reveal opportunities for interventions among cancer survivors . IMPLICATION S FOR NURSING Nurses should be proactive in providing guidance to survivors regarding the adoption of healthy lifestyle behaviors . Those who encounter younger cancer survivors need to be alert to the higher potential for distress in that population , perform appropriate screenings , and be prepared to offer guidance , supportive care , and referrals for psychological care if needed |
13,296 | 25,159,027 | The overall results of this review showed no clear evidence of benefit of haemodilution therapy for acute ischaemic stroke .
These results are compatible with no persuasive beneficial evidence of haemodilution therapy for acute ischaemic stroke .
This therapy has not been proven to improve survival or functional outcome | BACKGROUND Ischaemic stroke interrupts the flow of blood to part of the brain .
Haemodilution is thought to improve the flow of blood to the affected areas of the brain and thus reduce infa rct size .
OBJECTIVES To assess the effects of haemodilution in acute ischaemic stroke . | BACKGROUND AND PURPOSE The purpose of this study was to prospect ively evaluate a protocol with hypertonic saline hydroxyethyl starch ( HS-HES ) and mannitol in stroke patients with increased intracranial pressure ( ICP ) . METHODS We studied 30 episodes of ICP crisis in 9 patients . ICP crisis was defined as ( 1 ) a rise of ICP of more than 25 mm Hg ( n = 22 ) , or ( 2 ) pupillary abnormality ( n=3 ) , or ( 3 ) a combination of both ( n=5 ) . Baseline treatment was performed according to a st and ardized protocol . For initial treatment , the patients were r and omly assigned to either infusion of 100 mL HS-HES or 40 g mannitol over 15 minutes . For repeated treatments the 2 substances were alternated . ICP , blood pressure , and cerebral perfusion pressure ( CPP ) were monitored over 4 hours . Blood gases , hematocrit , blood osmolarity , and sodium were measured before and 15 and 60 minutes after the start of infusion . Treatment was regarded as effective if ICP decreased > 10 % below baseline value or if the pupillary reaction had normalized . RESULTS Treatment was effective in all 16 HS-HES-treated and in 10 of 14 mannitol-treated episodes . ICP decreased from baseline values in both groups , P < 0.01 . The maximum ICP decrease was 11.4 mm Hg ( after 25 minutes ) in the HS-HES-treated group and 6.4 mm Hg ( after 45 minutes ) in the mannitol-treated group . There was no constant effect on CPP in the HS-HES-treated group , whereas CPP rose significantly in the mannitol-treated group . Blood osmolarity rose by 6.2 mmol/L in the mannitol-treated group and by 10.5 mmol/L in the HS-HES-treated group ; sodium fell by 3.2 mmol/L in the mannitol and rose by 4.1 mmol/L in the HS-HES-treated group . CONCLUSIONS Infusion of 40 g mannitol and 100 mL HS-HES decreases increased ICP after stroke . The maximum effect occurs after the end of infusion and is visible over 4 hours . HS-HES seems to lower ICP more effectively but does not increase CPP as much as does mannitol In a prospect i ve study , we r and omly allocated 70 patients with acute ischemic stroke to two therapy groups . Up to interim analysis , 33 patients underwent bloodletting , with simultaneous infusion of an identical volume of hydroxyethyl starch ( 10 % , 200/0.5 ) . The target hematocrit was 35 % . A control group of 37 patients did not receive hemodilution . Apart from an unequal sex distribution , the two groups were comparable with regard to age , cardiovascular risk factors , and medical history . In the hemodilution group , the mean hematocrit fell from 44.4 % to 37.7 % . After 14 days , improvement on the neurological score scale was 3.3 points in the hemodilution group compared with 6.5 points in the control group ( p = 0.12 ) . Subgroups with early inclusion ( less than 12 hours ) or pronounced lowering of hematocrit ( greater than 15 % of initial hematocrit ) also did not profit from hemodilution . Clinical deterioration observed in eight hemodilution group patients ( p less than 0.01 ) led to discontinuation of the study for ethical reasons BACKGROUND In animal models of ischaemic stroke , 25 % albumin reduced brain infa rct ion and improved neurobehavioural outcome . In a pilot clinical trial , albumin doses as high as 2 g/kg were safely tolerated . We aim ed to assess whether albumin given within 5 h of the onset of acute ischaemic stroke increased the proportion of patients with a favourable outcome . METHODS We did a r and omised , double-blind , parallel-group , phase 3 , placebo-controlled trial between Feb 27 , 2009 , and Sept 10 , 2012 , at 69 sites in the USA , 13 sites in Canada , two sites in Finl and , and five sites in Israel . Patients aged 18 - 83 years with ischaemic ( ie , non-haemorrhagic ) stroke with a baseline National Institutes of Health stroke scale ( NIHSS ) score of 6 or more who could be treated within 5 h of onset were r and omly assigned ( 1:1 ) , via a central web-based r and omisation process with a biased coin minimisation approach , to receive 25 % albumin ( 2 g [ 8 mL ] per kg ; maximum dose 750 mL ) or the equivalent volume of isotonic saline . All study personnel and participants were masked to the identity of the study drug . The primary endpoint was favourable outcome , defined as either a modified Rankin scale score of 0 or 1 , or an NIHSS score of 0 or 1 , or both , at 90 days . Analysis was by intention to treat . Thrombolytic therapies were permitted . This trial is registered with Clinical Trials.gov , number NCT00235495 . FINDINGS 422 participants were r and omly assigned to receive albumin and 419 to receive saline . On Sept 12 , 2012 , the trial was stopped early for futility ( n=841 ) . The primary outcome did not differ between patients in the albumin group and those in the saline group ( 186 [ 44 % ] vs 185 [ 44 % ] ; risk ratio 0·96 , 95 % CI 0·84 - 1·10 , adjusted for baseline NIHSS score and thrombolysis stratum ) . Mild-to-moderate pulmonary oedema was more common in patients given albumin than in those given saline ( 54 [ 13 % ] of 412 vs 5 [ 1 % ] of 412 patients ) ; symptomatic intracranial haemorrhage within 24 h was also more common in patients in the albumin group than in the placebo group ( 17 [ 4 % ] of 415 vs 7 [ 2 % ] of 414 patients ) . Although the rate of favourable outcome in patients given albumin remained consistent at 44 - 45 % over the course of the trial , the cumulative rate of favourable outcome in patients given saline rose steadily from 31 % to 44 % . INTERPRETATION Our findings show no clinical benefit of 25 % albumin in patients with ischaemic stroke ; however , they should not discourage further efforts to identify effective strategies to protect the ischaemic brain , especially because of pre clinical literature showing convincing proof-of-principle for the possibility of this outcome . FUNDING National Institute of Neurological Disorders and Stroke , US National Institutes of Health ; and Baxter Healthcare Corporation In a multicenter trial , 183 patients with acute ischemic stroke of less than 48 hours ' duration and hematocrits of 38 - 50 % were r and omized to st and ardized hemodilution treatment ( venesection and dextran 40 administration ) and 190 to a control group . We have previously reported that there were no beneficial effects of hemodilution in the total patient population . In this report , the case fatality rates and neurologic outcome in survivors ( 3 months ' follow-up ) in subsets of patients have been analyzed . The patients were subgrouped by sex , age , medical history , smoking habits , delay from the onset of symptoms to the start of treatment , hematocrit at entry , venesection volume , neurologic score at entry into the study , blood pressure changes in the acute phase , presence of atrial fibrillation , location of brain lesion by computed tomography , type of diagnostic procedures , and hospital setting . No subset in which hemodilution reduced mortality or improved neurologic outcome could be identified . Case fatality rate was apparently higher in hemodiluted patients with infa rct ion affecting deep brain structures than in control patients with such lesions . By simple clinical criteria , we have been unable to define subsets of stroke patients who benefit from the present st and ardized regimen of moderate hemodilution . The sample sizes are , however , too small to refute the possibility that a modest clinical effect of hemodilution may be present in some patients with stroke BACKGROUND AND PURPOSE Experimental studies suggest a beneficial effect of hemodilution on acute ischemic stroke . This was not proven by previous multicenter trials in the clinical setting . Various reasons have been suggested for the failure of these studies , which we attempted to consider in the Multicenter Austrian Hemodilution Stroke Trial ( MAHST ) . METHODS MAHST is a r and omized , double-blind , placebo-controlled study of hypervolemic hemodilution ( HHD ) within 6 hours of a clinical ly first ischemic stroke localized in the middle cerebral artery territory . The treatment consisted of 10 % hydroxyethyl starch 200/0.5 ( HES ) and was tested against pure rehydration with Ringer 's lactate over a period of 5 days . Our primary outcome measure was clinical improvement within 7 days as measured by the Grade d Neurologic Scale ( GNS ) . We performed an adaptive interim analysis to reevaluate the study goal after entering half of the projected number of patients ( n = 200 ) . At least 600 patients per group would have been required for significant results , and therefore we decided to terminate the trial . RESULTS Ninety-eight patients received HHD and 102 patients placebo . The baseline characteristics were comparable between both groups . In the HHD group the absolute reduction of the hematocrit was 2.5 % on day 2 with a maximum of 3.7 % on day 5 , which compares with a reduction in the placebo group of 1 % and 1.9 % , respectively . Intention-to-treat analysis showed no significant difference of the change of the GNS scores between HHD-treated ( median , -8.5 ; 95 % confidence interval , -14.2 to -4.0 ) and placebo-treated patients ( median , -6.0 ; 95 % confidence interval , -11.0 to 0.0 ) on day 7 , and GNS scores remained similar in both treatment groups throughout the trial . At 3 months , slightly more HHD patients showed complete independence on the Barthel Index ( 28 versus 24 ) , and fewer HHD than placebo patients had died ( 13 versus 17 ) , but these differences were not statistically significant . HHD treatment was not associated with any specific adverse event . CONCLUSIONS Mild HHD is safe but failed to demonstrate a significant beneficial effect over the pure rehydration regimen in patients with acute ischemic stroke In a r and om manner , 100 patients with acute cerebral infa rct ion due to thromboembolism were assigned to two groups . The patients in one group received continuous intravenous therapy with dextran 40 for three days ; the others received an equivalent volume of fluid without the dextran 40 . In the treated group , levels of dextran 40 remained greater than 1 % for three to five days after the infusion was stopped . The group treated with dextran 40 showed lower mortality and better quality of survival in terms of the neurological status . The improvement in the treated group was significantly better than in the untreated group ( OBJECTIVE To determine the effect of normovolaemic haemodilution in patients after a cerebrovascular accident . DESIGN Prospect i ve , r and omized clinical trial . SETTING St Lucas Hospital , Amsterdam . METHOD Normovolaemic haemodilution was achieved by means of bloodletting and administration of a 20 % solution of albumin plus crystalline infusion fluids under haemodynamic and rheological monitoring during the acute phase of the cerebral infa rct ion . All patients were subjected to general intensive care and monitoring with a pulmonary artery catheter . This custom-tailored fluid therapy was guided by a pulmonary wedge pressure of 12 mm Hg ( SD 3 ) and a haematocrit ( Ht ) of 0.32 l/l ( SD 0.02 ) . The control group only received individually dosed rehydration with crystalline infusion fluids . Endpoints of the study after 3 months were mortality and dependence/independence concerning everyday functioning . RESULTS The results in the total haemodilution group and the control group did not differ significantly . However , in the subgroup with normal Ht ( < 0.45 l/l ; n = 201 ) there was a significant reduction ( p < 0.05 ) of the mortality after 3 months ( 27 % and 16 % , respectively ) and an increase of independence at home ( 35 % and 48 % , respectively ) due to a reduction of the viscosity by means of haemodilution with albumin ( a specific viscosity effect in the normovolaemic group ) . In the control group with raised Ht ( dehydration ; Ht > or = 0.45 l/l ; n = 50 ) there was a significant decrease ( p < 0.005 ) of the mortality after 3 months ( 27 % and 8 % , respectively ) and an increase of independence at home ( 35 % and 59 % , respectively ) compared with the control group with normal Ht without signs of dehydration ( Ht < 0.045 l/l ; n = 102 ) , due to rehydration exclusively with crystalline infusion fluids ( a specific rehydration effect in the dehydrated group ) . CONCLUSION In cerebrovascular accident patients haemodilution should be adjusted individually ; in normovolaemic patients haemodilution should be carried out with an albumin solution ; the higher the Ht , the more rehydration with crystalline infusion fluids is to be carried out Background and Purpose — The Albumin in Acute Stroke ( ALIAS ) Part 2 Trial is directly testing whether 2 g/kg of 25 % human albumin ( ALB ) administered intravenously within 5 hours of ischemic stroke onset results in improved clinical outcome . Recruitment into Part 1 of the ALIAS Trial was halted for safety reasons . ALIAS Part 2 is a new , reformulated trial with more-stringent exclusion criteria . Our aim was to explore the efficacy of ALB in the ALIAS Part 1 data and to assess the statistical assumptions underlying the ALIAS Part 2 Trial . Methods — ALIAS is a multicenter , blinded , r and omized controlled trial . Data on 434 subjects , comprising the ALIAS Part 1 subjects , were analyzed . We examined both the thrombolysis and nonthrombolysis cohorts combined and separately in a “ target population ” by excluding subjects who would not have been eligible for the ALIAS Part 2 Trial ; the latter comprised patients > 83 years of age , those with elevated baseline troponin values , and those with in-hospital stroke . We examined the differences in the primary composite outcome , defined as a modified Rankin Scale score of 0 to 1 and /or a National Institutes of Health Stroke Scale score of 0 to 1 at 90 days after r and omization . Results — In the combined thrombolysis plus nonthrombolysis cohorts of the target population , 44.7 % of subjects in the ALB group had a favorable outcome compared with 36.0 % in the saline group ( absolute effect size=8.7 % ; 95 % CI , −2.2 % to 19.5 % ) . Among thrombolyzed subjects of the target population , 46.7 % had a favorable outcome in the ALB group compared with 36.6 % in the saline group ( absolute effect size=10.1 % ; 95 % CI , −2.0 % to 20.0 % ) . Conclusions — Preliminary results from the ALIAS Part 1 suggest a trend toward a favorable primary outcome in subjects treated with ALB and support the validity of the statistical assumptions that underlie the ALIAS Part 2 Trial . The ALIAS Part 2 Trial will confirm or refute these results . Clinical Trial Registration — URL : http://www . clinical trials.gov/ALIAS . Unique identifier : NCT00235495 The results of clinical trials investigating various therapies in acute ischemic stroke have been inconsistent . The effect of glycerol therapy and a combination therapy of glycerol and dextran was evaluated in a double-blind , placebo-controlled study . Repeated neurologic examinations ( Day 0 , Weeks 1 , 6 , 12 , and 24 ) according to a modified Mathew score were performed on 62 patients . Statistical analysis showed no superiority of either treatment compared with placebo in acute ischemic stroke . A retrospective estimation of the Type II error of the study yielded approximately p = 0.25 . A major side effect was hemolysis in 98 % of patients treated with glycerol The effect of hemodilution was studied in 106 acute ischaemic stroke patients ( 55 hemodiluted and 51 control subjects ) . The investigation did not show statistically significant differences between the two groups regarding the mortality rate and the degree of rehabilitation ( modified Rankin Scale ) but revealed a significant neurologic score ( proposed by the Sc and inavian Stroke Study Group ) in the hemodiluted group . A correlation between the favourable score modification and the degree of hematocrit modification was also observed Hemodilution in the acute phase of ischemic stroke is still controversial . Multicenter studies have failed to demonstrate any benefit . The present study focuses attention on analysis of circulation in stroke and on individual restabilization of circulation . Methods The Amsterdam Stroke Study is a prospect i ve , single-center , r and omized clinical trial ( n=300 ) . Normovolemic hemodilution is accomplished in a customized procedure by administration of 20 % albumin plus crystalloids under hemodynamic and rheological monitoring in the acute phase of stroke . All patients receive general intensive care treatment and monitoring with a pulmonary artery catheter . This custom-tailored fluid therapy is guided on the basis of a target pulmonary capillary wedge pressure ( 12±3 mm Hg ) and hematocrit ( 0.32±0.02 ) . The control group receives only customized rehydration by infusion of crystalloids . Results We obtained significant ( p<0.05 ) reduction in mortality at 3 months ( from 27 % to 16 % ) and an increase in independence at home ( from 35 % to 48 % ) after viscosity reduction by means of hemodilution with albumin in the subgroup with a hematocrit < 0.45 ( n=201 ) ( specific viscosity effect ) . We also obtained a significant ( p<0.005 ) reduction in mortality at 3 months ( from 27 % to 8 % ) and an increase in independence ( from 35 % to 59 % ) after only rehydration with crystalloids in the subgroup with overt dehydration ( hematocrit ≥0.45 ; n=51 ) as compared with the normal-hematocrit group without signs of dehydration ( hematocrit < 0.45 ; n=103 ) ( specific rehydration effect ) . Conclusions This study may provide an explanation for the failures in former hemodilution trials and may re-establish proper hemodilution and rehydration as a valuable therapy in the acute phase of stroke , thus reducing mortality and improving independence after 3 months We prospect ively r and omized 47 patients with acute ischemic stroke of the middle cerebral artery of less than 24 hours ' duration to either adjusted hypervolemic hemodilution or control treatment and followed them up for 90 days . Rapid hemodilution to a target hematocrit of 30 - 35 % as monitored with bedside determinations was achieved by using infusions of dextran 40 , venesections , and infusions of additional crystalloid solution when necessary . There was no difference in the death rate between the two treatment groups . Of these 47 patients , 37 ( 19 in the hemodilution group and 18 in the control group ) could be followed up for the entire study period of 3 months . The relative improvement in neurologic function from day 1 to days 8 , 21 , and 90 was significantly better in the hemodilution group than in the control group . In accordance , special tests for fine motor control of the paretic arm disclosed better performance in the hemodilution group . The frequency of patients with severe disability was significantly lower in the hemodilution group on days 8 and 21 . Plasma viscosity ( measured in 11 patients ) was not affected by infusions of dextran 40 . Vigorous hypervolemic hemodilution in patients with acute ischemic stroke is well tolerated and improves early neurologic outcome with an effect lasting at least 3 months Fifty-nine patients with onset of moderate to severe unimproving paralysis of less than 24 hours ' duration were r and omized into treatment ( Dextran 40 ) and control groups , managed similarly except for the dextran . A strict effort to study a uniform cerebral process by rejecting patients with hypertension , insulin-dependent diabetes , potential emboli , and pulmonary or renal disease result ed in a small sample . Most patients considered for the study had begun to improve before the initial examination . All patients had spinal tap prior to the decision to r and omize . Results were evaluated independently by the three authors over a three-week interval and tabulated after three years . A greater percentage of dextran-treated patients improved with respect to consciousness and strength in upper and lower extremities , but showed less restoration of language than the untreated patients . The differences in the two groups were not significant . One of 30 patients given dextran may have had a reaction Abstract Pre clinical studies have recently shown that albumin has neuroprotective effects for stroke in animal models . Thus , we sought to evaluate the effects of albumin therapy in patients with acute cerebral infa rcts . We prospect ively studied 49 patients with moderate-to-severe cerebral infa rcts within the middle cerebral arterial territory into one of two groups : the control group ( N = 18 ) received saline , whereas the albumin group ( N = 31 ) received either 40 g or 80 g of albumin within 24 h from symptom onset . The modified National Institutes of Health Stroke Scale ( mNIHSS ) and diffusionweighted imaging ( DWI ) were serially checked . There was no adverse effect related to albumin therapy . Although there was no significant difference in both baseline mNIHSS score and DWI lesion volume on admission , the mNIHSS scores at the 14th day after treatment and the increase in DWI lesion volume 72–96 h after treatment were significantly reduced in patients of the albumin group ( p = 0.001 and 0.012 , respectively ) ; these effects were dose- and timerelated . The outcome on the 90th day after stroke onset was more favorable in the albumin group than in the control group . Within the albumin group , patients who had patent or recanalized vessels showed more significant improvement than patient without recanalization ( p = 0.046 ) . Our results indicate that albumin therapy is a safe and effective modality in patients with acute cerebral infa rct ion . This study also suggests that the effects of albumin therapy may vary depending on vessel status of the patient In stroke penumbra perfusion depends passively on hemodynamics . So far hemodynamic effects of low molecular weight hydroxyethylstarch ( HES ) has not been investigated . Ten stroke patients received hypervolemic HES therapy . Cardiac output and heart rate were monitored using the bioimpedance method , blood pressure by conventional measurement . The Sc and inavian Stroke Scale assessed clinical outcome . Circadian cardiac output changes were measured in 20 controls . Patients ' cardiac output increased after the loading dose ( 5.3 + /- 1.4 l min(-1 ) to 6.5 + /- 1.7 l min(-1 ) , p < 0.01 ) , fluctuating then between 5 and 7 l min(-1 ) without nocturnal decrease . Beside an initial increase , the heart rate showed , like blood pressure , no remarkable changes . The Sc and inavian Stroke Scale score did not change significantly . The controls showed a circadian cardiac output fluctuation ( 2.00 am , 5.3 + /- 0.3 l min(-1 ) ; 8.30 am , 8.1 + /- 0.6 l min(-1 ) . Our patients showed a hemodynamic and clinical stabilization under therapy with low molecular weight HES . The physiological nocturnal decrease of cardiac output and blood , which might cause clinical deterioration in stroke patients , was avoided Background and Purpose In a previous single-center , r and omized controlled trial including 102 patients treated in a stroke unit , we showed that rapid , modest hemodilution improved short-term clinical outcome in ischemic stroke patients . I now evaluate the long-term outcome and potential risks of this combined venesection/dextran 40 therapy in the same 52 treated and 50 control patients . Methods Mortality , need for institutional care , and recurrent strokes were registered during 1 year following inclusion in the trial , and a final evaluation of functional outcome was performed at 12 months after the stroke . Cerebrospinal fluid was analyzed for protein content and hemorrhagic admixture at two occasions during the acute phase . Results Thirty-six hemodiluted and 30 control patients survived the first year following the stroke ( difference not significant ) . One year after the stroke , persistent neurological deficits were less frequent among the hemodiluted patients and a larger proportion of hemodiluted survivors was independent in walking ( 92 % versus 73 % , p<0.05 ) . Two hemodiluted patients ( 6 % ) and nine control patients ( 30 % ) were totally dependent in the activities of daily living ( p<0.05 ) . Three hemodiluted patients ( 8 % ) and eight control patients ( 27 % ) remained hospitalized 1 year after the stroke ( p<0.05 ) . With the possible exception of patients with a medical history of congestive heart failure , subset analyses revealed a tendency toward improved outcome for hemodiluted patients in all clinical ly important subgroups compared with the controls . When analyzing cerebrospinal fluid , signs of blood – brain barrier breakdown and hemorrhagic admixture to the cerebrospinal fluid during the acute phase were less frequent in the hemodiluted subjects . Conclusions These results suggest that , when applied in a stroke unit , the combination of venesection and dextran 40 administration is a clinical ly safe , therapeutic regimen in the treatment of acute cerebralinfa rct ion that improves long-term clinical outcome A blind controlled trial of dextran 40 in ischaemic stroke is reported . In the treated group mortality in the acute stage in patients with severe strokes was significantly reduced but survivors were severely disabled and six months later no significant benefit could be detected . In less severe strokes no effect of treatment was found . It is concluded that the action of dextran 40 in reducing acute mortality probably lay in preventing or reversing cerebral swelling but no evidence of the expected action in reducing the area of infa rct ion following improved blood flow was found . The importance of extending assessment beyond the two weeks customary in therapeutic trials in stroke is emphasized To eluci date the relation of hematocrit ( Hct ) to the incidence of cerebral infa rct ion , a prospect i ve follow-up study of 16 years ( 1965 - 81 ) was performed in a general population sample of 1220 Hisayama residents aged 44 and over , of both sexes . Most of the subjects who died during the follow-up period were autopsied , the rate being 89.0 % . Hct decreased with advancing age in men , but not in women . The average value for Hct was significantly lower in women than in men . According to the mean value + /- 1 SD of Hct , the subjects were grouped into 3 , in each sex as follows : low ( less than 35 % ) , normal ( 35 - 45 % ) and high ( greater than or equal to 45 % ) for men , and , low ( less than 30 % ) , normal ( 30 - 40 % ) and high ( greater than or equal to 40 % ) for women . During the follow-up period , cerebral infa rct ion occurred in 117 patients . The cumulative incidence of cerebral infa rct ion in the low Hct group for men was the lowest , even after adjustments for age and blood pressure . Conversely , the incidence in the low Hct group of women was significantly higher than that in the normal Hct group and was consistently increased with time during 2 - 5 years of the follow-up . After the 6th year or later , however , the incidence was gradually but significantly increased in the high Hct group , compared with the normal Hct group . Since Hct levels were related with other variables such as serum total cholesterol , serum total protein , Quetelet index and prevalence of hypertension in both sexes , heavy alcohol consumption in men , and glucose intolerance in women , such variables were taken into account using Cox 's proportional hazards regression model . ( ABSTRACT TRUNCATED AT 250 WORDS Rapid hemodilution in the early phase of ischemic stroke by the combination of venesection ( 250 - 650 ml during the first 2 days ) and administration of low-molecular weight dextran was evaluated in a prospect i ve controlled trial . Fifty-two patients were r and omized to hemodilution therapy and 50 to a control group ; the two groups were comparable in important prognostic variables . Mean hemoglobin was reduced from 147 to 127 g/1 , hematocrit from 43 to 37 % and , in a sub sample of patients , whole-blood viscosity at a shear rate of 23 sec'1 from 7.0 to 4.3 cps over the first 2 days . Hemodilution was then maintained by repeated dextran infusions . Of the hemodiluted patients , 85 % improved in neurological scoring over the first 10 days as compared to 64 % of the control patients ( P < 0.025 ) . The case fatality rate during the first 3 months was little affected by hemodilution . Among the survivors , 8 % of the hemodiluted and 31 % of the non-hemodiluted patients were unable to walk at 3 months . The proportion of surviving patients still hospitalized at the 3-month follow-up was 13 % in the hemodilution group and 39 % in the control group ( P < 0.01 ) . The combination of venesection and dextran 40 administration is thus an unsophisticated but effective way to achieve rapid hemodilution in patients with acute cerebral infa rct ion , and it improves the overall clinical outcome over the first 3 months . Stroke Vol 15 , No 6 , In a clinical ly applicable cat stroke model , 16 purpose -bred adult animals were used to evaluate the beneficial effects of two treatment regimens : isovolemic hemodilution with either a perfluorocarbon emulsion or dextran 40 ( a glucose polymer ) . Animals that received these treatment regimens were then compared with a control group of untreated animals . Focal cerebral infa rct ions were produced by transorbital ligation of the left middle cerebral artery . The r and omly allocated treatment arms of the study were instituted 3 hours after ligation of the middle cerebral artery , thereby simulating a human clinical situation . In vivo mitochondrial metabolic activity of the peri-infa rct cerebral tissue was continually assessed by means of a multiwavelength near-infrared spectrophotometer . This allowed measurement of cellular oxygenation at the cytochrome aa3 level , the terminal member of the cytochrome chain . Sequential proton-based magnetic resonance imaging was used to measure intracerebral water in vivo . Cardiac output , oxygen consumption/delivery , chemical , histologic , and rheologic parameters were also assessed . The data collected were analyzed by group means and st and ard statistical analyses , which revealed that the group treated with the perfluorocarbon emulsion had both less brain edema in the early post-infa rct period ( p less than 0.05 ) , as well as a higher level of oxidation of cytochrome aa3 ( p less than or equal to 0.025 ) . This evidence supports the premise that isovolemic hemodilution with an oxygen-carrying hemodiluent may be beneficial in the treatment of ischemic strokes Intramuscular dexamethasone combined with intravenous low-molecular-weight dextran ( dextran 40 ) was compared with placebo in 40 patients with acute ischaemic cerebral infa rct ion . A double-blind procedure was used . Dexamethasone was given for up to 14 days and dextran 40 for up to three days after the infa rct ion . A weighted scoring system was used to evaluate neurological state and mobility . There were no differences in mortality or in improvement of the neurological or mobility scores between the two groups The impact of diabetes was prospect ively studied during a 5-year period in 428 unselected and consecutive patients with acute cerebrovascular disease of whom 18 % were diabetic . Cerebral infa rct ion was more frequent in diabetics ( 81 vs 70 % , p less than 0.02 ) whereas transient cerebral ischaemia was less frequent ( 4 vs 14 % , p less than 0.01 ) . Case fatality rate during hospitalization was higher in the diabetic than in the non-diabetic patients ( 28 vs 15 % , p less than 0.02 ) . Patients who died during hospitalization , diabetic as well as non-diabetic , had significantly higher blood glucose concentrations on admission compared with patients who survived . Hematocrit values were higher in the diabetic than in the non-diabetic patients ( p less than 0.02 ) . Diabetics had higher systolic blood pressure levels than the non-diabetics in the acute phase ( p less than 0.005 ) . The diabetic stroke patients more often had a history of hypertension , atrial fibrillation , heart failure and angina pectoris than non-diabetics stroke patients and diabetic control patients without stroke . Stroke patients , not known to be diabetic , had larger mean oral glucose tolerance test curve areas when compared with healthy controls but not when compared with hospitalized controls . We propose that diabetes increases the risk for stroke through other concurrent risk factors , cardiac disorders in particular Background and Purpose — Enrollment in the Albumin in Acute Stroke ( ALIAS ) Trial was suspended in late 2007 due to a safety concern . We present the safety data of that Trial ( “ Part 1 ” ) and the rationale for the design of Part 2 . Methods — ALIAS Part 1 was design ed to assess whether 25 % albumin ( ALB ) started within 5 hours of stroke onset would confer neuroprotection in subjects with acute ischemic stroke and baseline National Institutes of Health Stroke Scale of ≥6 . Exclusion criteria included recent or current congestive heart failure , myocardial infa rct ion , or cardiac surgery . The study comprised 2 cohorts : subjects who received thrombolysis and those who did not , each with 1:1 r and omization to ALB or placebo . The primary outcome was the National Institutes of Health Stroke Scale and modified Rankin Scales at 90 days . The intended sample size was 1800 . Results — Four hundred thirty-four subjects were enrolled , and 424 were used in the safety analysis ( ALB 207 , saline 217 ) . There were 36 deaths within the first 30 days in the ALB group and 21 in the saline group . In contrast , death rates after 30 days were similar by treatment . Large strokes were the predominant cause of early death in both groups . In subjects > 83 years of age , 90-day death rates were 2.3-fold higher with ALB than with saline ( 95 % CI , 1.04 to 5.12 ) . Similarly , 90-day deaths in subjects receiving excessive fluids were 2.10-fold greater with ALB than with saline ( CI , 1.10 to 3.98 ) . Conclusions — The ALIAS Part 2 Trial , which started in early 2009 , was modified as follows to enhance safety : upper age limit of 83 years ; requirement for normal baseline serum troponin level ; restriction of total intravenous fluids in the first 48 hours to ≤4200 mL ; m and atory diuretic at 12 to 24 hours ; and detailed site retraining . Because of insufficient nonthrombolysed subjects ( 22 % ) in Part 1 , the 2-cohort design was eliminated . The Data Safety Monitoring Board has review ed the safety data of Part 2 3 times and has approved continuation of the trial Patients with acute ischemic stroke were r and omized less than 24 hours after onset to st and ard ( S ) therapy ( n = 43 ) or to hypervolemic hemodilution ( HH ) with pentastarch ( n = 45 ) . The therapeutic goal of hypervolemic hemodilution was to rapidly reduce hematocrit to 33 % , to raise cardiac output , and to continue hypervolemic hemodilution for 3 days . A grade d neurologic examination was scored by a blinded observer at r and omization ( baseline ) , at the end of treatment or after 72 hours , and at a 3-month follow-up ; each patient was also rated using Barthel 's disability scale at the 3-month follow-up . Group demographics and results of the grade d neurologic examination were similar at baseline , except that the HH group contained twice the number of patients with severe strokes and fewer patients r and omized within 12 hours compared with the S group . The HH group improved an average of 7 points in neurologic score from baseline to the end of treatment ( the S group deteriorated 1 point ) and 24 points by the 3-month follow-up ( the S group improved 16 points ; p = 0.11 ) . The HH group reached an average Barthel disability scale index of 85 while the S group averaged 70 ( p = 0.8 ) . Deaths associated with cerebral edema occurred in five patients with severe stroke ( four in the HH group vs. one in the S group , p = 0.36 ) . The following subgroups of HH patients showed better overall improvement in neurologic scores : patients entered within 12 hours after stroke onset , patients with a 15 % decrease in hematocrit , and patients with a 10 % increase in cardiac output . ( ABSTRACT TRUNCATED AT 250 WORDS Background : Hypervolemic hemodilution ( HH ) with hydroxyethyl starch ( HES ) significantly increases cerebral blood flow and thus may reduce ischemic tissue damage in the penumbra zones when given within the therapeutic time window . The objective of this study was to investigate the safety of a 10 % solution of HES 130/0.4 versus 0.9 % saline solution in acute ischemic stroke by the incidence of adverse events ( AEs ) . Methods : In a controlled , double-blind , r and omized , multicenter , phase II , parallel-group study , 106 patients with acute ischemic stroke received high-dose HH with HES 130/0.4 or placebo within 6 h of symptom onset with a r and omization ratio of 2:1 in favor of HES therapy . Results : There were no significant differences between the groups with regard to the incidence of the specific AEs ( cardiovascular events , bleeding complications , allergic reactions ) assessed over days 1–30 , or mortality over days 1–8 . In addition , global tests of efficacy showed a trend towards a better functional outcome with HES therapy ; however , the study was not design ed to prove efficacy . Conclusions : High-dose HH with HES or NaCl was generally safe and well tolerated . Safety profiles were similar for the two treatment groups , and there was a nonsignificant trend towards a better functional outcome with HES therapy The Italian Acute Stroke Study is a prospect i ve , multicenter , r and omized , clinical trial to evaluate hemodilution in acute stroke . Thirty — one centers will recruit 1,200 patients with a recent ( < 12 hours ) hemispheric acute stroke . R and omization is performed central ly , and patients are stratified by center and severity of neurologic deficit . Hemodilution is achieved by venesection and infusion of the same amount of dextran 40 . Otherwise , both treated and control groups receive the st and ard treatment provided by each center within agreed guidelines . At 6 months after stroke , one member of the Clinical Coordinating Center , blind as to treatment allocation , collects data on mortality and disability by telephone . We expect to terminate the r and omization on December 31,1986 , and the follow — up evaluation on June 30,1987 . The aim of the study is to evaluate whether mortality and disability are significantly reduced in the group treated with hemodilution compared with the control group . ( Stroke 1987 ; 18:670–676 OBJECTIVES perioperative stroke reduces the clinical effectiveness of carotid endarterectomy ( CEA ) . Postoperative thrombotic stroke may be reduced in incidence by the use of transcranial Doppler-directed Dextran-40 therapy . This programme requires the purchase of additional equipment and employment of more staff . This study examined whether this additional financial outlay was cost-effective in terms of saving expenditure by preventing postoperative thrombotic stroke . MATERIAL S AND METHODS data was collected prospect ively on a series of 600 consecutive CEAs . The costs of the monitoring programme were analysed over 1- and 5-year periods . Formulae were derived allowing other units to calculate whether this technique will be cost-effective for them . RESULTS after the introduction of TCD monitoring the postoperative thrombotic stroke rate fell from 2.7 % to 0 % ( 8 strokes prevented ) . Our local unit cost for the treatment of stroke was 25,702 pounds . After allowing for the additional costs of the monitoring programme , we calculate that postoperative TCD has saved 171,393 pounds . CONCLUSIONS postoperative TCD monitoring is a clinical ly effective and also cost-effective method of reducing the stroke rate associated with CEA . For units performing more than 50 CEAs per year who experience occasional postoperative carotid thrombosis , its introduction should be considered In thromboembolic brain infa rct ions high fibrinogen levels are associated with an increase of both plasma and whole blood viscosity as well as increased aggregability of blood cells . This decreases cerebral perfusion and might reduce blood flow in the penumbra surrounding infa rct ion . An important goal in the treatment of acute cerebral infa rct ion is to reduce fibrinogen and thereby improve the haemorheological state . Heparin-induced extracorporeal low-density lipoprotein/fibrinogen precipitation ( HELP ) appears to be successful in achieving this . Such treatment reduces lipid fractions , including total cholesterol , low-density lipoproteins ( LDL ) and triglycerides ( p < 0.0001 each ) , as well as fibrinogen ( p < 0.0001 ) in a safe and efficacious manner . Whole blood and plasma viscosity are also improved when measured by oscillo-rheometry . Furthermore , the number and aggregation tendency of blood cells is influenced positively as determined by Coulter counting and aggregometry . HELP improves the haemorheological profile to a degree which has not been achieved by haemorheologically active substances The Amsterdam Stroke Study was a prospect i ve , single-center , r and omized clinical trial , investigating the effect of normovolemic hemodilution and rehydration with albumin 20 % and crystalloids . All patients ( n = 300 ) received general intensive care treatment and monitoring with a pulmonary artery catheter . The therapy was individually " customized " and guided on the pulmonary capillary wedge pressure of 12 + /- 3 mm Hg and for the hemodilution group on a hematocrit of 0.32 + /- 0.02 l/l . The significant differences in the subgroups emphasize the importance of a differentiation between a viscosity effect and an effect in hemodilution therapy , sometimes intensifying , sometimes counteracting each other Haemorheological parameters on long-term treatment of ischaemic stroke were measured in two groups of 12 patients receiving dextran 40 or hydroxyethyl starch ( HES 200 ) . Both substances similarly lowered haematocrit and whole-blood viscosity . Dextran produced a clear-cut increase in plasma viscosity and red-cell aggregation . The effects were due to a marked increase in the plasma concentration of dextran caused by an accumulation of large molecules . HES 200 improved plasma viscosity and red-cell aggregation . Since these haemorheological parameters are of special importance for improving a disordered microcirculation as would occur at the margins of the ischaemic lesion , HES 200 would seem to be the appropriate plasma exp and er in long-term treatment with haemodilution . The differences between dextran 40 and HES 200 become the more marked the higher the volume infused Stroke is a serious global illness . Human albumin has emerged as a putative therapy for ischaemic stroke based on strong evidence from animal models . Following confirmation of the safety and feasibility of high-dose albumin treatment for acute ischaemic stroke in a pilot study , the Albumin in Acute Stroke trial , a phase 3 r and omised , double-blinded , placebo-controlled clinical trial was initiated to evaluate the efficacy of high-dose albumin compared to saline control within 5 h of ischaemic stroke onset . Methods : The trial will enrol 1800 patients in two cohorts – a thrombolytic and a nonthrombolytic arm . High-dose ( 2 g/kg ) human albumin will be administered in a 2-h straight intravenous infusion to ischaemic stroke patients , within 5 h of symptom onset . The primary outcome will be an NIH stroke scale score of 0–1 or a modified Rankin scale score of 0–1 at 90 days . Safety outcomes will include the incidence of congestive heart failure after study drug administration . Results : Enrolment opened at 40 sites in August 2006 ; new sites continue to be added . Recruitment is ongoing and is projected to be completed by 2010 . Conclusions : The trial will continue through 2010 . The study is proceeding as planned Ninety two 50-year-old-or-more patients with acute ( less than 72 hours ) cerebral infa rct ion involved middle cerebral artery region and hematocrit of 40 % or more were prospect ively r and omised to either hemodilution group ( by rapid venesection , venous infusion of autologous plasma and 500 ml dextran 40 ) or st and ard therapy group . Effects of hemodilution on acute cerebral infa rct ion were evaluated by clinical ly neurological deficit scores , hemorheological parameters and size of infa rct ion . The results of our clinical trial are : 1 . Clinical efficacy of hemodiluted patients is significantly superior to that of st and ard treatment patients . Effective rates are 63.04 % and 41.30 % respectively ( P less than 0.05 ) . 2 . At 48th hour after hemodilution there are profound decreases in hematocrit , blood viscosity at high shear rate and blood viscosity at low shear rate . These changes last more than four weeks . Whereas in st and ard group , hemorheological parameters do not evidently change . 3 . Sizes of cerebral infa rct ion do not distinctly change in both groups between at entry and at the fourth weekend after treatment Acute perioperative anaemia may affect neurological injury from permanent focal ischaemic insults . We modelled the opposing effects of haemodilution ( increasing cerebral blood flow , decreasing arterial oxygen content ) on oxygen availability and uptake in the ischaemic penumbra . First , we vali date d a mathematical model of regional cerebral oxygen uptake by using published arterial oxygen content and cerebral blood flow values from normal rabbits with progressive anaemia . Then we applied the model to the problem of interest ( i.e. the ischaemic penumbra of a focal embolic stroke ) . We re-analysed published experimental data giving the cerebral blood flow response to anaemia in the ischaemic penumbra . Penumbral extraction reserves were nearly exhausted at a haemoglobin concentration of approximately 10 g 100ml-1 . Oxygen uptake in the ischaemic penumbra decreased progressively when haemoglobin concentrations decreased to less than 10 g 100ml-1 . We conclude that , given the available clinical and experimental literature , and until a suitable r and omized clinical study has been performed , a haemoglobin concentration of 10 g 100 ml-1 is the rational transfusion " trigger " for the acutely anaemic stroke patient On presente les objectifs et le protocol e general de l'essai , les centres participants , l ' inclusion des patients , les taux de l'hematocrite , les criteres d'inclinaison et exclusion , la cotation et la stratification , le protocol e du traitement , l'evaluation du traitement , l'ethique , la taille de l'echantillon de malade , le controle de la qualite et le programme |
13,297 | 26,602,059 | Although many medications may affect the salivary flow rate and composition , most of the studies considered only xerostomia . | The aim of this paper was to perform a systematic review of the pathogenesis of medication-induced salivary gl and dysfunction ( MISGD ) .
Medications may act on the central nervous system ( CNS ) and /or at the neurogl and ular junction on muscarinic , α- and β-adrenergic receptors and certain peptidergic receptors . | The goal of the current clinical study , conducted in the United States ( US ) , was to evaluate the efficacy and tolerability of vortioxetine 5 mg vs placebo in adults with a primary diagnosis of generalized anxiety disorder ( GAD ; HAM-A total score ≥20 and MADRS score ≤16 ) . Subjects were r and omized ( 1:1 ) to receive vortioxetine 5 mg ( n=152 ) or placebo ( n=152 ) for 8 weeks . Efficacy was assessed using change from baseline in HAM-A total scores after 8 weeks of treatment compared with placebo , using mixed-model repeated measures ( MMRM ) analyses . Adverse events ( AEs ) were assessed throughout the study . A total of 304 subjects were r and omized ( mean age , 41.2 years ) . After 8 weeks of treatment , there was no statistically significant difference in the reduction in HAM-A total score from baseline between the Vortioxetine ( n=145 ) and placebo ( n=145 ) groups . There were no statistically significant differences in any key secondary efficacy outcome between vortioxetine and placebo . Factors potentially contributing to the differences between the results of this study and those of one of identical design conducted outside the US are discussed . The most common treatment-emergent AEs were nausea , headache , dizziness , and dry mouth . Nausea was more frequently reported in the vortioxetine group ( 25 % vs 4.6 % for the placebo group ) . Most AEs were mild to moderate in severity . In conclusion , in this trial , vortioxetine did not improve symptoms of GAD ( compared with placebo ) over 8 weeks of treatment . Vortioxetine was well tolerated in this study Background Cigarette smoking is a tough addiction to break . Therefore , improved approaches to smoking cessation are necessary . The electronic-cigarette ( e-Cigarette ) , a battery-powered electronic nicotine delivery device ( ENDD ) resembling a cigarette , may help smokers to remain abstinent during their quit attempt or to reduce cigarette consumption . Efficacy and safety of these devices in long-term smoking cessation and /or smoking reduction studies have never been investigated . Methods In this prospect i ve proof-of-concept study we monitored possible modifications in smoking habits of 40 regular smokers ( unwilling to quit ) experimenting the ' Categoria ' e-Cigarette with a focus on smoking reduction and smoking abstinence . Study participants were invited to attend a total of five study visits : at baseline , week-4 , week-8 , week-12 and week-24 . Product use , number of cigarettes smoked , and exhaled carbon monoxide ( eCO ) levels were measured at each visit . Smoking reduction and abstinence rates were calculated . Adverse events and product preferences were also review ed . Results Sustained 50 % reduction in the number of cig/day at week-24 was shown in 13/40(32.5 % ) participants ; their median of 25 cigs/day decreasing to 6 cigs/day ( p < 0.001 ) . Sustained 80 % reduction was shown in 5/40(12.5 % ) participants ; their median of 30 cigs/day decreasing to 3 cigs/day ( p = 0.043 ) . Sustained smoking abstinence at week-24 was observed in 9/40(22.5 % ) participants , with 6/9 still using the e-Cigarette by the end of the study . Combined sustained 50 % reduction and smoking abstinence was shown in 22/40 ( 55 % ) participants , with an overall 88 % fall in cigs/day . Mouth ( 20.6 % ) and throat ( 32.4 % ) irritation , and dry cough ( 32.4 % ) were common , but diminished substantially by week-24 . Overall , 2 to 3 cartridges/day were used throughout the study . Participants ' perception and acceptance of the product was good . Conclusion The use of e-Cigarette substantially decreased cigarette consumption without causing significant side effects in smokers not intending to quit ( http:// Clinical Trials.gov number NCT01195597 ) Although constipation is a well-known side effect of calcium channel blockers such as verapamil , this side effect has not been evaluated in a quantitative manner . In a double-blind , r and omized , crossover trial , the effect of verapamil ( 240 mg/day ) was compared to placebo in 15 normal male volunteers . Subjects recorded their bowel movements and any side effects . Scintigraphy was used to quantitate gastric emptying , small intestinal transit , and colonic transit . In the study period of four days , verapamil did not change the frequency , consistency , or passage of bowel movements . A significantly increased number of side effects was noted during verapamil treatment — notably abdominal pain and dry mouth . The slope of gastric emptying was not significantly different for verapamil ( 0.012±0.02 ) than for placebo ( 0.013±0.001 ) . Distal ileum filling was also not different for verapamil ( 0.41±0.13%/min ) than placebo ( 0.33±0.05%/min ) . Progression of the colonic geometric center was significantly delayed at 48 hr by verapamil ( 5.2±0.4 vs 6.2±0.23;P<0.01 ) . This study suggests that the constipating effect of verapamil is due to a delay of colonic transit and not due to an effect on upper gastrointestinal transit Background In clinical practice , clinicians often need to switch antipsychotic medications in patients with schizophrenia to optimize treatment outcomes . Here , we describe the safety and tolerability of switching existing antipsychotic treatments to asenapine or olanzapine monotherapy using various switching regimens . Methods Data were pooled from 949 patients in two 26-week r and omized double-blind studies . Patients with persistent negative symptoms of schizophrenia , stable for at least 5 months prior to screening and 1 additional month before r and omization , were r and omized to and treated with either asenapine ( n = 485 ) or olanzapine ( n = 464 ) , and were tapered off existing antipsychotic(s ) at variable rates within 28 days . Results Prior to r and omization , most patients were treated with second-generation antipsychotics ( SGAs ) ( asenapine : 79.6 % ; olanzapine : 78.2 % ) and first-generation antipsychotics ( FGAs ) ( 31.1 % ; 29.7 % ) , while depot formulations were used by 12.4 % and 11.4 % , respectively . Median time to taper off previous antipsychotics was 7 days , with approximately 40 % of patients abruptly discontinuing their previous medication . Similar percentages of patients in each group reported at least one adverse event ( AE ) ( asenapine : 76.9 % ; olanzapine : 75.2 % ) . The majority of AEs occurred within the first 28 days . The most frequently reported AEs were somnolence , insomnia , and headache . The incidence of AEs in patients switching from SGAs , FGAs , or depot medications was similar between asenapine and olanzapine ( 77.5 % vs 74.6 % , 75.5 % vs 79.7 % , 85.0 % vs 86.8 % , respectively ) . AEs were more frequent in subjects previously treated with two antipsychotics ( asenapine : 79.4 % ; olanzapine : 83.9 % ) versus one antipsychotic ( asenapine : 76.3 % ; olanzapine : 72.2 % ) in the switch period . Conclusion The presented data from post hoc pooled analyses may provide practical guidance for physicians switching partially stabilized patients with schizophrenia and persistent negative symptoms to asenapine or olanzapine Although dopamine agonists ( DAs ) are sometimes perceived as poorly tolerated by the elderly , there is little clinical evidence to support these concerns . Safety and tolerability of rotigotine have been demonstrated in four 6-month r and omized placebo-controlled studies : two in early Parkinson 's disease ( PD ) and two in advanced PD . A post hoc analysis of data from these pivotal trials was carried out to compare the adverse event ( AE ) profiles of younger and older patient population s. Data from early and advanced PD trials were separately pooled and evaluated using two age cut-offs ( < 65 vs. ≥ 65 years ; < 75 vs. ≥ 75 years ) . For most AEs , no age-related differences in incidence were observed . In the early PD pool , nausea ( 38 % vs. 30 % ) and headache ( 15 % vs. 9 % ) were more frequent in younger ( < 65 years ) compared with older ( ≥ 65 years ) patients using the 65-year age cut-off . Using the 75-year cut-off , nausea ( 36 % vs. 21 % ) was more frequent in younger patients ( < 75 years ) and dizziness ( 15 % vs. 28 % ) was more frequent in older patients ( ≥ 75 years ) . In the advanced PD pool , nausea was more frequent in younger patients using the 65-year age cut-off ( 24 % vs. 19 % ) and falls were more frequent in older patients using the 75-year age cut-off ( 8 % vs. 13 % ) . In this relatively healthy population which included only few patients aged 75 years or older , rotigotine was generally well tolerated regardless of age . Data from more representative PD population s are required to fully assess potential risks of DA therapy in elderly patients Abstract Introduction / Objective : Executive function ( EF ) impairment in attention-deficit/hyperactivity disorder ( ADHD ) may account for behavioral symptoms such as poor concentration , impaired working memory , problems in shifting among tasks , and prioritizing and planning complex sets of tasks or completing long-term projects at work or school . Poor self-regulation and control of emotional behaviors frequently are seen in patients with ADHD . This study assessed EF behaviors in adults with ADHD at baseline and after 4 weeks of treatment with lisdexamfetamine dimesylate ( LDX ) . Methods : Executive function behavior was assessed using the Brown Attention-Deficit Disorder Scale ( BADDS ) during the 4-week open-label dose-optimization phase prior to a 2-period , r and omized , double-blind , placebo-controlled crossover study of LDX ( 30–70 mg/day ) . The ADHD Rating Scale IV ( ADHD-RS-IV ) with adult prompts assessed ADHD symptoms . Change in EF behavioral symptoms was evaluated based on week 4 BADDS total and cluster scores ; analyses of shifts from baseline among subjects with BADDS scores < 50 , 50 to 59 , 60 to 69 , and ≥ 70 ; and scores less than or greater than baseline 90 % confidence range ( eg , reliably improved or worsened , respectively ) . Treatment-emergent adverse events ( TEAEs ) were described . Results : At week 4 , BADDS total and cluster scores were reduced ( ie , improved ; all P < 0.0001 vs baseline [ n = 127 ] ) . The ADHD-RS-IV with adult prompts scores also improved ( all P < 0.0001 vs baseline ) . At week 4 , 62.7 % of subjects had a BADDS total score of < 50 , and 78.9 % were reliably improved ; 1.4 % were reliably worsened . Common TEAEs ( ≥ 5 % ) during the dose-optimization phase were decreased appetite ( 36.6 % ) , dry mouth ( 30.3 % ) , headache ( 19.7 % ) , insomnia ( 18.3 % ) , upper respiratory tract infection ( 9.9 % ) , irritability ( 8.5 % ) , nausea ( 7.7 % ) , anxiety ( 5.6 % ) , and feeling jittery ( 5.6 % ) . Conclusion : Clinical ly optimized doses of LDX ( 30–70 mg/day ) significantly improved EF behaviors in adults with ADHD . Treatment-emergent adverse events with LDX were consistent with those observed with long-term stimulant use Background The current article is a systematic review concerning the efficacy and safety of aripiprazole in the treatment of bipolar disorder . Methods A systematic Medline and repositories search concerning the usefulness of aripiprazole in bipolar disorder was performed , with the combination of the words ' aripiprazole ' and ' bipolar ' . Results The search returned 184 articles and was last up date d on 15 April 2009 . An additional search included repositories of clinical trials and previous systematic review s specifically in order to trace unpublished trials . There were seven placebo-controlled r and omised controlled trials ( RCTs ) , six with comparator studies and one with add-on studies . They assessed the usefulness of aripiprazole in acute mania , acute bipolar depression and during the maintenance phase in comparison to placebo , lithium or haloperidol . Conclusion Aripiprazole appears effective for the treatment and prophylaxis against mania . The data on bipolar depression are so far negative , however there is a need for further study at lower dosages . The most frequent adverse effects are extrapyramidal signs and symptoms , especially akathisia , without any significant weight gain , hyperprolactinaemia or laboratory test changes BACKGROUND Buprenorphine is a mixed-activity , partial mu-opioid agonist . Its lipid solubility makes it well suited for transdermal administration . OBJECTIVE This study assessed the efficacy and safety profile of a 7-day buprenorphine transdermal system ( BTDS ) in adult ( age > 18 years ) patients with moderate to severe chronic low back pain previously treated with > or = 1 tablet daily of an opioid analgesic . METHODS This was a r and omized , double-blind , placebo-controlled crossover study , followed by an open-label extension phase . After a 2- to 7-day washout of previous opioid therapy , eligible patients were r and omized to receive BTDS 10 microg/h or matching placebo patches . The dose was titrated weekly using 10- and 20-microg/h patches ( maximum , 40 microg/h ) based on efficacy and tolerability . After 4 weeks , patients crossed over to the alternative treatment for another 4 weeks . Patients who completed the double-blind study were eligible to enter the 6-month open-label phase . Rescue analgesia was provided as acetaminophen 325 mg to be taken as 1 or 2 tablets every 4 to 6 hours as needed . The primary outcome assessment s were daily pain intensity , measured on a 100-mm visual analog scale ( VAS ) , from no pain to excruciating pain , and a 5-point ordinal scale , from 0 = none to 4 = excruciating . Secondary outcome assessment s included the Pain and Sleep Question naire ( 100-mm VAS , from never to always ) , Pain Disability Index ( ordinal scale , from 0 = no disability to 11 = total disability ) , Quebec Back Pain Disability Scale ( categorical scale , from 0 = no difficulty to 5 = unable to do ) , and the 36-item Short Form Health Survey ( SF-36 ) . Patients and investigators assessed overall treatment effectiveness at the end of each phase ; they assessed treatment preference at the end of double-blind treatment . After implementation of a pre caution ary amendment , the QTc interval was measured 3 to 4 days after r and omization and after any dose adjustment . All assessment s performed during the double-blind phase were also performed every 2 months during the open-label extension . Adverse events were collected by non-directed question ing throughout the study . RESULTS Of 78 r and omized patients , 52 ( 66.7 % ) completed at least 2 consecutive weeks of treatment in each study phase without major protocol violations ( per- protocol [ PP ] population : 32 women , 20 men ; mean [ SD ] age , 51.3 [ 11.4 ] years ; mean weight , 85.5 [ 19.5 ] kg ; 94 % white , 4 % black , 2 % other ) . The mean ( SD ) dose of study medication during the last week of treatment was 29.8 ( 12.1 ) microg/h for BTDS and 32.9 ( 10.7 ) microg/h for placebo ( P = NS ) . During the last week of treatment , BTDS was associated with significantly lower mean ( SD ) pain intensity scores compared with placebo on both the VAS ( 45.3 [ 21.3 ] vs 53.1 [ 24.3 ] mm , respectively ; P = 0.022 ) and the 5-point ordinal scale ( 1.9 [ 0.7 ] vs 2.2 [ 0.8 ] ; P = 0.044 ) . The overall Pain and Sleep score was significantly lower with BTDS than with placebo ( 177.6 [ 125.5 ] vs 232.9 [ 131.9 ] ; P = 0.027 ) . There were no treatment differences on the Pain Disability Index , Quebec Back Pain Disability Scale , or SF-36 ; however , BTDS was associated with significant improvements compared with placebo on 2 individual Quebec Back Pain Disability Scale items ( get out of bed : P = 0.042 ; sit in a chair for several hours : P = 0.022 ) . Of the 48 patients /physicians in the PP population who rated the effectiveness of treatment , 64.6 % of patients ( n = 31 ) rated BTDS moderately or highly effective , as did 62.5 % of investigators ( n = 30 ) . Among the 50 patients in the PP population who answered the preference question , 66.0 % of patients ( n = 33 ) preferred the phase in which they received BTDS and 24.0 % ( n = 12 ) preferred the phase in which they received placebo ( P = 0.001 ) , with the remainder having no preference ; among investigators , 60.0 % ( n = 30 ) and 28.0 % ( n = 14 ) preferred the BTDS and placebo phases , respectively ( P = 0.008 ) , with the remainder having no preference . The mean placebo-adjusted change from baseline in the QTc interval ranged from -0.8 to + 3.8 milliseconds ( P = NS ) . BTDS treatment was associated with a significantly higher frequency of nausea ( P < 0.001 ) , dizziness ( P < 0.001 ) , vomiting ( P = 0.008 ) , somnolence ( P = 0.020 ) , and dry mouth ( P = 0.003 ) , but not constipation . Of the 49 patients completing 8 weeks of double-blind treatment , 40 ( 81.6 % ) entered the 6-month , open-label extension study and 27 completed it . Improvements in pain scores achieved during the double-blind phase were maintained in these patients . CONCLUSIONS In the 8-week , double-blind portion of this study , BTDS 10 to 40 microg/h was effective compared with placebo in the management of chronic , moderate to severe low back pain in patients who had previously received opioids . The improvements in pain scores were sustained throughout the 6-month , open-label extension . ( Current Controlled Trials identification number : IS RCT N 06013881 ) Levocetirizine has been shown in observational studies in the west as an effective and satisfactory therapy for patients with allergic respiratory and skin disease . An open-label , multicentre observational study was conducted to investigate the patients ' perception of levocetirizine in the treatment of allergic rhinitis ( AR ) and urticaria in Taiwanese patients . Three hundred and thirty-three patients ( 236 AR and 97 urticaria patients ) attending out-patient clinics of medical centres across Taiwan were included in the study . Patients were treated with levocetirizine 5 mg once daily ( AR patients for 2 - 4 weeks and urticaria patients for 2 - 6 weeks ) and at the end of treatment , they evaluated for symptoms of disease , perception of change in symptoms , global efficacy and tolerability , global preference over previous antiallergic treatment , change in quality of sleep/daily activities , and safety and adverse events ( AEs ) . Levocetirizine markedly improved the symptoms of AR and urticaria ; with 70 - 75 % of AR patients and 60 - 80 % of urticaria patients reporting complete or marked improvements in individual symptoms . Asthma symptoms were completely or markedly improved in 44 % of patients with AR and concomitant asthma . A majority of the patients was satisfied with levocetirizine therapy and 50 - 70 % indicated preference for levocetirizine over previous therapy . Overall , 50 - 74 % of all patients perceived improvements in quality of sleep/daily activities and 50 - 65 % of the patients rated the onset of action for levocetirizine as very rapid or rapid . Somnolence was the most common AE , reported by 7.4 % of AR and 7.0 % of urticaria patients . The results of this study indicated that levocetirizine is an effective and satisfactory therapy for the management of allergic respiratory and skin disease in Taiwanese subjects Abstract Objective : The present study compares the effects of yohimbine , an alpha2 adrenoceptor antagonist , and anetholtrithione , a reference drug in the treatment of dry mouth , in patients treated with psychotropic drugs ( tricyclic antidepressants or neuroleptics ) and suffering from xerostomia . Methods : Ten patients were included in a r and omized , double-blind , cross-over study , and receiving after yohimbine ( 3 × 6 mg per day ) or anetholtrithione ( 3 × 25 mg per day ) orally for 5 days . Salivary secretion was estimated under resting conditions , before any drug , and then on day 6 , 1 h after the ingestion of yohimbine or anetholtrithione . Results : Compared with basal secretion , the increase in salivary flow was significantly more marked after yohimbine than after anetholtrithione . Conclusion : This study demonstrates the sialogenic effect of yohimbine in drug-induced dry mouth Pilocarpine induces a profuse flow of saliva , and it may re-establish saliva production in cases of drug-induced oral dryness . The aim of the study ( a sub- study to the previous trial investigating the pilocarpine fluid effects in individuals suffering from drug-induced dry mouth ) was to search for saliva quality changes induced by the treatments . Sixty-five individuals were enrolled in a r and omized , double-blind , placebo-controlled trial . The subjects received tramadol to induce oral dryness . Secretion rate was measured before and after tramadol , and then after pilocarpine , placebo , or no treatment . All saliva was analyzed for its protein and IgA content in the pilocarpine ( n=15 ) and placebo groups ( n=12 ) . At baseline , the flow of saliva was 0.47±0.05ml/min , the protein output 0.17±0.2mg/min and the IgA output 0.022±0.002mg/min . After tramadol treatment ( 50 mg 3 × /day over two days ) , the flow was reduced by 64 % , protein output by 52 % and the IgA output by 38 % . While placebo treatment did not affect any of the variables , the flow was 120 % , the protein output 193 % and the IgA output 83 % of the baseline characteristics after pilocarpine treatment ( 5 mg ) . Thus , the pilocarpine-induced increase in the flow rate in the state of tramadol-induced oral dryness results in saliva with a well preserved protein concentration but with a decrease in IgA concentration . However , compared to baseline , there was neither a decrease in output nor in concentration of OBJECTIVE To evaluate the safety and antiretroviral activity of ritonavir ( Norvir ) and saquinavir ( Invirase ) combination therapy in patients with HIV infection . DESIGN A multicenter , r and omized , open-label clinical trial . SETTING Seven HIV research units in the USA and Canada . PATIENTS A group of 141 adults with HIV infection , CD4 T lymphocyte counts of 100 - 500 x 10(6 ) cells/l , whether treated previously or not with reverse transcriptase inhibitor therapy , but without previous HIV protease inhibitor drug therapy . INTERVENTIONS After discontinuation of prior therapy for 2 weeks , group I patients were r and omized to receive either combination ( A ) ritonavir 400 mg and saquinavir 400 mg twice daily or ( B ) ritonavir 600 mg and saquinavir 400 mg twice daily . After an initial safety assessment of group I patients , group II patients were r and omized to receive either ( C ) ritonavir 400 mg and saquinavir 400 mg three times daily or ( D ) ritonavir 600 mg and saquinavir 600 mg twice daily . Investigators were allowed to add up to two reverse transcriptase inhibitors ( including at least one with which the patient had not been previously treated ) to a patient 's regimen after week 12 for failure to achieve or maintain an HIV RNA level < or = 200 copies/ml documented on two consecutive occasions . MEASUREMENTS Plasma HIV RNA levels and CD4 + T-lymphocyte counts were measured at baseline , every 2 weeks for 2 months , and monthly thereafter . Safety was assessed through the reporting of adverse events , physical examinations , and the monitoring of routine laboratory tests . RESULTS The 48 weeks of study treatment was completed by 75 % ( 106/141 ) of the patients . Over 80 % of the patients on treatment at week 48 had an HIV RNA level < or = 200 copies/ml . In addition , intent-to-treat and on-treatment analyses revealed comparable results . Suppression of plasma HIV RNA levels was similar for all treatment arms ( mean areas under the curve minus baseline through 48 weeks were-1.9 , -2.0 , -1.6 , -1.8 log10 copies/ml in ritonavir-saquinavir 400 - 400 mg twice daily , 600 - 400 mg twice daily , 400 - 400 mg three times daily , and 600 - 600 mg twice daily , respectively ) . Median CD4 T-lymphocyte count rose by 128 x 10(6 ) cells/l from baseline , with an interquartile range ( IQR ) of 82 - 221 x 10(6 ) cells/l . The most common adverse events were diarrhea , circumoral paresthesia , asthenia , and nausea . Reversible elevation of serum transaminases ( > 5 x upper limit of normal ) occurred in 10 % ( 14/141 ) of the patients enrolled in this study and was associated with baseline abnormalities in liver function tests , baseline hepatitis B surface antigen positivity , or hepatitis C antibody positivity ( relative risk , 5.0 ; 95 % confidence interval 1.5 - 16.9 ) . Most moderate or severe elevations in liver function tests occurred in patients treated with ritonavir-saquinavir 600 - 600 mg twice daily . CONCLUSIONS Ritonavir 400 mg combined with saquinavir 400 mg twice daily with the selective addition of reverse transcriptase inhibitors was the best-tolerated regimen of four dose-ranging regimens and was equally as active as the higher dose combinations in HIV-positive patients without previous protease inhibitor treatment Two single-center , double-blind , r and omized , placebo-controlled , sequentially enrolled studies were conducted . In study 1 , 8 subjects ( 6 active/2 placebo ) received 60- , 90- , 120- , 180- , or 240-mg tolvaptan/matching placebo . In study 2 , 9 subjects ( 6 active/3 placebo ) received 180- , 240- , 300- , 360- , 420- , or 480-mg tolvaptan/matching placebo . Increases in tolvaptan C(max ) were less than dose-proportional and plateaued at doses greater than 240 mg ; AUC(infinity ) increased proportionally with dose . Changes in serum K(+ ) , creatinine clearance , and Na(+ ) , K(+ ) , and osmolality urinary excretion were similar to the placebo group for the 0- to 24-hour interval following dosing . Changes were observed in plasma arginine vasopressin , serum aldosterone , and plasma renin activity but were not clinical ly significant . Increases were seen in mean serum Na(+ ) concentrations ( 4 - 6 mEq/L ) , plasma osmolality ( approximately 8 mOsm/kg ) , and free water clearance ( approximately 6 mL/min ) throughout 0 to 24 hours ; none of these increases was dose dependent . Only total urine volume excretion ( 0 - 72 hours postdose ) increased linearly with dose . As plasma tolvaptan concentrations increased , the duration that the urine excretion rate remained above baseline rates also increased . The most frequent adverse events -- excess thirst , frequent urination , and dry mouth -- appeared to be related to the pharmacological action of tolvaptan . No dose-limiting toxicities were observed Objective Probable migraine is a common , disabling migraine subtype fulfilling all but one of the diagnostic criteria for migraine . This study was conducted to evaluate the efficacy and tolerability of sumatriptan/naproxen sodium for the acute treatment of probable migraine without aura . Methods Patients treated a headache of probable migraine without aura when pain was moderate or severe with sumatriptan/naproxen sodium ( n = 222 intent-to-treat ( ITT ) ) or placebo ( n = 221 ITT/complete case analysis a ) in this r and omized , double-blind , parallel-group study . Results Sumatriptan/naproxen sodium was more effective than placebo with respect to the co- primary efficacy endpoints two-hour pain-free response ( 29 % sumatriptan/naproxen sodium vs 11 % placebo , p < 0.001 ) and two- to 24-hour sustained pain-free response ( 24 % sumatriptan/naproxen sodium vs 9 % placebo , p < 0.001 ) . Sumatriptan/naproxen sodium was significantly more effective than placebo with respect to the secondary efficacy endpoints of pain-free response four hours postdose ( p < 0.001 ) , pain-free response maintained one to two hours postdose ( p = 0.034 ) and two to four hours postdose ( p < 0.001 ) , headache relief four hours postdose ( p < 0.001 ) , headache relief maintained two to four hours postdose ( p = 0.015 ) , sustained headache relief two through 24 hours postdose ( p = 0.002 ) , and rescue medication use ( p < 0.001 ) ; but not productivity scores . The most common adverse events were dizziness ( 4 % sumatriptan/naproxen sodium,<1 % placebo ) , dry mouth ( 2 % sumatriptan/naproxen sodium , < 1 % placebo ) , and nausea ( 2 % sumatriptan/naproxen sodium , < 1 % placebo ) . Conclusion Sumatriptan/naproxen sodium is effective in the acute treatment of probable migraine as demonstrated by higher rates of freedom from pain and restoration of function The aim of this study was to determine whether mexiletine , a CYP1A2 inhibitor , altered the pharmacokinetics and pharmacodynamics of tizanidine . The pharmacokinetics of tizanidine were examined in an open-label study in 12 healthy participants after a single dose of tizanidine ( 2 mg ) with and without mexiletine coadministration ( 50 mg , 3 times as a pretreatment for a day and 2 times on the study day ) . Compared with tizanidine alone , mexiletine coadministration increased the peak plasma concentration ( 1.8 + /- 0.8 vs 5.3 + /- 1.8 ng/mL ) , area under the curve ( 4.5 + /- 2.2 vs 15.4 + /- 6.5 ng x h/mL ) , and the half-life ( 1.3 + /- 0.2 vs 1.8 + /- 0.7 h ) of tizanidine , respectively ( P < .05 ) . Reduction in systolic blood pressure ( -10 + /- 8 vs -24 + /- 7 mm Hg ) and diastolic blood pressure ( -10 + /- 7 vs -18 + /- 8 mm Hg ) after tizanidine administration was also significantly enhanced by coadministration of mexiletine ( P < .01 ) . Of the 15 patients treated with tizanidine and mexiletine , 4 suffered tizanidine-induced adverse effects such as drowsiness and dry mouth in the retrospective survey . Present results suggested that coadministration of mexiletine increased blood tizanidine concentrations and enhanced tizanidine pharmacodynamics in terms of reduction in blood pressure and adverse symptoms CONTEXT Insomnia and generalized anxiety disorder ( GAD ) are prevalent disorders that may coexist . OBJECTIVE To determine the efficacy of eszopiclone combined with escitalopram oxalate in treating insomnia comorbid with GAD . DESIGN Double-blind , r and omized , placebo-controlled , parallel-group , add-on therapy 10-week study . SETTING Multicenter outpatient study from July 2005 to April 2006 . PATIENTS Adults aged 18 to 64 years meeting DSM-IV-TR criteria for GAD and insomnia . INTERVENTIONS Patients received 10 mg of escitalopram oxolate for 10 weeks and were r and omized to also receive either 3 mg of eszopiclone ( n = 294 ) or placebo ( n = 301 ) nightly for 8 weeks . For the last 2 weeks , eszopiclone was replaced with a single-blind placebo . MAIN OUTCOME MEASURES Sleep , daytime functioning , psychiatric measures , and adverse events . RESULTS Compared with treatment with placebo and escitalopram , treatment with eszopiclone and escitalopram result ed in significantly improved sleep and daytime functioning ( P < .05 ) , with no evidence of tolerance . Patients taking eszopiclone and escitalopram had greater improvements in total Hamilton Anxiety Scale ( HAM-A ) scores at each week ( P < .05 ) and at weeks 4 through 10 with the insomnia item removed . Clinical Global Impressions ( CGI ) of Improvement scores were improved with eszopiclone and escitalopram at every point ( P < .02 ) , while CGI of Severity of Illness scores were not significantly different after week 1 . The HAM-A response ( 63 % vs 49 % , respectively , P = .001 ) and remission ( 42 % vs 36 % , respectively , P = .09 ) rates at week 8 were higher in patients treated with eszopiclone and escitalopram than those treated with placebo and escitalopram , and median time to onset of anxiolytic response was significantly reduced ( P < or = .05 ) . After eszopiclone discontinuation , there was no evidence of rebound insomnia , and while treatment differences in anxiety measures were maintained , differences in sleep outcomes were not . Overall adverse event rates were 77.6 % with cotherapy and 67.9 % with monotherapy . The most common adverse events with cotherapy were unpleasant taste , headache , dry mouth , and somnolence . CONCLUSIONS Coadministration of eszopiclone and escitalopram was well tolerated and associated with significantly improved sleep , daytime functioning , anxiety , and mood in patients with insomnia and GAD . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00235508 Abstract α1-Adrenoceptor blockers such as prazosin and doxazosin are used to treat hypertension as well as benign prostatic hyperplasia ( BPH ) , whereas the new αl-adrenoceptor blocker tamsulosin is used only for BPH and does not reduce blood pressure at the doses used to relax prostatic smooth muscle . In contrast to prazosin , tamsulosin has a higher affinity for prostatic than vascular α1-adrenoceptors in vitro . The functional correlate of this observation in humans is the subject of this study . The α1-adrenoceptor blockade by oral tamsulosin ( 0.2 mg ) , doxazosin ( 1 mg ) or placebo on finger tip vascular and dorsal h and venous α1-adrenoceptors stimulated by cold treatment ( immersion in ice water ) and the αl-adrenoceptor agonist phenylephrine , was thus studied in a 3-way crossover study in eight , healthy , male adults . Finger tip vasoconstriction after cold stimulation was assessed by laser Doppler flowmetry . A linear variable differential transformer was used to assess the drug effect on phenylephrine-induced venoconstriction . All study parameters were assessed at around 2 and 3.5 h after oral intake of doxazosin and tamsulosin respectively . The drug plasma levels were not significantly different . No significant differences were found for blood pressure or heart rate in the three treatments in supine and erect position . The reduction in finger tip blood flow after cold stimulation was significantly smaller after doxazosin treatment ( P<0.01 ) than after tamsulosin or placebo , whereas there was no significant difference between tamsulosin and placebo treatments . The infusion rate of phenylephrine producing a half-maximum venoconstriction was significantly larger after doxazosin than after tamsulosin ( P<0.05 ) or placebo ( P<0.01 ) , whereas there was again no significant difference between tamsulosin and placebo treatments . The data suggest that , at doses producing equal plasma levels after single oral doses in human subjects , the blocking activity at vascular α1-adrenoceptors is lower for tamsulosin than for doxazosin The tolerance of zopiclone , a hypnotic belonging to a new chemical group , the cyclopyrrolones , was studied in a follow-up trial in 23,000 insomniac out patients treated for 3 weeks . The results from the interim analysis of the first 10,000 cases confirm the efficacy and safety of zopiclone under usual prescribing conditions . The average daily dose of zopiclone was 0.97 + /- 0.21 tablet ( 7.275 + /- 1.575 mg ) . The study population included 63.1 % of female and 36.9 % of male patients ; the mean age was 52.3 + /- 16.6 years . 93.1 % of the patients completed the trial . 8.2 % of the patients experienced adverse reactions which result ed in drug discontinuation in only 2.8 % of cases . In the global evaluation , the efficacy was rated excellent or good in more than 80 % of the patients Background and objective Postoperative pain therapy is still a problem for clinicians . Continuous basal infusion of drugs combined with st and ard patient-controlled analgesia ( PCA ) is considered to be an effective means of postoperative acute pain management . This study was design ed to investigate the analgesic efficacy , morphine-sparing effects and side effects of butorphanol delivered as a continuous infusion adjunct to intravenous morphine PCA after abdominal hysterectomy . Methods One hundred and eighty-six ASA physical status I – II patients , undergoing total abdominal hysterectomy , were allocated to this r and omized double-blind controlled study and assigned to one of two groups . In the butorphanol ( n = 96 ) group , patients received an intravenous loading dose of 10 μg kg−1 butorphanol followed by infusion of 2 μg kg−1 h−1 butorphanol combined with intravenous PCA set at a bolus of 0.02 mg kg−1 morphine after surgery . The control group ( n = 90 ) received a physiological saline infusion combined with the same morphine PCA . Pain intensity on movement and at rest , sedation , satisfaction with analgesia , morphine consumption and side effects were recorded . Results A total of 164 patients completed the study . The butorphanol group had analgesia superior to the physiological saline control ( P < 0.001 ) . The butorphanol infusion group produced higher sedation ratings ( P < 0.001 ) and better satisfaction ( P < 0.05 ) and a lower incidence of side effects ( P < 0.001 ) with the exception of sweating and dry mouth ( P < 0.05 ) than the physiological saline group . The butorphanol group consumed less morphine over 48 h , 24.6 mg ( 95 % confidence interval , 18.7–46.6 ) , than the physiological saline group , 58.5 mg ( 95 % confidence interval , 41.5–79.2 ; P = 0.006 ) . There were no differences between urinary catheterization of more than 24 h , first time out of bed and time to discharge to home . Conclusion Basal infusion of butorphanol combined with intravenous morphine PCA in patients undergoing abdominal hysterectomy shows effective analgesia with sedation and fewer side effects BACKGROUND There has been a paucity of well- design ed studies comparing selective serotonin reuptake inhibitor ( SSRI ) medications in the treatment of depression in the elderly . This multicenter study was design ed to examine the efficacy and safety of sertraline and fluoxetine in depressed elderly out patients . A secondary objective was to examine the effects of SSRI treatment on quality of life and cognitive function . METHOD Two hundred thirty-six out patients 60 years of age and older who met DSM-III-R criteria for major depressive disorder received 1 week of single-blind placebo before being r and omly assigned to 12 weeks of double-blind , parallel-group treatment with flexible daily doses of either sertraline ( range , 50 - 100 mg ) or fluoxetine ( range , 20 - 40 mg ) . Primary efficacy measures consisted of the 24-item Hamilton Rating Scale for Depression and Clinical Global Impressions scale ratings . Secondary outcome assessment s included clinician- and patient-rated measures of depression symptoms and factors , cognitive functioning , and quality of life , as well as plasma drug concentrations , which were correlated with clinical response . RESULTS Both drugs produced a similarly positive response on the primary efficacy measures , with 12-week responder rates of 73 % for sertraline and 71 % for fluoxetine . Sertraline-treated patients showed statistically greater cognitive improvement on several measures . Both drugs were safe and well tolerated . CONCLUSION Data indicate that both drugs are effective antidepressants for the treatment of depressed elderly out patients . Differences in cognitive performance effects deserve further investigation Summary The antihypertensive effect of moxonidine·HCl·H2O ( MOX ) was compared with that of clonidine·HCl ( CLON ) in a r and omized double-blind crossover study in 20 hypertensive out patients ( BP range 154–178/96–108 mmHg ) . After 2 weeks without antihypertensive medication , either MOX 0.2 mg daily or CLON 0.2 mg daily was given and the dose was titrated until the diastolic blood pressure fell below 90 mmHg . The first treatment period was continued for 2 weeks and , after crossover without a wash-out period , it was followed by the second treatment for a further 2 weeks . Within the first 4 days of administration 0.2–0.4 mg of either agent caused a significant decrease in BP ( p<0.001 ) from a mean of 166/100 mmHg to 149/86 mmHg after CLON ( approx . −10/−14 % ) , and 163/99 mmHg to 146/84 mmHg after MOX ( approx . −10/−15 % ) . No significant difference in the fall in BP or pulse rate was detected between the two drugs . In the mean daily dose of 0.3 mg both drugs showed the same antihypertensive activity , but on CLON a higher incidence of side effects ( p=0.003 ) was noted , and after discontinuation of therapy a more rapid rise in BP ( systolic BP p<0.01 , diastolic BP p<0.02 ) was found . 17 patients on CLON complained of side effects , especially tiredness and dry mouth , whilst only 6 patients on MOX were affected ( p=0.003 ) OBJECTIVE To evaluate the antidepressant effect of oral scopolamine as an adjunct to citalopram . METHOD In this r and omized double-blind placebo-controlled study , patients were assessed in the outpatient clinics of 2 large hospitals from November 2011 to January 2012 . Forty patients ( 18 - 55 years ) with major depressive disorder ( DSM-IV-TR criteria ) and 17-Item Hamilton Depression Rating Scale ( HDRS ) score ≥ 22 were r and omly assigned to scopolamine hydrobromide ( 1 mg/d ) ( n = 20 ) or placebo ( n = 20 ) in addition to citalopram for 6 weeks . HDRS score was measured at baseline and days 4 , 7 , 14 , 28 , and 42 . The primary outcome measure was HDRS score change from baseline to week 6 in the scopolamine group versus the placebo group . Response was defined as ≥ 50 % decrease in HDRS score ; remission , as HDRS score ≤ 7 . RESULTS Augmentation with scopolamine was significantly more effective than placebo ( F(1,38 ) = 5.831 , P = .021 ) . Patients receiving scopolamine showed higher rates of response ( 65 % , 13/20 at week 4 ) and remission ( 65 % , 13/20 at week 6 ) than the placebo group ( 30 % , 6/20 and 20 % , 4/20 , respectively ; P = .027 , P = .004 , respectively ) . Patients in the scopolamine group showed higher rates of dry mouth , blurred vision , and dizziness than the placebo group . CONCLUSIONS Oral scopolamine is a safe and effective adjunct for treatment of patients with moderate to severe major depressive disorder . TRIAL REGISTRATION Iranian Registry of Clinical Trials identifier : I RCT 201201181556N31 OBJECTIVE To investigate the associations between age , gender , systemic diseases , medications , labial and whole salivary flow rates and oral and ocular dryness in older people . METHODS Symptoms of oral and ocular dryness , systemic diseases , medications ( coded according to the Anatomical therapeutic chemical ( ATC ) classification system ) , tobacco and alcohol consumption were registered , and unstimulated labial ( LS ) and unstimulated ( UWS ) and chewing-stimulated ( SWS ) whole salivary flow rates were measured in 668 r and omly selected community-dwelling elderly aged 65 - 95 . RESULTS Presence of oral ( 12 % ) and ocular ( 11 % ) dryness was positively correlated . Oral dryness was associated with low UWS , SWS and LS , and ocular dryness with low UWS and SWS . Oral and ocular dryness was related to female gender , but not to age . Only four persons in the healthy and nonmedicated subgroups reported oral and ocular dryness . The numbers of diseases and medications were higher in the older age groups and associated with oral and ocular dryness , low UWS , SWS and LS . On average , women were slightly older , reported more oral and ocular dryness and had lower UWS , SWS , LS and higher numbers of diseases and medications . High prevalence and odds ratios for oral dryness were associated with metabolic , respiratory and neurological diseases and intake of thyroid hormones , respiratory agents ( primarily glucocorticoids ) , psycholeptics and /or psychoanaleptics , antineoplastics , proton pump inhibitors , antidiabetics , loop diuretics , antispasmodics , quinine and bisphosphonates . Ocular dryness was especially associated with neurological diseases and intake of psycholeptics and /or psychoanaleptics . Intake of magnesium hydroxide , antithrombotics , cardiac agents , thiazides , beta-blockers , calcium channel blockers , ACE inhibitors/angiotensin II antagonists , statins , glucosamine , paracetamol/opioids , ophthalmologicals and certain combination therapies was related to oral and ocular dryness . CONCLUSIONS In older people , oral and ocular dryness are associated with low salivary flow rates , specific as well as high number of diseases and medications , but neither with age and gender per se nor with tobacco and alcohol consumption . New detailed information concerning associations between medications and oral and ocular dryness has been obtained using the ATC classification system Although antihistamines are highly effective in alleviating many symptoms associated with seasonal allergic rhinitis ( SAR ) , relief from nasal congestion is variable . The efficacy of desloratadine , an effective antihistamine , in combination with pseudoephedrine , a potent nasal decongestant , was evaluated to determine whether combination therapy was more effective than individual component therapy in reducing nasal congestion , as well as other SAR symptoms . This multicenter , r and omized , double-blind , three-arm study included 650 patients with SAR . For 2 weeks , patients were administered a combination tablet of desloratadine plus pseudoephedrine ( desloratadine/pseudoephedrine , 2.5/120 mg ) twice per day ( b.i.d . ) , desloratadine ( 5 mg ) once per day , or pseudoephedrine ( 120 mg ) b.i.d . Patients assessed the severity of their SAR symptoms twice daily on symptom diary cards . The primary variable-change from baseline in the reflective A.M./P.M. total symptom score , excluding nasal congestion-was significantly superior ( -6.7 ) compared with desloratadine ( -5.4 ) or pseudoephedrine ( -5.3 ) alone ( p < or = 0.001 versus either group ) . Secondary efficacy variables including total symptom scores ( plus congestion ) , total nasal symptom scores , and total nonnasal symptom scores were significantly reduced after desloratadine/pseudoephedrine therapy compared with the individual components . The most frequently reported adverse events were insomnia , headache , and dry mouth . Desloratadine/pseudoephedrine , 2.5/120 mg b.i.d . , therapy was more effective in reducing total symptom scores of SAR , including nasal congestion , than were the individual components . These results support the use of this combination therapy over desloratadine or pseudoephedrine alone Early studies of extended-release oxybutynin in patients with overactive bladder used adjusted-dose regimens ranging from 5 to 30 mg/day to achieve an optimal balance of efficacy and tolerability . The safety and tolerability of extended-release oxybutynin at a fixed dose of 10 mg once daily ( commonly prescribed in clinical practice ) is reported using pooled data from 2 multicenter , r and omized , double-blind , parallel-group trials with a similar study design . One study compared extended-release oxybutynin with immediate-release tolterodine 2 mg bid . The other study compared extended-release oxybutynin with extended-release tolterodine 4 mg qd . In total , 576 patients received extended-release oxybutynin , 399 received extended-release tolterodine , and 193 received immediate-release tolterodine . The incidence of adverse events ( AEs ) was similar in the three treatment groups ( extended-release oxybutynin , 70 % ; extended-release tolterodine , 64 % ; and immediate-release tolterodine , 79 % ) . The most common adverse event was dry mouth ( extended-release oxybutynin , 29 % ; extended-release tolterodine , 22 % ; and immediate-release tolterodine , 33 % ) . Other AEs occurring in more than 5 % of patients in any treatment group included constipation , diarrhea , headache , urinary tract infection , pain , dyspepsia , and peripheral edema , with no apparent difference across treatment groups . Most AEs ( > 90 % ) were mild or moderate in intensity in all treatment groups . The proportion of patients who discontinued study medication due to AEs was 6.1 , 4.8 , and 7.8 % in the extended-release oxybutynin , extended-release tolterodine , and immediate-release tolterodine groups , respectively . In total , 1.2 , 1.0 , and 1.6 % of patients in the extended-release oxybutynin , extended-release tolterodine , and immediate-release tolterodine groups , respectively , discontinued study medication due to dry mouth Background and Aims : Opioids as epidural adjunct to local anesthetics ( LA ) have been in use since long and α-2 agonists are being increasingly used for similar purpose . The present study aims at comparing the hemodynamic , sedative , and analgesia potentiating effects of epidurally administered fentanyl and dexmedetomidine when combined with ropivacaine . Methods : A total of one hundred patients of both gender aged 21 - 56 years , American Society of Anaesthesiologist ( ASA ) physical status I and II who underwent lower limb orthopedic surgery were enrolled into the present study . Patients were r and omly divided into two groups : Ropivacaine + Dexmedetomidine ( RD ) and Ropivacaine + Fentanyl ( RF ) , comprising 50 patie nts each . Inj . Ropivacaine , 15 ml of 0.75 % , was administered epidurally in both the groups with addition of 1 μg/kg of dexmedetomidine in RD group and 1 μg/kg of fentanyl in RF group . Besides cardio-respiratory parameters and sedation scores , various block characteristics were also observed which included time to onset of analgesia at T10 , maximum sensory analgesic level , time to complete motor blockade , time to two segmental dermatomal regressions , and time to first rescue analgesic . At the end of study , data was compiled systematic ally and analyzed using ANOVA with post-hoc significance , Chi-square test and Fisher 's exact test . Value of P<0.05 is considered significant and P<0.001 as highly significant . Results : The demographic profile of patients was comparable in both the groups . Onset of sensory analgesia at T10 ( 7.12±2.44 vs 9.14±2.94 ) and establishment of complete motor blockade ( 18.16±4.52 vs 22.98±4.78 ) was significantly earlier in the RD group . Postoperative analgesia was prolonged significantly in the RD group ( 366.62±24.42 ) and consequently low dose consumption of local anaesthetic LA ( 76.82±14.28 vs 104.35±18.96 ) during epidural top-ups postoperatively . Sedation scores were much better in the RD group and highly significant on statistical comparison ( P<0.001 ) . Incidence of nausea and vomiting was significantly high in the RF group ( 26 % and 12 % ) , while incidence of dry mouth was significantly higher in the RD group ( 14 % ) ( P<0.05 ) . Conclusions : Dexmedetomidine seems to be a better alternative to fentanyl as an epidural adjuvant as it provides comparable stable hemodynamics , early onset , and establishment of sensory anesthesia , prolonged post-op analgesia , lower consumption of post-op LA for epidural analgesia , and much better sedation levels OBJECTIVE To investigate the associations between age , gender , systemic diseases , medications and labial and whole salivary flow rates in older people . METHODS Unstimulated labial ( LS ) and unstimulated ( UWS ) and chewing-stimulated ( SWS ) whole salivary flow rates were measured in 389 r and omly selected community-dwelling Danish women and 279 men aged 65 - 97 years . Systemic diseases , medications ( coded according to the Anatomical Therapeutic Chemical ( ATC ) Classification System ) , tobacco and alcohol consumption were registered . RESULTS The number of diseases and medications was higher and UWS lower in the older age groups . On average , women were slightly older , had more diseases , higher medication intake and lower UWS , SWS and LS than men . High number of diseases and medications was associated with low UWS , SWS and LS . In the healthy ( 14 % ) and nonmedicated ( 19 % ) participants , flow rates were not associated with age and gender , apart from SWS being lower in nonmedicated women . Low UWS were associated with psychiatric and respiratory disorders , type 2 diabetes and intake of psycholeptics , psychoanaleptics ( especially SRRIs ) , respiratory agents , oral antidiabetics ( particularly sulfonylureas ) , magnesium-hydroxide , cardiac agents , quinine , thiazides , calcium channel blockers , statins , urinary antispasmodics , glucosamine , NSAIDs , opioids and ophthalmologicals . SWS were lower in participants with ophthalmological disorders using ophthalmologicals ( especially antiglaucoma agents and miotics ) , but also in those taking antidepressants , cardiac agents ( mostly digitalis glycosides ) and calcium channel blockers . Cardiovascular diseases and intake of anti-thrombotics ( mainly low dose aspirins ) , calcium channel blockers and oral antidiabetics were associated with low LS . CONCLUSIONS In older people , low salivary flow rates are associated with specific and high number of diseases and medications , but neither with age and gender per se nor with tobacco and alcohol consumption . Low UWS are associated with more diseases and medications than SWS and LS , which were primarily associated with cardiovascular diseases and medications including preventive agents such as low-dose aspirins and statins . New insights into medications and their association with salivary gl and function were achieved using the ATC classification system To evaluate the pharmacodynamic effects of darifenacin ( a muscarinic M3 selective receptor antagonist ) and dicyclomine ( an M1 selective receptor antagonist ) in healthy male volunteers Application of physostigmine to the oromucosal surface with the aim of stimulating underlying mucin-producing gl and s while reducing cholinergic systemic effects might be a strategy for treating dry mouth . Subjects suffering from dry mouth and with hyposalivation participated in a crossover , double-blind , r and omized study . A gel containing physostigmine ( 0.9 , 1.8 , 3.6 , and 7.2 mg ) or placebo was applied to the inside of the lips and distributed with the tongue . The feeling of dryness was assessed using a visual analogue scale ( VAS ) ( where a score of 100 = extremely dry ) and systemic effects were registered . Based on assessment s of efficacy and safety , the dose of 1.8 mg of physostigmine was selected for use in the second part of the study to make objective measurements of saliva volumes . Physostigmine ( 1.8 mg ) produced long-lasting ( 120 min ) relief ( evident as a score reduction of 25 on the VAS ) in the feeling of dryness . Judging from AUC values related to baseline over 180 min , the improvement for both mouth and lips in response to physostigmine was six times greater than that to placebo . At higher doses of physostigmine , gastrointestinal discomfort predominantly occurred . The volume of saliva collected in response to physostigmine was five times higher over 180 min than that collected in response to placebo . Physostigmine , applied locally , therefore appears to be a promising modality for dry-mouth treatment Cevimeline hydrochloride , a specific agonist of the M3 muscarinic receptor , is beneficial in the treatment of symptoms of xerostomia and xerophthalmia associated with Sjögren ’s syndrome ( SS ) . Cevimeline has not been evaluated in southern Chinese patients . Furthermore , the effects of cevimeline on health-related quality of life and oral health status are not known . In this r and omised , double-blind , placebo-controlled crossover study , patients received cevimeline 30 mg or matched placebo three times per day over 10 weeks followed by a 4-week washout period before treatment crossover . Participants self-completed the following question naires : Xerostomia Inventory ( XI ) , the General Oral Health Assessment Index ( GOHAI ) , the Ocular Surface Disease Index ( OSDI ) and the Medical Outcomes Short Form ( SF-36 ) . Clinical assessment s included sialometry , examination of the oral cavity for the degree of xerostomia and dental complications of xerostomia . Fifty patients ( 22 primary SS and 28 secondary SS ) were enrolled in the trial . Forty-four patients completed the study . There was a significant improvement in the XI and GOHAI scores as well as the objective rating of xerostomic signs of the oral cavity after treatment with cevimeline . However , there was no improvement in salivary flow rates and dry eye symptoms . SS patients had lower SF-36 scores , but these did not improve after treatment with cevimeline BACKGROUND Attention-Deficit/Hyperactivity Disorder ( ADHD ) is a disorder characterized by hyperactivity , impulsiveness , and inattention that affects 4 % of adults . Atomoxetine hydrochloride is an FDA -approved treatment for adult ADHD , but no studies have clarified whether there are advantages to once versus twice daily dosing . METHODS This r and omized , double-blind , multicenter study compared safety and tolerability of 80 mg atomoxetine QD versus 40 mg atomoxetine BID in 218 adults with ADHD . Treatment-emergent adverse events ( TEAEs ) , laboratory values , vital signs , weight , electrocardiograms , scores on the Arizona Sexual Experiences Scale , and efficacy ( using the Conners ' ADHD Rating Scale-Investigator Rated : Screening Version ) were assessed . RESULTS The overall incidence for any one TEAE was low . There was no significant treatment group difference in likelihood of patients experiencing > /=1 of the four most commonly observed TEAEs ( dry mouth , insomnia , nausea , and erectile dysfunction ) . Frequency of nausea was significantly lower in the 40 mg BID group ( 16.4 % ) than the 80 mg QD group ( 32.4 % ; p = .007 ) . There were no unexpected safety results . Although both QD and BID treatments were efficacious , the reduction in scores was greater for BID treatment . CONCLUSIONS Data indicate both dosing strategies are safe , well tolerated , and efficacious in the treatment of adult ADHD . Changes in dosing strategy are unlikely to be accompanied by safety risks , implying that there is room for prescribers to use discretion and to base dosing strategies on individual factors OBJECTIVE This investigation was performed to assess the efficacy and safety of zolpidem extended-release in patients with insomnia associated with major depressive disorder ( MDD ) . METHOD Patients ( N = 385 ) received open-label escitalopram 10 mg/d and were r and omized to concomitant zolpidem extended-release 12.5 mg/night or placebo for 8 weeks ( phase 1 ) in a r and omized , parallel-group , multicenter trial . Responders ( ≥ 50 % in 17-item Hamilton Depression Rating Scale [ HDRS(17 ) ] score ) continued 16 weeks of double-blind treatment ( phase 2 ) ; escitalopram only was given during a 2-week run-out period . The study was conducted between February 2006 and June 2007 . The primary efficacy measure was change from baseline in subjective total sleep time . Secondary efficacy measures included subjective sleep-onset latency , number of awakenings , wake time after sleep onset , sleep quality , sleep-related next-day functioning , HDRS(17 ) , Sleep Impact Scale score , Patient and Clinical Global Impressions of Insomnia Treatment , the Massachusetts General Hospital Cognitive and Physical Functioning Question naire , and the Quality of Life Enjoyment and Satisfaction Question naire . Adverse events were recorded throughout the study ; sleep measures were also evaluated during the run-out period . RESULTS Throughout phase 1 , zolpidem extended-release led to significantly greater improvements in total sleep time ( P < .0001 ) , wake time after sleep onset , sleep onset latency , number of awakenings , and sleep quality ( P ≤ .0003 ) , and some measures of sleep-related next-day functioning but not in depressive symptoms or quality of life . During phase 2 , improvements with the zolpidem extended-release/escitalopram group occurred for total sleep time ( significant [ P < .05 ] at weeks 12 and 16 ) , as well as for a few other secondary efficacy measures but not in depressive symptoms or quality of life . The most common adverse events associated with combination treatment included nausea , somnolence , dry mouth , dizziness , fatigue , and amnesia . CONCLUSIONS Zolpidem extended-release administered concomitantly with escitalopram for up to 24 weeks was well tolerated and improved insomnia and some sleep-related next-day symptoms and next-day functioning in patients with MDD but did not significantly augment the antidepressant response of escitalopram . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00296179 Abstract Objective : It is widely recognized that patient perception of overactive bladder ( OAB ) symptoms can vary considerably from mild to severe bother . This post hoc analysis reports outcomes in patients with severe OAB symptoms at baseline taken from the VESIcare Efficacy and Safety in PatieNts with Urgency Study ( VENUS ) . Methods : VENUS was a 12-week , r and omized , double-blind , placebo-controlled trial of solifenacin ( 5 or 10 mg/day , flexibly dosed ) in OAB patients . The primary endpoint in VENUS was mean change from baseline to study end in urgency episodes/day using 3-day bladder diaries . Secondary endpoints included other diary endpoints ( frequency , incontinence , and nocturia ) , warning time ( WT ; time between first sensation of urgency to voiding ) , and patient-reported outcome ( PRO ) measures of urgency ( the Indevus Urgency Severity Scale [ IUSS ] and Urgency Perception Scale [ UPS ] ) and of symptom bother and health-related quality of life ( HRQL ) ( the Patient Perception of Bladder Condition [ PPBC ] and Overactive Bladder Question naire ) . For this analysis , severe OAB was defined as baseline PPBC score ≥5 ( 1 = no problems , 6 = many severe problems ) . Trial registration : NCT00454896 Results : In total , 158/707 ( 22.3 % ) patients in the full analysis set ( FAS ) reported severe OAB symptoms . Solifenacin reduced mean urgency episodes/day versus placebo in the severe subgroup ( −4.6 vs. −3.1 , p = 0.1150 ) , similar to the significant reduction observed in the FAS ( −3.9 vs. −2.7 , p < 0.0001 ) . Solifenacin also improved the other diary endpoints and PRO measures in the severe subgroup ; these changes were consistent with the significant solifenacin- versus placebo-related improvements for the FAS . Treatment-emergent adverse events were mostly mild/moderate , and few patients taking solifenacin or placebo discontinued treatment in the severe subgroup ( 4.5 % vs. 6.5 % ) or FAS ( 6.5 % vs. 4.6 % ) . Key limitations are that VENUS was not powered to detect treatment differences in subgroups , and that the lack of a st and ardized definition of OAB symptom severity may limit the generalizability of the findings . Conclusions : Patients with severe OAB symptoms showed objective and subjective improvements in symptoms , symptom bother , HRQL , and urgency severity with solifenacin similar to the FAS . Solifenacin was also well-tolerated in this subgroup A large number of the population , especially the elderly , suffers from dry mouth . The aim of the present investigation was to stimulate the minor salivary gl and s by the topical application of the cholinesterase inhibitor physostigmine . In eight healthy subjects . 100 microl of the substance , in the concentration interval 2 - 8 mg/ml , was applied locally to the inside of the lower lip for 1 min . In a separate study comprising 12 dry-mouth patients . 10 ml of 0.4 1.6 mg/ml physostigmine was administered as a mouth rinse solution for 2 min . Secretion from the labial gl and s. assessed using the Periotron method , increased in a dose-dependent manner in response to physostigmine in both groups . Average peak secretion exceeded baseline by more than 50 % throughout the 30- to 45-min observation period ; from 1.71 to 2.62 microl cm(-2 ) min(-1 ) among the healthy subjects and from 1.17 to 1.84 microl cm 2 min among the dry mouth patients . No systemic effects were registered as reflected by ECG , heart rate or blood pressure . It is assumed that intraorally applied physostigmine diffuses through the oral mucosa and acts by preserving acetylcholine released from the cholinergic , parasympathetic nerves that innervate the minor salivary gl and s. The topical application of physostigmine to the oral mucosa may , therefore , be an interesting approach for the treatment of dry mouth Furosemide , a potent loop diuretic , has been reported to cause xerostomia , a sensation of oral dryness . We obtained urine and salivary secretions from five normal males after oral intake of either 0.5 mg/kg body weight of furosemide or placebo . The experimental treatment result ed in a five-fold increase in urinary output . In contrast , analysis of salivary secretions indicated there were no significant differences in flow rates , total output , total protein , or Na+ , K+ , or Cl- concentrations following drug or placebo . Subjectively , xerostomia was experienced 10 times more frequently after ingestion of furosemide . These data suggest that , in vivo , furosemide had a greater effect on the kidney than on the salivary gl and and that the sensation of oral dryness is not solely a function of the quantitative salivary output OBJECTIVE This study evaluated the efficacy and tolerability of agomelatine in the prevention of relapse in patients with generalized anxiety disorder ( GAD ) . METHOD Patients with GAD ( Hamilton Anxiety Rating Scale [ HARS ] ≥ 22 , with items 1 and 2 ≥ 2 , item 1 + 2 ≥ 5 ; Montgomery-Asberg Depression Rating Scale [ MADRS ] ≤ 16 ; and < 20 % decrease in HARS total score between screening and baseline ) who responded to a 16-week course of agomelatine 25 - 50 mg/d treatment were r and omly assigned to receive continuation treatment with agomelatine ( n = 113 ) or placebo ( n = 114 ) for 26 weeks . The main outcome measure was time to relapse during this maintenance period . The estimated risk of relapse was calculated using the Kaplan-Meier method , and groups were compared using a log-rank test stratified for country . The study was undertaken in 31 clinical centers in Canada , Denmark , Estonia , Finl and , Hungary , and Sweden from November 2007 to September 2009 . RESULTS During the 6-month maintenance period , the proportion of patients that relapsed during the double-blind period in the agomelatine group ( 22 patients , 19.5 % ) was lower than in the placebo group ( 35 patients , 30.7 % ) . The risk of relapse over time was significantly lower for patients who continued treatment than for those switched to placebo ( P = .046 , log-rank test stratified for country ) . Agomelatine was also superior to placebo in preventing relapse in the subset of more severe patients with baseline HARS total score ≥ 25 and CGI-S score ≥ 5 . The tolerability of agomelatine was good throughout the study , and there were no differences in discontinuation symptoms after withdrawal of agomelatine in comparison to maintenance on agomelatine . CONCLUSIONS The present study extends the positive findings of an earlier short-term study of agomelatine in GAD , demonstrating that agomelatine is effective and well-tolerated in the longer-term treatment of this chronic disorder . TRIAL REGISTRATION www.is rct n.org identifier : IS RCT N38094599 Abstract Objective : To assess the efficacy and safety of morphine sulfate and naltrexone hydrochloride extended release capsules ( EMBEDA ® ; MS-sNT ) , which contain morphine sulfate pellets with a sequestered naltrexone core , in treating patients with chronic , moderate-to-severe osteoarthritis ( hip or knee ) pain . Patients and Methods : This phase 3 study had an enriched-enrollment , r and omized-withdrawal , double-blind , multicenter design . Patients ( N = 547 ) were titrated to an effective dose of MS-sNT ( 20–160 mg/day ) . Responders ( n = 344 ) were r and omized to 12 weeks maintenance with an effective MS-sNT dose or were tapered to placebo over 2 weeks . The primary efficacy measure was the change from baseline ( CFB ) in diary average-pain scores ( 0–10 scale , Brief Pain Inventory [ BPI ] ) from r and omization to the last 7 days of the maintenance period . Secondary efficacy measures included the remaining BPI scores and Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index . Opioid withdrawal symptoms were assessed by the Clinical Opiate Withdrawal Scale ( COWS ) and Subjective Opiate Withdrawal Scale ( SOWS ) . The study ran from January 10 , 2007 through November 8 , 2007 . Results : MS-sNT maintained pain control better than placebo ( mean CFB , diary average-pain score , −0.2 ± 1.9 vs + 0.3 ± 2.1 ; P = 0.045 ) . Change from baseline for MS-sNT pain-diary score ( worst , least , average , current ) was superior during the maintenance period visits , weeks 2 to 12 ( P < 0.05 ) . WOMAC composite score CFB was superior at most visits . MS-sNT was generally well tolerated , with a typical morphine safety profile . No patient taking MS-sNT as directed experienced withdrawal symptoms . Conclusion : MS-sNT provided effective analgesia in patients with chronic , moderate-to-severe osteoarthritis pain , with a safety profile typical of morphine-containing products . Naltrexone sequestered in MS-sNT had no clinical ly relevant effect when MS-sNT was taken as directed The main objective of this thesis was to estimate the prevalence of subjectively perceived dry mouth , xerostomia , in a representative general adult population , and the possible co-morbidity between xerostomia and on-going pharmacotherapy . Further , to evaluate the effects of beta-adrenoceptor antagonists on saliva flow rate and composition . The prevalence of xerostomia was evaluated by means of a question naire mailed to a r and om sample of 4.200 adult subjects living in the southern part of the province of Hall and , Sweden . Three hundred men and equally many women aged 20 , 30 , 40 , 50 , 60 , 70 and 80 years were selected from the national census register . From 3311 ( 81 % ) evaluable question naires was concluded that , in the studied population , 21.3 % of the men and 27.3 % of the women reported xerostomia . The difference between the sexes was statistically significant , women reporting higher prevalence of dry mouth than men . It was also found that xerostomia was significantly age-related . Further , it was demonstrated that there was a strong co-morbidity between reported prevalence of dry mouth and on-going pharmacotherapy . Generally , no specific drug or drug-group proved to be especially xerogenic , rather , polypharmacy was strongly correlated to reported symptoms of dry mouth , and it was also a significant correlation between increasing xerostomia and the number of medications taken . The effects of beta-adrenoceptor antagonists on saliva flow rate and composition were evaluated both in healthy volunteers and in hypertensive patients . The effects of one week of treatment with the non-selective ( propranolol ) and the beta 1-selective ( atenolol ) adrenoceptor antagonists were compared with that of placebo in three different clinical trials , including 38 , 11 and 19 healthy volunteers , respectively . Two of these studies were focused on the effects on whole saliva secretion rate and composition and the third study on the secretions from the parotid and the subm and ibular-sublingual gl and s. Salivary composition but not saliva flow rates were affected by the beta-adrenoceptor antagonists , and the most pronounced effects were observed for total protein composition and amylase activity , both being significantly decreased during treatment with any of the antagonists , however , more accentuated during treatment with atenolol . Twelve hypertensive patients who were well-controlled in their blood-pressure by means of monotherapy with metoprolol , a beta 1-selective adrenoceptor antagonist , were observed during four weeks of withdrawal and after re-exposure to this antihypertensive treatment . The observed effects on salivary composition were essentially the same as those found in healthy volunteers . In the hypertensive group , however , whole saliva flow rates increased significantly on drug withdrawal and decreased again on re-exposure to metoprolol The small salivary phosphoproteins , histatins and statherins , have important functions in the oral cavity in terms of antimicrobial actions and regulation of calcium phosphate homeostasis . Neither the effects of various physiological stimuli on their secretion nor the nature of the efferent receptor involved in the stimulus-secretion coupling has been determined previously . These aspects are important for improved underst and ing of the secretory control of salivary proteins and may have implication s regarding the effects of specific medications on salivary constituents and oral health . The effects of grade d mechanical ( chewing on short and long silicone tubings ) and gustatory stimulation ( 0.5 , 1.5 , and 5.0 % citric acid ) on the secretion of histatins and statherins were studied in the presence and absence of adrenolytic agents ( n = 10 ) . In this model , secretory rates of both proteins increased with increases in flow rate , with 5.0 % citric acid representing a particularly potent stimulus . Histatin and statherin secretory rates were significantly reduced by the β 1-adrenolytic agent ( histatins to 58 to 72 % and statherins to 11 to 29 % of that in corresponding control experiments ) , but not by the α 1-adrenolytic agent . Since the β1-adrenergic receptors played an important role in the stimulus-secretion coupling of these proteins , protective salivary functions in the oral cavity may be compromised during β 1-adrenolytic treatment BACKGROUND Weight-loss drugs produce an additional mean weight loss of only 3 - 5 kg above that of diet and placebo over 6 months , and more effective pharmacotherapy of obesity is needed . We assessed the efficacy and safety of tesofensine-an inhibitor of the presynaptic uptake of noradrenaline , dopamine , and serotonin-in patients with obesity . METHODS We undertook a phase II , r and omised , double-blind , placebo-controlled trial in five Danish obesity management centres . After a 2 week run-in phase , 203 obese patients ( body-mass index 30-</=40 kg/m(2 ) ) were prescribed an energy restricted diet and r and omly assigned with a list of r and omisation numbers to treatment with tesofensine 0.25 mg ( n=52 ) , 0.5 mg ( n=50 ) , or 1.0 mg ( n=49 ) , or placebo ( n=52 ) once daily for 24 weeks . The primary outcome was percentage change in bodyweight . Analysis was by modified intention to treat ( all r and omised patients with measurement after at least one dose of study drug or placebo ) . The study is registered with Clinical Trials.gov , number NCT00394667 . FINDINGS 161 ( 79 % ) participants completed the study . After 24 weeks , the mean weight loss produced by diet and placebo was 2.0 % ( SE 0.60 ) . Tesofensine 0.25 mg , 0.5 mg , and 1.0 mg and diet induced a mean weight loss of 4.5 % ( 0.87 ) , 9.2 % ( 0.91 ) , and 10.6 % ( 0.84 ) , respectively , greater than diet and placebo ( p<0.0001 ) . The most common adverse events caused by tesofensine were dry mouth , nausea , constipation , hard stools , diarrhoea , and insomnia . After 24 weeks , tesofensine 0.25 mg and 0.5 mg showed no significant increases in systolic or diastolic blood pressure compared with placebo , whereas heart rate was increased by 7.4 beats per min in the tesofensine 0.5 mg group ( p=0.0001 ) . INTERPRETATION Our results suggest that tesofensine 0.5 mg might have the potential to produce a weight loss twice that of currently approved drugs . However , these findings of efficacy and safety need confirmation in phase III trials Treatment-resistant depression is an important clinical problem presenting a major challenge to clinical psychiatry . While several strategies have been attempted , including medication switch , antidepressant polypharmacy and various augmentative regimens , success remains limited . Amantadine ( AMN ) , an agent traditionally used in the treatment and prophylaxis of influenza , is now known to exhibit prominent effects at the level of dopaminergic , monoamine oxidase and N-methyl-D-aspartate systems . The present reports on the efficacy of AMN as augmentation to st and ard antidepressant treatment in patients with treatment-resistant depression . Eight patients with treatment-resistant depression consented to receive AMN , titrated up to a dose of 300 mg , over a period of 4 weeks in a non-blinded fashion . Improvement in both depression and anxiety scores were observed from week 1 , with patients exhibiting improvement of depressive scores of up to 49 % by study completion . Females appeared to exhibit a stronger response , and within a shorter period of time . Side-effects reported included dry mouth and sedation . AMN appears to demonstrate efficacy as a safe and effective augmentative agent in treatment-resistant depression . Further studies are clearly m and ated to test these preliminary observations in a double-blinded manner Abstract Objective : This open-label , phase 3b study evaluated the effectiveness and tolerability of tapentadol prolonged release and tapentadol immediate release ( for acute pain episodes ) for severe , chronic low back pain with or without a neuropathic pain component that was inadequately managed in patients taking World Health Organization ( WHO ) Step I or II analgesics or who were not regularly treated with analgesics . Research design and methods : Average baseline pain intensity was greater than 5 ( 11-point numerical rating scale-3 [ NRS-3 ; 3-day average pain intensity ] ) with WHO Step I or II analgesics and greater than 6 with no regular analgesic regimen . WHO Step II analgesics were discontinued before starting study treatment ; WHO Step I analgesics or co-analgesics were continued at the same dose . Patients received tapentadol prolonged release ( 50–250 mg bid ) during a 5-week titration and 7-week maintenance period . Tapentadol immediate release was permitted for acute pain episodes ( tapentadol prolonged release and immediate release maximum combined dose , ≤500 mg/day ) . The painDETECT question naire was used to define subsets of patients based on the probability of a neuropathic pain component to their low back pain as ‘ negative ’ , ‘ unclear ’ , or ‘ positive ’ . Clinical trial registration : NCT00983385 . Main outcome measure : The primary endpoint was the change from baseline to week 6 in average pain intensity ( NRS-3 ) , using the last observation carried forward to impute missing scores . Results : In the painDETECT negative ( n = 49 ) and unclear/positive ( n = 126 ) subsets , respectively , mean ( SD ) changes in pain intensity from baseline to week 6 were −2.4 ( 2.18 ) and −3.0 ( 2.07 ; both p < 0.0001 ) . Among patients who had not received prior WHO Step II treatment , lower doses of tapentadol prolonged release were generally required with increasing likelihood of a neuropathic pain component . Based on the painDETECT question naire and the Neuropathic Pain Symptom Inventory ( NPSI ) , tapentadol prolonged release treatment was also associated with significant improvements in neuropathic pain symptoms , with decreases in the number of pain attacks and the duration of spontaneous pain in the last 24 hours in patients with low back pain with a neuropathic pain component ( painDETECT unclear or positive score at baseline or screening ) . The most common treatment-emergent adverse events ( incidence ≥10 % , n = 176 ) were nausea , dizziness , headache , dry mouth , fatigue , constipation , diarrhea , nasopharyngitis , and somnolence . Conclusions : Tapentadol prolonged release was well tolerated and effective for managing severe , chronic low back pain with or without a neuropathic pain component BACKGROUND This post-hoc analysis evaluated the effects of paliperidone extended-release ( ER ) in patients with schizophrenia and prominent affective symptoms . METHODS Pooled data from three 6-week , r and omized , double-blind , placebo-controlled studies were analyzed . Subjects received fixed doses of paliperidone ER 3 - 12 mg/day or placebo . Prominent affective symptoms were defined as depressive ( Positive and Negative Syndrome Scale [ PANSS ] depression item score of > or = 5 [ moderately severe ] ) and /or manic ( PANSS gr and iosity score of > or = 4 [ moderate ] , plus a score of > or = 4 [ moderate ] on at least 1 PANSS item for excitement , hostility , uncooperativeness , or poor impulse control ) . Assessment s included PANSS , Clinical Global Impressions-Severity ( CGI-S ) , Personal and Social Performance ( PSP ) scale , and adverse events ( AEs ) . RESULTS Among 193 patients with prominent affective symptoms , 140 received paliperidone ER and 53 received placebo . Paliperidone ER showed significant mean ( SD ) improvements vs. placebo in PANSS total ( -20.5 [ 23.8 ] vs. -6.3 [ 27.2 ] ; p<0.001 , respectively ) and all factor scores ( p<0.01 ) . Significant mean ( SD ) improvements were observed in PSP ( 7.2 [ 15.8 ] vs. 0.4 [ 14.6 ] ; p=0.004 ) and CGI-S ( -0.9 [ 1.2 ] vs. -0.3 [ 1.2 ] ; p<0.001 ) scores . Most common AEs with paliperidone ER vs. placebo : headache ( 16.4 % vs. 13.2 % ) , insomnia ( 7.9 % vs. 9.4 % ) , akathisia ( 7.1 % vs. 1.9 % ) , sedation ( 7.1 % vs. 3.8 % ) . LIMITATIONS These studies were not design ed to examine patients with prominent affective symptoms . Authors ' clinical judgment was used to define prominent affective symptoms , using relevant PANSS items . CONCLUSIONS Paliperidone ER was well tolerated and associated with significantly greater improvements in symptomatology , functioning , and overall clinical status vs. placebo in patients with schizophrenia and prominent affective symptoms SUMMARY Objective : Eszopiclone is a new , single-isomer , non-benzodiazepine , cyclopyrrolone agent under investigation for the treatment of insomnia . The present study was a r and omized , double-blind , multicenter , placebo-controlled trial conducted to assess the efficacy and safety of eszopiclone in adults with chronic primary insomnia . Research design and methods : Patients ( n = 308 ) were r and omized to receive placebo or eszopiclone ( 2 mg or 3 mg ) for 44 consecutive nights , followed by 2 nights of single-blind placebo . Efficacy was evaluated with polysomnography ( Nights 1 , 15 and 29 ) and patient-reports ( Nights 1 , 15 , 29 and 43/44 ) . Next-day residual effects were evaluated using the Digit-Symbol Substitution Test ( DSST ) . Results : Eszopiclone 3 mg had significantly less time to sleep onset ( p ≤ 0.0001 ) , more total sleep time and sleep efficiency ( p ≤ 0.0001 ) , better sleep maintenance ( p ≤ 0.01 ) , and enhanced quality and depth of sleep ( p < 0.05 ) across the double-blind period compared with placebo . Eszopiclone 2 mg had significantly less time to sleep onset ( p ≤ 0.001 ) , more total sleep time ( p ≤ 0.01 ) and sleep efficiency ( p ≤ 0.001 ) , and enhanced quality and depth of sleep ( p < 0.05 ) compared with placebo , but did not significantly improve sleep maintenance . There was no evidence of tolerance or rebound insomnia after therapy discontinuation . Median DSST scores showed no decrement in psychomotor performance relative to baseline and did not differ from placebo in either eszopiclone group . Treatment was well tolerated ; the most common adverse event related to eszopiclone was unpleasant taste . Conclusions : Patients treated with nightly eszopiclone 3 mg had better polysomnographic ( through Night 29 ) and patient-reported measures ( through Night 44 ) of sleep over the 6-week trial . There was no evidence of tolerance or rebound insomnia and no detrimental effects on next-day psychomotor performance using the DSST OBJECTIVE To evaluate the safety and efficacy of 2 dosages of cevimeline for the treatment of xerostomia and keratoconjunctivitis sicca in patients with Sjögren 's syndrome . METHODS A 12-week double-blind , r and omized , placebo-controlled study was performed . Patients were r and omly assigned to receive either placebo , 15 mg of cevimeline 3 times daily , or 30 mg of cevimeline 3 times daily . Patients were evaluated at baseline and throughout the study for their global assessment of dryness ( mouth , eyes , overall ) as well as their subjective assessment of the specific symptoms of dry mouth and dry eyes . Total saliva and tear flow also were measured . RESULTS Patients taking 30 mg of cevimeline 3 times daily had statistically significant improvements in their subjective global assessment of dry eyes ( P = 0.0453 ) , dry mouth ( P = 0.0004 ) , and increased salivary flow ( P = 0.007 ) . Patients receiving the 30-mg dosage also showed greater objective improvement ( increased salivary and lacrimal flow rates , as measured by Schirmer 's test ) than did patients receiving placebo . Frequently reported adverse events included headache , increased sweating , abdominal pain , and nausea . CONCLUSION Treatment with cevimeline at a dosage of 30 mg 3 times daily result ed in substantive improvement by increasing the rate of saliva and tear flow in patients with Sjögren 's syndrome , as well as improving subjective symptoms of dry mouth , dry eyes , and overall dryness . The 15-mg dosage relieved some symptoms , and both dosages were well tolerated Several concepts of minor depression in the sense of acute but less severe symptomatology than major depression have been proposed in the literature , but currently none of them is generally accepted . For the treatment of these conditions , only few recommendations based on empirical data are available . We conducted a r and omized double-blind multicentre study in depressed out patients comparing paroxetine and maprotiline in both patients with minor ( n = 245 ) and major depression ( n = 298 ) . For the diagnosis , Research Diagnostic Criteria were used in a modified version . Two response criteria were applied : a reduction of 50 % or more in total HAMD-17 scores from baseline ( criterion 1 ) , and a reduction of the HAMD-17 total score to 9 points or less ( criterion 2 ) . A completer and an endpoint analysis was performed . For patients with minor depression , remarkably high response rates were found for paroxetine ( criterion 1 : 90.9 % completer , 82.1 % endpoint ; criterion 2 : 89.1 % completer , 82.4 % endpoint ) while the respective rates for maprotiline tended to be lower ( criterion 1 : 80.4 % completer , 71.4 % endpoint ; criterion 2 : 84.9 % completer ; 76.1 % endpoint ) . Response rates in patients with major depression were for paroxetine : criterion 1 : 74.3 % completer , 62.8 % endpoint ; criterion 2 : 76.4 % completer , 65.2 % endpoint ; and for maprotiline : criterion 1:82.4 % completer , 68.5 % endpoint ; criterion 2 : 80.6 % completer ; 66.0 % endpoint , which resembles rates reported from previous antidepressant trials . Both drugs were generally well tolerated . Though no placebo control was carried out , our results suggest that minor depression is a disorder that is very likely to respond to antidepressant pharmacotherapy with paroxetine , but also with maprotiline at a favourable risk/benefit ratio OBJECTIVE To compare the safety and efficacy of bupropion with methylpheni date in children and adolescents with attention-deficit/hyperactivity disorder ( ADHD ) . METHODS In a 6-week r and omized double-blind study , 44 patients with a DSM-IV-TR diagnosis of ADHD were r and omly assigned to receive bupropion 100 - 150 mg/day ( 100 mg/day for < 30 kg and 150 mg/day for > 30 kg ) or methylpheni date 20 - 30 mg/day . Symptoms were assessed using Teacher and Parent Attention-Deficit/Hyperactivity Disorder Rating Scale-IV ( ADHD-RS-IV ) at baseline and weeks 3 and 6 . RESULTS Forty patients had at least one post-baseline measurement , and 38 patients completed the trial . No significant difference was found between the two groups on the Parent and Teacher ADHD-RS-IV scores ( [ F(1 , 38 ) = 0.266 , p = 0.609 ] and [ F(1 , 38 ) = 0.001 , p = 0.972 ] , respectively ) . By week 6 , 18 patients ( 90 % ) in each group achieved response on the Parent scale ( Fisher 's exact test p-value = 1.0 ) . With the Teacher ADHD-RS-IV used , eight ( 40 % ) patients in the bupropion group and 12 ( 60 % ) patients in the methylpheni date group achieved response by week 6 ( χ(2 ) ( 1 ) = 1.600 , p = 0.206 ) . Headache was observed more frequently in the methylpheni date group . Frequency of other side effects was not significantly different between the two groups . CONCLUSIONS Bupropion has a comparable safety and efficacy profile with methylpheni date in children and adolescents with ADHD The objective of this study was to compare the efficacy and safety of Claritin-D 24 Hour ( once daily ) with that of Claritin-D 12 Hour ( twice daily ) and placebo in the treatment of patients with seasonal allergic rhinitis ( SAR ) . In this double-blind , placebo-controlled , multicenter study , 469 patients with moderate-to-severe SAR symptoms were treated for 2 weeks with one of the following : Claritin-D 24 Hour ( a combination tablet formulation of loratadine 10 mg in the coating and pseudoephedrine sulfate 240 mg in an extended-release core ) , Claritin-D 12 Hour ( a combination tablet formulation of loratadine 5 mg in the tablet coating and 120 mg pseudoephedrine sulfate , 60 mg in the coating and 60 mg in the core ) , or placebo . Claritin-D 24 Hour and Claritin-D 12 Hour were consistently superior to placebo ( P < 0.01 ) in reducing total , nasal , and nonnasal symptom scores . Patients in the Claritin-D 24 Hour and Claritin-D 12 Hour groups also had significantly greater ( P lE 0.05 ) relief of rhinorrhea and nasal stuffiness as compared with placebo . Insomnia was reported significantly more often ( P < 0.01 ) in Claritin-D 12 Hour ( 15 % ) patients compared with Claritin-D 24 Hour ( 4 % ) and placebo ( 2 % ) patients . Dry mouth was reported significantly more often ( P < 0.05 ) in Claritin-D 24 Hour ( 13 % ) and Claritin-D 12 Hour ( 13 % ) groups compared with placebo ( 4 % ) . Claritin-D 24 Hour has efficacy comparable to Claritin-D 12 Hour in relieving allergic rhinitis symptoms while producing significantly less insomnia Aim of this study was to evaluate the effect on saliva flow rate and composition and on perceived xerostomia . The study used a Latin square design , all subjects being once daily ( at 7.00 a.m. ) taking the bendroflumethiazide ( 2.5 mg ) , furosemide ( 40 mg ) , or placebo , in a r and omised order . Each treatment period of 7 days was separated by wash-out periods of 14 days . Unstimulated and paraffin chewing stimulated whole saliva , and 3 % citric acid stimulated parotid and subm and ibular-sublingual secretion were collected twice daily , at 7.30 a.m. , with the patients in a fasting condition ( morning values ) , and at 10.30 a.m. , about 2 h after intake of a st and ard breakfast ( lunchtime values ) , on day 0 ( baseline ) , day 1 ( acute treatment ) , and day 7 ( chronic treatment ) . Saliva flow rates were measured and all four secretions were analysed for the concentration of sodium , potassium , chloride , and total protein . Xerostomia was assessed by means of a Visual Analogue Scale . Statistical analysis used the Wilcoxon signed rank test . For flow rate , only that of subm and ibular-sublingual secretion was affected , significantly so in the morning during chronic treatment with both drugs . In resting whole saliva the output of both sodium and chloride tended to decrease especially during treatment with bendroflumethiazide , while in subm and ibular-sublingual secretion the output of all the electrolytes was decreased , especially for potassium and chloride and during treatment with furosemide . Further , xerostomia tended to increase during treatment with furosemide , statistically significant at lunchtime during chronic treatment . In conclusion , this study has demonstrated a modest effect on salivary flow rate and a more pronounced effect on saliva composition , especially in subm and ibular-sublingual secretion during treatment of healthy volunteers with therapeutic doses of two different diuretics , encouraging clinical studies in hypertensive patients and basic research as to the presence of a thiazide sensitive Na-Cl cotransporter in human salivary gl and OBJECTIVE Brimonidin tartrate is a highly selective alpha 2-agonist . This study investigates the safety and efficacy of 0.2 % brimonidine administered twice daily for 1 year in patients with glaucoma or ocular hypertension . METHODS The study design was a multicenter , double-masked , r and omized , parallel-group , active-controlled comparison clinical trial . Subjects instilled 0.2 % brimonidine or 0.5 % timolol maleate twice daily for 12 months . Subjects were examined at baseline , week 1 , and months 1 , 2 , 3 , 6 , 9 , and 12 . A subset of subjects was examined at week 2 . RESULTS Of 443 subjects enrolled in this study , 374 met the entry criteria ; 186 received brimonidine and 188 received timolol . Brimonidine-treated subjects showed an overall mean peak reduction in intraocular pressure ( IOP ) of 6.5 mm Hg ; timolol-treated subjects had a mean peak reduction in IOP of 6.1 mm Hg . Brimonidine lowered mean peak IOP significantly more than timolol at week 2 and month 3 ( P < .03 ) ; no significant difference was observed between the groups for this variable at other visits throughout the 1-year course of the study . No evidence of tachyphylaxis was seen in either group . Allergy was seen in 9 % of subjects treated with brimonidine . Dry mouth was more common in the brimonidine-treated group than in the timolol-treated group ( 33.0 % vs 19.4 % ) , but complaints of burning and stinging were more common in the timolol-treated group ( 41.9 % ) than in the brimonidine-treated patients ( 28.1 % ) . Headache , fatigue , and drowsiness were similar in the 2 groups . In general , the tolerance to medication was acceptable . CONCLUSIONS Brimonidine is safe and effective in lowering IOP in glaucomatous eyes . Brimonidine provides a sustained long-term ocular hypotensive effect , is well tolerated , and has a low rate of allergic response BACKGROUND Cytisine , a partial agonist that binds with high affinity to the α(4)β(2 ) nicotinic acetylcholine receptor , is a low-cost treatment that may be effective in aiding smoking cessation . This study assessed the efficacy and safety of cytisine as compared with placebo . METHODS We conducted a single-center , r and omized , double-blind , placebo-controlled trial . Participants were r and omly assigned to receive cytisine or matching placebo for 25 days ; participants in both groups received a minimal amount of counseling during the study . The primary outcome measure was sustained , biochemically verified smoking abstinence for 12 months after the end of treatment . Of 1542 adult smokers screened , 740 were enrolled and 370 were r and omly assigned to each study group . RESULTS The rate of sustained 12-month abstinence was 8.4 % ( 31 participants ) in the cytisine group as compared with 2.4 % ( 9 participants ) in the placebo group ( difference , 6.0 percentage points ; 95 % confidence interval [ CI ] , 2.7 to 9.2 ; P=0.001 ) . The 7-day point prevalence for abstinence at the 12-month follow-up was 13.2 % in the cytisine group versus 7.3 % in the placebo group ( P=0.01 ) . Gastrointestinal adverse events were reported more frequently in the cytisine group ( difference , 5.7 percentage points ; 95 % CI , 1.2 to 10.2 ) . CONCLUSIONS In this single-center study , cytisine was more effective than placebo for smoking cessation . The lower price of cytisine as compared with that of other pharmacotherapies for smoking cessation may make it an affordable treatment to advance smoking cessation globally OBJECTIVES To compare the efficacy and tolerability of imidafenacin , a novel antimuscarinic agent , with propiverine and a placebo in Japanese patients with overactive bladder ( OAB ) . METHODS Men and women having OAB symptoms were r and omized to double-blind treatment with 0.1 mg of imidafenacin twice daily , 20 mg of propiverine once daily , or a placebo for 12 weeks , and assessed for efficacy and safety . RESULTS Overall , 781 patients were r and omized to imidafenacin ( 324 ) , propiverine ( 310 ) , or a placebo ( 147 ) . After 12 weeks of treatment , a significantly larger reduction in the mean number of incontinence episodes was observed in the imidafenacin group than in the placebo group ( P < 0.0001 ) . The non-inferiority of imidafenacin compared with propiverine was confirmed for the reduction in using incontinence episodes ( P = 0.0014 , non-inferiority margin : 14.5 % ) . Imidafenacin was well tolerated . The incidence of adverse events with imidafenacin was significantly lower than with propiverine ( P = 0.0101 ) . Dry mouth , the most common adverse event , was significantly more common in the propiverine group than in the imidafenacin group ( P = 0.0302 ) . There were no significant increases in either the imidafenacin or placebo group in the mean QTc interval , whereas there was a significant increase in the mean QTc interval in the propiverine group ( P < 0.0001 ) , but there were no clinical arrhythmia and clinical arrhythmic events in any of the treatment groups . CONCLUSIONS The novel antimuscarinic agent imidafenacin at a dose of 0.1 mg twice daily was not inferior to propiverine for the reduction of incontinence episodes , and well tolerated for the treatment of OAB symptoms BACKGROUND Although treatments for Alzheimer 's disease sometimes improve cognition , functional ability , or behaviour compared with baseline levels , such improvements are inconsistent across studies and measures , and effects diminish over time . More effective treatments are needed . We assessed the safety , tolerability , and efficacy of dimebon in the treatment of patients with mild-to-moderate Alzheimer 's disease . METHODS We enrolled 183 patients with mild-to-moderate Alzheimer 's disease ( mini-mental state examination [ MMSE ] scores 10 - 24 ) at 11 sites in Russia . Patients were r and omly assigned by a computer-generated r and omisation scheme to receive oral dimebon , 20 mg three times a day ( 60 mg/day [ n=89 ] ) , or matched placebo ( n=94 ) . Other antidementia drugs were not allowed . The primary outcome measure assessed cognition , the difference in mean change from baseline to week 26 , or last completed observation on the cognitive subscale of the Alzheimer 's disease assessment scale ( ADAS-cog ) . All patients and study personnel were blinded throughout the study . We compared dimebon with placebo with an intention-to-treat analysis , with last observation carried forward ( ITT-LOCF ) imputation . Analyses were repeated on the fully evaluable population , defined as all patients in the intention-to-treat population who had an ADAS-cog at week 26 and at least 80 % compliance . 134 patients ( 68 in dimebon group , 66 in placebo group ) enrolled in the 6-month blinded extension phase of the study . This trial is registered with Clinical trials.gov , number NCT00377715 . FINDINGS 155 ( 85 % ) patients completed the trial ( 78 [ 88 % ] in dimebon group , 77 [ 82 % ] in placebo group ) . Treatment with dimebon result ed in significant benefits in ADAS-cog compared with placebo ( ITT-LOCF ) at week 26 ( mean drug-placebo difference -4.0 [ 95 % CI -5.73 to -2.28 ] ; p<0.0001 ) . Results of the ITT-LOCF and the evaluable population analyses were much the same for all measures . Patients given dimebon were significantly improved over baseline for ADAS-cog ( mean difference -1.9 [ -2.92 to -0.85 ] ; p=0.0005 ) . Dimebon was well tolerated : dry mouth and depressed mood or depression were the most common adverse events associated with dimebon ( 12 [ 14 % ] patients for each symptom by week 26 ) . The percentage of patients who had adverse events in the two groups did not differ . INTERPRETATION Dimebon was safe , well tolerated , and significantly improved the clinical course of patients with mild-to-moderate Alzheimer 's disease PURPOSE Efficacy , safety , and quality of life ( QoL ) for patients receiving larger doses of controlled-release oxycodone ( CR oxycodone ) in outpatient clinics are evaluated . METHODS The use of high-dose CR oxycodone and adjuvant drugs for pain management , pain intensity , parameters associated with quality of life , and adverse effects in cancer patients treated with high-dose CR oxycodone ( ≥80 mg/day ) was prospect ively observed for 8 weeks . Data from 486 cancer patients receiving high-dose CR oxycodone were collected from 44 hospitals during the period from February 2009 to March 2010 . RESULTS Three hundred eighteen of the total 486 patients treated with high-dose CR oxycodone were followed up for 8 weeks . Pain intensity significantly improved from a mean numeric rating scale ( NRS ) 5.49 to NRS 4.33 ( P < 0.0001 ) . Dosage of CR oxycodone increased from a mean of 130.0 to a mean of 174.9 ( P < 0.0001 ) . QoL including activity , walking , and sleeping significantly improved after 8 weeks . At baseline , 138 complained of adverse effects , of which constipation ( 30.2 % ) was the most common followed by dry mouth ( 8.8 % ) and dizziness ( 8.2 % ) . After 8 weeks , 128 patients complained of adverse effects such as constipation ( 27.0 % ) , nausea ( 5.7 % ) , dry mouth ( 5.7 % ) , and dizziness ( 5.0 % ) . After 8 weeks of high-dose CR oxycodone , adverse effects did not increase . CONCLUSION This study suggests that over an 8-week period , the use of high-dose CR oxycodone for cancer pain management is efficient , safe , and tolerable in outpatient clinics AIM To determine the efficacy of toterodine extended release ( ER ) treatment for 1 year in older men with benign prostatic hyperplasia ( BPH ) and storage symptoms treated with alpha-blockers and /or 5-alpha-reductase inhibitors ( 5ARI ) . METHODS Men aged over 70 years with BPH/bladder outlet obstruction ( BOO ) and clinical storage symptoms were r and omly treated with or without tolterodine ER in combination with alpha-blockers and /or 5ARI for 12 months . Among them , 50 patients ( group 1 ) received additive tolterodine extended release ( ER ) 4 mg q.d . , another 87 patients ( group 2 ) did not . All patients had a baseline and 12th month post-treatment evaluation , which comprised of uroflowmetry , post-void residual ( PVR ) volume , International Prostate Symptom Score ( IPSS ) , and quality of life index ( QoL-I ) , transrectal ultrasound of the prostate and serum prostate specific antigen . RESULTS One hundred thirty-seven of 153 enrolled patients with a mean age of 74.9 years completed the study . Treatment benefit demonstrated in both groups included deceased total , voiding and storage IPSS scores , increased peak urinary flow rate and deceased QoL-I. Inter-group difference was only observed on the storage domain of IPSS score ( P = 0.012 ) . The mean PVR after treatment did not significantly differ between two groups . Two patients of group 1 and three of group 2 developed acute urinary retention . Among group 1 , six patients discontinued tolterodine ER for intolerable dry mouth ; among group 2 , three patients reported dizziness . CONCLUSIONS This longer comparative study indicated that additive treatment with tolterodine ER in older men with BPH/BOO and significant storage symptoms is a beneficial and safe therapeutic option Abstract Objective : To evaluate the efficacy of levocetirizine 5 mg once daily in reducing seasonal allergic rhinitis ( SAR ) symptoms in US adults . Research design and methods : This multicenter , r and omized , double-blind , placebo-controlled , parallel-group study enrolled adults aged 18 to 65 years with SAR symptoms in the spring in the US . After a single-blind placebo run-in period , subjects received levocetirizine 5 mg or placebo once daily over 14 days . Clinical Trials.gov registry no. : Trial registration : Clinical Trials.gov identifier : NCT00621959 . Main outcome measures : Primary efficacy variable was the Total 5-Symptom Score ( T5SS ) . Secondary variables included Rhinoconjunctivitis Quality of Life Question naire ( RQLQ ) , Work Productivity and Activity Impairment – Allergy Specific ( WPAI-AS ) question naire , and Epworth Sleepiness Scale ( ESS ) . Safety assessment s were based on adverse events ( AEs ) . Results : The intent-to-treat population comprised 596 subjects ( levocetirizine , n = 301 ; placebo , n = 295 ) . Comparison of mean T5SS over the total treatment period showed a nonsignificant between-group difference ( levocetirizine , 8.90 ± 0.19 ; placebo , 9.04 ± 0.19 ; adjusted mean difference , −0.14 ; p = 0.546 ) . Levocetirizine showed numerical ( mean RQLQ , WPAI-AS , ESS ) and statistically superior differences ( two domains within WPAI-AS ) compared with placebo upon analysis of secondary efficacy variables . The incidence of treatment-emergent AEs was similar ( levocetirizine , 23.9 % ; placebo , 24.4 % ) . As the lack of efficacy was inconsistent with all previous levocetirizine studies , post hoc analyses were performed to assess the influence of pollen counts , geography , and other factors ; however , no conclusive explanation could be identified . Conclusions : In this study , levocetirizine 5 mg QD was well tolerated but failed to show significant efficacy compared with placebo in a US adult population with SAR . This finding is inconsistent with all previous studies with levocetirizine and in contrast to a concurrently run , similarly design ed US study . It reflects the importance of conducting duplicate studies as there is always a small but real risk of false negative results in clinical studies , irrespective of the method ologic quality Introduction This post-hoc analysis examined time to recovery in patients with acute , painful musculoskeletal conditions following cyclobenzaprine extended release ( CER ; AMRIX ® Cephalon , Inc. , Frazer , PA , USA ) , cyclobenzaprine immediate release ( CIR ; Flexeril ® Pliva , Pomona , NY , USA ) , or placebo administration . Methods Data were pooled from two identically design ed , double-blind , placebo-controlled , parallelgroup studies . Adults with acute , painful local muscle spasm were r and omized to once-daily CER 15 mg , once-daily CER 30 mg , three-timesdaily CIR 10 mg , or placebo for 14 days . Efficacy assessment s were time to first rating of “ a lot ” or “ complete ” relief from local pain or restriction of movement and patient-rated medication helpfulness . Results A total of 504 patients were r and omized , and 330 ( 65.5 % ) completed the studies . Median times to “ a lot ” or “ complete ” relief from local pain were faster with CER 15 mg ( 6 days , P=0.016 ) , CER 30 mg ( 5 days , P=0.002 ) , and CIR ( 5 days , P=0.002 ) versus placebo ( 8 days ) . Time to “ a lot ” or “ complete ” relief from restriction of movement was faster with CER 30 mg ( 5 days , P=0.004 ) and CIR ( 5 days , P=0.009 ) versus placebo ( 7 days ) . Median times to “ very good ” or “ excellent ” medication helpfulness were 10 days ( CER 15 mg , P=0.020 ) , 8 days ( CER 30 mg , P=0.004 ) , and 7 days ( CIR , P<0.001 ) versus > 14 days ( placebo ) . Dry mouth , constipation , dizziness , headache , and somnolence were the most commonly reported adverse events . Somnolence rates were lower with CER 15 mg ( 0.8 % , P=0.008 ) and CER 30 mg ( 1.6 % , P=0.028 ) versus CIR ( 7.3 % ) . Conclusion Relief from local pain and restriction of movement occurred sooner with CER and CIR than placebo . CER was associated with less somnolence than CIR |
13,298 | 32,035,805 | Developed countries were the most productive in the field of central venous catheters .
Most meta-analyses focused on complications associated with central -venous catheters such as infection and thrombosis | OBJECTIVE The central venous catheter is used extensively worldwide .
The purpose of this bibliometric analysis was to identify the 100 top-cited systematic review s/meta-analyses in the literature on central venous catheters and to capture the most important trends in this area of research . | Editor 's Note : This issue of In the Clinic has been up date d. One third of the world population has Mycobacterium tuberculosis infection ( 1 ) . Despite recent progress in the United States , tuberculosis infection remains prevalent in immigrants , immunosuppressed persons , and other high-risk groups ( 3 ) . Latent tuberculosis infection ( LTBI ) is the most prevalent form of tuberculosis in the United States ( 2 ) . LTBI can progress to active tuberculosis disease , especially in individuals with a suppressed cell-mediated immunity . Active tuberculosis disease in immuno-suppressed patients can be difficult to diagnose and can progress to disseminated forms of tuberculosis disease associated with high mortality ( 4 ) . New methods of diagnosing tuberculosis disease have entered practice in recent years ( 5 ) , but the diagnosis of LTBI can be challenging in some high-risk population s ( 6 , 7 ) . The introduction of directly observed therapy with first-line antituberculous regimens ( 8) was an important advance in therapy , but multidrug-resistant tuberculosis ( MDR-TB ) and the extensively resistant form of MDR-TB remain significant threats to international and local tuberculosis control efforts ( 9 , 10 ) . Screening and Prevention Who should be screened for tuberculosis ? Clinicians should screen all individuals at risk for tuberculosis infection , including close contacts of persons who have active pulmonary tuberculosis . Table 1 identifies asymptomatic individuals who should be screened because they are at high risk for exposure to active tuberculosis or at high risk for disease once infected . Table 1 . Risk Factors for Tuberculosis Infection or Progression to Disease After Infection What tests are used to screen for tuberculosis ? The tuberculin skin test ( TST ) with purified protein derivative ( PPD ) and the Mantoux method have been in use for more than 100 years to screen for tuberculosis . The TST result may not become positive for 8 to 10 weeks after exposure to active tuberculosis . The TST can give false-positive results in patient with previous bacille Calmette-Gurin ( BCG ) vaccination or other mycobacterial infections and false-negative results in anergic or immunosuppressed patients ; however , previous BCG vaccination should not change the interpretation of the TST in most adults . The newer interferon- release assays ( IGRAs ) , including the 2 U.S. Food and Drug Administration-approved commercial tests ( T-SPOT.TB [ Oxford Immunotec , Oxford , United Kingdom ] , and QuantiFERON-TB Gold and its In-tube version [ Cellestis , Valencia , California ] ) can also be used in circumstances in which the TST is currently used ( 11 ) . IGRAs assess the T-cell lymphocyte response to specific M. tuberculosis antigens ( for example , ESAT-6 and CFP-10 ) and are more specific , and possibly more sensitive , than TST ( 12 , 13 ) . However , information about IGRA performance is limited in immunocompromised patients and patients receiving immunosuppressive therapy ( 6 , 14 ) . The commercially available IGRAs also have limitations ; indeterminate results can occur in immunosuppressed patients , more so with QuantiFERON TB Gold than T-SPOT.TB ( 6 ) . Discordant results between TST and IGRA testing also occur in about 20 % of individuals ( 13 ) , which could be related , at least in part , to differences in performance characteristics of these tests ( 5 ) and to characteristics of the studied population s , such as the prevalence of persons previously vaccinated with BCG and the proportion of persons born outside the United States ( 15 , 16 ) . In addition to their improved specificity compared with TST , IGRAs have several practical advantages . They do not require a second visit for reading and they do not trigger amnestic responses . Longitudinal data supporting the predictive value of IGRA testing is limited , however , in contrast to the many studies of TST for predicting active tuberculosis ( 17 ) . A recent study from a high-incidence area of tuberculosis in Africa found that initial test results were positive in only 56 % of TST testing and 52 % of IGRA testing in close household contacts who developed active tuberculosis during 2 years of follow up . Of these close household contacts who developed active tuberculosis , 71 % had a positive result with either TST or IGRA during their initial evaluations ( 18 ) . Another prospect i ve study ( 19 ) from a country with a low incidence of tuberculosis suggests that IGRA testing could be more accurate than TST for diagnosing LTBI and for detecting individuals who will progress to active tuberculosis , but more longitudinal data are needed , especially in immunosuppressed individuals . What can patients do to reduce their likelihood of becoming infected with tuberculosis ? Tuberculosis is mainly transmitted by the airborne route from a patient with respiratory symptoms , and its ability to infect others decreases significantly after 2 weeks of effective therapy ( 20 , 22 ) . Therefore , prevention of tuberculosis transmission involves promptly identifying and treating patients with active tuberculosis . For hospitalized patients , prevention includes isolating patients with tuberculosis from other patients and strictly applying other hospital infection control practice s ( 23 , 24 ) . Patients usually can be removed from airborne infection isolation when they are no longer considered infectious . Patients are no longer infectious when they are on adequate tuberculosis drug therapy , have had a significant clinical response to therapy , and have had negative results on 3 consecutive sputum smears for acid-fast bacilli ( AFB ) . Some patients can be isolated from outsiders at home after appropriate evaluation and the initiation of outpatient treatment . Isolation of patients at home assumes that household contacts already have been exposed and that further exposure will not affect their outcomes . Two studies , one in India and one in Arkansas , showed similar rates of disease or infection in exposed household contacts whether the patient was admitted to the hospital or allowed to remain at home for initial treatment ( 25 , 26 ) . However , if household contacts of the patients with infectious tuberculosis are at high risk ( for example , infants or immuno-compromised persons ) , housing the patient elsewhere until he or she meets noninfectious criteria should be strongly considered . Hospitalization may be required until housing can be obtained ( 27 ) . Educating health care workers to evaluate exposed persons for active tuberculosis by obtaining sputum for AFB testing when they have respiratory symptoms has been shown to improve the case detection rates in primary care setting s ( 28 ) . What should clinicians tell patients with active tuberculosis to protect household members and other contacts from infection ? Clinicians should teach patients to cough into disposable tissues and to cover their nose and mouth when coughing or sneezing to contain droplet nuclei before they are expelled into the air . Patients who are placed in airborne infection isolation rooms should be educated about the transmission of tuberculosis , the reasons for isolation , and the importance of staying in their rooms . Every effort should be made to help the patient follow the isolation policy ( 29 ) . Hospital employees and physicians who come in contact with an infectious or suspected infectious patient should wear previously fitted particulate respirators certified by the National Institute for Occupational Safety and Health for protection against tuberculosis , which does not include surgical masks . What are the physician 's public health responsibilities after making a diagnosis of active tuberculosis ? All 50 U.S. states require physicians to notify public health authorities about all patients suspected of having active tuberculosis ( 22 , 23 ) , which can enable identification of other cases and potentially prevent further transmission of tuberculosis in the community . Genetic fingerprinting of tuberculosis isolates during an outbreak can help public health authorities detect tuberculosis infection in the community ( 30 ) . Clinical Bottom Line : Screening and Prevention Clinicians should screen persons who have close contact with a person who has active pulmonary tuberculosis , and screen other persons who are at high risk for infection or for progression to disease once infected . Clinicians should screen with TST or IGRAs and should prevent infection by identifying and treating persons with active pulmonary tuberculosis . Patient airborn infection isolation is an important part of early treatment and prevention of transmission . Persons who provide care to patients with active pulmonary tuberculosis should wear particulate respirators . Clinicians should notify public health authorities about patients with suspected active tuberculosis . Diagnosis What signs and symptoms suggest active tuberculosis ? Although tuberculosis can cause disease in many parts of the body , this article focuses on pulmonary tuberculosis because it is the most common form of the disease . Clinicians should consider a diagnosis of pulmonary tuberculosis and evaluate patients for tuberculosis if the patient has constitutional or pulmonary signs and symptoms , such as cough longer than 2 to 3 weeks ( may not be productive until later in course of disease ) , hemoptysis ( more likely with cavitation and rarely a presenting symptom ) , chest pain , fever , chills , night sweats , weight loss , easy fatigability , or anorexia . Some patients have classic signs and symptoms , but it is rare for someone to have most of the classic signs and symptoms except in advanced disease , and many patients will have few of them . Some patients with active pulmonary tuberculosis infection can be fairly asymptomatic . Table 2 shows some of the main findings from the history and the physical examination that are associated with active tuberculosis disease . Table 2 . Findings from the History and Physical Examination in Patients with Active Tuberculosis One study review ed 101 patients admitted to respiratory isolation to |
13,299 | 28,392,717 | WBE may have benefits with respect to maintaining or improving bone health in postmenopausal women but less benefit when compared to LBE . | BACKGROUND Age-related bone loss is a major health concern .
Only exercises associated with high-impact and mechanical loading have been linked to a positive effect on bone turnover ; however , these types of exercises may not always be appropriate for middle-aged and older adults due to physical decline or chronic disorders such as osteoarthritis .
Water-based exercise ( WBE ) has been shown to affect different components of physical fitness , has lower risks of traumatic fracture , and applies less stress to joints .
However , the effects of WBE on bone health are unclear .
OBJECTIVE This study aim ed to explore whether WBE is effective in preventing age-related bone deterioration in middle-aged and older adults . | The aim of this study was to assess the effectiveness of a 24-week exercise protocol carried out in geothermal spring water to improve overall physical function and muscle mass in a group of healthy elderly subjects . A further aim was to compare this water-based protocol with a l and -based protocol and a control group . For this purpose , 59 subjects were recruited and r and omly allocated to three groups : aquatic group ( AG ) , l and group ( LG ) , and control group ( CG ) . AG and LG followed a 6-month , twice-weekly , multimodality exercise intervention . AG underwent the protocol in hot-spring water ( 36 ° C ) while LG did it in a l and -based environment . After the intervention , knee-extension strength was maintained in AG and LG . The 8-foot up- and -go test showed a reduction in both exercise groups ( AG −19.3 % , P < 0.05 ; LG −12.6 % , P < 0.05 ) , with a significantly greater decrease in AG . The back-scratch test revealed an improvement only in AG ( 25.8 % ; P < 0.05 ) , while the sit- and -reach test improved in all groups . Finally , AG reduced fat mass by 4 % ( P < 0.05 ) , and dominant forearm fat decreased by 9.2 % ( P < 0.05 ) . In addition , calf muscle density increased by 1.8 % ( P < 0.05 ) . In summary , both water- and l and -based activities were beneficial in maintaining strength and in improving lower-body flexibility . Aquatic exercise appeared a better activity to improve dynamic balance . Thermal swimming pools and the use of rating of perceived exertion as a method of exercise monitoring should be considered potentially useful tools to enhance physical performance and body composition in healthy elderly The aim of the present study was to evaluate the effects of an AAG on BMD , osteocalcin and functional autonomy in older women . The sample consisted of eighty-two post-menopausal women with low BMD , r and omly divided into two groups : the Aquatic Aerobics Group [ AAG ; n=42 ; age : 66.8±4.2years ] , su bmi tted to two weekly sessions over eight months , and the Control Group ( GC ; n=42 ; age : 66.9±3.2years ) , which did not participate in regular exercise . BMD was measured by Dual Energy X-ray Absorptiometry [ DXA ] of the lumbar and femur , and serum osteocalcin was measured using electrochemiluminescence . A functional autonomy assessment protocol ( GDLAM , 2004 ) was also applied . Statistical analyses used were repeated measures ANOVA and Tukey 's post hoc tests . The results showed a significant improvement in tests following the GDLAM protocol : 10 meters walk ( 10mw ) -p=0.003 ; rising from a ventral decubitus position ( RVDP ) - Δ%=0.78 , p<0.001 ; rising from a chair and moving around the house ( RCMH ) -p<0.001 and autonomy index ( AI ) -p=0.007 , with more favorable results observed in the AAG when compared to the CG . The AAG achieved the best results for BMD ; however , no inter or intragroup statistical differences were recorded for total femur -p=0.975 and lumbar L(2)-L(4)p=0.597 . For serum osteocalcin , intra and intergroup statistical differences of p=0.042 and p=0.027 were observed in the AAG , respectively . This demonstrates that an eight-month aquatic aerobic exercise program can improve functional autonomy and osteocalcin levels , although training did not improve lumbar and total femur BMD in the older women BACKGROUND Fractures have been associated with subsequent increases in mortality , but it is unknown how long that increase persists . METHODS A total of 5580 women from a large community-based , multicenter US prospect i ve cohort of 9704 ( Study of Osteoporotic Fractures ) were observed prospect ively for almost 20 years . We age-matched 1116 hip fracture cases with 4 control participants ( n = 4464 ) . To examine the effect of health status , we examined a healthy older subset ( n = 960 ) 80 years or older who attended the 10-year follow-up examination and reported good or excellent health . Incident hip fractures were adjudicated from radiology reports by study physicians . Death was confirmed by death certificates . RESULTS Hip fracture cases had 2-fold increased mortality in the year after fracture compared with controls ( 16.9 % vs 8.4 % ; multivariable adjusted odds ratio [ OR ] , 2.4 ; 95 % CI , 1.9 - 3.1 ] . When examined by age and health status , short-term mortality was increased in those aged 65 to 69 years ( 16.3 % vs 3.7 % ; OR , 5.0 ; 95 % CI , 2.6 - 9.5 ) , 70 to 79 years ( 16.5 % vs 8.9 % ; OR , 2.4 ; 95 % CI , 1.8 - 3.3 ) , and only in those 80 years or older with good or excellent health ( 15.1 % vs 7.2 % ; multivariable adjusted OR , 2.8 ; 95 % CI , 1.5 - 5.2 ) . After the first year , survival of hip fracture cases and controls was similar except in those aged 65 to 69 years , who continued to have increased mortality . CONCLUSIONS Short-term mortality is increased after hip fracture in women aged 65 to 79 years and in exceptionally healthy women 80 years or older . Women 70 years or older return to previous risk levels after a year . Interventions are needed to decrease mortality in the year after hip fracture , when mortality risk is highest OBJECTIVE To analyze the effects of a water-based exercise program on peak torque ( PT ) and rate of torque development ( RTD ) during maximal voluntary ballistic isometric contractions of the lower limb muscles and the performance of a number of functional tests in the elderly . METHOD Thirty-seven elderly were r and omly assigned to water-based training ( 3 d/wk for 12 wk ) or a control group . Extensor and flexor PT and RTD of the ankle , knee , and hip joints and functional tests were evaluated before and after training . RESULTS PT increased after training for the hip flexors ( 18 % ) and extensors ( 40 % ) and the plantar-flexor ( 42 % ) muscles in the water-based group . RTD increased after training for the hip-extensor ( 10 % ) , knee-extensor ( 11 % ) , and ankle plantar-flexor ( 27 % ) muscles in the water-based group . Functional tests also improved after training in the water-based group ( p < .05 ) . CONCLUSION The water-based program improved PT and RTD and functional performance in the elderly Background and Purpose Aquatic physical therapy is frequently used in the management of patients with hip and knee osteoarthritis ( OA ) , yet there is little research establishing its efficacy for this population . The purpose of this study was to evaluate the effects of aquatic physical therapy on hip or knee OA . Subjects A total of 71 volunteers with symptomatic hip OA or knee OA participated in this study . Methods The study was design ed as a r and omized controlled trial in which participants r and omly received 6 weeks of aquatic physical therapy or no aquatic physical therapy . Outcome measures included pain , physical function , physical activity levels , quality of life , and muscle strength . Results The intervention result ed in less pain and joint stiffness and greater physical function , quality of life , and hip muscle strength . Totals of 72 % and 75 % of participants reported improvements in pain and function , respectively , compared with only 17 % ( each ) of control participants . Benefits were maintained 6 weeks after the completion of physical therapy , with 84 % of participants continuing independently . Discussion and Conclusion Compared with no intervention , a 6-week program of aquatic physical therapy result ed in significantly less pain and improved physical function , strength , and quality of life . It is unclear whether the benefits were attributable to intervention effects or a placebo response BACKGROUND Osteoporosis is a multifactorial progressive skeletal disorder characterized by reduced bone mass . Exercise is widely recommended to reduce osteoporosis , falls and related fragility fractures . The purpose of this study was to investigate the effects of l and exercise ( LE ) and aquatic exercise ( AE ) on physical function and bone mineral density ( BMD ) . MATERIAL AND METHODS Fifty-eight postmenopausal women , aged 50 - 70 years , diagnosed with osteoporosis according to BMD measures , enrolled in this study . The subjects were r and omly assigned to either the intervention group ( LE group ) or the control group ( AE group ) . Physical function and BMD were assessed in all subjects in both groups before and after 10 months of intervention . Muscle strength , flexibility , balance , gait time and pain were measured to assess physical function . Bone mineral density at the lumbar spine was measured by dual energy X-ray absorptiometry ( DEXA ) . RESULTS There were no significant differences between the two groups in the baseline anthropometric data . The two groups were similar with respect to age , weight , height , and body mass index ( p>0.05 ) . After the exercise program , muscle strength , flexibility , gait time , pain , and bone density ( p<0.001 ) improved significantly with LE compared to AE . There was no significant difference between the two groups with regard to balance at the 10-month follow-up . CONCLUSION Significant improvements in physical function and BMD suggest that LE is a possible alternative for postmenopausal women with OP Abstract . Osteoporosis is one of the most common skeletal disorders affecting postmenopausal women . The purpose of this study was to investigate whether a 24-week program of aerobic high-impact loading exercise was beneficial for enhancing physical fitness and bone mineral density ( BMD ) in osteopenic postmenopausal women . Forty-three postmenopausal women aged 48–65 years participated in this study . The BMD of the spine ( L2–L4 ) and right femoral neck of each woman was below 1 SD of the mean of premenopausal women , as examined by dual X-ray absorptiometry . The assignment of subjects into exercise or control group was not r and omized but based on each subject 's anticipated compliance to the 6-month long exercise program . Twenty-two subjects joined the exercise group and attended the training programs and 21 served as the control group . Exercise programs included treadmill walking at an intensity above 70 % of maximal oxygen consumption ( VO2max ) for 30 minutes , followed by 10 minutes of stepping exercise using a 20-cm-high bench . The program was conducted three times per week for 24 weeks . Physical fitness measurements included testing of flexibility , muscular strength and endurance , body composition , and cardiopulmonary fitness . The results showed that the quadriceps strength , muscular endurance , and VO2max in the exercise group had significant improvements , whereas no improvement was found in any of the physical fitness parameters in the control group . The BMD of the L2–L4 and the femoral neck in the exercise group increased 2.0 % ( P > 0.05 ) and 6.8 % ( P < 0.05 ) and those in the control group decreased 2.3 % ( P < 0.05 ) and 1.5 % ( P > 0.05 ) , respectively . In conclusion , aerobics combined with high-impact exercise at a moderate intensity was effective in off setting the decline in BMD in osteopenic postmenopausal women Summary In women aged 50 years or more who experienced a fracture , 81 % suffered a fragility fracture . Six to eight months after fragility fracture , 79 % had either not been investigated for osteoporosis or prescribed anti-fracture therapy . Despite fragility fractures being common in this population osteoporosis is under-diagnosed and under-treated . Introduction The objective of this study was to evaluate the diagnostic and treatment rates for osteoporosis six months following fragility fracture . Methods This prospect i ve cohort study was set in the general community from the Province of Quebec , Canada . Women at least 50 years of age who suffered a fracture were recruited during their initial visit to the hospital and had their fracture type classified as either fragility or traumatic . Six-to-eight months after fragility fracture , women were again contacted to evaluate the diagnostic and treatment rates of osteoporosis . Results Of the 2,075 women recruited over a 25 month period 1688 ( 81 % ) sustained a fragility fracture and 387 ( 19 % ) sustained a traumatic fracture . Nine hundred and three participants with a fragility fracture were again contacted six-to-eight months after fracture . For the 739 women not on treatment on the recruitment day , only 15.4 % initiated pharmacological therapy in the six-to-eight-month period following fracture and 79.0 % had either not been investigated for osteoporosis or prescribed anti-fracture treatment . Conclusions The proportion of fragility fractures to total fractures is higher than previously reported . Despite the availability of diagnostic modalities , effective treatments , and adequate health care assessment s , there is a substantial care gap in the management of osteoporosis PURPOSE The purpose of this study was to identify the effects of water-based exercises on the physical functions and quality of life ( QOL ) in community-dwelling elderly people with history of falling . MATERIAL S AND METHODS Participants were r and omly assigned to the water-based exercise group ( n=34 ) or l and -based exercise groups ( n=32 ) . To identify the effects on physical functions , muscle strength , flexibility , and mobility were measured . QOL and fear of falling were evaluated using the Short Form 36-item question naire and the modified falls efficacy scale ( M-FES ) . The measurements were performed before and after the 10-week training period . RESULTS Within-group analysis indicated that hip abduction and adduction strength improved significantly in both groups ( p=0.005 ; p=0.007 ) . However , no statistically significant within-group differences were found in the back scratch test ( p=0.766 ) and chair sit- and -reach test ( p=0.870 ) . QOL was significantly different in both groups ( health transition : p=0.014 , physical functioning : p<0.001 , role physical : p<0.001 , role emotional : p=0.002 , bodily pain : p<0.001 , vitality : p<0.001 , and mental health : p<0.001 ) . There was a significant difference in the M-FES in both groups ( p=0.040 ) . CONCLUSIONS These results indicate that water-based exercises are beneficial to improve the QOL , as well as physical activities , of community-dwelling elderly compared with l and -based exercise . Water-based exercises would be useful to improve physical and psychological health in the elderly people with history of falling The effects of water exercise , as a form of daily physical activity ( water exercise in a warm water pool ) , on bone loss in healthy Japanese postmenopausal women have been cross-sectionally and longitudinally investigated from the viewpoint of preventing osteoporosis . In the cross-sectional study , the bone mineral density ( BMD ) of the lumbar spine ( Z-score ( % ) ) in the Veterans group ( N = 27 ) , who had been exercising for 35.2 months on average , was significantly higher than that in the Newcomers ( N = 40 ) , who had only begun to exercise 3 or 4 weeks before , and that in the Non-exercisers ( N = 30 ) , serving as a control group . The rate of change in the BMD of the lumbar spine was -0.92%/year in the Non-exercisers ( N = 30 ) , + 1.55%/year in the Veterans ( N = 20 ) , and + 2.16%/year in the Newcomers ( N = 15 ) , based on BMD Z-scores . In the Exercisers groups , it was found that the rate of change in the BMD showed a slight increase rather than a decrease irrespective of the duration of menopause . On the other h and , in the Non-exercisers group , the rate of change in the BMD decreased slightly . The results of question naires showed that the subjects ' general awareness of health and fitness in daily life was enhanced after starting the water exercise program . These results suggest that consistently participating in water exercise is an important factor in preventing bone loss , and moreover , appears not only to indirectly improve awareness of daily physical activity but also to promote health and improve daily life Introduction : The purpose of this r and omized controlled study was to assess the effects of high-impact exercise on the bone mineral density ( BMD ) of premenopausal women at the population level . Material s and methods : The study population consisted of a r and om population -based sample of 120 women from a cohort of 5,161 women , aged 35 to 40 years . They were r and omly assigned to either an exercise or control group . The exercise regimen consisted of supervised , progressive high-impact exercises three times per week and an additional home program for 12 months . BMD was measured on the lumbar spine ( L1–L4 ) , proximal femur , and distal forearm , by dual-energy X-ray absorptiometry at baseline and after 12 months . Calcaneal bone was measured using quantitative ultrasound . Results : Thirty-nine women ( 65 % ) in the exercise group and 41 women ( 68 % ) in the control group completed the study . The exercise group demonstrated significant change compared with the control group in femoral neck BMD ( 1.1 % vs −0.4 % ; p=0.003 ) , intertrochanteric BMD ( 0.8 % vs −0.2 % ; p=0.029 ) , and total femoral BMD ( 0.1 % vs −0.3 % ; p=0.006 ) . No exercise-induced effects were found in the total lumbar BMD or in the lumbar vertebrae L2–L4 . Instead , L1 BMD ( 2.2 % vs −0.4 % ; p=0.002 ) increased significantly more in the exercise group than in the control group . Calcaneal broadb and ultrasound attenuation showed also a significant change in the exercise group compared with the control group ( 7.3 % vs −0.6 % ; p=0.015 ) . The changes were also significant within the exercise group , but not within the control group . There were no significant differences between or within the groups in the distal forearm . Conclusions : This study indicates that high-impact exercise is effective in improving bone mineral density in the lumbar spine and upper femur in premenopausal women , and the results of the study may be generalized at the population level . This type of training may be an efficient , safe , and inexpensive way to prevent osteoporosis later in life Background Following publication of the PRISMA statement , the UK Centre for Review s and Dissemination ( CRD ) at the University of York in Engl and began to develop an international prospect i ve register of systematic review s with health-related outcomes . The objectives were to reduce unplanned duplication of review s and provide transparency in the review process , with the aim of minimizing reporting bias . Methods An international advisory group was formed and a consultation undertaken to establish the key items necessary for inclusion in the register and to gather views on various aspects of functionality . This article describes the development of the register , now called PROSPERO , and the process of registration . Results PROSPERO offers free registration and free public access to a unique prospect i ve register of systematic review s across all areas of health from all around the world . The dedicated web-based interface is electronically search able and available to all prospect i ve registrants . At the moment , inclusion in PROSPERO is restricted to systematic review s of the effects of interventions and strategies to prevent , diagnose , treat , and monitor health conditions , for which there is a health-related outcome .Ideally , registration should take place before the research ers have started formal screening against inclusion criteria but review s are eligible as long as they have not progressed beyond the point of completing data extraction .The required data set captures the key attributes of review design as well as the administrative details necessary for registration .Su bmi tted registration forms are checked against the scope for inclusion in PROSPERO and for clarity of content before being made publicly available on the register , rejected , or returned to the applicant for clarification . The public records include an audit trail of major changes to planned methods , details of when the review has been completed , and links to result ing publications when provided by the authors . Conclusions There has been international support and an enthusiastic response to the principle of prospect i ve registration of protocol s for systematic review s and to the development of PROSPERO .In October 2011 , PROSPERO contained 200 records of systematic review s being undertaken in 26 countries around the world on a diverse range of interventions UNLABELLED Based on data search es and life-table analyses , we determined the long-term ( remaining lifetime ) and short-term ( 10- and 5-year ) absolute risks of hip fracture after sustaining a Colles ' or spine fracture and search ed for potential gender-related differences . In aging men , Colles ' fractures carry a higher absolute risk for hip fracture than spinal fractures in contrast to women . These findings support the concept that forearm fracture is an early and sensitive marker of male skeletal fragility . INTRODUCTION Colles ' fracture occurrence has been largely ignored in public health approaches to identify target population s at risk for hip fracture . The aim of this study was to estimate the long-term and short-term absolute risks of hip fracture after sustaining a Colles ' or spine fracture and to search for potential gender-related differences in the relationship between fracture history and future fracture risk . MATERIAL S AND METHODS To determine the long-term ( remaining lifetime ) and short-term ( 10- and 5-year ) absolute risks of hip fracture , we applied life-table methods using U.S. age- and sex-specific hip fracture incidence rates , U.S. age-specific mortality rates for white women and men , pooled hazard ratios for mortality after Colles ' and spine fracture , and pooled relative risks for hip fracture after Colles ' and spine fracture , estimated from cohort studies by st and ard meta-analytic methods . RESULTS Our results indicate that the estimated remaining lifetime risks are dependent on age in both genders . In women , remaining lifetime risks increase until the age of 80 years , when they start to decline because of the competing probabilities of fracture and death . The same pattern is found in men until the age of 85 years , the increment in lifetime risk being even more pronounced . As expected , the risk of sustaining a hip fracture was found to be higher in postmenopausal women with a previous spine fracture compared with those with a history of Colles ' fracture . In men , on the other h and , the prospect i ve association between fracture history and subsequent hip fracture risk seemed to be strongest for Colles ' fracture . At the age of 50 , for example , the remaining lifetime risk was 13 % in women with a previous Colles ' fracture compared with 15 % in the context of a previous spine fracture and 9 % among women of the general population . In men at the age of 50 years , the corresponding risk estimates were 8 % , 6 % , and 3 % , respectively . Similar trends were observed when calculating 5- and 10-year risks . CONCLUSIONS In aging men , Colles ' fractures carry a higher absolute risk for hip fracture than spinal fractures in contrast to women . These findings support the concept that forearm fracture is an early and sensitive marker of male skeletal fragility . The gender-related differences reported in this analysis should be taken into account when design ing screening and treatment strategies for prevention of hip fracture in men The purpose of the present study was to determine the effectiveness of a 24-week aquatic training ( AT ) program , which included both aerobic and resistance components , on muscle strength ( isometric and dynamic ) , flexibility , and functional mobility in healthy women over 60 years of age . Twenty-two subjects were assigned r and omly to either an AT ( n = 12 ) or a control ( C , n = 10 ) group . Volunteers participated in a supervised shallow-water exercise program for 60 minutes a day , 3 days a week ; the exercise program consisted of a 10-minute warm-up and stretching , 25 minutes of endurance-type exercise ( dancing ) at 80 % of heart rate (HR)max , 20 minutes of upper- and lower-body resistance exercises with specialized water-resistance equipment , and a 5-minute cool down . Maximal isometric torque of knee extensors ( KEXT ) and knee flexors ( KFLEX ) were evaluated by a Cybex Norm dynamometer , grip strength ( HGR ) was evaluated using a Jamar hydraulic dynamometer , and dynamic strength was evaluated via the 3 repetition maximum ( 3RM ) test for chest press , knee extension , lat pull down , and leg press . Jumping performance was evaluated using the squat jump ( SJ ) , functional mobility with the timed up- and -go ( TUG ) test , and trunk flexion with the sit- and -reach test . Body composition was measured using the bioelectrical impedance method . The AT induced significant improvements in KEXT ( 10.5 % ) and KFLEX ( 13.4 % ) peak torque , HGR strength ( 13 % ) , 3RM ( 25.7–29.4 % ) , SJ ( 24.6 % ) , sit- and -reach ( 11.6 % ) , and TUG ( 19.8 % ) performance . The AT group demonstrated a significant increase in lean body mass ( 3.4 % ) . No significant changes in these variables were observed in the C group . The results indicate that AT , with both aerobic and resistance components , is an alternative training method for improving neuromuscular and functional fitness performance in healthy elderly women |
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